Biomedical subjects
Publications and source records attributed to S Shah.
A 15-year-old patient with stage-Ia epithelial ovarian cancer was managed conservatively after simple excision of the tumor. The remaining ovary is screened at regular intervals by ultrasound. It is hoped that this policy is justified to allow future childbearing after which total pelvic clearance is proposed.
We describe short-term and long-term safety studies after low repetition rate magnetic brain stimulation in 10 normal subjects. We obtained quantitative EEG data, psychometric test results, serum prolactin and cortisol levels before and after brain stimulation. EEG and psychometric data were also obtained in 5 of these subjects 16-24 months after the initial experiment. Short- and long-term studies did not show any deleterious effects. Randt delayed recalls, however, showed a transient reduction in the score immediately after stimulation which resolved on retesting in 2 weeks. To address the question of fatigue we repeated Randt tests in 4 subjects before and after magnetic brain stimulation but without the other extensive psychometric, EEG and blood tests. Pre- and post-stimulation scores on this occasion showed no significant difference in these 4 subjects suggesting that the transient changes in the previous Randt score were related to fatigue. We conclude that single-pulse magnetic brain stimulation has no deleterious effects after magnetic brain stimulation.
We describe a technique of percutaneous magnetic coil (MC) stimulation of the phrenic nerve trunk on one side of the neck and phrenic roots over the upper cervical vertebral column in 10 normal subjects and 2 patients. We were able to obtain compound muscle action potentials (CMAPs) from the diaphragm at two sites (xiphoid process and 7th intercostal space) after stimulation of the phrenic nerve trunk and roots. We noted that the onset latencies after phrenic root stimulation remained fixed despite increasing the stimulus intensity from 50% to 100% and on moving the MC vertically or laterally, suggesting that stimulation of the fastest conducting fibers was occurring at a fixed site, most likely at the intervertebral foramina. Absent responses unilaterally in one and prolonged latencies to diaphragmatic CMAPs in another patient confirmed phrenic neuropathy in these patients.
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Arbekacin (1-N-((S)-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B) was active against 54 strains of methicillin-resistant Staphylococcus aureus from 16 different countries, all of which were resistant to > or = 32 mg/L amikacin. MICs of arbekacin ranged from 1 to 16 mg/L, the MIC50 was 3.2 mg/L and the mode geometric mean MICs were 4 and 4.5 mg/L respectively.
The nuclear medicine evaluation of the immunocompromised patient with fever of unknown origin may include the use of either labeled leukocytes or Ga-67 citrate, or both, in the search for an infectious focus. In recent years, labeled leukocytes (In-111 or Tc-99m) seem to have been employed preferentially by some. This is especially the case when the abdomen is a suspected site of involvement because of the normal colonic excretion of gallium that may complicate the interpretation of this study. The authors present the case of an immunocompromised patient with the interesting scintigraphic pattern of diffuse large and small bowel uptake of gallium secondary to biopsy proven Yersinia and tuberculous enterocolitis. A review of the recent literature reveals only one other similar case in which Yersinial disease was detected by Ga-67 scintigraphy. The present case illustrates that gallium's avidity for the atypical, less pyogenic, opportunistic infections common in immunocompromised patients justifies its continued use in such settings and, specifically, whenever tuberculosis is suspected.
The peripheral hyperinsulinaemia of hypertriglyceridaemic subjects has only been defined using insulin immunoassays in which proinsulin and proinsulin fragments cross-react. Relative contributions of pancreatic secretion and hepatic extraction of insulin to this hyperinsulinaemia have not been studied. We, therefore, reassessed the hyperinsulinaemia of hypertriglyceridaemia by measuring fasting plasma concentrations of intact proinsulin, glucose, insulin, and C-peptide in 24 hypertriglyceridaemic subjects with normal glucose tolerance (n = 14) and with impaired glucose intolerance (n = 10) and in normal subjects (n = 14). Hypertriglyceridaemic subjects had higher (p < 0.01) fasting concentrations of insulin and C-peptide and greater (p < 0.01) fasting insulin: C-peptide molar ratios than in control subjects. Fasting intact proinsulin concentrations were similar in hypertriglyceridaemic subjects with normal glucose tolerance and control subjects but these were lower (p < 0.01) than in hypertriglyceridaemic subjects with impaired glucose tolerance. These results suggest that the fasting peripheral hyperinsulinaemia of hypertriglyceridaemic subjects is due to increased pancreatic secretion and reduced hepatic fractional extraction of insulin. The peripheral hyperinsulinaemia of hypertriglyceridaemia appears to reflect peripheral insulin resistance and is not attributable to elevated proinsulin concentrations which are characteristic of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus.
Major errors arise if E test strips are placed upside down. Asymmetric zones, or no zone at all, may result. MICs indicated by upside-down tests were almost always considerably higher than true values. This situation differs markedly from that for conventional testing, where orientation of disks is not important.
BACKGROUND: A variety of autogenous and alloplastic materials have been used as subperiosteal implants to correct anophthalmic enophthalmos. Proplast II is a synthetic porous composite of Teflon polymer and alumina. Proplast II offers a number of advantages over other commonly used alloplastic materials such as silicone and polymethyl methacrylate. It is light, porous, resilient, malleable, and easy to shape. It can be readily sterilised after shaping. It has been found to integrate with the surrounding tissues, thereby minimising the risk of subsequent implant migration and extrusion. METHODS: Proplast II was used as a subperiosteal implant in a total of 15 anophthalmic patients during the period June 1990 to March 1994. The indication for this procedure in all patients was poor orbital volume replacement despite the prior insertion of an adequately sized spherical socket implant. RESULTS: The results were excellent with a good correction of preoperative upper eyelid sulcus deformity. There were no operative complications nor any serious postoperative complications. The implants were well tolerated. CONCLUSION: Proplast II can be highly recommended for use as a subperiosteal implant.
In vitro binding assays and inhibition of cell adhesion with monoclonal antibodies have implicated the integrin alpha 3 beta 1 as a receptor for a variety of extracellular ligands. However, reports of alpha 3 beta 1-ligand interactions are inconsistent, and transfection studies have suggested that alpha 3 beta 1 is not sufficient for cell attachment to ligands other than kalinin/laminin 5. We used immunofluorescence to study subcellular localization of the alpha 3A cytoplasmic domain variant in different cultured cell types. Using standard fixation and permeabilization methods, antibodies specific for alpha 3A stained most cell types in a diffuse pattern, consistent with previous reports. Surprisingly, however, chemical cross-linking of integrins to the extracellular matrix and extraction of the cytoskeleton prior to immunofluorescence revealed alpha 3A in focal contacts of most cells tested, suggesting that the cytoplasmic domain was concealed in intact focal contacts by cytoskeletal or other cytoplasmic proteins. The alpha 3A subunit localized to focal contacts in several cell types cultured on fibronectin, kalinin/laminin 5, EHS-laminin/laminin 1, type IV collagen, or vitronectin. In contrast, alpha 5 and alpha V integrins were detected in focal contacts only in cells grown on their known ligands (fibronectin, and fibronectin or vitronectin, respectively). Therefore, our results show that alpha 3A beta 1 responds to a broad spectrum of extracellular ligands. Time course comparisons of the recruitment of alpha subunits from different fibronectin receptors suggested that localization of alpha 3A beta 1 to fibronectin-induced focal contacts was independent of the recruitment of alpha 5 and alpha 4 integrins. However, other studies have shown that alpha 3A beta 1 does not mediate initial cell adhesion to many of the ligands that induced its focal contact localization, including fibronectin. Therefore, we suggest that alpha 3A beta 1 may be a secondary receptor with post-cell-adhesion functions for a broad spectrum of extracellular matrices.
BACKGROUND: Atherosclerosis and arterial injury are characterized by vascular smooth muscle cell (VSMC) migration and growth and an increase in synthesis of extracellular matrix. Platelet-derived growth factor (PDGF) has been implicated in these processes. This study was designed to identify additional PDGF-regulated genes in VSMC. EXPERIMENTAL DESIGN: A cDNA library prepared from PDGF-stimulated rat aortic VSMC was screened by differential hybridization to identify clones representing PDGF-inducible genes. The time course of growth factor-induced changes in gene expression was examined by RNA blot hybridization. Assays of protein activity were also performed for selected gene products. RESULTS: Four PDGF-regulated cDNA clones were identified by DNA sequencing. These encoded the extracellular matrix proteins lysyl oxidase (LO), thrombospondin, and osteopontin and the intracellular enzyme lactate dehydrogenase (LDH). Levels of mRNA corresponding to all four genes were low in quiescent VSMC and were markedly induced by PDGF, angiotensin II, and 10% calf serum. The regulation of LO and LDH mRNA by these agonists in VSMC has not been previously reported. LO enzymatic activity in the culture media was increased by approximately equals to 700% after exposure to PDGF. In contrast, LDH activity was not increased by PDGF treatment. CONCLUSIONS: The induction of LO mRNA and its secretion by VSMC is an early event accompanying growth factor stimulation and may contribute to organization of the extracellular matrix.
The commonest cause for ocular pain, presenting to an ophthalmic emergency centre, is due to corneal foreign bodies. Although the problem is transient, the degree of morbidity is often underestimated. The object of this study was to assess the degree of pain associated with these lesions.
Sarcoidosis commonly presents in young adults with bilateral hilar lymphadenopathy, lung parenchymal disease and/or skin lesions. Ocular symptoms are the presenting feature in up to 10% of cases, but eye involvement can be demonstrated in around a quarter of all patients. Renal disease is much rarer, and may manifest with hypercalcaemic nephropathy, granulomatous interstitial nephritis, tubular dysfunction or glomerulonephritis. Eye and renal involvement are rarely found together, and may be confused with Wegener's granulomatosis or polyarteritis. We report a case of a young man who developed renal failure due to sarcoidosis soon after presenting with uveitis. The case illustrates an unusual combination of systemic features that may not be widely recognized.
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Phylogenetic comparisons of gene and protein sequences between related species are often used to identify evolutionarily conserved elements that are important for gene expression, function, or regulation. However, homologoues may sometimes be difficult to identify by conventional low stringency hybridisation techniques, if they have undergone substantial sequence divergence. A new approach, cloning by synteny, is described that was used to identify the C. briggsae homologue of the C. elegans sex-determining gene tra-2. We show that four genes tra-2, ppp-1, art-1, and sod-1 are organised in a syntenic cluster and suggest that extensive conservation of gene linkage may exist between C. briggsae and C. elegans. We have also constructed a C. briggsae cDNA library to facilitate characterisation of these genes. Given the rapid progress in the physical mapping and sequencing of the C. elegans genome, cloning by synteny may provide the fastest method for identifying C. briggsae gene homologues, especially for genes encoding novel proteins.
BACKGROUND: Previously, the authors found that immortalized ovarian cancer cell lines generally were resistant to the growth inhibitory effect of transforming growth factor-beta and frequently had lost the ability to produce or activate this growth factor. In this study, the authors examined whether early passage epithelial ovarian cancer cells obtained from ascites are growth-inhibited by or produce transforming growth factor-beta. METHODS: Ovarian cancer cells were purified from ascites by percoll gradient density centrifugation, and inflammatory cells were removed using anti-CD45 antibody. The effect of transforming growth factor-beta on the proliferation of ovarian cancer cells was assessed using the thymidine incorporation assay. Immunohistochemical staining for transforming growth factor-beta 1 and beta 2 also was performed in these cells. RESULTS: Transforming growth factor-beta (10 ng/ml) significantly inhibited [3H]thymidine incorporation in 19 of 20 (95%) primary ovarian cancers (P < 0.05). In cases in which significant inhibition was seen, the mean thymidine incorporation was 33 plus or minus 28% of control values. In addition, there was no difference in dose-dependent inhibition of proliferation between ovarian cancer cells and normal ovarian epithelial cells. Eleven of 18 ovarian cancers (61%) were found to express immunohistochemically detectable transforming growth factor-beta, but immunostaining was not observed in 39% of cases. CONCLUSIONS: Although most primary ovarian cancer cells remain sensitive to the growth-inhibitory effect of transforming growth factor-beta, loss of production may interrupt the transforming growth factor-beta autocrine inhibitory loop and play a role in the development of some ovarian cancers.
The relationship between changes in binding for delta 1 (DPDPE) and delta 2 (DSLET) selective ligands were compared to potency changes for these ligands following naltrindole (NTI) in mice. Mice were injected s.c. with NTI (1 or 20 mg/kg) or saline and 1 hr later sacrificed for binding studies ([3H]DSLET, [3H]DPDPE) using whole brain or spinal cord. Other mice were injected s.c. with NTI (1 or 20 mg/kg) or saline and then injected IT or ICV with DSLET or DPDPE and were tested for analgesia using the tailflick test. In saturation binding studies, NTI decreased specific binding of [3H]DPDPE and [3H]DSLET in brain and spinal cord, but had no selective effect on either ligand. In contrast, in functional studies, NTI decreased analgesic potency of spinally and supraspinally administered DSLET more than DPDPE. Thus in functional studies NTI produced a selective effect on the delta 2 agonist DSLET; but in binding studies, NTI had no selective effect on the binding of [3H]DSLET and [3H]DPDPE.