Path: utzoo!utgpu!watserv1!watmath!uunet!bionet!GENBANK.BIO.NET!kristoff From: kristoff@GENBANK.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 19, no. 40, pt. 2, 9 November 1990 Message-ID: Date: 9 Nov 90 18:55:17 GMT Sender: kristoff@genbank.bio.net Lines: 1033 ALZHEIMER'S DISEASE CENTER CORE GRANTS RFA AVAILABLE: AG-91-02 P.T. 04; K.W. 0715180, 0710010, 0715138 National Institute on Aging Letter of Intent Receipt Date: December 3, 1990 Application Receipt Date: February 11, 1991 BACKGROUND The National Institute on Aging (NIA) is inviting applications from qualified institutions for Alzheimer's Disease Center Core grants (ADCC), which are designed to serve as shared research resources to facilitate research in Alzheimer's disease (AD). The NIA currently supports five ADCCs. This one-time solicitation is designed to increase the number of ADCCs. The NIA Alzheimer's Disease Centers program is authorized by the Public Health Service Act, Section 445, and includes 15 Alzheimer's Disease Research Centers (ADRC) and the five ADCCs. The ADRC program was designed to support multi-disciplinary research on AD including clinical and other core resources, basic and clinical research, and information and education activities. Expansion of the program of the ADCCs will complement the program of ADRCs and will enhance the capacity of the institutions to conduct basic and clinical research in AD by increasing the available research resources. An ADCC will provide support for cores, which are shared resources, to be utilized by ongoing and to-be-developed scientifically meritorious research projects. An ADCC is required to have an administrative, clinical, neuropathological, and education and information transfer core. Additional cores can be proposed. Each ADCC will fund two pilot research projects per year through the administrative core. The ADCCs will provide well- characterized patients, patient and family information, and tissue and biological samples for use in research projects. Research proposals that will use ADCC core resources will be supported through the usual NIH and other federal and non- federal mechanisms for the funding of investigator-initiated applications. ELIGIBILITY Institutions eligible for Center Core Grants (P30s) are those at which there are (1) at least three prinicipal investigators with any PHS agency grant or comparable peer reviewed research project (including those funded by State governments or private foundations) related to Alzheimer's disease, each with at least two years of committed support remaining at the time of application or (2) one or more program projects (P01) grants related to AD, which also have at least two years of committed support remaining. Institutions that can demonstrate the ability to launch such a research effort are also eligible. MECHANISM OF SUPPORT The support mechanism for this program will be the Center Core Grant. Investigators may request up to five years of support. The award of grants pursuant to this Request for Applications (RFA) is contingent upon the availability of funds for this purpose. The intent is to fund up to five ADCC grants in Fiscal Year 1991. The specific number will depend upon the merit of the applications received. These applications are not expected to compete for funding within the general pool of dollars available for investigator-initiated research proposals. The total costs for each ADCC are limited to $600,000 for the first year. Direct cost requests for subsequent years may increase above the prior year direct cost award no more than the standard NIH inflation factor. While no future funds are set-aside, awards made in response to this RFA may be renewed through the submission of a competitive continuation application. REVIEW CRITERIA Applications received in response to the RFA will be reviewed for scientific and technical merit by an NIA initial review group. The factors to be considered in evaluating the merit of each application will be those used in the review of the cores in multiproject research grant applications. A core is justified primarily on the basis of (1) the degree to which its resources will be utilized by and benefit individual ongoing funded projects and investigators and (2) the likely impact of the core in fostering new meritorious research projects. In addition, applicants should clearly demonstrate the ways in which the ADCC will build the local research program, will support ongoing projects, and will attract both senior and new investigators to AD research. REVIEW PROCEDURES Proposals judged by staff to be non-responsive to the RFA will be administratively withdrawn and returned to the applicant without review. Responsive proposals may first receive a preliminary review by a subcommittee of the review panel to establish those applications deemed to be competitive. Those judged noncompetitive will be so designated, and an abbreviated summary statement noting the major areas of concern will be sent to the principal investigator. Applications judged to be competitive will be given full review. Following review by the initial review group, the applications will be considered by the National Advisory Council on Aging. All proposals should be complete in themselves. It is unlikely that site visits will be conducted, therefore, each application should be prepared as if no such visit will occur. In preparing proposals, applicants should follow the instructions for PHS Form 398 and the specific supplemental instructions available from NIA program staff. All human and animal welfare assurances must be complete for a proposal to be reviewed. All follow-up assurances and approval for protocols submitted as pending must be received within 60 days of the application receipt deadline or earlier if requested by the Executive Secretary. It is incumbent upon the applicant to ensure that the Executive Secretary receives all clearances by the established deadline or the application will not be reviewed. NIH requires applicants for grants to give added attention (where feasible and appropriate) to the inclusion of women and minorities in study populations and as units of analysis. If minorities and women are not included in a study population, a clear and convincing rationale for their exclusion must be provided. METHOD OF APPLYING The application must be submitted on the 10/88 revision of the form PHS 398. Supplemental instructions for preparing ADCC proposals are available from the address below. To identify these applications as being in response to the RFA, check "yes" on item 2 of page 1 of the application and enter the title: "ALZHEIMER'S DISEASE CENTER CORE GRANT" and the RFA number. The RFA label available in the 10/88 revision of the Application Form 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. Although not a prerequisite for applying, potential applicants are encouraged to submit to the Chief, Dementias of Aging, Neuroscience and Neuropsychology of Aging Program (NNA), at the address indicated below, a non-binding letter of intent to apply by December 3, l990. The letter of intent should include a brief descriptive title, the names of the principal investigator(s) and other key investigators, and any other participating institutions. The letter of intent is not mandatory and does not influence review or funding decisions, but it will enable the NIA to plan the review, and will ensure that each potential applicant receives relevant program information prior to expending considerable effort in application preparation. Applications must be received by February 11, 1991 for an earliest start date of September 30, l991. If received late, the application will be returned without review. Applicants are strongly encouraged to obtain supplemental information and to discuss their plans with and direct any other inquirires to: Chief, Dementias of Aging NNA, NIA, NIH Building 31, Room 5C35 9000 Rockville Pike Bethesda, MD 20892 Telephone: (301) 496-9350 FAX: (301) 496-1494 Application kits may be secured from institutional offices of grants and contracts or from: Office of Grants Inquiries DRG, NIH Westwood Building, Room 449 5333 Westbard Avenue Bethesda, MD 20892 Mail the complete application and four copies to: DRG, NIH Westwood Building, Room 240 Bethesda, MD 20892** To expedite review, two exact copies should be sent to: Chief, SRO, OEA, NIA, NIH Building 31, Room 5C12 9000 Rockville Pike Bethesda, MD 20892 COLLABORATIVE RESEARCH PLANNING GRANT - DIABETES IN AMERICAN INDIANS AND ALASKA NATIVES RFA NUMBER: DK-91-01 P.T. 34, FE; K.W. 0715075, 0755030, 0765033, 0745070, 0745027 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: December 15, 1990 Application Receipt Date: February 15, 1991 PURPOSE, SCOPE AND OBJECTIVE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Indian Health Service (IHS) have initiated a joint program on Diabetes in American Indians and Alaska Natives to help improve the health status of these populations. In this Request for Applications (RFA), NIDDK invites applications for Collaborative Research Planning Grants to support the development of plans for collaborative research projects that address critical questions related specifically to the etiology, pathogenesis, diagnosis, treatment, cure, and prevention of diabetes mellitus and its complications in American Indians and Alaska Natives. DISCIPLINES AND EXPERTISE Collaborative research studies proposed in response to this RFA may involve basic biomedical research, clinical research, behavioral research, education research, clinical trials, and epidemiologic research. Accordingly, the applicant research team should include individuals with the appropriate scientific, medical, and sociocultural expertise to pursue the proposed research project. In this regard, special consideration should be given to including team members with demonstrated access, knowledge, and cultural sensitivity to the specified study population. GENERAL BACKGROUND The Report of the Secretary of Health and Human Services Task Force on Black and Minority Health (1) identified noninsulin-dependent diabetes (NIDDM) and its complications as major public health problems in several minority populations, including American Indians. Diabetes and its complications have become an increasingly important health problem for certain American Indian populations. Rates of NIDDM are often 2-5 times higher among American Indians than among other populations in the U.S. The incidence of diabetes in the Pima Indians of Arizona is 19 times greater than in Caucasians in Rochester, Minnesota, and the difference continues to increase with time. With respect to complications, diabetic end-stage renal disease (ESRD) is more than five times more common in American Indians than in the U.S. White population. Heart disease is the leading cause of death in the Indian community and diabetes is a major risk factor. Currently 4.1 percent of all births at IHS facilities are complicated by diabetes. In addition, mortality associated with diabetes in American Indians is almost three times greater than for the U.S. as a whole. In the United States, approximately half of the people with NIDDM do not know they have the disease, and the proportion of American Indians and Alaska Natives with unrecognized NIDDM is unknown. Among American Indians and Alaska Natives, as in other populations, the symptoms of NIDDM can be very subtle and remain undetected for a long time. When diagnosed, NIDDM is usually treated with diet and exercise to control blood glucose levels. Oral hypoglycemic agents or insulin injections are employed if necessary. A variety of other interventions is also employed to help prevent or delay the chronic complications of diabetes that affect organs and tissues throughout the body. SCIENTIFIC BACKGROUND The NIDDK and IHS cosponsored a conference entitled Diabetes in American Indians and Alaska Natives to review the state of the art of science and to assess related progress, needs, and opportunities for future research. Although the precise reasons for the disproportionate prevalence, morbidity, and mortality associated with NIDDM in American Indians and Alaska Natives are still unknown, the results of research studies suggest that the fundamental disease process involved is essentially the same in both American Indian and Caucasian populations. American Indians may differ, however, in the nature and level of risk factors--genetic, metabolic, and environmental--for NIDDM. For instance, it is well established that obesity is a major risk factor for NIDDM, and certain Indian populations have a much higher prevalence of obesity than the majority of the U.S. population. Americans Indians have undergone rapid cultural changes during this century, with many changes having taken place during the last 40 to 50 years. Currently, the amount of cultural and genetic admixture of American Indians with the remaining U.S. population varies substantially. Far more integration has occurred in some areas and some native populations than in others (2). These changes may account for part of the apparent tribal and geographic variation in reported diabetes rates. A frequently overlooked, but potentially important distinction, is the interplay of the genetic, cultural, and historical heterogeneity of the American Indian population. Tribal groups now living within U.S. borders originated from several distinct migrations from Asia into North America over a 40,000-year period. Distinct subgroups of American Indians of different origin can be identified by cultural descriptions, linguistic analyses, and determination of genetic markers (3). Multiple factors may contribute to current levels of risk for diabetes in American Indians. Variations may exist among tribal groups, secondary to genetic admixture, to both the degree and duration of acculturation, and to attained socioeconomic status. Therefore, it is important to recognize that generalization about risk factors for diabetes and its complications in American Indians may be inappropriate and that extant data may only be valid in groups with similar origins and history. Many studies have been conducted only on individual tribes and have never been repeated; therefore, data on temporal trends in diabetes incidence, prevalence, and morbidity in American Indians and Alaska Natives are limited. MECHANISM OF SUPPORT This RFA is a one-time solicitation by NIDDK for applications for Collaborative Research Planning Grants (R21) to help support the unique short-term needs of investigators planning research studies related to diabetes in American Indians and Alaska Natives. It is anticipated that five to ten Collaborative Research Planning Grant Awards will be made in response to this solicitation, contingent on the receipt of meritorious applications and the actual availability of appropriated funds. The award of these Collaborative Research Planning Grants will be followed within approximately one year by an RFA for investigator-initiated research project grant applications (RO1) related to this same program area. This subsequent RFA will provide the opportunity for investigators to establish support for periods up to five years for meritorious research projects that address critical questions related specifically to the etiology, pathogenesis, diagnosis, treatment, cure, and prevention of diabetes and its complications in American Indians and Alaska Natives. PROVISIONS OF THE AWARD Approved Collaborative Research Planning Grant applications should request no more than one year of funding for up to $25,000 direct costs. Examples of the allowed uses of these funds include: paying travel expenses of scientists, clinicians, epidemiologists, tribal representatives, and other essential personnel who will assist in the preparation of the collaborative research plan; supporting retrieval and analysis of extant data; supporting preliminary studies to refine procedures, document recruitment potential, etc; paying for secretarial assistance, telephone, postage, and office supplies. In addition, the study team should also have access to individuals with appropriate expertise in statistics and data management, and consultant fees may be paid for biostatisticians and epidemiologists (but not generally for other personnel). Applicants should also budget funds for the Principal Investigator and up to two co-investigators to attend a two-day workshop in Phoenix, Arizona, in November/December 1991. At that time, recipients of Collaborative Research Planning Grants will be invited to present their preliminary research proposals and to participate with NIDDK and IHS staff in discussions regarding specific problems, needs, and opportunities related to both research and health care delivery. SPECIAL REQUIREMENTS A. The research team, composed of the Principal Investigator, Co-Investigator(s), and/or collaborators must include individual(s) who are experienced in health science research. Involvement of individuals who have demonstrated experience working with or delivering health services to American Indian populations is highly desirable. The application should include a succinct discussion of previous relevant investigational and health care activities. Letters of collaboration should be included for all proposed consultants. B. The applicant must demonstrate that the research team has an understanding of, and is sensitive to, the target population. Where specific language or cultural barriers are important, the applicant must provide a plan for addressing these barriers. The applicant must also document that all affected tribes have been consulted. Letters must be provided from the tribal leadership to document that they have agreed to participate in the proposed research planning process. C. Since evidence exists of geographic variation in diabetes rates and risk-factor levels among American Indians and Alaska Natives, NIDDK staff may take into account demographic and geographic distribution of peer reviewed and approved applications in the final selection process in order to support the development of research projects involving an appropriate distribution of populations from different geographic locations and linguistic groups. ELIGIBILITY REQUIREMENTS Applicants may be non-profit or for-profit organizations. Teams of applicants are encouraged which could include universities, public health departments, IHS hospitals, voluntary organizations, health clinics, and federally recognized Indian tribe or tribal organizations as defined in P.L. 93-638 and amended by P.L. 100-472, etc., or combinations thereof. Among a team of applicants, one institution must be proposed as the lead organization to serve as the Grantee Institution and assume responsibility for the fiscal and programmatic conduct of the project. Other members of the team should be proposed based on individual consortium agreements (subcontracts) with those organizations. The grantee organization and any proposed consortium must have the staff and facilities required for the proposed program. REVIEW PROCEDURE Applications received by February 15, 1991, will be reviewed initially by the Division of Research Grants (DRG) for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA will be conducted by NIDDK program staff. Applications that are judged non-responsive will also be returned. Those applications judged to be responsive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NIDDK, in consultation with the Indian Health Service Research Program. Subsequently, a second level of review will be performed by staff of the National Institute of Diabetes and Digestive and Kidney Diseases to consider the special needs and priorities of the Institute. Applications recommended for approval will be considered for funding beginning July 1, 1991. REVIEW CRITERIA Applicants are encouraged to submit and describe their own ideas on how best to meet the objective of this RFA. Applications will be judged primarily on (1) the likelihood that the new knowledge that may be gained will subsequently help to reduce the burden of diabetes and its complications on the health status of American Indians and Alaska Natives; (2) the potential scientific and technical merit of the proposed project including the significance of the scientific question(s), rationale, appropriateness of the proposed planning process, consideration of appropriate ethical issues, and availability of preliminary data; (3) the agreement of a suitable American Indian population to participate in planning the proposed study, and potential to establish collaboration with the tribal groups and other agencies involved in health care of the selected populations; and (4) the qualifications and experience of the proposed investigators. Applicants are strongly encouraged to note these criteria and to include sufficient information in their Collaborative Research Planning Grant Application so that these aspects of their proposal can be adequately assessed. The review group will also critically examine the requested budget and will recommend an appropriate budget and period of support for each approved application. Applicants are reminded of the NIH policy regarding the inclusion of women in clinical research. For further information, consult the NIH Guide for Grants and Contracts, August 24, 1990, (Vol. 19, No. 31, pp. 18-19). LETTER OF INTENT Prospective applicants are requested to submit a letter of intent by December 15, 1990, that includes a descriptive title of the proposed research, the name, telephone number and mailing address of the Principal Investigator, the names of other key personnel, the name of the applicant institution and other collaborating entities, and the number and title of this RFA. Although a letter of intent is not required, it allows NIDDK Review Staff to estimate the potential review workload and to avoid possible conflict of interest in selecting reviewers. This letter of intent should be sent to: Dr. Robert D. Hammond Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases, NIH Westwood Building, Room 406 Bethesda, MD 20892 INQUIRIES NIDDK welcomes inquiries from potential applicants to clarify any issues or questions regarding this RFA. Such inquiries should be directed to the following NIDDK Program Staff: Dr. Robert E. Silverman Chief, Diabetes Programs Branch Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases, NIH Westwood Building, Room 626 Bethesda, MD 20892 Telephone: (301) 496-7888 or Dr. Joan T. Harmon Executive Director, Diabetes Research Program Diabetes Program Branch Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases, NIH Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 496-7731 METHOD OF APPLYING The regular research grant application Form PHS-398 (revised 10/88) must be used. This form is available from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Room 449, Westwood Building, 5333 Westbard Avenue, Bethesda, Maryland 20892. The RFA label available in the 10/88 revision of Application Form 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. In addition, the title of the RFA and the number should be typed on line 2 of the face page on the application form. Submit a signed, typewritten original of the application, including the Checklist, and four (4) signed, exact photocopies, in one package to the DRG at the address below. The photocopies must be clear and on single sides. Application Receipt Office Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, MD 20892 At time of submission, send two (2) additional copies of the application to: Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases, NIH Westwood Building, Room 406 Bethesda, MD 20892 Applications must be received by February 15, 1991. If an application is received after that date, it will be returned to the applicant. If the application submitted in response to this RFA is substantially similar to a research grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REFERENCES 1. U.S. Department of Health and Human Services. Report of the Secretary's Task Force on Black and Minority Health. Vol. VII, U.S. Government Printing Office, Washington, D.C., January 1986. 2. U.S. Department of Health, Education, and Welfare. Indian Health Trends and Services. U.S. Government Printing Office. Washington, D.C. 1978. HSA 78-12009. 3. Williams RC, Steinberg AG, Gershowitz H, Bennett PH, Knowler WC, Pettitt DJ, Butler W, Baird R, Dowda-Rea L, Burch TA. GM allotypes in American Indians: evidence for three distinct migrations across the Bering land bridge. Am J Phys Anthropology 1985, 66:9-19. REQUEST FOR APPLICATIONS: RFA RFA: HL-91-02-H MECHANISMS OF RESTENOSIS AFTER CORONARY ANGIOPLASTY P.T. 34; K.W. 0715040, 1002004, 0760020 National Heart, Lung, and Blood Institute Application Receipt Date: March 18, 1991 PURPOSE The Division of Heart and Vascular Diseases invites grant applications for up to five years of support for research to elucidate the fundamental mechanisms responsible for restenosis after angioplasty, preferably coronary (PTCA). Applications focusing on peripheral angioplasty will also be accepted. Applications received in response to this request will participate in a single competition. BACKGROUND PTCA procedures can relieve myocardial ischemia in many patients with coronary heart disease (CHD) by reducing luminal obstruction and improving coronary flow. PTCA was first performed in a patient with coronary artery disease in 1977 and there has been a rapid increase in the number of angioplasties performed, with over 200,000 in 1988. The major limitation of PTCA is the high rate of restenosis, reported to range from 13-48% and peaking 1-3 months after successful dilatation. Restenosis is most likely to occur in patients over 60 years of age, diabetics, smokers, and those with Class IV angina. The angiographic correlates of restenosis include significant residual stenosis after dilatation, lesion eccentricity, lesion length over 10 mm, calcification, proximal lesion location (particularly in the left anterior descending coronary artery), and major intimal/medial dissection. Mechanical factors, such as oversized balloon and high inflation pressures may also play a role. Other variables include: a magnitude of stretch with subsequent damage to deeper layers of vessel wall; and extent of vessel wall changes resulting from plaque formation and rupture. Thus, the design of experimental approaches to unravel the pathophysiology of restenosis presents a considerable challenge. PTCA results in unavoidable vessel wall injury. Disruption of endothelial and vessel wall structure triggers molecular and cellular responses that lead, in some patients, to restenosis. Pathological evidence strongly supports the concept of intimal hyperplasia as the cause of restenosis. Intimal hyperplasia is a complex process involving endothelial and vascular smooth muscle cells, platelets, growth factors, immune responses and the multiple consequences of disrupting an atherosclerotic plaque. Platelets are believed to adhere to the arterial wall immediately after balloon injury and to release growth factors. Among these growth factors are PDGF and PF4. PDGF and/or closely related proteins are also produced by injured smooth muscle and endothelial cells and activated macrophages. However, there is as yet no direct evidence of the role of these growth factors in intimal proliferation. Endothelial cells are also thought to play a major role in intimal hyperplasia, but the nature of their influence is unclear. When small vessel wall areas are denuded, endothelial regrowth is rapid with little intimal hyperplasia. In large denuded areas, intimal hyperplasia is greatest in the part of the vessel last to be re- endothelialized. However, when the denudation is so large that endothelial cell replication ceases before the injured area is completely covered, smooth muscle proliferation peaks soon after injury. Smooth muscle cell proliferation appears to be an early response to balloon dilatation of the artery. Cell replication has been reported to peak within seven days. The number of cells remains relatively constant after 14 days. It is postulated that intimal thickening after two weeks proceeds by cell volume growth and by accumulation of extracellular matrix and connective tissue, thus giving rise to the typical fibrocellular lesion. The ultrastructural and functional properties of the cells in the lesion are typical of the synthetic phenotype seen in culture, rather than the contractile phenotype seen in the normal arterial wall. Little is known about the factors which control the phenotypic expression of vascular smooth muscle cells in the setting of a dilated atherosclerotic artery. Since intimal hyperplasia has been consistently observed in patients after angioplasty, whether or not restenosis occurred, it would appear that this narrowing of the dilated artery is intimately related to the healing process that follows dilatation. Research directed at elucidation of the mechanisms of this healing process should afford insights into the molecular and cellular responses which lead to restenosis. Although laboratory investigations have led to a number of important observations, understanding of restenosis is hampered by the many gaps in knowledge of the biological determinants of the healing process. Given the importance of this problem, there have been clinical assessments of a number of pharmacologic agents that empirically were thought to have the potential to prevent restenosis. High-dose steroid therapy, various calcium channel antagonists, and anticoagulants have shown no benefit. Although the importance of anti-platelet agents in preventing acute complications of PTCA has been confirmed, neither ticlopidine, aspirin-dipyridamole combination, sulfinpyrazone, nor intravenous dextran have been shown to prevent restenosis. A small benefit has been reported with use of more potent anti-platelet agents such as the prostacyclin analog, ciprostene. Monoclonal antibodies to platelet receptors are currently being investigated. Relatively large amounts of omega-3 fatty acids given shortly before angioplasty and continued for 3 months afterwards have been shown to reduce the frequency of restenosis in one study of male veterans. Several promising agents with anti- proliferative properties are under investigation. These include low molecular weight/subfragments of heparin, and ACE inhibitors. Preliminary data indicate that the ACE inhibitors, cilazopril and captopril, prevent myointimal proliferation after vascular injury in a non-atherosclerotic rat carotid artery. Additionally, captopril has been shown to have anti-atherogenic effects in the Watanabe heritable hyperlipidemic rabbit aorta. Trapidil (triazolopyrimidine), a PDGF antagonist, prevented restenosis in an experimental model. Lovastatin, an HMG-CoA reductase inhibitor, has also been shown to inhibit smooth muscle proliferation. The applicability and efficacy of these agents in a clinical setting remain to be established. Thus there is a significant need to foster research into the pathophysiology of restenosis, so that a rational approach can be developed for modulation of the repair process and ultimately for prevention of this complication of angioplasty. OBJECTIVES AND SCOPE Applicants are encouraged to submit applications for support of studies designed to elucidate the fundamental processes whereby a dilated artery lesion undergoes changes leading to restenosis. The proposed studies should have clearly stated hypotheses and be focussed on a well-defined problem. Interdisciplinary studies are encouraged; however, the format should be that of the traditional research grant (R01) application. PROPOSED RESEARCH Examples of possible research areas are given below. They are for illustrative purposes only. Investigators are strongly urged to consider other relevant approaches: o Elucidation of the phenotypic changes that occur in endothelial and vascular smooth cells and fibroblasts in response to PTCA. o Evaluation of the changes occurring in the communications among vascular cells and between vascular cells, platelets and circulating blood cells during restenosis. o Elucidation of the pathways whereby immune responses modulate the activities of vascular cells in restenosis. o Mechanistic studies of cytokines, mitogens, arachidonic acid metabolites, and other factors involved in the process of restenosis. o Structure, function, and regulation of vascular cell receptors and transport systems participating in restenosis. o Elucidation of genetic or other markers which may be indicators for restenosis. o Studies of gender differences in the cellular responses to PTCA. Investigators should be aware that NIH requires applicants to give added attention, where feasible and appropriate, to the inclusion of minorities and women in study populations. Gender and minority population differences must be noted and analyzed whenever possible. If minorities and/or women are not included in a given study, a clear reason for their exclusion must be provided. Merely including an arbitrary number of minority group and women participants in a given study is insufficient to guarantee generalization of results. EXCLUSIONS This solicitation deals only with restenosis of coronary arteries following PTCA. Studies that focus on angiographic characterization of restenosis, pathologic surveys, long-term clinical studies, or clinical trials will not be accepted. Applicants may request equipment; however, funds will not be provided for major, expensive items or for outfitting a laboratory. MECHANISM OF SUPPORT The support mechanism for this program will be the traditional, individual research project grant. Although the financial plans for fiscal year 1991 include $1,000,000 for the total costs of this program, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that up to four grants will be awarded under this program. The specific amount to be funded will, however, depend on the merit and scope of the applications received and on the availability of funds. Since a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. It is not the intent of this announcement to solicit applications for large studies encompassing a variety of independent projects, i.e., program projects. If collaborative arrangements involve sub-contracts with other institutions, the NHLBI Grants Operations Branch should be consulted regarding procedures to be followed (tel: 301-496-7536). Upon initiation of the program, the Division of Heart and Vascular Diseases will sponsor annual meetings to encourage an exchange of information among investigators who participate in this program. In the preparation of the budget for the grant application, applicants should REQUEST ADDITIONAL TRAVEL FUNDS for a two-day meeting each year to be held in Bethesda, Maryland. Applicants should also include a statement in their applications indicating their willingness to participate in such meetings. Applicants, who will plan and execute their own research programs, are requested to furnish their own estimates of the time required to achieve the objectives of the proposed research project. Up to FIVE YEARS of support may be requested. At the end of the official award period, renewal applications may be submitted for peer review and competition for support through the regular grant program of the National Institutes of Health (NIH). It is anticipated that support for the present program will begin on September 30, 1991. Administrative adjustments in project period and/or amount of support may be required at the time of the award. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded in connection with this RFA. Awards in connection with this announcement will be made to foreign institutions only for research of very unusual merit, need, and promise, and in accordance with Public Health Service policy governing such awards. REVIEW PROCEDURES AND CRITERIA Review Method All applications responding to this RFA will be reviewed for scientific and technical merit by an initial review group, which will be convened by the Division of Extramural Affairs, NHLBI. Upon receipt, applications will be reviewed for their responsiveness to the objectives of this RFA. If an application is judged unresponsive at this stage, the applicant will be contacted and given an opportunity to withdraw the application or to have it considered for the regular research grant program of NIH. If the application submitted in response to this RFA is substantially similar to a research grant application already submitted to the NIH for review, but that has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA which is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an Introduction addressing the previous critique. Review Criteria The factors to be considered in the evaluation of each application will be similar to those used in the review of traditional research project grant applications. The major factors to be considered in the evaluation of applications will include: 1 The scientific merit of the proposed projects, including the originality and feasibility of the approach, and the adequacy of the experimental design; 2 The competence of the investigators to accomplish the proposed research goals, their commitment, and the time they will devote to the program; 3 The adequacy of facilities for performance of the proposed research including the laboratory facilities, the proposed instrumentation and, when needed, the data management systems; 4 The integration of any interdisciplinary components into a coherent enterprise with adequate plans for interaction and communication of new information and concepts among the collaborating investigators; 5 The appropriateness of the budget for the proposed program. METHOD OF APPLYING Letter of Intent Prospective applicants are asked to submit a one-page letter of intent that includes identification of any other participating investigators and institutions, together with a descriptive title. The National Heart, Lung, and Blood Institute requests such letters only for the purpose of providing an indication of the number and scope of applications to be received and, therefore, usually does not acknowledge their receipt. A letter of intent is not binding, and it will not enter into the review of any application subsequently submitted, nor is it a necessary requirement for application. This letter of intent, which should be received no later than January 4, 1991. should be sent to: Dr. Charles Turbyfill Review Branch/Division of Extramural Affairs National Heart, Lung and Blood Institute National Institutes of Health Westwood Building, Room 553 Bethesda, MD 20892 Format for Applications Submit applications on form PHS 398, (revised 10/88) the application form for the traditional research project grant. This form is available in the applicant institution's office of sponsored research or business office. Use the conventional format for research project grant applications and ensure that the points identified in the section on "Review Procedures and Criteria" in this announcement are fulfilled. Be sure to observe the new page limitation requirements. To identify the application as a response to this RFA, CHECK "YES" on Item 2 of page 1 of the application and enter the title "Mechanisms of Restenosis After Coronary Angioplasty" and the RFA number HL-91-02-H. IN ADDITION, BE SURE TO ATTACH THE RFA LABEL FROM THE APPLICATION KIT TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL APPLICATION AND PLACE THIS ON TOP OF THE FOUR COPIES TO BE MAILED TO THE DIVISION OF RESEARCH GRANTS. FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION SUCH THAT IT MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR REVIEW. Application Procedure Send or deliver the completed application and four (4) signed, exact photocopies of it to the following, making sure that the original application with the RFA label attached is on top: Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, MD 20892** SEND AN ADDITIONAL TWO (2) COPIES OF THE APPLICATION TO DR. CHARLES L. TURBYFILL AT THE ADDRESS LISTED UNDER LETTER OF INTENT. IT IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH GRANTS. OTHERWISE THE NHLBI CANNOT GUARANTEE THAT THE APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA. Applications must be received by March 18, 1991. An application not received by this date will be considered ineligible. Timetable Letter of Intent January 4, 1991 Application receipt date March 18, 1991 Review by National Heart, Lung and Blood Advisory Council September 12-13, 1991 Anticipated Award Date September 1991 Inquiries Inquiries regarding this announcement may be directed to the program administrator: George Sopko, M.D., M.P.H. Federal Building, Room 3C06 National Heart, Lung and Blood Institute, NIH Bethesda, MD 20892 Telephone: (301) 496-1081 This program is described in the Catalog of Federal Domestic Assistance number 93.837, Heart and Vascular Diseases. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency Review. Brought to you by Super Global Mega Corp .com