Biomedical subjects
Publications and source records attributed to M Patel.
Protein C is a vitamin K-dependent anticoagulant that functions by inhibiting the activity of factors Va and VIIIa. An inherited deficiency of this protein may enhance the risk of thrombosis. The first kindred with levels of protein C that averaged 50% of normal in association with recurrent thrombotic events were described in 1981. A black South African family with an inherited deficiency of this protein is reported.
We and others have previously shown that in vitro conversion of Epstein-Barr virus (EBV)-negative Burkitt lymphoma (BL) cell lines with the immortalizing B95-8 strain of EBV results in a marked elevation in levels of c-fgr proto-oncogene mRNA. We now show, using a nuclear run-off assay, that this induction results from an increase in the rate of transcription of the c-fgr gene. We also show that BL cell lines freshly converted with the non-immortalizing HR-I strain of EBV do not accumulate higher levels of c-fgr mRNA, suggesting that EBNA-2 and/or LMP, the genes which are deleted in the HR-I strain, may be involved in the pathway which leads to changes in c-fgr gene expression. In order to assess the generality of a role for the c-fgr gene in the response of B-lymphocytes to EBV-infection, which is controversial, we have analysed c-fgr expression in 6 freshly immortalized cell lines established by EBV (B95-8) infection of B-lymphocytes from the peripheral blood of normal adults and of adults with rheumatoid arthritis, from cord blood, and from foetal liver. All 6 cell lines expressed c-fgr mRNA at elevated levels compared to EBV-negative BL cell lines.
A new technique measuring serum antoantibodies to lens proteins, employing antigen linked to magnetisable cellulose particles and fluorescent end-point detection, was used to examine patients with senile cataract and inflammatory eye disease. 40% of patients with senile cataract had antibodies to lens proteins, as did 28% of patients with heterochromic cyclitis and 20% of patients with uveitis, while there were no positive sera from patients with scleritis. The single patient with lens-induced uveitis had a high titre, but so did some patients with senile cataract. With the incorporation of a standard curve this technique offers a reliable quantitative assay for lens autoantibodies. It may provide a valuable tool for the investigation of pathogenetic mechanisms in cataract and inflammatory eye disease.
Characterization of sinefungin related antifungal antibiotics from fermentation broth was accomplished by coupling photodiode array (PDA) detection to high performance liquid chromatography (HPLC). From the combined HPLC-PDA evaluation of broth filtrate, we detected five sinefungin related components. Fast atom bombardment (FAB) mass spectroscopic evaluations, mass-analysed ion kinetic energy spectra (MIKES) and collision activated (CA) MIKES of these components confirmed their respective identities. Our findings from the combination of HPLC photodiode array acquisition and FAB-mass spectrometry suggest we have detected the presence of a previously unreported sinefungin analogue.
Staphylococcal enterotoxin B (SEB) binds specifically to major histocompatibility complex class II molecules on the surface of accessory cells and stimulates virtually all T cells bearing certain, but not all, T cell-receptor V beta alleles. We have previously shown that this superantigen is a potent inducer of multiple regulatory T cell populations. In the present report we show that SEB induces a population of suppressor T cells which inhibits the generation of alloantigen-induced cytotoxic T cell activity. Using both negative- and positive-selection analysis, we found that this suppressor population is a CD4- CD8- CD5+ IL-2R+ T cell. This cell population inhibited both syngeneic and allogeneic cytotoxic T lymphocyte activity, but the cell population which inhibited allogeneic CTL activity was radiation sensitive. In addition, allogeneic SEB-primed cells appeared to develop cytolytic activity as a result of the additional stimulation in the mixed-lymphocyte reaction culture. The relationship of the SEB-primed CD4- CD8- CD5+ T cells to related regulatory T cell populations is discussed.
Adult male Lewis (LEW) rats were used to investigate the effects of unilateral testicular trauma on fertility. Comparisons were made between normal and experimental rats immunized with syngeneic sperm in Complete Freund's Adjuvant (CFA). Matings within the three groups yielded offspring to all normal males, no offspring to the immunized rats, and 27% (3/11) fertility in the trauma group (p less than 0.001). The contralateral testis demonstrated decreased volumes, various degrees of aspermatogenesis and smaller seminiferous tubular diameters, in both the trauma and immunized groups compared to the controls. Similar histopathologic findings of chronic granulomatous inflammation within contralateral testes in both the trauma and immunized groups suggested a common immune etiology for infertility via possible disruption of the blood-testis barrier.
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Androgen receptors were measured in soluble and nuclear fractions of tissues obtained from 25 patients. A method using mibolerone, a synthetic androgen, as a ligand is described. This method, which includes the presence of excess ORG 2058 to eliminate interaction with progesterone receptors, gives a reliable determination of androgen receptor content and has been used to predict response to hormonal treatment. However, the results suggest that the presence of functional receptor is not, in itself, a sufficient index of hormonal dependence of the tumour.
The secretion of atrial natriuretic peptide by the heart is not simply the arterial-coronary sinus concentration difference times coronary blood flow, because only a small fraction of total coronary blood flow passes through the atria. We measured coronary sinus and arterial plasma atrial natriuretic factor (ANF) concentrations and blood flow to each part of the heart using the radioactive microsphere technique. Before acute volume expansion, the arterial-coronary sinus ANF difference was 305 +/- 23 pg/ml and rose to 1,009 +/- 220 pg/ml during volume expansion, whereas total coronary blood flow rose from 167 to 465 ml/min. Atrial blood flow rose from 2.9% to 4.6% of total coronary blood flow during volume expansion. ANF secretion rate increased from 51 to 469 ng/min. When divided by atrial weight, ANF secretion rate increased from 4.0 +/- 0.3 to 56 +/- 12 ng/min/g atrial tissue-in other words, from 0.3% to 3.7% of tissue ANF content each minute. Dividing by atrial blood flow indicated that the concentration of ANF leaving atrial tissue was 10,000 to 29,651 pg/ml, and the additional secretion of ANF was determined by the increase in coronary blood flow. Therefore, at least two mechanisms are responsible for altering coronary sinus ANF and circulating ANF: the release rate from atrial myocytes and the washout via changes in atrial blood flow.
Isolated GH deficiency (IGHD) cannot be distinguished on the grounds of anti-human (h) GH antibodies and stunted growth response to exogenous hGH. DNA analysis was proposed to classify children with IGHD. Genomic DNA was extracted and studied by restriction endonuclease analysis after extraction from the circulating lymphocytes of 53 children with IGHD. These children included 5 pairs of siblings and 5 individuals from 10 families, whose parents (n = 20) and brothers and sisters (n = 5) were also analyzed. Twenty-five adults, including individuals from 3 families of normal height, were studied as controls. No deletion within the hGH gene cluster was identified using a [32P]hGH cDNA clone as a probe. A compound heterozygosity for a hGH-1 deletion or a mutation have not been found. The allelic frequencies for 5 common restriction fragment length polymorphisms were similar in patients and controls. The distribution and frequency of the distinct haplotypes in the hGH gene family revealed no differences between IGHD (n = 30 chromosomes) and controls (n = 48 chromosomes). No deletion or restriction fragment length polymorphisms could be found using a hGH-releasing hormone cDNA clone as a probe in patients or controls. This large volume of data gathered from a caucasian population indicates that the great majority of patients with IGHD has no structural abnormalities of the hGH gene cluster, particularly no hGH-1 gene deletion. In addition, they have no gross deletions within the hGH-releasing hormone gene.
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Here we report the isolation of cosmid clones containing the whole of the human c-fgr proto-oncogene. We have used these to determine the organization and nucleotide sequence of the exons upstream of exon 4, which have not previously been analysed. We show that, like exons 4 to 12, exon 3 closely resembles its counterpart in the avian c-src and murine lck genes. In contrast, the organization of the upstream exons of c-fgr differs markedly. In particular, the 5' untranslated regions of the c-fgr gene is interrupted by an extra intron. We have also mapped multiple transcriptional start sites within the 5' flanking region of the c-fgr gene and present an analysis of the nucleotide sequences within this region which may be responsible for regulating c-fgr expression.
Neuralgic amyotrophy or brachial plexus neuralgia is a condition of uncertain etiology. It needs to be differentiated from the usual brachial plexus injuries. Nerves outside the plexus especially the spinal accessory nerve are involved. Neuralgia is also a feature. Four cases were followed-up in detail over a period of two years. The condition usually resolves almost completely on its own.
Trimethyltin (TMT) produces selective hippocampal lesions similar to that caused by convulsants which interact with the brain excitatory amino acid transmission. The hippocampal glutamate system was studied because of its possible contribution to neuronal damage produced by TMT. At 24 hr following administration of TMT (3 mg/kg; ip) to mice, hippocampal glutamate levels were decreased, although no changes in levels were observed at 1 hr, 6 hr or 15 hr. In partially depolarized hippocampal slices, TMT (10 microM), produced a release of endogenous glutamate. Continuous monitoring by fluorometry found glutamate release to occur immediately following addition of TMT to partially depolarized slices; this release was dependent on extracellular calcium. These results indicate TMT can activate the endogenous excitotransmitter system, which may contribute to the neuronal damage associated with TMT exposure.
This study was designed to determine if the adventitial vasa vasorum contribute to re-endothelialization of the canine carotid artery after removal of the endothelial flow surface. Casting studies demonstrated that vasa vasorum are present only in the adventitia of the canine carotid artery. Ninety autograft segments of the carotid artery from which the endothelium had been removed were implanted in both carotid arteries of 45 dogs. Glutaraldehyde-processed canine carotid allografts were positioned at each end to prevent pannus ingrowth and a Gore-Tex wrap to prevent periarterial tissue growth was placed into the outer wall. Three methods were used, with observations at 4 and 8 weeks. In method 1 the test segment was treated with superficial endarterectomy. In method 2 a balloon catheter was used to remove the endothelium. In method 3 balloon catheter denudation of the flow surface was also employed and, in addition, the adventitia was removed surgically as completely as possible, although a few vasa vasorum were shown to remain in some grafts. In method 1 all the patent endarterectomized arteries were partially re-endothelialized at both the 4- and 8-week intervals. In method 2, 72% of the balloon-denuded patent arteries with intact adventitial vasa vasorum were partially re-endothelialized at 4 weeks and 84% at 8 weeks. However, in method 3 the flow surfaces had no endothelium at 4 weeks and 83% still had none at 8 weeks. These findings suggest that, in the absence of pannus ingrowth, re-endothelialization of the canine carotid artery depends on not only the presence but also the number of adventitial vasa vasorum.
Although much has been published about growth of Vibrio cholerae in natural sources of water, little or nothing has been written on its survival in common household water storage containers. This study compared the behaviour of the El Tor and Classical biotypes of V. cholerae in different containers commonly used in Africa for domestic water storage. These included traditional clay pots, wooden barrels, galvanised iron drums (corroded and non-corroded) and plastic (polyethylene) drums. The findings are considered to be of public health interest with reference to selection of the most suitable containers for the storage of water drawn from a treated source. Although survival of V. cholerae was much shorter in clay pots than in any of the other containers, the numbers of viable V. cholerae were higher than in non-corroding iron drums and plastic drums. The clay pots, being porous, also showed a tendency to constant outward seepage of water which, when collected, was also shown to harbour cholera bacilli. These containers are therefore considered hazardous as pathogens in the stored water are easily disseminated to contaminate either hands or food prepared in the vicinity. The longest survival occurred in damaged metal drums. Presence of other bacteria greatly inhibited survival of V. cholerae. The response of the two biotypes was much the same in all the experiments.
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