The toxicity of selenium in experimental freshwater ponds.
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Biomedical subjects
Publications and source records attributed to S Watson.
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Plain radiographs of the limbs were reviewed after replantation procedures following traumatic amputation in 5 patients at the wrist (2), mid-forearm (2) and knee (1). Following upper limb replantation, rapid development of osteopaenia was initially noted in the juxta-articular regions and metaphyses of the tubular bones of the hand. These changes were followed by diaphyseal cortical bone loss with evidence of subperiosteal, intracortical and endosteal bone resorption. Juxta-articular erosions developed at the margins of the small joints in the hand in all cases. Gradual resolution of bone changes was noted in 3 of the 4 cases where follow-up exceeded 5 years. Following lower limb replantation, there was no evidence of bone loss; however, severe neuropathic joint disease developed within 18 months and progressed over the following 9 years. We suggest that the radiographic changes observed after upper limb replantation reflect regional hyperaemia secondary to neurovascular damage, whilst the changes in the lower limb reflect a similar process in a limb subjected to weight bearing.
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There is no satisfactory biomarker yet available for predicting the likelihood of premalignant changes or carcinoma developing in Barrett's or columnar lined oesophagus. In this study we have evaluated the proliferation of squamous epithelium, columnar epithelium from columnar lined oesophagus and gastric columnar epithelium from 23 Barrett's patients using positive immunoreactivity with the mouse monoclonal antibody Ki67 (which recognises an antigen associated with proliferative cells) with a view to using this parameter as a biomarker. Squamous epithelium had significantly higher Ki67 immunostaining as compared with columnar epithelium from columnar lined oesophagus (when examining the tissue with greater than 15% cells staining positive for Ki67, Fisher's exact test p = 0.004) but there was no difference found between the epithelium from the columnar lined oesophagus and gastric columnar epithelium. There was no correlation between histological inflammation and Ki67 immunoreactivity of Barrett's mucosa, and the Ki67 immunostaining of two patients with dysplasia was no different from the rest of the group. There was, however, a significant correlation between the Ki67 immunoreactivity of columnar epithelium from columnar lined oesophagus and columnar epithelium from the stomach (correlation coefficient = 0.44, p = 0.03) suggesting that epithelium from columnar lined oesophagus behaves in a similar fashion to gastric epithelium.
Genetic fingerprinting is one of the most challenging applications of any hybridization membranes. Forensic DNA fingerprinting typically uses samples in the range of 100-400 ng of genomic DNA. To ensure the ability to successfully reprobe the samples, it is imperative that repeated stripping of sample DNA be minimized while stripping of the probe DNA be maximized. By using standard dilutions of K562 cell line, we compared the following three stripping techniques: NaOH at 25 degrees C, formamide (HCONH2) at 65 degrees C and 0.1 x standard saline citrate and 0.1% sodium dodecyl sulfate at 95 degrees C (high-temperature stripping). The largest amount of genomic DNA was stripped from the membrane with NaOH, with the other two techniques removing less. Formamide and high-temperature procedures resulted in a loss of approximately 5-10 ng of DNA per strip. In contrast, the NaOH resulted in a loss of approximately 10-20 ng per strip.
A selective gastrin receptor (GR) antagonist, L-365,260 is bound to the GR on AR42J cells with a potency 7.5-fold less than G17 (50% inhibitory concentration [IC50] G17, 6 x 10(-9) mol/l; IC50 L365-260, 4.5 x 10(-8) mol/l). G17 is mitogenic for AR42J cells, as assessed by 75Se-selenomethionine uptake and L-365,260 at concentrations of 2.5 x 10(-6) mol/l and 2.5 x 10(-7) mol/l, (55X and 5.5 X the dose required to displace 50% 125I G17, respectively), and reduced optimal G17 stimulated mitogenesis in 75% of experiments. The basal growth of two human colon cancer cell lines, LoVo and C146 was reduced by L-365,260 (2.5 x 10(-7) mol/l) after 5 days of treatment to 44% and 64% of the control, respectively. However, inhibition was followed by a rebound of growth to control levels. The growth of AR42J xenografts in nude mice was increased by administration of G17 (10 micrograms/mouse/d, P less than 0.027). This increase was blocked by coadministration of oral L-365,260 (5 mg/kg/d, P less than 0.034). L-365,260 could be an important therapeutic agent in slowing the growth of GR-positive, G17-sensitive gastrointestinal tumors.
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We have investigated the action of a novel inhibitor of DG-kinase, R59949. This agent was found to produce partial inhibition of formation of phosphatidic acid in human platelets challenged with thrombin, DC8 or OAG. However, this effect was not associated with enhanced phosphorylation of a 47 kDa protein, a known substrate for protein kinase C. We therefore believe that this compound does not represent a major advance on its earlier prototype, R59022.
The technology for culture of epidermis is one of the most advanced to date for generation of a tissue in vitro. Cultured epidermis is already used for a number of applications ranging from use as a permanent skin replacement to use as an organotypic culture model for toxicity testing and basic research. While simple epidermal sheets have been grafted successfully, more advanced models for skin replacement consisting of both dermal and epidermal components are in development and being tested in a number of laboratories. One of the most advanced in vitro models is the living skin equivalent, an organotypic model consisting of a collagen lattice contracted and nourished by dermal fibroblasts overlaid with a fully formed epidermis.
Although the data used to explain a relationship between hyperparathyroidism and pancreatitis remain incomplete, there does appear to be a relationship between the two. We believe our patient's clinical course strongly supports this.
The class II genes of the sheep major histocompatibility complex (MHC) have been cloned from two unrelated heterozygous sheep into cosmid vectors. By restriction mapping and hybridization with a number of class II probes of human and mouse origin, the cloned genetic material has been assigned to seven distinct alpha genes, 10 distinct beta genes and 14 beta-related sequences. It was difficult to identify homologues of specific HLA class II genes because of a tendency for the ovine genes to cross-hybridize between HLA probes representing different loci. Such cross-hybridization was especially marked among the beta genes. While DQ and DR homologues have been tentatively identified by several criteria, no genes corresponding to DP have been identified. Cosmids containing class II alpha and beta genes have been transfected into mouse LTK- cells, and surface expression of a sheep class II molecule has been obtained.
Fimbrin is an actin-bundling protein found in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia. The complete protein sequence (630 residues) of chicken intestine fimbrin has been determined from two full-length cDNA clones. The sequence encodes a small amino-terminal domain (115 residues) that is homologous with two calcium-binding sites of calmodulin and a large carboxy-terminal domain (500 residues) consisting of a fourfold-repeated 125-residue sequence. This repeat is homologous with the actin-binding domain of alpha-actinin and the amino-terminal domains of dystrophin, actin-gelation protein, and beta-spectrin. The presence of this duplicated domain in fimbrin links actin bundling proteins and gelation proteins into a common family of actin cross-linking proteins. Fimbrin is also homologous in sequence with human L-plastin and T-plastin. L-plastin is found in only normal or transformed leukocytes where it becomes phosphorylated in response to IL 1 or phorbol myristate acetate. T-plastin is found in cells of solid tissues where it does not become phosphorylated. Neoplastic cells derived from solid tissues express both isoforms. The differences in expression, sequence, and phosphorylation suggest possible functional differences between fimbrin isoforms.
We have studied the effect of estradiol and the combined estradiol/nitrogen mustard compound estramustine on cell lines derived from human gastric and colorectal cancers. Significant stimulation of the two gastric and two fo the colorectal cell lines occurred at physiological concentrations of estradiol. Estramustine showed an inhibitory effect in all of the cell lines at 10 micrograms/l, and a direct dose-dependent inhibition was seen in two of the cell lines. Each of the cell lines was immunohistologically stained using the estrogen-receptor-related protein ERD5, and all of the cell lines except one were positive for this protein. The inhibitory effect of estramustine was lost with increasing concentrations of estradiol, suggesting that the effects of estramustine may be linked to estrogen receptors. We conclude that reduction of circulating levels of estradiol, or treatment with estramustine may have a beneficial effect in the palliation of gastrointestinal malignancy.
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In five rhesus monkeys surviving 'Peru strain' or 'strain 7' Trypanosoma cruzi infection for six to eight years, positive xenodiagnosis results and high indirect fluorescent antibody titres (4096 - 65536) persisted until the animals were killed. Abnormal electrocardiograph patterns in two monkeys (H and K) were possibly compatible with myocardial damage. Histopathological changes attributable to T. cruzi infection were minor in four monkeys but severe in one (R). In this animal, infected with what was judged previously to be the less virulent of the two T. cruzi stocks used ('strain 7'), there was severe myocarditis, with myofibre degeneration, and lesions of the oesophagus. Elevated serum levels of five enzymes were not detected in any of the chronically infected monkeys.
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