Bursal osteochondromatosis overlying an osteochondroma of a rib. A case report.
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Adult↗
Biomedical subjects
J M Wright
Publications and source records attributed to J M Wright.
Isoniazid-induced hepatic necrosis and steatosis in rabbits: absence of effect of gender.
Isoniazid, a highly effective drug for the chemoprophylaxis and treatment of tuberculosis, is associated with severe hepatotoxicity in 1-2% of individuals. In a rabbit model of isoniazid-induced hepatotoxicity, we have measured hepatic necrosis (quantitated by elevation of plasma argininosuccinic acid lyase (ASAL) activity), hepatic steatosis (quantitated by elevation of hepatic triglyceride content), and elevation in plasma triglyceride concentration in 15 rabbits. Eight of 15 rabbits were male, and 14 of 15 were rapid acetylators of sulfamethazine. Administration of isoniazid to rabbits resulted in a 27-fold increase in plasma ASAL activities, a 7.5-fold increase in hepatic triglyceride content, and a 13-fold increase in plasma triglyceride levels. This study demonstrated no effect of gender on these three pathological changes that occur in this model of isoniazid-induced hepatotoxicity in rabbits.
Animals↗
Single-channel and whole-cell analysis of ethanol inhibition of NMDA-activated currents in cultured mouse cortical and hippocampal neurons.
The effects of 0.1 to 500 mM ethanol on NMDA-activated currents were studied in primary cultures of mouse cortical and hippocampal neurons. In whole-cell recordings the IC50S for inhibition of NMDA-activated currents by ethanol were 129 mM +/- 20 mM in hippocampal neurons and 126 +/- 18 mM in cortical neurons. In single-channel recordings from excised outside-out patches of cortical neurons, ethanol inhibited total charge per minute with an IC50 of 174 +/- 23 mM, which was not significantly different from the IC50S for inhibition of whole-cell current. The reduction in mean open channel lifetime by ethanol was fit by the logistic equation with an apparent IC50 of 340 +/- 28 mM. Analysis of single-channel data indicated that ethanol inhibition of NMDA currents did not involve substantial changes in fast closed state kinetics, changes in open channel conductance, or block of the open channel. At the whole-cell IC50 of ethanol, mean open channel lifetime would decrease by 28% and frequency of opening would decline by 31% to account for the reduction in current. Single-channel data were consistent with ethanol being an allosteric modulator of gating which reduces agonist efficacy.
Analysis of Variance↗
Patterns of kinship in groups of free-living sperm whales (Physeter macrocephalus) revealed by multiple molecular genetic analyses.
Mature female sperm whales (Physeter macrocephalus) live in socially cohesive groups of 10-30, which include immature animals of both sexes, and within which there is communal care of the young. We examined kinship in such groups using analyses of microsatellite DNA, mitochondrial DNA sequence, and sex-linked markers on samples of sloughed skin collected noninvasively from animals in three groups off the coast of Ecuador. Social groups were defined through photographic identification of individuals. Each group contained about 26 members, mostly female (79%). Relatedness was greater within groups, as compared to between groups. Particular mitochondrial haplotypes were characteristic of groups, but all groups contained more than one haplotype. The data are generally consistent with each group being comprised of several matrillines from which males disperse at about the age of 6 years. There are indications of paternal relatedness among grouped individuals with different mitochondrial haplotypes, suggesting long-term associations between different matrilines.
Age Factors↗
Androgen inhibition of vitellogenin gene expression in tilapia (Oreochromis niloticus).
Treatment of mature female tilapia (Oreochromis niloticus) with high levels of androgen (17 alpha-methyltestosterone, 17 alpha MT) results in a pronounced decline in plasma vitellogenin levels as determined by gel electrophoresis. Total RNA extracted from livers of treated fish and vehicle-injected controls was analyzed by Northern and slot blot hybridization using an oligonucleotide complementary to a sequence in the 3' end of tilapia vitellogenin mRNA. The probe revealed an mRNA of 6.5 kb in liver from the control mature female fish which was decreased by 85% by androgen treatment. As expected, estradiol (E2) treatment induced the 6.5-kb mRNA in mature male tilapia. The antiestrogen, tamoxifen, strongly decreased vitellogenin mRNA levels in mature females. Radioimmunoassay of serum from control and 17 alpha MT-treated female tilapia showed a marked reduction in serum E2 levels, from 11.4 +/- 2.6 ng/ml in controls to 2.2 +/- 0.13 ng/ml in treated fish. Tamoxifen, however, resulted in increased serum E2 levels, probably by blocking E2 negative feedback. The serum E2-lowering effect of 17 alpha MT suggests an inhibitory site of action on gonadotropin production at the hypothalamic-pituitary axis, possibly through an androgen receptor or through an estrogen receptor after local aromatization of 17 alpha MT.
Animals↗
Role of hydrazine in the mechanism of isoniazid hepatotoxicity in rabbits.
Isoniazid (INH) continues to be a highly effective drug in the chemoprophylaxis and treatment of tuberculosis; however, its use is associated with hepatotoxicity (predominantly hepatic necrosis) in 1-2% of individuals. The INH metabolites, acetylhydrazine and hydrazine, have each been implicated as the causative hepatotoxin in INH-induced hepatotoxicity. Using a model of INH-induced hepatotoxicity in rabbits, in which INH-induced hepatotoxicity manifests as hepatic necrosis, hepatic steatosis (hepatic fat accumulation) and hypertriglyceridaemia (elevated plasma triglycerides), we compared the severity of these measures of toxicity with plasma levels of INH, acetylhydrazine and hydrazine. Plasma INH and acetylhydrazine were not correlated with markers of INH-induced hepatic necrosis or fatty changes. Plasma hydrazine at 32 h was correlated significantly with plasma argininosuccinic acid lyase (ASAL, a sensitive marker of hepatic necrosis) activity as area under the curve (r2 = 0.54, P < 0.002) and log plasma ASAL activity at 48 h after the first dose of INH (r2 = 0.53, p < 0.005), but not with fatty changes. These results show in this model of INH-induced hepatotoxicity in rabbits that hydrazine, and not INH or acetylhydrazine, is most likely involved in the pathogenic mechanism of hepatic necrosis.
Animals↗
Microsatellites at a common site in the second ORF of L1 elements in mammalian genomes.
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Animals↗
Nucleotide sequence of transferrin cDNAs and tissue-specific of the transferrin gene in Atlantic cod (Gadus morhua).
Atlantic cod (Gadus morhua) transferrin cDNAs were isolated from a liver cDNA library using a cod transferrin-derived polymerase chain reaction product as a hybridization probe. The composite nucleotide sequence of two overlapping clones was 2223 bp in length excluding the poly(A) sequence and was equivalent to 87% of the 3' end of the Atlantic salmon transferrin cDNA sequence. Comparison of the deduced amino acid sequence of cod, salmon, Xenopus and several mammalian transferrins revealed that the two fish sequences are more similar with respect to their amino acid sequence and the position of additions/deletions than to other vertebrate transferrins. Conservation of the iron-binding domains and cysteine residues involved in disulphide bridges indicates that all transferrins share similar tertiary structure and support the hypothesis that extant vertebrate transferrin genes were derived from a gene duplication before the divergence of fish, frogs and mammals. Cod transferrin mRNA was detected in both brain and liver RNA and to a much lesser extent in RNA isolated from kidney and heart in contrast to salmon and several other vertebrates in which the transferrin gene is not expressed in brain.
Amino Acid Sequence↗
Weaver granule neurons are rescued by calcium channel antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin.
The weaver mutation impairs migration of the cerebellar granular neurons and induces neuronal death during the first two weeks of postnatal life. To elucidate the molecular mechanisms for the impaired neuronal migration, we investigated the rescue mechanisms of the weaver (wv/wv) granule neurons in vitro. We found that Fab2 fragments of antibodies against a neurite outgrowth domain of the B2 chain of laminin enhanced neurite outgrowth and neuronal migration of the weaver granule neurons on a laminin substratum and in the established cable culture system. The rescue of the weaver granule neurons by antibodies against the B2 chain of laminin may result from the neutralizing effect of these antibodies against the elevated B2 chain levels of the weaver brain. The L-type calcium channel blocker, verapamil (1-5 microM), also rescued the weaver granule neurons. High concentrations of MK-801 (10-20 microM), a glutamate receptor antagonist and voltage-gated calcium channel blocker, rescued the weaver granule neurons similar to verapamil, but low concentrations of MK-801 (1 microM) had no rescue effect. Simultaneous patch-clamp studies indicated that the weaver granule neurons did not express functional N-methyl-D-aspartate receptors further indicating that the rescue of the weaver granule neurons by MK-801 resulted from its known inhibition of voltage-gated calcium channels. The present results indicate that antibodies against the B2 chain of laminin, verapamil, and high concentrations of MK-801 protect the weaver granule neurons from the otherwise destructive action of the weaver gene. Thus, both the laminin system and calcium channel function contribute to the migration deficiency of the weaver granule neurons.
Animals↗
Demonstration of an in vitro direct vascular relaxant effect of diuretics in the presence of plasma.
OBJECTIVE: To determine whether diuretics have direct vascular actions and to compare the in vitro effects of a loop diuretic with thiazide and thiazide-like diuretics. DESIGN: A randomized, double-blind, vehicle-controlled design was used to avoid experimenter bias. METHODS: Concentration-response curves to hydrochlorothiazide, chlorthalidone, indapamide, and furosemide were tested on the following male Wistar rat vascular smooth muscle preparations: rat aortic rings, rat pulmonary artery rings, and rat mesenteric portal vein. RESULTS: All four diuretics demonstrated no vasorelaxant action in Krebs solution. They all exhibited vasorelaxant actions in aortic and pulmonary artery rings when plasma was mixed with Krebs solution in a 50:50 ratio. The magnitude of the relaxation was greater in the aortic ring preparation. This direct vascular action was found to be concentration dependent and endothelium independent. The order of potency of the vasorelaxant action of the diuretics was (from most to least) indapamide, hydrochlorothiazide, chlorthalidone, and furosemide on both aortic and pulmonary artery rings. CONCLUSION: Diuretics possess direct vasorelaxant effects that are dependent upon the presence of plasma; this action may contribute to their antihypertensive properties.
Animals↗
PCR primers for harbour seal (Phoca vitulina concolour) microsatellites amplify polymorphic loci in other pinniped species.
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Alleles↗
Development of PCR primers for nine polymorphic American mink Mustela vison microsatellite loci.
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Animals↗
Polymorphic microsatellites from sperm whales and their use in the genetic identification of individuals from naturally sloughed pieces of skin.
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Animals↗
Hypothyroxinemia and phenytoin toxicity: a vicious circle.
Phenytoin is a widely used anticonvulsant which has a relatively narrow therapeutic range of serum concentrations, 40-80 mmol/l (10-20 mg/l). Phenytoin is known to show concentration-dependent kinetics within this therapeutic range. Because of this, small changes in dose and minor alterations in hepatic metabolism of phenytoin may cause a disproportionately large affect on serum concentrations. Hypothyroidism is associated with inhibition of hepatic oxidative metabolism of many drugs. However, there is a general consensus in the literature that serum phenytoin clearance is not influenced by thyroid functional status. This report describes a 63 year-old female who developed decreased serum free T4 (8 pmol/l) and phenytoin toxicity. We identified three other similar case reports. We propose that the following vicious circle may be involved in this interaction: induction by phenytoin of hepatic enzymes involved in the metabolism of T4 and T3, decreased serum free T4 levels causing decreased activity of hepatic NADPH cytochrome P-450 reductase, a resultant decrease in hepatic P-450 IIC9 catalyzed hydroxylation of phenytoin, increased serum phenytoin concentrations and further induction of T4 and T3 hepatic metabolism.
Anticonvulsants↗
The effects of platelet-derived growth factor-BB and insulin-like growth factor-1 on epithelial dysplasia.
Growth factors are multi-functional and multi-targeted proteins which play a significant role in wound healing. Platelet-derived growth factor B-chain homodimer (PDGF-BB) and insulin-like growth factor-1 (IGF-1) have demonstrated efficacy for periodontal regeneration in animal models. Although primarily associated with wound healing, PDGF-BB and IGF-1 also facilitate growth of a number of malignant neoplasms. Of particular concern to periodontists is epithelial dysplasia, a necessary precursor to squamous cell carcinoma, the most common oral malignancy. Certain risk factors for oral cancer, such as tobacco, age, and alcohol, are also associated with an increased incidence of periodontal disease. The effects of the combination of PDGF-BB and IGF-1 on epithelial dysplasia have not previously been reported. The purpose of this study was to examine the effects of the combination of PDGF-BB and IGF-1 on epithelial dysplasia induced in the buccal cheek pouch of the Syrian golden hamster. A total of 66 hamsters received 18 applications of 0.5% dimethylbenzanthracene (DMBA), a topical carcinogen, over a 6-week period for the induction of dysplasia. The hamsters were subsequently divided into a baseline and 3 experimental groups (growth factors, saline vehicle, untreated control). Following the final DMBA application (day 0), the baseline group (N = 6) was sacrificed, the growth factor group (N = 21) received a single injection in the cheek pouch containing 4 micrograms of PDGF-BB and 4 micrograms of IGF-1 in saline, the saline group (N = 19) received an injection in the cheek pouch containing the saline vehicle only, and the untreated control group (N = 20) received no injection. Animals in experimental groups were sacrificed on days 3, 6, and 10. The cheek pouches were harvested for histologic and histochemical evaluation. Dysplasia was histologically graded from 0 to 4. Statistical analysis of the histologic data revealed no significant differences either by sacrifice date or by group. Histochemical evaluation, via staining for gamma-glutamyl transpeptidase (GGT), a marker for dysplastic cell colonies, revealed that the density of GGT-positive cells in experimental groups differed significantly from baseline levels. No significant differences were detected between experimental groups. There was poor correlation between the density of GGT-positive cells and the histologic grading of dysplasia. It is concluded that exposure to PDGF-BB and IGF-1 had no demonstrable effect on epithelial dysplasia in this hamster model.
9,10-Dimethyl-1,2-benzanthracene↗
Back pain in aircrew--an initial survey.
BACKGROUND: In the early 1990's staff at a Royal Naval Air Station formed the view that pilots and observers of the Navy Lynx helicopter fleet appeared to have a higher incidence of back pain, to be seeking medical assistance more frequently and to be spending more time medically "unfit to fly" when compared to their counterparts in other helicopters. HYPOTHESIS: To quantify the incidence of low back pain in helicopter aircrew by use of a questionnaire. METHODS: A questionnaire was used to establish the prevalence and nature of back pain in Naval aircrew (161) compared to a control group of randomly selected non-flying military personnel (310). RESULTS: Results show that aircrew (82%) experience significantly more back pain than controls (52%) (p < 0.01) though the nature of pain was similar in both groups. Significantly more aircrew (73%) than controls (49%) (p < 0.01) reported a previous history of back pain and report pain in shoulders (19%), midback (42%), lower back (72%) and across the buttocks (12%). Ergonomic factors were thought to be causative. Of aircrew surveyed, 11 (8%) had been issued with personal lumbar supports which resulted in major subjective improvements in flight-related symptoms. CONCLUSIONS: Helicopter aircrew have a higher incidence of back pain. Crew station design was identified as a major contributor to the prevalence of back pain while personal supports reduced the levels of discomfort. While these findings are not new, no significant steps have been taken to redesign the crew station. It is recommended that personal supports are provided to all aircrew and that a more detailed study of crew station ergonomics is indicated following a more comprehensive study of prevalence of back pain in Royal Navy aircrew.
Adult↗
Immunohistochemical analysis of an equine model of synovitis-induced arthritis.
OBJECTIVES: To use lipopolysaccharide (LPS) to create synovitis in the midcarpal joint of ponies, and to assess the morphologic, histochemical, and immunohistochemical effects of synovitis on articular cartilage of the third carpal bone. ANIMALS: 2- to 3-year-old ponies, 6 control (group 1) and 6 treated (group 2). PROCEDURE: Synovitis was induced in 1 midcarpal joint of group-2 ponies by intra-articular injections of LPS (0.02 micrograms/kg of body weight), morphine (0.1 mg/kg), and saline solution (group 2a) and a morphine and saline solution alone in the contralateral midcarpal joint (group 2b). Articular cartilage sections and attached synovial membrane from the third carpal bones were examined by immunohistochemical distribution of interleukin 1 beta, tumor necrosis factor (TNF)-alpha, TNF receptors (P55, P75) and 3-B-3(-) epitopes, and by localization of proteoglycans (metachromatic staining). Proteoglycan extracts were assessed by metachromatic staining or western blotting and immunohistochemical staining, using anti-3-B- antibodies. RESULTS: Enhanced immunoreactivity for the cytokines and receptors was found in inflamed synovial membrane and noncalcified cartilage (group 2a more than 2b). Metachromasia of the noncalcified cartilage was greater in group-1 than in group-2a and group-2b specimens. In group 2a, chondrocyte hypertrophy and enhanced immunoreactivity for 3-B-3(-) epitope in areas of increased cytokine immunoreactivity suggested possible phenotypic change of the chondrocytes in response to synovitis. Immunohistochemical analysis by western blotting of proteoglycan extracts indicated strong 3-B-3(-) epitope immunolocalization in group-2a, weaker staining in group-2b, and barely detectable stain in group-1 specimens, which correlated with in situ immunolocalization. CONCLUSIONS: Intra-articular administration of LPS may be used to induce a synovial environment conductive to increased immunoreactivity of interleukin 1 beta, TNF-alpha, and its receptors in equine synovial membrane and articular cartilage. These cytokines may be involved in the early phenotypic change of chondrocytes that is believed to occur in osteoarthritis and is characterized in this study by enhanced 3-B-3(-) epitope immunoreactivity and chondrocyte hypertrophy.
Animals↗