A5031182905- Hormonal and reproductive studies
- Growth Hormone and Insulin-like Growth Factors
- Sexual Differentiation and Disorders
- Sperm and Testicular Function
- Animal Genetics and Reproduction
- Urological Disorders and Treatments
- Urinary Bladder and Prostate Research
- Estrogen and related hormone effects
- Veterinary Medicine and Surgery
- Birth, Development, and Health
- Cytomegalovirus and herpesvirus research
- Cancer-related Molecular Pathways
- Hypothalamic control of reproductive hormones
- Metabolism, Diabetes, and Cancer
- Reproductive Biology and Fertility
- Prostate Cancer Treatment and Research
- Carcinogens and Genotoxicity Assessment
- Drug Transport and Resistance Mechanisms
- Herpesvirus Infections and Treatments
- Prostate Cancer Diagnosis and Treatment
- T-cell and Retrovirus Studies
- Effects and risks of endocrine disrupting chemicals
- Bone health and treatments
- Pregnancy and Medication Impact
- Diabetes Treatment and Management
United States Military Academy
1992-2017
Merck & Co., Inc., Rahway, NJ, USA (United States)
1987-2014
Merck (Germany)
1999
Colorado State University
1994
Argus International (United States)
1993
University of California, Davis
1983-1989
Indian Institute of Science Bangalore
1976
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite three decades investigation, the biological roles AMPK and its potential as drug target remain incompletely understood, largely because lack optimized pharmacological tools. We developed MK-8722, potent, direct, allosteric activator all 12 mammalian complexes. In rodents rhesus monkeys, MK-8722-mediated activation skeletal muscle induced robust, durable,...
Abstract A series of studies was conducted to determine the developmental toxicity 5α‐reductase inhibitor finasteride (MK‐0906) in rats. This compound administered orally once daily pregnant rats during various extended treatment periods gestation. F 1 offspring were evaluated on Day 20 gestation as well postnatally through mating produce an 2 generation. MK‐0906 induced dosage‐related incidences hypospadias (penischisis) male with a threshold dosage level near 0.1 mg/kg/day and 100% effect...
In genetic male fetuses, dihydrotestosterone (DHT) plays an important role in normal prostatic and external genital differentiation. The enzyme steroid 5-alpha reductase (5αR) catalyzes the conversion of testosterone (T) to DHT. importance 5αR sexual differentiation is evident from study human males who congenitally lack this consequently develop ambiguous genitalia. These individuals are specifically deficient type 2 isozyme, whereas 1 isozyme activity has been found. purpose was determine...
Inactivating point mutations and small deletions in the p53 tumor suppressor gene have been found human liver lung tumor--derived cell lines tumors. However, little evidence has reported concerning inactivation or mutation of mouse primary To examine CD-1 tumors for gene, we first sequenced introns 5-8 so that polymerase chain reaction amplification sequencing primers located within could be prepared. Use these prevented pseudogene allowed exons their entirety as well intron-exon junctions....
Male rats bearing implants of the Dunning rat prostatic carcinoma, R-3327, were used in a 42-day study to determine effect castration or orally administered flutamide (FL), DES (diethylstilbestrol) 5 alpha-reductase inhibitor, MK-906, on growth this androgen-responsive cancer. The rate and final weights tumor ventral prostate (VP) all reduced (P less than 0.05) by castration. Flutamide (25 mg/kg/day) significantly decreased VP intact castrates given 100 micrograms/day (SC) testosterone...
Simian acquired immunodeficiency syndrome (SAIDS), a disease clinically and pathologically similar to in humans, was transmitted from diseased rhesus monkeys (Macaca mulatta) normal by inoculation with heparinized whole blood or plasma that had been passed through filters of 0.45 micrometer pore size. This suggests the causative agent is small most probably virus. No viruses, however, were isolated standard cell culture techniques filtered which caused SAIDS. Both cellular humoral immunity...
The purpose of this study was to evaluate the pharmacological and toxicological effects exogenous GH administration in normal adult dogs. Because porcine (pGH) is structurally identical canine GH, pGH selected for a 14-wk Thirty-two dogs (<2 yr) were randomized 4 groups (4 dogs/sex/group); 1 group treated with vehicle 3 received at 0.025. 0.1, or 1.0 IU/kg/day subcutaneously. Daily clinical signs weekly body weights recorded. Hematology, serum biochemistry, urinalyses, electrocardiograms,...
Abstract Young mature dogs received finasteride, a selective 5α‐reductase inhibitor, orally at 0, 5, 15, and 45 mg/kg/day for 27 or 53 weeks. The effect of finasteride administration on prostatic size morphology was evaluated macroscopically microscopically. Changes in glandular fibromuscular compartments were quantitated by point counting method trichrome‐stained sections. Finasteride induced decrease mean weights epithelial atrophy all treated groups. No changes testicular observed....
Simian acquired immune deficiency syndrome (SAIDS) type D retrovirus (SRV) was isolated from saliva, urine, and peripheral blood mononuclear cells of a 6-year-old healthy rhesus monkey (Macaca mulatta) seronegative for antibodies to human T-lymphotropic virus (HTLV) I, HTLV III, simian III (STLV-III), identified as an inapparent SAIDS carrier in retrospective epidemiologic studies. This animal linked 34 cases over 3-year period. Two juvenile monkeys inoculated iv with the SRV-containing...
Abstract Two sex steroid compounds which have been used clinically for parenteral supportive therapy of pregnancy were examined embryotoxic effects in rhesus and cynomolgus macaques. Hydroxyprogesterone caproate (HPC) alone or combination with estradiol valerate (EV) administered intramuscularly (i.m.) to pregnant monkeys at 7‐day intervals between 20 146 days gestation fetuses following cesarean section 150 ± 2 days. HPC was tested both species doses ranging from 0.01 × 10 the human dose...
A single dose of MPA (Depo-Provera; Upjohn Co., Kalamazoo, Michigan) was administered intramuscularly to 12 time-mated pregnant cynomolgus monkeys on day 27 (+/- 2) gestation at 25 mg/kg or 100 mg/kg. Maternal blood samples were collected immediately prior injection and then regular intervals until cesarean section term (day 152 +/- 3). Infants in both groups had external genital abnormalities. Female infants the low-dose partial complete labial fusion, prominent median raphe, clitoral...
Abstract Two sex steroid hormone combinations which have been used clinically as tests for detection of early pregnancy were examined embryotoxic effects in macaques and baboons. Norethisterone acetate ethinyl estradiol (NEA + EE) orally administered to rhesus cynomolgus monkeys baboons at dosages ranging from one 1,000 times the human dose equivalent (HDE) during days 20–50 pregnancy. Progesterone benzoate (P EB) delivered by two six intramuscular injections between gestational 20 35 0.1–25...
Recombinant rat growth hormone (rrGH) and recombinant mouse (rmGH) were developed to evaluate the potential carcinogenicity of each biologically active (GH) as assessed in respective species. Biological activities rrGH rmGH demonstrated by showing an increase body weight gain serum levels insulin-like factor-1 (IGF-1) hypophysectomized rats receiving daily sc injections for 6 days. With exception pharmacologically mediated gain, had no adverse effects 5-week oral toxicity studies production...
In rats, the prostate is divided into three distinct lobes, and lobes are dependent on androgens [testosterone (T) dihydrotestosterone (DHT)] as trophic hormones. However, reasons for difference in incidence of proliferative changes reported not well-understood. Administration finasteride, a 5-alpha reductase (5alphaR) inhibitor which selectively inhibits conversion T to DHT, results elevated intraprostatic levels. long-term (2 years) administration finasteride no increase ventral rat...