kristoff@GENBANK.BIO.NET (Dave Kristofferson) (05/29/91)
NOTE: The NIH Guide may be split into more than one mail message to
avoid truncation during e-mail distribution. The first message always
begins with the RFP/RFA summary sections followed by the appended
texts of the full RFP/RFAs.
----------------------------------------------------------------------
$$XID NIHGUIDE 19910524 V20N20 P1O2 ************************************
X-comment: RFAs described: CA-91-16
NIH GUIDE - Vol. 20, No. 20, May 24, 1991
$$INDEX BEGIN **********************************************************
NOTICES
$$INDEX N1 *************************************************************
NUCLEIC ACID AND PROTEIN SEQUENCE ANALYSIS WORKSHOP FOR BIOMEDICAL
RESEARCHERS
National Center for Research Resources
Index: RESEARCH RESOURCES
$$INDEX N2 *************************************************************
AVAILABILITY OF RESOURCE FOR DIETARY INTAKE AND NUTRITION RESEARCH
National Heart, Lung, and Blood Institute
Index: HEART, LUNG, BLOOD
$$INDEX N3 *************************************************************
CURRENTLY ACTIVE NCI PROGRAM ANNOUNCEMENTS
National Cancer Institute
Index: CANCER
NOTICES OF AVAILABILITY (RFPs AND RFAs)
$$INDEX R1 *************************************************************
MICROSTIMULATORS AND MICROTRANSDUCERS FOR FUNCTIONAL NEUROMUSCULAR
STIMULATION (RFP)
National Institute of Neurological Disorders and Stroke
Index: NEUROLOGICAL DISORDERS, STROKE
$$INDEX R2 10/15/91 ****************************************************
NEW THERAPEUTIC APPROACHES TO THE TREATMENT OF PROSTATE CANCER
(RFA CA-91-16)
National Cancer Institute
Index: CANCER
ONGOING PROGRAM ANNOUNCEMENTS
$$INDEX P1 *************************************************************
COMBINED PSYCHOSOCIAL AND PHARMACOLOGIC TREATMENTS RESEARCH (PA-91-54)
National Institute of Mental Health
Index: MENTAL HEALTH
$$INDEX P2 *************************************************************
NEUROPEPTIDE MODULATION OF SALIVARY IMMUNITY (PA-91-55)
National Institute of Dental Research
Index: DENTAL RESEARCH
$$INDEX P3 *************************************************************
CLINICAL INVESTIGATOR AWARD - NURSING (PA-91-56)
National Center for Nursing Research
Index: NURSING RESEARCH
$$INDEX P4 *************************************************************
ACADEMIC INVESTIGATOR AWARD - NURSING (PA-91-57)
National Center for Nursing Research
Index: NURSING RESEARCH
$$INDEX P5 *************************************************************
RESEARCH ON HOSPITALIZATION OF ADOLESCENTS FOR MENTAL DISORDERS
(PA-91-58)
National Institute of Mental Health
Index: MENTAL HEALTH
$$INDEX END ************************************************************
NOTICES
$$N1 BEGIN *************************************************************
NUCLEIC ACID AND PROTEIN SEQUENCE ANALYSIS
WORKSHOP FOR BIOMEDICAL RESEARCHERS
P.T.
National Center for Research Resources
The Pittsburgh Supercomputing Center (PSC) is conducting a
five-day workshop on "Nucleic Acid and Protein Sequence
Analysis," August 5-9, 1991. This workshop is funded by a
grant from the National Center for Human Genome Research of
the National Institutes of Health.
The workshop will familiarize biomedical researchers with
computational methods and provide practice in applying
supercomputing resources to problems of concern in
macromolecular sequence analysis. The workshop will
emphasize alignment of and pattern extraction from multiple
sequences. Participants will gain practical experience on
Pittsburgh Supercomputing Center's Cray Y-MP/832 in (1)
comparing and aligning sequences, (2) identifying informative
patterns in a set of sequences, and (3) using extracted
informative patterns to identify related sequences.
Participants will gain experience with rigorous dynamic
programming approaches to multiple sequence alignment as well
as with consensus word approaches; they will also learn how
to use profile analysis effectively on their own problems.
Participants are encouraged to bring sequence analysis
problems from their current research.
Workshop Leaders: Stephen Altschul and Greg Schuler from
the National Library of Medicine and Michael Gribskov from
the Frederick Cancer Research
Facility of the National Cancer Institute.
This five-day workshop will introduce participants to VAX
VMS and Unicos, the Cray version of the AT&T System V Unix
operating system. No prior computing experience is required.
A limited number of grants to cover travel and hotel
accommodations are available for U.S. academic participants.
A few openings for industry-based biomedical researchers may
be available for a fee of $1000. Enrollment is limited to 20
participants. The deadline for the submission of
applications is June 14, 1991.
Grants of supercomputing time to allow biomedical researchers
to explore the appropriateness of supercomputing for their
computational problems are available through a program
funded by the Biomedical Research Technology Program,
National Center for Research Resources, National Institutes
of Health.
For application forms and further information, call or write:
Nancy Kiser
Biomedical Coordinator
Pittsburgh Supercomputing Center
4400 Fifth Avenue
Pittsburgh, PA 15213
Telephone: (412) 268-5206 or 1-800-222-9310 (PA)
1-800-221-1641 (outside PA)
E-mail: kiser@a.psc.edu or kiser@cpwpsca.bitnet
$$N1 END ***************************************************************
$$N2 BEGIN *************************************************************
AVAILABILITY OF RESOURCE FOR DIETARY INTAKE AND NUTRITION RESEARCH
P.T.
National Heart, Lung, and Blood Institute
The Nutrition Coordinating Center (NCC) at the University of Minnesota
is a unique national resource available for dietary data collection and
nutrient calculation for epidemiological studies, clinical trials, and
other medical research studies. The center provides standardized
procedures for collecting food intake data and calculating nutrient
intakes at the high level of specificity needed for investigations of
the relationship between diet and disease.
Investigators can use the services of the NCC in two ways. First, they
can license use of the Minnesota Nutrition Data System (NDS). NDS is a
microcomputer-based software package for interactive dietary data
collection and nutrient calculation. NDS prompts the user to describe
food intake at the level of detail required for dietary research and
calculates the nutrient content of the intake. Then NDS presents the
data on the screen, in printed reports, or in ASCII files that can be
merged with other study data or with statistical analysis software. The
NDS database allows the user to describe over 150,000 foods and 6,000
brand name products. The database contains values for 93 nutrients,
including soluble and insoluble fiber fractions, 23 individual fatty
acids, and 18 amino acids. NDS can be used to guide 24-hour dietary
recall interviews or to process food intake records. NDS can also be
used to collect and analyze diet histories and to calculate the nutrient
content of recipes. A customized version of NDS is being used in the
National Health and Nutrition Examination Survey (NHANES III) to collect
dietary data from more than 30,000 Americans.
Alternatively, investigators can send dietary intake records to NCC for
processing. Data collection and processing procedures can be customized
to meet the needs of specific studies. Investigators may reanalyze data
collected in the past to take advantage of improved analytical data and
new nutrients added to the database. Over the past 17 years, NCC has
processed more than 250,000 records.
NCC also provides a two-day training program for dietary interviewers.
For investigators who send dietary intake records to NCC for processing,
the training ensures the use of standardized data collection procedures
tailored to the research protocol. Interviewers are certified following
satisfactory completion of the training. For investigators using the
NDS directly, the training is designed to enhance use of the software to
meet research protocol requirements. Over the past 17 years, NCC has
trained and certified more than 600 dietary interviewers.
NCC receives its major support from the National Heart, Lung, and Blood
Institute, the National Cancer Institute, and the National Center for
Health Statistics. NCC services and software are used by investigators
in academia, government, non-profit organizations, and industry. Users
are required to pay a fee to cover part of the operational costs.
For information and fee schedules, contact:
Marilyn Buzzard, PhD
Director
Coordinating Center
2221 University Avenue, SE
Suite 310
Minneapolis, MN 55414
Telephone: (612) 627-4869
FAX: (612) 626-9054
$$N2 END ***************************************************************
$$N3 BEGIN *************************************************************
CURRENTLY ACTIVE NATIONAL CANCER INSTITUTE PROGRAM ANNOUNCEMENTS
P.T.
National Cancer Institute
In addition to unsolicited grant applications and grant applications in
response to other Program Announcements, the National Cancer Institute
is current accepting applications in response to the following Program
Announcements, which appeared in the NIH Guide for Grants and Contracts
on the dates indicated. Also, refer to the the publication, "NIH
Extramural Programs, available from the Office of Grants Inquiries,
Division of Research Grants, National Institutes of Health, Westwood
Building, Room 449, Bethesda, MD 20892.
o Individual Postdoctoral National Service Award Fellowships in
Radiological Sciences Related To Cancer (Vol. 20, No. 17, April
26, 1991)
o Clinical Cancer Therapy Research (Vol. 20, No. 15, April 12, 1991)
o The NCI Outstanding Investigator Grant (Vol. 20, No. 9, March 1,
1991)
o Surgical Oncology (Vol. 19, No. 46, December 28, 1990)
o Multidisciplinary Research on Solid Tumors (Vol. 19, No. 23, June
22, 1990)
o Obesity, Endocrine and Fat Metabolism and Cancer Risk (Vol. 19,
No. 19, May 18, 1990)
o Domestic Animal Models of Retroviral Associated Malignancies (Vol.
19, No. 19, May 18, 1990)
o Epidemiologic Studies of Cancer and Human Retroviruses (Vol. 19,
No. 18, May 4, 1990)
o Underlying Molecular, Cellular and Immunological Factors in
Age-Related Cancers (Vol. 19, No. 16, April 20, 1990)
o NCI/MARC Summer Training Supplement (Vol. 18, No. 43, December 1,
1989)
o Studies on Cancer Etiology in Finfish and Shellfish (Vol. 18, No.
33, September 22, 1989)
o Specific Cancer Cell Targeting Using Molecular Genetic Technology
(Vol. 18, No. 6, February 24, 1989)
o Regulation of Prostatic Involution as Related to Prostatic Cancer
(Vol. 18, No. 6, February 24, 1989)
o Small Grants Program for Epidemiology (Vol. 17, No. 25, August 5,
1988)
o The Role of Growth Regulatory Factors in Normal and Neoplastic
Prostate (Vol. 16, No. 42, December 25, 1987)
Copies and information related to the background of the above Program
Announcements are available by contacting:
Vincent T. Oliverio, Ph.D.
Associate Director
Division of Extramural Activities
National Cancer Institute
National Institutes of Health
Building 31, Room 10A05
Bethesda, MD 20892
Telephone: (301) 496-9138
FAX: (301) 402-0062
$$N3 END ***************************************************************
NOTICES OF AVAILABILITY (RFPs AND RFAs)
$$R1 BEGIN NIH-NINDS-91-12 *********************************************
MICROSTIMULATORS AND MICROTRANSDUCERS FOR FUNCTIONAL
NEUROMUSCULAR STIMULATION
RFP AVAILABLE: NIH-NINDS-91-12
P.T.
National Institute of Neurological Disorders and Stroke
The Neural Prosthesis Program (NPP) of the National Institute of
Neurological Disorders and Stroke, NIH, is developing safe, reliable,
and effective systems for functional neuromuscular stimulation (FNS) in
spinal cord injured individuals. Such systems require the integration
of both motor and sensory function into a paralyzed limb. A contract to
develop an implantable microstimulator was begun two years ago and
considerable progress has been made. In this requested research effort,
the development of the microstimulator will be continued and the
development of a microtransducer to sense joint angle will be initiated.
The Contractor will be required to exert its best efforts to develop
implantable, microsized receiver-stimulators and transducer-telemeters
for functional neuromuscular stimulation (FNS). It is anticipated that
one award will be made for a period of three years in January 1992.
This is not a Request for Proposals (RFP). To receive a copy of the
RFP, please submit a written request to the following address, and
supply this office with two self-addressed mailing labels. All
responsible sources shall be considered by the agency. The RFP will be
issued on or about May 29, 1991, with proposals due on July 29, 1991.
Contracting Officer
Contracts Management Branch, DEA
National Institute of Neurological Disorders and Stroke, NIH
Federal Building, Room 901
7550 Wisconsin Avenue
Bethesda, MD 20892
Attention: RFP No. NIH-NINDS-91-12
$$R1 END ***************************************************************
$$R2 BEGIN CA-91-16 FULL-TEXT ******************************************
NEW THERAPEUTIC APPROACHES TO THE TREATMENT OF PROSTATE CANCER
RFA AVAILABLE: CA-91-16
P.T. 34; K.W. 0715035, 0705075, 0745070, 0755015, 0760020, 0760025
National Cancer Institute
Letter of Intent Receipt Date: July 22, 1991
Application Receipt Date: October 15, 1991
PURPOSE
The Division of Cancer Treatment (DCT) of the National Cancer Institute
(NCI) invites research grant applications (R01) from interested
investigators to perform clinical studies in prostate cancer to improve
treatment results and clinical outcome. Investigators are encouraged to
utilize laboratory advances in understanding tumor growth and hormonal
control in prostate cancer to develop an integrated research program of
laboratory experimentation and concurrent clinical studies. New and
experienced investigators in relevant fields and disciplines may apply
to fund therapeutic clinical studies.
The PHS is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas. This RFA, New Therapeutic
Approaches to the Treatment of Prostate Cancer, is related to the
priority area of cancer. Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or
"Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, D.C. 20402-9325 (telephone 202-783-3238).
BACKGROUND INFORMATION
The incidence of prostate cancer continues to increase each year and has
now surpassed lung cancer to become the most common carcinoma in males.
It is estimated that approximately 122,000 new cases will be diagnosed
in 1991 accounting for 19 percent of all male cancers. Black men in the
United States have the highest rate of prostate cancer in the world. At
the time of presentation, more than 50 percent of newly diagnosed
patients will have either locally advanced or metastatic disease.
Prostate cancer is the second leading cause of death from neoplasia
among men, with more than 32,000 deaths estimated for 1990. It is an
important cause of morbidity and mortality in the elderly. These upward
trends are expected to continue as the male population ages.
When prostate cancer is diagnosed early while still confined to the
prostate, the disease is curable with radical prostatectomy or radiation
therapy. For patients with more advanced stages, initial treatment is
based on prostatic cancer cell growth's presumed hormonal dependence and
includes surgical castration and diethylstilbestrol. In recent years,
new methods of hormone treatment utilize pharmacologic agents capable of
reducing or blocking the action of testosterone, the major circulating
androgenic hormone, by interrupting the complex interactions between the
hypothalamus, pituitary, testis, and adrenal glands. However, these new
therapeutic agents do not prevent the emergence of hormone-resistant
cells. Advanced prostate cancers ultimately fail to respond to androgen
deprivation. The mechanisms involved in the development of androgen
resistance are not understood. There is no alternative therapy that can
be offered at present to these patients that consistently results in
reduction in tumor mass or palliation of symptoms.
In recent years, basic researchers have made promising new advances in
understanding the mechanisms of growth control in the human prostate
cell. The growth and differentiation of benign and malignant prostatic
epithelial cells are regulated by androgens which in turn are modulated
by growth factors and other hormones. Clinical trials utilizing
suramin, which interferes with heparin-binding growth factors, have
recently shown responses in advanced prostate cancer. The mechanism of
action of suramin is still not completely understood and ancillary
laboratory studies are needed. In addition, biological response
modifiers in combination with chemotherapy have achieved promising
results in other tumor models but have not been adequately explored in
prostate cancer. Recent advances in understanding the molecular and
cellular mechanisms operative in resistance to chemotherapy have led to
the design of new therapeutic strategies to overcome drug resistance in
other tumors. Many opportunities exist to develop new treatment
strategies in prostate cancer utilizing laboratory advances in
understanding tumor growth and hormonal control.
RESEARCH GOALS AND SCOPE
The major goal of this Request for Applications (RFA) is to foster
interactions between basic science laboratories and clinicians
performing clinical trials for patients with prostate cancer.
Investigators are encouraged to propose pilot therapeutic clinical
studies or new clinical trials (Phase I, II, or III) designed to improve
therapy in prostate cancer patients. The application may include
ancillary laboratory studies linked to the clinical trial. Applications
must be focused on integrating clinical goals with laboratory research
areas.
This RFA envisions funding therapeutic clinical studies that test and
exploit basic findings concerning cellular targets of treatment or
response to drug or hormone therapies. Clinical studies should involve
human subjects and be designed to improve cancer treatment. Examples of
clinical studies include: (1) growth factor or hormone therapies
utilizing new agents; (2) treatment therapies for overcoming hormone,
drug, or radiation resistance; (3) treatment therapies based on novel
mechanisms of action; (4) biologics in combination with drug or
radiation regimens; (5) new therapies combining endocrine manipulations
with chemotherapeutic agents; and (6) radiation modifiers to enhance
cell kill or protect normal tissue.
Laboratory research studies that are relevant to the therapeutic
clinical studies may be included. Investigators already participating
in relevant ongoing clinical trials are encouraged to develop related
complementary laboratory studies. Laboratory experimentation may be
designed to examine mechanism of action, mechanism of resistance, or
conduct pharmacological analysis of the antitumor agents utilized in the
patient studies. Laboratory studies designed to improve diagnosis or
studies examining benign prostate disease are not applicable.
MECHANISM OF SUPPORT
Support of the program will be through the National Institutes of Health
(NIH) grant-in-aid (R01). Applicants will be responsible for the
planning, direction, and execution of the proposed project.
Approximately $750,000 in total costs per year for three years will be
committed specifically to fund applications submitted in response to
this RFA. It is anticipated that three to four awards will be made.
Applications with requested budgets greatly exceeding these general
parameters may be at a disadvantage with respect to final funding
decisions. This funding level is dependent on the receipt of a
sufficient number of applications of high scientific merit. The total
project period for applications submitted in response to the present RFA
should not exceed three years. The earliest feasible start date for the
initial award will be July 1, 1992.
ELIGIBILITY REQUIREMENTS
Non-profit organizations and institutions, governments and their
agencies, and occasionally individuals are eligible to apply.
For-profit organizations are also eligible unless specifically excluded
by legislation. Both domestic and foreign applicants may apply.
Applications may be submitted from a single institution or may include
arrangements with multiple institutions (e.g., consortia and Clinical
Trials Cooperative Group) where appropriate.
SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDIES
For projects involving clinical research, NIH requires applicants to
give special attention to the inclusion of women and minorities in study
populations. If women or minorities are not included in the study
populations for clinical studies, a specific justification for this
exclusion must be provided. Applications without such documentation
will not be accepted for review. The inclusion of women is standard
terminology for all grants and contracts; however, due to the specific
cancer subject of this RFA (Prostate), it is not applicable under this
RFA.
INQUIRIES
This is an abbreviated version of the RFA. Copies of the complete RFA
and additional information concerning the objectives and scope of this
research may be obtained from:
Ms. Diane Bronzert
Program Director
Cancer Therapy Evaluation Program
Division of Cancer Treatment
National Cancer Institute
Executive Plaza North, Room 734
Bethesda, MD 20892
Telephone: (301) 496-8866
FAX: (301) 480-4663
Written or telephone inquires of a budgetary, administrative, and/or
policy nature should be directed to:
Ms. Carolyn Mason
Grants Management Specialist
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Blvd.
Bethesda, MD 20892
Telephone: (301) 496-7800, extension 59
FAX: (301) 496-8601
$$R2 END ***************************************************************
ONGOING PROGRAM ANNOUNCEMENTS
$$P1 BEGIN PA-91-54 ****************************************************
COMBINED PSYCHOSOCIAL AND PHARMACOLOGIC TREATMENTS RESEARCH
PA: PA-91-54
P.T. 34; K.W. 0414000, 0710100, 0715129, 0715177
National Institute of Mental Health
The National Institute of Mental Health (NIMH) seeks applications from
investigators to study the efficacy of combined psychosocial and
pharmacologic treatment of specific mental disorders. Disorders of
interest include schizophrenia, mood disorders, anxiety, somatoform,
personality disorders, eating disorders, childhood and adolescent
disorders, and mental disorders of the aging. NIMH is particularly
interested in research on the relative efficacy of combined treatment
compared with psychosocial or pharmacologic treatments administered
singly in any of the above-mentioned disorders. Research investigations
on acute, longer term, and maintenance phases of treatment are welcome.
NIMH is also interested in the development of new empirical models for
testing the efficacy of combined pharmacologic and psychosocial
treatments.
ELIGIBILITY
These grants are available to any public, private, profit, or nonprofit
institution such as a university, college, hospital, or community
agency, and units of State or local governments and authorized units of
the Federal government.
MECHANISMS OF SUPPORT
Research support may be requested through applications for the full
range of research grant mechanisms, including but not limited to a
regular research grant (R01), small grant (R03), First Independent
Research Support and Transition (FIRST) award (R29), program project
(P01), and Clinical Research Centers Program (P30). Applications must
be prepared on the current version of the Public Health Service Form 398
(revised 10/88).
Support may be requested for a period of 5 years for individual research
project grants (R01), program projects (P01), Clinical Research Centers
(P30), and FIRST awards (R29), and up to 2 years for small grants (R03).
FIRST and small grants are not renewable. Competing continuation
applications may be submitted for R01s, P01s, and P30s for projects that
plan to build on the findings of the previously supported research. A
competing supplemental application may be submitted for R01s and P01s
during an approved period of support to expand the scope or protocol of
a project.
Applications for all mechanisms under this program announcement will
compete with other investigator-initiated applications. In fiscal year
1992, subject to availability of funds, it is estimated that
approximately $500,000 will be made available to support three or four
new regular research grants under this announcement at an average annual
award amount of $150,000 - $200,000 in direct costs. Applications
submitted in future years will compete with others submitted for
funding.
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of the disease, disorder or
condition under study; special emphasis should be placed on the need for
inclusion of minorities and women in studies of diseases, disorders and
conditions which disproportionately affect them. This policy is
intended to apply to males and females of all ages. If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale should be provided.
The composition of the proposed study population must be described in
terms of gender and racial/ethnic group. In addition, gender and
racial/ethnic issues should be addressed in developing a research design
and sample size appropriate for the scientific objectives of the study.
This information should be included in the form PHS 398 in Section 2,
A-D of the Research Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognizes that it may not be feasible or appropriate in
all research projects to include representation of the full array of
United States racial/ethnic minority populations (i.e., Native Americans
(including American Indians or Alaskan Natives), Asian/Pacific
Islanders, Blacks, Hispanics).
The rationale for studies on single minority population groups should be
provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.
The usual NIH policies concerning research on human subjects also apply.
Basic research or clinical studies in which human tissues cannot be
identified or linked to individuals are excluded. However, every effort
should be made to include human tissues from women and racial/ethnic
minorities when it is important to apply the results of the study
broadly, and this should be addressed by applicants.
For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.
If the required information is not contained within the application, the
application will be returned.
Peer reviewers will address specifically whether the research plan in
the application conforms to these policies. If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.
All applications for clinical research submitted to NIH are required to
address these policies. NIH funding components will not award grants or
cooperative agreements that do not comply with these policies.
Investigators are encouraged to pay attention to certain methodological
issues on the preparation of their applications. For example, the
design should permit comparison of the combined treatment with one or
both of its components and at lest one control condition. The
investigator may consider a parallel group design in which all
treatments are initiated concurrently or a sequencing or constructive
design in which psychotherapy is substituted for or added to a
pharmacotherapeutic regimen or vice versa. There should be
randomization or some form of systematic assignment to treatment and
control groups that does not bias outcome in favor of one class of
treatment.
Patient samples should meet DSM-III-R criteria for the disorder under
study. The research protocol should include appropriate inclusion and
exclusion criteria as well as information regarding how patients and
control or comparison subjects will be recruited, assessed, and
diagnosed. The type and format of psychosocial therapy must be
specified, and in manual form. The pharmacologic treatment should also
be specified with a well-defined dosage schedule and procedures for
administration and management of the medication. It is desirable that
no combination of treatment be studied unless evidence exists from
controlled investigations of the efficacy of the individual modalities
being combined for the specific disorder under study.
Outcome measures should be appropriate for the therapies being
evaluated. Also, it is important to consider the patterns of effects,
such as additive effects, interactive effects, facilitating,
potentiating effects, negative effects, and effects over time.
Investigators should give attention to possible bias in the research
setting, and the data analysis plan should be appropriate to the
research questions posed. This plan should be capable of providing
statistical analysis of the interactive effects of treatment.
REVIEW PROCEDURES
Applications in response to this announcement will be reviewed on a
nationwide basis in accordance with the usual Public Health Service peer
review procedures for research grant applications. Applications will be
accepted in accordance with the usual receipt dates for new
applications. Award criteria include the quality of the application as
determined by the initial review group and the appropriate Advisory
Council, program relevance, and availability of funds.
For further information on programmatic issues and to request a copy of
the full announcement, contact:
Barry E. Wolfe, Ph.D.
Mood, Anxiety and Personality Disorders Research Branch
Division of Clinical Research
Room 10C-24
Telephone: (301) 443-3568
H. Alice Lowery
Schizophrenia Research Branch
Division of Clinical Research
Room 10C-06
Telephone: (301) 443-3524
George T. Niederehe, Ph.D.
Mental Disorders of the Aging Branch
Division of Clinical Research
Room 7-105
Telephone: (301) 443-1185
Peter S. Jensen, M.D.
Chief, Child and Adolescent Disorders Research Branch
Division of Clinical Research
Room 10-104
Telephone: (301) 443-5944
Robert F. Prien, Ph.D.
Associate Director for Clinical Psychopharmacology
Division of Clinical Research
Room 10C-26
Telephone: (301) 443-4527
For further information on grants management issues,
contact:
Stephen J. Hudak
Grants Management Section
Grants Management Branch
Room 7-23
Telephone: (301) 443-4456
The mailing address for all of the above is:
National Institute of Mental Health
5600 Fishers Lane
Rockville, MD 20857
This program is described in the Catalog of Federal Domestic Assistance
No. 93.242, Mental Health Research Grants. Under the authority of
Section 301 of the Public Health Service Act, P.L. 78-410, as amended,
42 U.S.C. 241, and subject to availability of funds, NIMH will accept
grant applications in response to this announcement.
$$P1 END ***************************************************************
$$P2 BEGIN PA-91-55 ****************************************************
NEUROPEPTIDE MODULATION OF SALIVARY IMMUNITY
PA: PA-91-55
P.T. 34; K.W. 0710070, 0715148, 0760060, 0760075
National Institute of Dental Research
PURPOSE
The National Institute of Dental Research (NIDR) supports studies to
improve knowledge of the development, structure, function, and diseases
of the salivary glands and to determine the influence of salivary
constituents on oral health. Toward this end, the NIDR seeks to
stimulate basic and clinical research, research training, and manpower
development in the broad area of neuropeptide modulation of the salivary
immune system.
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000," a
PHS-led national activity for setting priority areas. This Program
Announcement (PA), Neuropeptide Modulation of Salivary Immunity, is
related to the priority area of Oral Health. Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report: Stock No.
017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, D.C. 20402-9325 (telephone 202-783-3238).
BACKGROUND
The ability of the host to resist infection or to modify the
colonization patterns of microorganisms that enter the oral cavity is,
in part, dependent upon the presence of a fully functional mucosal
immune system. In immunologically sufficient adults, secretory IgA is
the major immunoglobulin species detected in salivary secretions and
thus is considered to be the principal mediator of salivary immunity.
Although antibody induction and cell migration studies have provided
evidence supporting a linkage of salivary glands to the mucosal immune
network, detailed investigations on the mechanism by which IgA committed
B cells from gut-associated lymphoid tissue (GALT) "home" to the
individual salivary glands, and studies on cell traffic between salivary
glands have not yet been performed.
Two subclasses (IgA1 and IgA2) of IgA exist in serum and secretions of
adults. In secretions, including saliva, as much as half of the IgA may
be IgA2. The functional significance of these two subclasses is as yet
unresolved. However, the IgA1 subclass proteins are cleaved by a group
of bacterial proteases that do not affect the IgA2 subclass. These
proteases, which are produced by several pathogenic species including
suspected periodontal pathogens, may thus interfere with IgA-mediated
immunity.
IgM, with a secretory component non-covalently attached, also can be
detected in major salivary gland secretions of many adults. In
conditions of IgA deficiency, this pentameric immunoglobulin often can
be found to replace the absent IgA in saliva, thus providing a
compensatory mucosal defense mechanism. IgG is only marginally detected
in major salivary gland saliva, but is present in detectable and often
significant amounts in saliva from minor salivary glands.
Increasing attention is being paid to the effect of the nervous system
on immune function. Stress and mental illnesses are known to affect
immune responses. The results of studies over the last decade indicate
that the immune and neuroendocrine tissues produce, communicate, and
regulate with a battery of similar, if not identical, informational
molecules. Cells of these two systems produce molecules that were
previously thought to be unique. It has been hypothesized for many
years and now well documented that this communication is bidirectional
with products of the neuroendocrine system affecting the biological
behavior of cells of the immune system and vice versa. Recent studies
have demonstrated that neuropeptides, such as vasoactive intestinal
peptide, substance P, and somatostatin, can differentially affect
lymphocyte proliferation, immunoglobulin synthesis, and lymphokine
production. Moreover, it has been established that lymphocytes can
produce neuropeptides, such as endorphins and corticotropin hormone, and
that lymphoid tissues are extensively innervated by adrenergic and
peptidergic nerves. It is almost certain that these nerves release
neuropeptides locally in lymphoid organs. Taken together with the fact
that lymphocytes express specific receptors for various neuropeptides
and that the concentration of neuropeptides in the mucosa is much higher
than in the blood, these data implicate neuropeptides in the control of
the mucosal immune system. This may be of importance for future
clinical studies because neuropeptide regulation of salivary immunity
could modulate inflammatory salivary diseases, dental caries, and
periodontal disease or may influence colonization of the oral mucosa by
opportunistic microflora. Furthermore, the development of pharmacologic
agents to modulate the effects of neuropeptides on the salivary immune
system will be of interest as the mechanisms by which neuropeptides
modulate salivary immune or inflammatory processes are delineated.
OBJECTIVES AND SCOPE
Based on a recommendation by the Dental Research Programs Advisory
Committee at its April 25-26, 1989 meeting, applications are invited for
research project grants (including minority research supplements),
program project grants, First Independent Research Support and
Transition (FIRST) awards, small grants, career development awards, and
postdoctoral fellowships in the broad area of neuropeptide modulation of
the salivary immune system, including secretory immunity. Some examples
of important aspects of salivary immunity for consideration in this
connection might include, but should not be limited to:
o The migration of lymphocytes from gut-associated lymphoid tissue to
and within salivary glands.
o The up/down regulation of cytokine receptors expressed by salivary
lymphocytes and the role of cytokines in inducing B cell switches
and terminal differentiation to immunoglobulin-producing plasma
cells within specific gland types.
o The role of lymphocyte subset distribution in "unimmunized" and
antigen-perturbed salivary glands in the regulation of
immunoglobulin and antibody production.
o The cytokine induction of salivary gland epithelial cell
differentiation with emphasis on enhanced secretory component
production and polymeric IgA transport.
o The isotype, subclass, and molecular form (monomeric, polymeric, or
secretory) distribution of immunoglobulins in salivas from neonatal
and adult glands.
o The enhancement of immune response upon immunization via various
routes (e.g., active stimulation of GALT and local antigen
delivery) for the prevention of oral diseases.
o The potentially progressive lymphocytic infiltration that is a
common feature of all organs (including salivary glands) affected
by Sjogren's syndrome.
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of the disease, disorder or
condition under study; special emphasis should be placed on the need for
inclusion of minorities and women in studies of diseases, disorders and
conditions which disproportionately affect them. This policy is
intended to apply to males and females of all ages. If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale should be provided.
The composition of the proposed study population must be described in
terms of gender and racial/ethnic group, together with a rationale for
its choice. In addition, gender and racial/ethic issues should be
addressed in developing a research design and sample size appropriate
for the scientific objectives of the study. This information should be
included in the form PHS 398 in Section 2, A-D of the Research Plan AND
summarized in Section 2, E, Human Subjects.
Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups. However, NIH
recognizes that it may not be feasible or appropriate in all research
projects to include representation of the full array of United States
racial/ethnic minority populations (i.e., Native Americans (including
American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks,
Hispanics).
The rationale for studies on single minority population groups should be
provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.
The usual NIH policies concerning research on human subjects also apply.
Basic research or clinical studies in which human tissues cannot be
identified or linked to individuals are excluded. However, every effort
should be made to include human tissues from women and racial/ethnic
minorities when it is important to apply the results of the study
broadly, and this should be addressed by applicants.
For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.
If the required information is not contained within the application, the
application will be returned.
Peer reviewers will address specifically whether the research plan in
the application conforms to these policies. If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority
All applications for clinical research submitted to NIH are required to
address these policies. NIH funding components will not award grants or
cooperative agreements that do not comply with these policies.
MECHANISMS OF SUPPORT
Applications considered appropriate responses to this announcement
include the traditional research project grant (R01), the program
project grant (P01), the First Independent Research Support and
Transition (FIRST) award (R29), the small grant (R03), the postdoctoral
individual fellowship (F32) and senior fellowship (F33) awards, and the
following career development awards: the Modified Research Career
Development Award (K04), the Physician Scientist for Dentists Award
(K11), and the Individual Dentist Scientist Award (K15). The specific
application forms and kits required in this connection are available in
the business or grants and contracts offices of most academic and
research institutions and may be obtained from:
Office of Grant Inquiries
Division of Research Grants
Westwood Building, Room 449
National Institutes of Health
Bethesda, MD 20892-4500
Telephone: (301) 496-7441
Applicants are encouraged to seek support from other public sources and
private sector sources, including foundations and industrial concerns,
for studies that will complement and expand the research supported by
the NIDR. A summary of the objectives and financial support for such
studies must be included in the application.
APPLICATION AND REVIEW PROCEDURES
Applications will be accepted on an indefinite basis in accordance with
the receipt dates specified in the pertinent application kits.
Applications in response to this announcement will be reviewed in
competition with other applications and in accordance with the usual
National Institutes of Health peer review procedures. The initial
review for scientific and technical merit will be by an appropriate
study section. Secondary review will be by an appropriate advisory
council. The review criteria will be those customary for the support
mechanism selected. Funding decisions will be based upon relative
scientific merit, program relevance, and the availability of
appropriated funds.
On the face page, item 2, of the application form PHS 398 (rev. 10/88),
the word "Yes" must be checked and the phrase "Neuropeptide Modulation
of Salivary Immunity, PA-91-55" must be typed in the space provided. In
the case of fellowship applications, the same phrase must be typed on
line 3 of the face page of form PHS 416-1 (rev. 7/88). The original
and six copies of the application must be sent or delivered to:
Grant Application Receipt Office
Division of Research Grants
National Institute of Health
Westwood Building, Room 240
Bethesda, MD 20892-4500**
For further information concerning this announcement and the available
mechanisms of support, applicants are encouraged to contact:
G.G. Roussos, Ph.D.
Chief, Caries, Restorative Materials, and Salivary Research Branch
National Institute of Dental Research
Westwood Building, Room 505
Bethesda, MD 20892-4500
Telephone: (301) 496-7884
For fiscal and administrative matters, contact:
Ms. Theresa Ringler
Grants Management Officer
National Institute of Dental Research
Westwood Building, Room 518
Bethesda, MD 20892
Telephone: (301) 496-7437
This program is described in the Catalog of Federal Domestic Assistance
No. 93.122. Awards will be made under authorization of the Public
Health Service Act, Title III, Section 301 (Public Law 78-410, as
amended; 42 USC 241) and administered under PHS grant policies and
Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is
not subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.
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