Surface adsorption and the collapse transition of a linear polymer chain: Some exact results on fractal lattices.
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Biomedical subjects
Publications and source records attributed to S Kumar.
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Mendenhall's syndrome, characterized by familial insulin resistant diabetes, pineal hyperplasia and multiple somatic abnormalities, is associated with defects involving the alpha-subunit of the insulin receptor. The associated insulin-resistant diabetes is extremely difficult to treat; insulin is required in very large doses to control hyperglycaemia and oral hypoglycaemic agents are ineffective. We report a case of severe, prolonged hypoglycaemia that occurred in a 24-year-old patient with Mendenhall's syndrome following therapy with glibenclamide. He had glibenclamide 10 mg daily for 1 week following which he was admitted to hospital in hypoglycaemic coma with blood glucose levels < 1.0 mmol/l. This subject had undergone hypophysectomy at the age of 11 years. Prior to pituitary ablation, oral hypoglycaemic agents did not improve glycaemic control. Thus, previous hypophysectomy in this patient appears to have made it possible for glibenclamide to exert its hypoglycaemic effect. The occurrence of hypoglycaemia in this patient suggests alternative mechanisms for insulin action in conditions characterized by severe insulin resistance due to insulin receptor defects.
In this study we have demonstrated significantly elevated levels of circulating IgG autoanti-IgE antibody in hookworm infected individuals from Kebasob village on Karkar Island, Papua New Guinea. Although anti-IgE activity was demonstrable in IgG1, IgG3 and IgG4, IgG1 was by far the most important subclass of IgG anti-IgE in terms of frequency of detection (34/39; 87.2%) and magnitude of increase (P = 0.0000); with IgG3 (16/39; 41.0%) and IgG4 (15/39; 38.5%) antibodies being considerably less prevalent. Plasma levels of IgG1 anti-IgE (P = 0.0019) and IgG3 anti-IgE (P = 0.0034) showed significant correlations with total IgE concentrations, but not with IgE specific to excretory-secretory worm products; thus suggesting that anti-IgE synthesis is more related to polyclonal hyper IgE production than to antigen-specific IgE stimulation. No correlation was seen between IgG subclass anti-IgE levels and faecal egg counts or worm burden. Given that our data failed to show a negative or a positive correlation between anti-IgE and the degree of infection with hookworm, it is tempting to speculate that the main role of autoanti-IgE is to provide the host with protection against immune complex- and IgE-mediated hypersensitivity reactions to parasitic antigens.
Levels of sCD23, total and specific IgE were found to be considerably elevated in the plasma of a helminth infected population from Papua New Guinea. Using age-corrected data, a significant negative correlation was seen between sCD23 and total IgE in the young, at a time when hookworms are being rapidly acquired, and total IgE levels are rising most dramatically. It is suggested on the basis of this data that this inverse correlation is due to the stabilizing effect of IgE on the Fc epsilon RII receptor in vivo, and that the high levels of sCD23 seen in hookworm infected individuals are partly responsible for the high levels of IgE recorded in these patients.
This study was conducted on 44 children aged 1-10 years, who had undergone lower extremity orthopaedic surgery under general anaesthesia. Patients were divided into two groups: Group 1 (n = 23) received buprenorphine caudally and Group 2 (n = 21) received buprenorphine intramuscularly, at the completion of the surgery. The dose of buprenorphine used in both the groups was 4 micrograms.kg-1 body weight. The quality and duration of postoperative analgesia were evaluated by a single observer using a 5-point score for the first 24 h postoperatively. The time until the patient required postoperative analgesic was recorded. The duration of analgesia was significantly greater with caudal buprenorphine (median 20.20 h) than with intramuscular buprenorphine (median 5.20 h). Of the patients in the caudal group, 43% did not require any supplemental analgesia during the first 24 h, whereas all the patients in the intramuscular group required supplements within 10 h postoperatively. Caudal buprenorphine (4 micrograms.kg-1 body weight) provided 10.8 h to more than 24 h of analgesia in children, with fewer side effects.
The extracellular matrix plays a vital role in regulating normal tissue development and function--largely via the specific arrangement of macromolecules such as collagens, proteoglycans, glycosaminoglycans and glycoproteins. Previous reports have concentrated on associations between combinations of collagens/proteoglycans, collagens/glycoproteins and proteoglycans/glycosaminoglycans whilst little information is available on associations between collagens and free glycosaminoglycans. In this review, we discuss possible associations between collagens and the glycosaminoglycan hyaluronan; macromolecules which are known to exhibit changes in amount and composition during development and under pathological conditions. We demonstrate two types of collagen/hyaluronan association in vivo: the first, during the formation of extracellular matrix structures where neither collagens nor hyaluronan are degraded, resulting in the regulation of collagen fibrillogenesis, and the second, involving an inverse correlation between collagen synthesis and hyaluronan degradation and vice versa. We suggest that associations between collagens and hyaluronan play an important role in the initiation and maintenance of angiogenesis and put forward a model of cartilage vascularisation which relies on these associations.
Seventeen patients with germ cell tumours of ovary were treated with 4 cycles of cisplatin, bleomycin and vinblastine (PVB) chemotherapy (CT). All patients had undergone prior surgery: hysterectomy + bilateral salpingo-oophorectomy + omentectomy-5, salpingo-oophorectomy + debulking surgery-10 and biopsy alone in 2 patients. Four of seventeen patients had relapsed earlier and received PVB as second line therapy. FIGO staging revealed: stage IIB in one, III C in 12 and stage IV in 4 patients. Gross residual disease (> 2 cm) was present in 13 patients. The most common cell types were dysgerminoma-5, endodermal sinus tumour-5, immature teratoma-5, choriocarcinoma and mixed germ cell tumour in one patient each. Twelve patients (70.5%) achieved significant response; complete response-11, partial response in one patient. The common side effects of CT were nausea/vomiting, myelosuppression, fever, mucositis, diarrhoea and alopecia. One patient died due to CT toxicity. Three complete responders underwent second look surgery and were found free of disease. This study confirms that PVB is an effective combination in the treatment of advanced and recurrent germ cell tumours of ovary and can be given over brief period. The toxicity of the regimen is moderate.
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Fifteen newly diagnosed obese Type 2 diabetic subjects were treated with diet alone for 3 months with a median 1.5 kg weight loss. Each had a Continuous Infusion of Glucose with Model Assessment (CIGMA) test, at diagnosis and at 3 months, measuring insulin and C-peptide responses, and deriving mathematically modelled measures of beta-cell function and insulin sensitivity. Median fasting glucoses were 9.6 mmol l-1 at diagnosis and 8.5 mmol l-1 at 3 months (NS). Median fasting insulin was 9.3 mU l-1 at diagnosis and 11.7 mU l-1 at 3 months (NS). Median fasting C-peptide was 0.58 nmol l-1 at diagnosis and 0.64 nmol l-1 at 3 months (p < 0.05). Median achieved plasma insulin increased from 13.8 mU l-1 at diagnosis to 17 mU l-1 at 3 months (p < 0.02); median achieved plasma C-peptide increased from 0.72 nmol l-1 at diagnosis to 0.81 nmol l-1 at 3 months (p < 0.002). Modelled beta-cell function rose from median 26% at diagnosis to 37% at 3 months (p < 0.02). Modelled insulin sensitivity showed no significant change (median 0.31 at diagnosis, 0.27 at 3 months, NS). Elevation of achieved C-peptide was positively correlated with weight loss (Rs = 0.53, p < 0.05), but not with change in fasting glucose. Diet treatment of newly diagnosed Type 2 diabetes, with modest weight loss, results primarily in improvement of insulin secretory capacity, rather than insulin sensitivity.
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The development of parasite-specific T-cell lines represents one approach to the potential identification of relevant immunogens in erythrocytic malarial infection. However, the use of parasitized-erythrocyte lysates as antigens inhibits the proliferation of T cells. To circumvent this problem, we preincubated antigen-presenting cells (APCs) from spleens of malaria-naive, BALB/c mice with a Plasmodium vinckei vinckei (hereafter referred to as P. vinckei)-parasitized erythrocyte lysate. APCs were subsequently irradiated and washed prior to being incubated with T lymphocytes from P. vinckei-immune, histocompatible mice. After 8 to 10 cycles of antigenic stimulation and rest, two T-cell lines were analyzed. Both lines were predominantly CD4+. Proliferation assays demonstrated marked lymphocyte blastogenesis to syngeneic but not allogeneic APCs that had preprocessed malarial antigen. Antigen incubated directly with T cells and nonpulsed APCs in vitro did not result in T-cell proliferation. Assays of interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon were compatible with one cell line being predominantly TH1 and the other being TH2. Thus, APCs that have preprocessed malarial antigen and are free of extraneous parasite material induce highly reactive, antigen-specific, major histocompatibility complex-restricted T-cell lines that functionally appear capable of inducing humoral and/or cell-mediated immunity.
We have characterized a new Escherichia coli operon consisting of two genes, ecpD and htrE. The ecpD gene encodes a 27-kDa protein which is 40% identical at the amino acid level to the pilin chaperone PapD family of proteins. Immediately downstream of the ecpD gene is the htrE gene. The htrE gene encodes a polypeptide of 95 kDa which is processed to a 92-kDa mature species. The HtrE protein is 38% identical to the type II pilin porin protein PapC. The ecpD htrE operon is located at 3.3 min on the genetic map, corresponding to the region from kbp 153 to 157 of the E. coli physical map. The htrE gene was identified on the basis of a Tn5 insertion mutation which resulted in a temperature-sensitive growth phenotype above 43.5 degrees C. The transcription of this operon is induced with a temperature shift from 22 to 37 or 42 degrees C but not to higher temperatures, e.g., 50 degrees C. Consistent with this result, the temperature-induced transcription was shown to be independent of the rpoH gene product (sigma 32). The transcription of this operon was further shown to require functional integration host factor protein, since himA or himD mutant bacteria possessed lower levels of ecpD htrE transcripts. Among the three transcriptional start sites discovered, one, defined by the P2 promoter, was found to be under the positive regulation of the katF (rpoS) gene, which encodes a putative sigma factor required for the transcription of many growth phase-regulated genes.
We have previously constructed vaccinia virus (VV) recombinants containing a complete or truncated envelope (env) gene of bovine leukemia virus (BLV). Only recombinants carrying the complete env gene (VV-BLV2 and VV-BLV3) expressed env glycoprotein on the surface of virus-infected cells and produced an antibody response in rabbits. In the present study, these VV recombinants were used to immunize sheep prior to challenge with BLV-infected peripheral blood mononuclear cells. Both humoral and cell-mediated immunity were monitored in infected animals. Sheep inoculated with recombinants containing the complete env gene showed a CD4 response to a defined epitope of gp51, but this response was absent 4 months postchallenge. Anti-gp51 antibodies appeared in animals inoculated with complete env 2 weeks after challenge, reached a peak at 4 weeks, and subsequently declined over 16 months. No CD4 response was recorded in animals inoculated with recombinants containing truncated env gene (VV-BLV1). BLV-infected control animals and those animals receiving VV-BLV1 were slower to develop antibodies postchallenge, and the titers of anti-gp51 antibodies continued to increase over 16 months. Proviral DNA was detected by the polymerase chain reaction in the four groups at 6 weeks after challenge. However, it could not be detected 4 months postinfection in the VV groups inoculated with complete env. Provirus was present in the VV-BLV1 and control groups over the 16-month trial period. These results demonstrate that vaccination with VV recombinants containing the complete env gene of BLV protects sheep against infection and that protection correlated with a CD4 T-cell response to a defined epitope.
The present study demonstrates a relationship between angiogenic oligosaccharides of hyaluronan (HA) and the production of collagens during the process of angiogenesis in vivo and in vitro. The addition of angiogenic oligosaccharides of HA to the chorioallantoic membrane of the chick embryo induced a deposition of collagen fibrils. The treatment of sub-confluent cultures of bovine aortic endothelial cells with the same oligosaccharides (1 microgram/ml) increased the uptake of [3H]proline by approximately 60%. SDS-polyacrylamide gel electrophoresis of treated cultures demonstrated the enhanced synthesis of type I and type VIII collagens. The production of type VIII collagen was confirmed by western blotting and immunocytochemistry using antibodies to sheep and bovine type VIII collagen. Type VIII collagen is a short chain collagen that has a high degree of homology to cartilage-specific type X collagen. The biological functions of type VIII and type X collagens are unknown. We have suggested that the two collagens play a role in the process of angiogenesis.
Eleven children from eight families with autosomal dominant polycystic kidney disease who were diagnosed in utero (6 children) or in the first year of life (5 children) are reported here. Four children were evaluated for symptoms and three because of a sibling with very early onset disease. In three children, abnormal kidneys were found incidentally on a pregnancy screening ultrasound, and in only one child, the diagnosis was made by an ultrasound specifically directed at detecting polycystic kidney disease. Females were disproportionately represented among both the affected parents and offspring. Eight of the children were girls, and all affected parents were mothers. In three families, the parent's diagnosis was established only after the birth of the affected child. In two of these and in one other family, the mother's disease appeared to be the result of a new mutation. The most consistent renal ultrasonographic findings in the children were enlargement and increased echogenicity. On follow-up over 3 to 15 yr (mean, 6.8 yr) two children had ESRD and eight children had normal or nearly normal renal function as assessed by creatinine clearance. Renal concentrating ability was reduced in four children in whom it was measured. All children had bilateral renal cysts on follow-up, and nine children were hypertensive. Possible risk factors for early-onset disease identified in this study were an affected mother, an affected sibling, and an apparent parental new mutation. Symptoms and complications occurred frequently, but outcome was better than reported previously.
Variability in microvessel changes of blood vessel density has prompted us to undertake quantitative morphometric studies of infarcted areas in human brain. In the initial study, brains were obtained at autopsy from 10 patients (ages 45-85). Samples were collected from infarcted hemisphere and controls from the contralateral hemisphere. Formalin fixed, paraffin embedded and thereafter routinely processed sections were stained after Pickworth and with HE. Altogether 6,520 microvessels, representing 10,801 microscopic fields were counted. The Wilcoxon Range test was used for statistical analysis. In 9 of 10 patients in infarcted brain hemispheres, there was a marked increase in microvessel density (p < 0.01), when compared with contralateral brain hemisphere. In addition, a positive correlation was also found between the time of survival and both total density and density of non-perfused blood vessels. To gain a deep insight into the enhanced activity of microvessels, immunocytochemical studies were performed, which have shown, that the vascular endothelial cells in infarcted brain were reactive to two monoclonal antibodies, one, E-9, directed against an activation/proliferation associated endothelial cell specific protein and the other recognizing adhesion molecule VCAM-1. Pan-endothelial Mab PECAM/CD31 was used in those studies for controls and confirmed the obtained results. Our findings strongly support the concept of angiogenesis in the infarcted area. If correlated with morphometric results, it may indicate an important role of microvessels in pathobiology of ischemic stroke.
Renal cell carcinoma can have solitary adrenal metastasis years or even decades after resection of the primary tumor. The difficulty in distinguishing an adrenocortical adenoma from a solitary metastasis of a renal cell carcinoma prompted us to study 10 adrenal adenomas, 11 primary renal cell carcinomas, and three renal cell carcinomas metastatic to the adrenal gland by immunohistochemical stains and flow cytometry to determine if these techniques could help make the distinction. Immunohistochemical staining was performed for detection of cytokeratin, vimentin, and epithelial membrane antigen (EMA). Cytokeratin, vimentin, and EMA were detected in 10/11, 9/11, and 11/11 primary renal cell carcinomas, respectively, and 1/3, 2/3, and 3/3 metastatic renal cell carcinomas, respectively. All cases of adrenal adenoma were negative for the three antigens. DNA content analysis by flow cytometry showed no evidence of an abnormal DNA stemline in any of the cases except one renal cell carcinoma. We conclude that staining for EMA is consistently strongly positive in primary and metastatic renal cell carcinomas and consistently negative in adrenal adenomas, proving to be a useful distinguishing marker. Cytokeratin and vimentin, although uniformly absent in adrenal adenomas, are variably and often only weakly positive in renal cell carcinomas, and therefore of less help in making the distinction. Flow cytometry analysis has no discriminatory value in these cases.
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