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J Bishop

Publications and source records attributed to J Bishop.

At least 55 records · Page 3Linked to original sources
PubMed1998

A simple inflammation model that distinguishes between the actions of anti-inflammatory and anti-rheumatic drugs.

OBJECTIVE AND DESIGN: To determine the effects of anti-inflammatory and anti-rheumatic drugs on paw swelling and changes in plasma levels of acute phase proteins (APPs) during acute inflammation in the rat. MATERIALS AND METHODS: Inflammation was induced in rats by the injection of adjuvant and the animals were bled five days later and plasma levels of seromucoid, haptoglobin, caeruloplasmin and albumin were determined spectrophotometrically using a Cobas-bio centrifugal analyzer. The effects of daily administration of a variety of drugs used to treat arthritis were determined on paw swelling and APP levels. RESULTS: Injection of the adjuvant induced a pronounced change in APP levels which correlated with the increase in paw swelling. In general, the NSAIDs tested significantly reduced paw swelling and significantly increased levels of haptoglobin and caeruloplasmin in a dose-related manner. Two dose-levels of steroids were administered, the higher dose reduced swelling, and reduced levels of seromucoid, haptoglobin and caeruloplasmin, but raised albumin levels; the lower dose also reduced paw swelling, but the only change in APPs was increased albumin levels. Anti-rheumatic drugs such as gold salts reduced levels of some APPs (seromucoid, haptoglobin and caeruloplasmin) without reducing paw swelling. Immunomodulators had a variety of effects on inflammation and APPs depending on mechanism of action. CONCLUSIONS: The different classes of anti-inflammatory/anti-rheumatic drug tested show distinct profiles of activity against APPs and paw swelling. These differential effects may result from modulation of cytokine activity.

Acute-Phase Proteins↗
PubMed1998

Clenbuterol induces cardiac hypertrophy with normal functional, morphological and molecular features.

OBJECTIVE: Several pharmacological agents have been shown to produce 'physiological' or 'pathological' hypertrophy based on their functional characteristics. The aim of this study was to examine the features of cardiac hypertrophy induced by the selective beta 2-adrenergic agonist, clenbuterol. METHODS: Cardiac hypertrophy was induced in 7-week-old Sprague-Dawley rats by daily injections of clenbuterol for 3 weeks. Thyroxine and isoproterenol were also used to produce cardiac hypertrophy to serve as positive controls for physiological and pathological hypertrophy, respectively. Left ventricular function was determined using an isolated rat heart preparation. Ventricular samples were used for morphological examination while interstitial collagen was measured using high-pressure liquid chromatography. Expression of sarcoplasmic reticulum Ca(2+)-ATPase2a (SERCA2a) and phospholamban (PLB) were measured by dot blot analysis. RESULTS: Clenbuterol treatment induced 26% left ventricular hypertrophy. These hearts demonstrated normal systolic isovolumic parameters and diastolic (active relaxation and passive stiffness) function. In addition, left ventricular concentration of collagen and morphology was normal as were the expression of SERCA2a and PLB mRNA. CONCLUSION: These results suggest that clenbuterol-induced hypertrophy is 'physiological' in terms of its function, extracellular structure and gene expression.

Adenosine Triphosphatases↗
PubMed1998

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

PURPOSE: Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS: A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION: Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

Adult↗
PubMed1998

Epididymal sperm aneuploidies in three strains of rats detected by multicolor fluorescence in situ hybridization.

A multicolor fluorescence in situ hybridization (FISH) method was developed to detect aneuploidy and diploidy in epididymal sperm of rats using DNA probes specific for chromosomes 4 and Y. Fourteen healthy young-adult rats from three strains were evaluated: inbred Fisher 344/N/ehs, outbred Sprague-Dawley, and outbred WU Wistar/CPB. The hybridization efficiency of the FISH procedure was > 99.9%, the sex-ratio in sperm was approximately 1 as expected, and there was no significant variation among two independent scorers. No significant variations were detected within or among strains in the frequencies of sperm disomy for chromosome 4 (1-6.5 per 10,000 cell per animal) or the Y chromosome (0-2.5 per 10,000 cells per animal). There was a trend toward increased variation among Wistar rats. The frequencies of sperm-carrying hyper- and hypohaploidy for chromosome 4 were similar, suggesting a symmetrical mechanism of chromosome gain and loss during meiosis. The frequencies of Y-Y-4-4 sperm, which represent genomic meiosis II errors, did not differ significantly across strains (0.1-0.7 per 10,000 cells per strain). This FISH method for detecting aneuploidy in rat epididymal sperm provides a promising interspecies biomarker of male germ cell aneuploidy and introduces the rat as an animal model for investigating the heritable risk to offspring associated with paternal genotype, physiology, and exposure to environmental mutagens. There appear to be no significant differences among young healthy rats, mice, and men in the baseline frequencies of sperm with Y chromosomal disomy, the only chromosome for which data currently exists for all three species.

Aneuploidy↗
PubMed1997

Epidemiologic study of Down syndrome in a racially diverse California population, 1989-1991.

The prevalence of Down syndrome was studied among all live births occurring between 1989 and 1991 in the California counties monitored by the California Birth Defects Monitoring Program. Objectives of this study were: 1) to calculate adjusted prevalence rates and quinquennial maternal age-specific risk rates of Down syndrome after adjusting for elective abortion of prenatally diagnosed fetuses; 2) to estimate the impact of prenatal diagnosis and subsequent elective abortion of affected fetuses on the observed prevalence of Down syndrome; and 3) to examine sex ratios among liveborn infants and fetuses with Down syndrome. The racial/ethnic diversity and large size of the population allowed the data to be stratified into five racial categories-Hispanics, whites, Asians, blacks, and others. For the period 1989-1991, the observed prevalence of Down syndrome was 1.13 per 1,000 live births, and the adjusted total prevalence, which took into account the termination of affected pregnancies following prenatal diagnosis, was 1.53 per 1,000 live births. In a comparison of quinquennial maternal age-specific risk rates of Down syndrome by race, Hispanics and whites were the only groups with rates that differed significantly from each other, with Hispanics exhibiting higher rates at maternal ages under 40 years. The overall reduction in live births with Down syndrome in 1989-1991 that could be attributed to prenatal diagnosis and elective abortion of affected fetuses was 25.8%, with a 49.1% reduction being observed at maternal ages > or = 35 years. In 1990-1991, Hispanics had the lowest overall reduction (10.0%), while whites had the highest reduction (46.3%). The male: female ratios among liveborns with Down syndrome were significantly higher than those among all live births, and race had a significant association with sex ratios in both cases and controls. These findings indicate that prenatal diagnosis and elective termination of affected pregnancies has had a substantial impact in reducing the number of liveborns with Down syndrome in the monitored California counties. The effect was greatest for whites and least for Hispanics, with results indicating considerable variation in the use of prenatal diagnostic services among racial/ethnic groups. Estimates of adjusted total prevalence and reduction in live births with Down syndrome in this study should be considered minimal because of some underascertainment of prenatally diagnosed cases.

Abortion, Induced↗
PubMed1997

17 alpha-estradiol exerts neuroprotective effects on SK-N-SH cells.

Estradiol (E2) has been shown to exert organizational, neurotrophic, and neuroprotective effects in the CNS. The present study assessed the specificity of the neuroprotective effects of estradiol for the potent 17 beta-isomer. SK-N-SH cells from a human neuroblastoma cell line, which we have shown to be estrogen-responsive, were cultured at low or high plating density. Then cells were exposed to 17 beta-E2 (0.2 or 2 nM), 17 alpha-E2 (0.2 or 2 nM), or cholesterol, testosterone, dihydrotestosterone, progesterone, or corticosterone (all at 2 nM). Cultures were insulted by serum deprivation, which caused a profound loss of cells. At 1 or 2 d of serum deprivation and steroid hormone replacement, the protection afforded cells by the steroid addition was assessed. Serum deprivation killed approximately 90% of cells cultured at both low and high plating density. Both 17 alpha- and 17 beta-E2 provided protection of SK-N-SH cells at either plating density. Further, a 10-fold molar excess of tamoxifen antagonized only approximately one-third of the neuroprotective effects of either isomer of estradiol, and a 100-fold excess of tamoxifen had no additional effect on the neuroprotection by 17 beta-E2. By contrast, none of the other steroids tested protected cells from the insult of serum deprivation. These results indicate that the neuroprotective effects of estrogens are not attributable to the general steroid structure, and the majority of the neuroprotection may not be mediated via a tamoxifenantagonized receptor mechanism.

Cholesterol↗
PubMed1997

Induction of chromosomal aberrations in mouse zygotes by acrylamide treatment of male germ cells and their correlation with dominant lethality and heritable translocations.

The objectives of this research were: 1) to investigate the time course of the cytogenetic defects induced by acrylamide (AA) treatment (5 x 50 mg/kg) of male germ cells in first-cleavage zygote metaphases using PAINT/DAPI analysis, and 2) to characterize the correlation between chromosomal aberrations at first cleavage, dominant lethality, and heritable translocations. PAINT/DAPI analysis employs multicolor fluorescence in situ hybridization painting plus DAPI staining to detect both stable and unstable chromosomal aberrations at first-cleavage metaphase of the zygote. High levels of chromosomally defective zygotes were detected after mating at all postmeiotic stages (20-190-fold, P < 0.001). Early spermatozoa (6.5 d post-treatment) were the most sensitive, with 76% of the zygotes carrying cytogenetic defects. A significant 10-fold increase was also detected 27.5 d post-treatment, indicating that AA had a cytogenetic effect on meiotic stages. PAINT/DAPI analysis revealed that: 1) AA-induced chromosomal breaks occurred at random, and 2) the frequencies of symmetrical and asymmetrical exchanges were similar at all mating days, except 9.5 d after AA treatment, where significantly (P < 0.02) more asymmetrical aberrations were found. Furthermore, the proportions of zygotes carrying unstable and stable chromosomal aberrations followed a similar post-treatment time course as the proportions of dominant lethality among embryos and heritable translocations among offspring. These findings indicate that PAINT/DAPI analysis of zygotic metaphases is a promising method for detecting male germ cell mutagens capable of inducing chromosomal aberrations and for evaluating the associated risks for embryonic loss and balanced translocations at birth.

Acrylamide↗
PubMed1997

Effects of thyroid hormone on embryonic oligodendrocyte precursor cell development in vivo and in vitro.

The oligodendrocyte precursor cell divides a limited number of times before terminal differentiation. The timing of differentiation depends on both intracellular mechanisms and extracellular signals, including mitogens that stimulate proliferation and signals such as thyroid hormone (TH) and retinoic acid (RA) that help trigger the cells to stop dividing and differentiate. We show here that, both in vivo and in vitro, TH is required for the normal development of rodent optic nerve oligodendrocytes, although in its absence some oligodendrocyte development still occurs, perhaps promoted by signals from axons. We also demonstrate that TH from both mother and pup plays a part in oligodendrocyte development in vivo. Finally, we show that precursors in embryonic nerve cultures differ from those in postnatal cultures in two ways: they respond much better to TH than to RA, and they respond more slowly to TH, suggesting that oligodendrocyte precursor cells mature during their early development.

Animals↗
PubMed1997

A phase III study of radiotherapy with and without continuous-infusion fluorouracil as palliation for non-small-cell lung cancer.

This study assesses the effect of adding continuous-infusion fluorouracil to palliative thoracic radiation therapy (RT) on the rate and duration of symptom relief in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred eligible patients with NSCLC were randomized to receive either 20 Gy in five daily fractions as palliation for intrathoracic disease or the same RT with concurrent continuous infusion of 1 g m(-2) day(-1) fluorouracil for 5 days. Survival, response and rates of symptom relief in the two groups were compared according to treatment intent, and toxicities were compared according to treatment received. The overall response rate was higher in patients randomized to the combination (29%) than in patients randomized to RT alone (16%) (P = 0.035). However, there were no significant differences between the treatment arms in terms of overall or progression-free survival or in palliation of symptoms. Patients treated with RT plus fluorouracil had significantly more acute toxicity, including nausea and vomiting (P = 0.01), oesophagitis (P = 0.0003), stomatitis (P = 0.0005) and skin reaction (P = 0.003). This study suggests for the first time an interaction between RT and infusional fluorouracil in NSCLC. Although RT plus fluorouracil resulted in a significantly higher response rate than achieved with RT alone, this did not translate into more effective palliation. Because the combination produced significantly more toxicity than RT alone, it is not recommended for the palliative treatment of NSCLC. Nevertheless, these results suggest that opportunities may exist for exploitation of the observed enhancement of antitumour effect in the setting of high-dose radical RT for NSCLC.

Adult↗
PubMed1997

Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo.

1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1- imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555 prevented granuloma-induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro 32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.

Administration, Oral↗
PubMed1997

Research methods for studying injecting drug users in a rural centre.

Targeted sampling, multiple data collection methods and peer interviewers have been used with success for studies of injecting drug users (IDUs) in main cities. This paper reports the success of a trial of these research methods with IDUs in a rural centre. Recruitment via outreach (for individual interviews and for focus groups), street intercept and service-based surveys (methadone clinic and prison based surveys) were found to be viable and to vary in their success in recruiting subgroups of IDUs. Their use in combination is recommended so that the largest possible range of IDUs can be recruited. The close involvement of peer interviewers and of an advisory group in planning and implementing these data collections was essential. Advertising was not found to be successful for recruiting to a phone-in, for focus groups nor to a community forum. Concerns about anonymity, 'paranoia' and a general lack of a cohesive IDU community were barriers to recruitment.

Journal Article↗
PubMed1997

Diet and cancer.

Explore the source record for details and available documents.

Colonic Neoplasms↗
PubMed1996

CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells.

Cytotoxic function of CD4+ Th1 cells is mediated by Fas (CD95, APO-1) and its ligand (Fas ligand). Recent studies using nontransformed B cells and the Ramos Burkitt's lymphoma (BL) B-cell line cells show that CD40 ligation at the B-cell surface by activated, CD40 ligand (CD40L)-bearing, CD4+ T cells upregulates Fas expression on B cells and primes B cells for Fas-mediated death signals. In this work, we examine whether this CD4+ T-cell-dependent molecular pathway for Fas upregulation and B-cell apoptosis reflects a peculiarity of the Ramos B-cell line or is applicable to other Burkitt's tumors as well. In 5 of the 6 Epstein-Barr virus-negative BL cell lines examined, the cells constitutively express undetectable or low levels of Fas and are resistant to Fas-mediated signals induced by monoclonal anti-Fas antibody. All 6 of the BL cell line B cells upregulate Fas in response to CD40 ligation, and in 4 of the cases they become sensitive to Fas-mediated death signals. In one BL cell line, the cells are constitutively sensitive to Fas-mediated cytolysis and are unaffected by CD40 signals. Next, we applied these immunologic manipulations to cells from a refractory clinical sample and observed that the tumor cells could be induced to express Fas and undergo apoptosis in our system. These results establish CD4+ T cells and the Fas-Fas ligand system as important immune regulators of Burkitt's lymphoma B cells and indicate that the susceptibility of tumor cells to Fas-mediated death signals can be modulated by specific activation events at the cell surface.

Apoptosis↗
PubMed1996

Paternally inherited chromosomal structural aberrations detected in mouse first-cleavage zygote metaphases by multicolour fluorescence in situ hybridization painting.

We describe a fluorescence in situ hybridization (FISH) procedure for assessing zygotic risk of paternal exposure to endogenous or exogenous agents. The procedure employs multicolour FISH with chromosome-specific DNA painting probes plus DAPI staining for detecting both balanced and unbalanced chromosomal aberrations in mouse first-cleavage (1-Cl) zygote metaphases. Four composite probes specific for chromosomes 1, 2, 3 or X, each labelled with biotin, plus a composite probe specific for chromosome Y labelled with digoxigenin, were used. We applied this method to evaluate the effects of paternal exposure to acrylamide, a model germ cell clastogen. First-cleavage zygote metaphases, collected from untreated females mated to males whose sperm or late spermatids were treated with acrylamide, were scored for the induction of structural aberrations using both chromosome painting (PAINT analysis) and DAPI analysis. Structural chromosomal aberrations were observed in the sperm-derived, but not in the egg-derived, pronuclei. While 59.4% of the zygotes had structural aberrations by DAPI analysis, 94.1% of the same zygotes had structural aberrations by PAINT analysis (P < 0.001), illustrating the increased sensitivity for detecting translocations and insertions obtained by adding chromosome painting. These findings show that FISH painting of mouse 1-Cl zygotes when used in conjunction with DAPI analysis is a powerful model for investigating the cytogenetic defects transmitted from father to offspring.

Animals↗
PubMed1996

Spontaneous rates of sex chromosomal aneuploidies in sperm and offspring of mice: a validation of the detection of aneuploid sperm by fluorescence in situ hybridization.

This study was designed to evaluate the frequency of aneuploid sperm in young adult mice of the genotype (102/E1 x C3H/E1)F1 determined by the fluorescence in situ hybridization (FISH) procedure and to evaluate the frequencies of aneuploid sperm observed by FISH compared with the frequencies of aneuploid offspring. Three-chromosome FISH was applied to determine the fractions of hyperhaploid and diploid sperm with DNA probes specific for chromosomes X, Y and 8. The animals were treated with three common solvents. Sperm smears were prepared for FISH by two similar protocols and were scored by different persons and in two different laboratories. There were no significant differences between scorers or laboratories. The frequencies of the sex chromosome aneuploidies in sperm (Y-Y and X-Y) were compared to the frequencies of mice carrying sex chromosome aneuploidy among controls of the heritable translocation assay in studies conducted from 1975-1995. To identify aneuploid individuals, untreated males and females of the genotype (102/E1 x C3H/E1)F1 were mated to assess their fertility by observing three consecutive litters. Semisterile and sterile animals were further analysed by meiotic cytogenetics and by karyotyping to determine the incidence of reciprocal translocations and sex chromosome aneuploidies (XXY and XYY). Based on the analysis of 175247 sperm and 9840 progeny, the frequency of Y-Y sperm was 0.01% while 0.03% of the offspring were XYY. The frequency of X-Y sperm was 0.005% while 0.02% of the offspring were XXY. The frequencies of aneuploid sex chromosomes were not significantly different between sperm and offspring. This allows two conclusions. First, there was no detectable prenatal selection against these sex-chromosomal aneuploid offspring, and second, germ cell aneuploidy can be reliably determined in mice by sperm FISH analyses.

Aneuploidy↗