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Biomedical subjects

R L Clark

Publications and source records attributed to R L Clark.

At least 37 records · Page 2Linked to original sources
PubMed1996

Human resource policies and older workers in Japan.

Substantial changes in human resource policies are occurring in Japanese firms in response to the rapid aging of the population. Employers are reconsidering the concept of lifetime employment, seniority-based wages, retirement policies, and employment opportunities for older workers. In response to government pressure, mandatory retirement ages are being raised. These trends are examined using a variety of sources of information concerning employment practices in Japan. The analysis indicates that important changes in human resource management practices are underway and further changes are anticipated as the labor force continues to age.

Aged↗
PubMed1996

Urothelial striations revisited.

PURPOSE: To confirm that use of low-osmolality contrast media (LOCM) in urography increases the frequency with which striations occur in otherwise healthy adults. MATERIALS AND METHODS: Two series of urograms obtained in 207 adult patients (101 men, 106 women) at two institutions after the administration of either LOCM or high-osmolality contrast media (HOCM) were reviewed. At the first, 106 patients had received LOCM; at the second, 101 had received HOCM. Protocols were similar. Urograms were evaluated for the presence and extent of striations. RESULTS: Of 106 LOCM urograms, 16 (15%) showed striations. Of 101 HOCM urograms, only two (2%) showed striations. The difference in striations shown between the two groups was significant (P < .002). Striations were most common in renal pelves and distal ureters and on radiographs obtained after voiding. CONCLUSION: Detection of urothelial striations on LOCM urograms in adults is most often normal. Increased prevalence of striations is likely due to decreased urinary tract distention associated with LOCM use.

Adult↗
PubMed1995

Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor.

Considerable evidence has associated the expression of matrix metalloproteinases (MMPs) with the degradation of cartilage and bone in chronic conditions such as arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of MMP inhibitors with appropriate pharmacological properties. We have identified butanediamide, N4-hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S- (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and stability to permit evaluation in an experimental model of chronic destructive arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia associated with osteoclasia, severe bone and cartilage destruction, and ectopic new bone growth are well developed by 3 wk after adjuvant injection. Rats were injected with Freund's adjuvant on day 0. GI168 was was administered systemically from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12, and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological and histological ankle joint evaluation on day 22 revealed a profound dose related inhibition of bone and cartilage destruction in treated rats relative to rats receiving vehicle alone. A significant reduction in edema, pannus formation, periosteal new bone growth and the numbers of adherent marrow osteoclasts was also noted. However, no significant decrease in polymorphonuclear and mononuclear leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen. This unique profile of antiarthritic activity indicates that GI168 is osteo- and chondro-protective, and it supports a direct role for MMP in cartilage and bone damage and pannus formation in adjuvant-induced arthritis.

Animals↗
PubMed1995

Cataractogenesis in rats induced by in utero exposure to RG 12915, a 5-HT3 antagonist.

RG 12915, a selective 5-HT3 antagonist developed for the treatment of emesis and nausea associated with cancer chemotherapy, was administered by gavage to four groups of pregnant rats from Gestation Day 6 to 17 at doses of 0, 1, 10, and 100 mg/kg/day, as part of a Segment II (developmental toxicity) study. The 100 mg/kg/day dose was maternally toxic as indicated by decreased body weight gain and food consumption during the treatment period. A portion of the rats were allowed to deliver and rear their litters and three pups from two litters in the 100 mg/kg/day group were observed to have lens opacities (visible to the naked eye) at weaning. At a later examination, when the offspring were approximately 4 months old, four additional animals from the same two litters had cataracts. A slight growth retardation was also observed postweaning in the offspring of the 100 mg/kg/day group. To confirm the lens findings and more precisely define the no-effect dose, another study was conducted in which pregnant rats were administered daily RG 12915 doses of 0, 10, 30, 60, or 100 mg/kg/day from Gestation Day 6 to 17. There was a dose-related decrement in maternal body weight gain during the treatment period in the 30, 60, and 100 mg/kg/day groups (12, 28, and 47%, respectively) compared to the control group. A treatment-related incidence of nuclear cataract was observed in the offspring of the 60 and 100 mg/kg/day groups (litter incidence 6 and 45%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A microcholangiographic study of liver disease models in rats.

RATIONALE AND OBJECTIVES: Rats develop hepatobiliary injury due to small bowel bacterial overgrowth (SBBO) that, at specimen, resembles cholangiography sclerosing cholangitis. To better visualize the smaller bile ducts, we used microcholangiography to determine the spectrum of biliary lesions in this and five other models of liver disease. METHODS: The models studied were as follows: (1) Surgically created jejunal, self-filling blind loops induce SBBO. (2) Intraperitoneal injection of a bacterial cell wall polymer, peptidoglycan-polysaccharide (PG-PS), causes granulomatous hepatitis. (3) Intraperitoneal injection of endotoxin (lipopolysaccharide) causes sinusoidal congestion and shock. (4) Bile duct ligation induces bile duct proliferation. (5) Alpha-naphthyl-isothiocyanate (ANIT) induces bile duct proliferation. (6) Carbon tetrachloride (CCl4) causes fibrosis and cirrhosis. Warmed barium sulfate, gelatin, and saline were injected in the extrahepatic bile duct. Liver slices (2 mm) underwent microradiographic techniques, and images were correlated with histology. RESULTS: Rats with SBBO had irregular and dilated extrahepatic bile ducts with thickened walls. Rats treated with endotoxin and CCl4 had normal microcholangiograms. Bile duct proliferation was identified following ANIT and bile duct ligation. Rats given PG-PS demonstrated irregular intrahepatic bile ducts. Microcholangiograms following SBBO and PG-PS showed similarities including focal ductal dilatation, narrowing, proliferation, and destruction. CONCLUSION: Various models of liver injury induce characteristic cholangiographic appearances. Microcholangiography is useful in examining biliary tract lesions and complements histology.

1-Naphthylisothiocyanate↗
PubMed1995

Anti-inflammatory activity of phosphodiesterase (PDE)-IV inhibitors in acute and chronic models of inflammation.

Inhibitors of cyclic nucleotide phosphodiesterases are known to suppress lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) production in vitro in human monocytes. The most potent of these have selectivity for type IV PDEs, suggesting that this class of PDE is the major type involved in the regulation of human TNF-alpha production. Using compounds of two distinct chemical structural classes, a quinazolinedione (CP-77059) and a 4 arylpyrrolidinone (rolipram), we show here that PDE-IV-specific inhibitors are also potent in suppressing LPS-induced TNF-alpha production in vitro in sodium periodate-elicited murine macrophages (IC50s of 1 and 33, respectively). We then report the in vivo anti-inflammatory effect of PDE-IV inhibition in five murine models of inflammation: (i) elevation of serum TNF-alpha induced by a sublethal LPS injection; (ii) LPS-induced endotoxic shock; (iii) LPS/galactosamine-induced endotoxic shock; (iv) carrageenan-induced paw oedema; and (v) adjuvant arthritis. Following a sublethal (5 micrograms/mouse) injection of LPS, serum TNF-alpha levels in mice peaked sharply, reaching concentrations of 3-12 ng/ml 90 min after injection. In this sublethal LPS assay, CP-77059 was about 30 times more potent than rolipram, with a minimum effective dose of 0.1 mg/kg versus 3 mg/kg for rolipram. This rank order is in keeping with the relative in vitro IC50s for CP-77059 and rolipram, as well as their relative Ki against the human PDE-IV enzyme (46 nM and 220 nM, respectively). In LPS-induced endotoxic shock, rolipram and CP-77059 at relatively high doses of 30 and 10 mg/kg, respectively, significantly reduced serum TNF-alpha levels, and also inhibited mortality 66%. In the LPS/galactosamine shock model, in which mice are rendered exquisitely sensitive to LPS by co-injection with galactosamine, only 0.1 microgram of LPS/mouse is necessary for serum TNF-alpha elevation and death. Both rolipram and the CP-77059 caused dose-dependent reduction of serum TNF-alpha and lethality. In the carrageenan-induced paw oedema model, in which there is a pronounced local TNF-alpha response (without a serum TNF-alpha elevation), rolipram significantly inhibited paw swelling as well as localized TNF-alpha levels in the paw. In the adjuvant arthritis model, a chronic model of inflammation also possessing localized TNF-alpha elevation in the inflamed paw, rolipram and CP-77059 suppressed ankle swelling and radiological evidence of joint damage. These data are consistent with a major role for PDE-IV in regulation of TNF-alpha production and inflammatory responses in murine systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Conversion of the biological specificity of murine to human leukemia inhibitory factor by replacing 6 amino acid residues.

Mouse and human leukemia inhibitory factor (mLIF and hLIF) have approximately 80% amino acid identity, but mLIF cannot bind to the hLIF receptor (hLIF-R), while hLIF binds to the alpha-chain of the mLIF receptor (mLIF-R) with a much higher affinity than does mLIF. We have previously shown that the same regions confer both these properties of hLIF and map to an area within the predicted third alpha-helix and two of the loops of hLIF (Owczarek, C. M., Layton, M. J., Metcalf, D., Lock, P., Wilson, T. A., Gough, N. M., and Nicola, N. A. (1993) EMBO J. 12, 3487-3495). The present studies, using interspecies chimeras of mLIF and hLIF, have defined 6 residues (Asp57, Ser107, His112, Ser113, Val155, and Lys158) that contribute most of the binding energy involved in the interaction of hLIF and the hLIF-R alpha-chain, and form a surface at one end of the predicted four alpha-helical bundle of the hLIF molecule. Mouse LIF is unable to bind to the hLIF-R alpha-chain or activate the cellular hLIF-R, but when these 6 residues were substituted onto an mLIF framework, they were able to reconstitute both the binding and biological activities specific to hLIF.

Amino Acid Sequence↗
PubMed1994

Retiree health insurance and pension coverage: variations by firm characteristics.

This study examined coverage by employer-sponsored retiree health insurance using the 1988 and 1989 Employee Benefits Surveys. The effects of firm characteristics on the probability of offering retiree health insurance and pension coverage are also estimated. We find that coverage by retiree health insurance varies across occupational groups, industries, and firm sizes. In addition, we find a strong relationship between a firm's decisions to offer retiree health insurance and pension coverage, with the retiree health insurance decision being more sensitive to specific firm characteristics.

Aged↗
PubMed1994

Pelvic granulomata mimicking endometriosis following the administration of oil-based contrast media for hysterosalpingography.

BACKGROUND: Hysterosalpingography is used commonly in the evaluation of infertility and in the diagnosis of anomalies of the uterus and fallopian tubes. There is continued debate over the safety and diagnostic or therapeutic efficacy of water-soluble versus oil-based contrast media. CASE: A 29-year-old woman with secondary infertility underwent hysterosalpingography with both water-soluble and oil-based contrast. The fallopian tubes appeared normal. Six months later, a plain abdominal radiograph obtained at the occasion of a minor motor vehicle accident revealed evidence of retained loculated pelvic contrast material. Subsequent laparoscopy identified adhesions and cul-de-sac implants strongly suspicious for endometriosis. Biopsy and pathologic study documented lipogranuloma. CONCLUSION: Oil-based contrast media instilled into the pelvis at hysterosalpingography can persist for prolonged periods and create granulomatous lesions mimicking endometriosis. In view of the controversy whether oil-based contrast materials are superior to water-soluble media, the routine use of oil-based contrast media should be considered carefully.

Adult↗
PubMed1993

Increasing mammography utilization: a controlled study.

BACKGROUND: Despite the effectiveness of breast cancer screening for women older than 50 years of age, only about one third of these women in the United States receive annual mammography. PURPOSE: This study was designed to determine if a community-wide intervention could increase use of mammography screening for breast cancer. Secondary end points were determination of changes in women's knowledge and attitudes toward mammography and physicians' self-reported screening practices. METHODS: We conducted a controlled study from January 1987 through January 1990 in two eastern North Carolina communities--New Hanover County (the experimental community) and Pitt County (the control community). Before development and implementation of the intervention program in New Hanover County and after the program had been in operation for 1 year, 500 women of ages 50-74 years and all primary-care physicians in each community were interviewed by telephone. In these interviews, we determined the use of mammography for breast cancer screening and the knowledge and attitudes about it. We also established the number of screening mammograms performed in 1987 and 1989 in each county and reviewed medical records to determine the percentage of women the physicians had referred for mammograms. RESULTS: The percentage of women who reported receiving a mammogram in the previous year increased from 35% to 55% in the experimental community and from 30% to 40% in the control community (difference of differences, 10%; P = .03 after adjustment for race, education, age, and having a regular doctor; 95% confidence interval, 1%-18%). Increases were greater in New Hanover County regardless of age, race, income, and education. However, the increase was less for Black women than for White women, both overall and in most demographic subgroups. The total number of mammograms performed increased 89% in the experimental community and 45% in the control community. Women's knowledge about mammography changed little, but the intention to get a mammogram increased 30% in New Hanover County, compared with a 17% increase in Pitt County--a statistically significant difference (P < .01). Physician reports and medical record reviews in the two communities showed similar increases in the number of mammograms ordered. CONCLUSIONS: A community-wide effort to increase use of breast cancer screening was successful, but more work must be done to reach the National Cancer Institute's goal of annual mammograms for 80% of women of ages 50-74.

Age Factors↗
PubMed1993

Application of the tukey trend test procedure to assess developmental and reproductive toxicity. I. Measurement data.

Developmental and reproductive (DAR) toxicity studies typically include a series of increasing doses of a compound and a zero dose control. Given this framework, Tukey et al. (Biometrics, 41, 295-301, 1985) proposed a procedure (referred to as either the Tukey trend or TCH test procedure) for detecting a nonzero trend in response to increasing doses of the test compound. The procedure considers three candidate dosage scalings to ensure high power against relatively common dose-response patterns and appreciable power against most reasonable patterns. For toxicologic effects with near monotonic dose-response patterns, simulation studies have shown the TCH test to be overall more powerful than pairwise comparison procedures. The TCH test can be applied sequentially, eliminating the highest dose each time a statistically significant trend is observed, until a no-statistical-significance-of-trend dose is reached. This is the highest dose through which there is no statistically trustworthy evidence of the compound's impact on the response. Since DAR toxicity usually exhibits a progressive (monotonic) dose-response, we advocate routine use of Tukey's trend test for the evaluation of treatment effects in these studies. In this article, we discuss the procedure in detail and apply it to fetal body weight, a continuous measurement variable, from a developmental toxicity study.

Animals↗
PubMed1993

Critical developmental periods for effects on male rat genitalia induced by finasteride, a 5 alpha-reductase inhibitor.

The conversion of testosterone to 5 alpha-dihydrotestosterone by the enzyme 5 alpha-reductase is inhibited by finasteride. In a study in which maternal dosing with finasteride commenced on Gestational Day 15 and terminated on Postpartum Day 21, there were 13 and 27% decreases in anogenital distance of male pups on Postnatal Day 1 at 0.03 and 3 mg/kg/day, respectively. These decreases were largely reversed by Postnatal Day 22 even though treatment of the dams continued. Treatment at 3 mg/kg/day also resulted in hypospadias with cleft prepuce and a 5-day delay in the separation of the prepuce from the glans penis in those animals without hypospadias. A second study in which 20 mg/kg/day finasteride was administered on successive 2-day periods during late gestation in rats demonstrated that the period of Gestational Days 16 to 17 was the most sensitive (critical period) for finasteride-induced hypospadias, cleft prepuce, decreased anogenital distance, reduced prostate weight, and nipple formation in F1 male offspring. This critical period is just prior to the appearance on Day 18 of gestation of a midline mesenchymal plate between the urogenital sinus and the rectum in normal male fetuses. This midline plate does not appear in finasteride-exposed fetuses destined to have hypospadias as demonstrated in a previous study. Based on these observations, we hypothesize that finasteride causes hypospadias by preventing the formation of the medial mesenchymal plate which is necessary for assisting the movement of the urogenital sinus from the base to the tip of the genital tubercle.

5-alpha Reductase Inhibitors↗
PubMed1993

A formal curriculum in breast imaging for radiology residents.

RATIONAL AND OBJECTIVES: Training in breast imaging is highly variable among radiology programs. The authors have developed a standardized breast imaging curriculum for radiology residents. METHODS: This curriculum has been implemented within the residency program at the University of North Carolina at Chapel Hill. It includes nine standardized components: 1) the clinical activities of the service; 2) the study of breast imaging teaching file films and contribution of new cases; 3) selected readings; 4) formal discussion with faculty on the readings; 5) review of this material using an interactive computer program; 6) formal conferences; 7) technical and quality control activities; 8) research activities; and 9) an evaluation. The participating residents have been surveyed regarding their opinions of their educational experience. RESULTS AND CONCLUSION: The standardized curriculum has been well received by the participating residents. Conclusions about the educational efficacy of such a curriculum cannot be made until more residents have used it.

Computer-Assisted Instruction↗
PubMed1993

Expression analysis of cloned chromosomal segments of Escherichia coli.

The novel transcription system of bacteriophage T7 was used to express Escherichia coli genes preferentially with a new low-copy-number plasmid vector, pFN476, to minimize toxic gene effects. Selected E. coli chromosomal fragments from an ordered genomic library (Y. Kohara, K. Ikiyama, and K. Isono, Cell 50:495-508, 1987) were recloned into this vector, and their genes were preferentially expressed in vivo utilizing its T7 promoter. The protein products were analyzed by two-dimensional gel electrophoresis. By using DNA sequence information, the gel migration was predicted for the protein products of open reading frames from these segments, and this information was used to identify gene products visualized as spots on two-dimensional gels. Even in the absence of DNA sequence information, this approach offers the opportunity to identify all gene products of E. coli and map their genes to within 10 kb on the E. coli genome; with sequence information, this approach can produce a definitive expression map of the E. coli genome.

Bacterial Proteins↗
PubMed1992

The gene-protein database of Escherichia coli: edition 5.

The gene-protein database of Escherichia coli is both an index relating a gene to its protein product on two-dimensional gels, and a catalog of information about the function, regulation, and genetics of individual proteins obtained from two-dimensional gel analysis or collated from the literature. Edition 5 has 102 new entries--a 15% increase in the number of annotated two-dimensional gel spots. The large increase in this edition was accomplished in part by the use of a new method for expression analysis of ordered segments of the E. coli genome, which has resulted in linking 50 gel spots to their genes (or open reading frames) and another 45 to specific regions of the chromosome awaiting the availability of DNA sequence information. Communication of information from the scientific community resulted in additional identifications and regulatory information. To increase accessibility of the database it has been placed in the repository at the National Center for Biotechnology Information (NCBI) at the National Library of Medicine under the name ECO2DBASE. It will be updated twice yearly. This edition of the gene-protein database is estimated to contain entries for one-sixth of the protein-encoding genes of E. coli.

Bacterial Proteins↗