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Biomedical subjects

S George

Publications and source records attributed to S George.

At least 163 records · Page 9Linked to original sources

Skin lesions in HIV-positive and HIV-negative patients in south India.

BACKGROUND: Various dermatologic conditions have been reported to occur with increased frequency in human immunodeficiency virus (HIV)-positive individuals, but there are only a few studies comparing the prevalences of skin diseases in HIV-positive patients with those in matched HIV-negative controls. METHODS: Skin lesions in 129 HIV-positive patients and 258 HIV-negative controls were studied prospectively over an 18-month period from October 1991 to March 1993. RESULTS: Oral candida, tinea cruris, and ichthyosis were significantly more common in HIV-positive patients compared to controls. Several other dermatologic conditions were found only in the HIV-positive group. CONCLUSIONS: The pattern of skin lesions in Indian patients with HIV infection may be different from that in the West.

Adult↗

Specificity of human bactericidal antibodies against PorA P1.7,16 induced with a hexavalent meningococcal outer membrane vesicle vaccine.

A set of isogenic strains was constructed from the meningococcal reference strain H44/76 (B:15:P1.7,16) which differed only in their outer membrane protein (OMP) compositions. First, three isogenic strains lacking the expression of either class 3 (PorB) or class 4 (RmpM) OMP or both were obtained. Second, three isogenic class 1 OMP loop-deficient strains of H44/76 lacking the predicted loop 1 or 4 or both of class 1 OMP (PorA) were obtained. Third, three isogenic class 1 OMP strains which differed by point mutations in the predicted loop 4 of subtype P1.16 were constructed. Strains were constructed through transformation with gene constructs made in Escherichia coli and their homologous recombination into the meningococcal chromosome. This study describes the contribution of one of the six class 1 OMPs, PorA P1.7,16, in the development of bactericidal antibodies after a single immunization of adult volunteers with 50 or 100 micrograms of protein within a hexavalent PorA outer membrane vesicle vaccine. PorA-, PorB-, and RpmM-deficient isogenic strains were used to define the human immune response against PorA. The loop-deficient isogenic strains were used to define the contribution of loops 1 and 4 of PorA in the development of bactericidal anti-PorA antibodies. The isogenic strains carrying a point mutation in loop 4 were used to study the cross-reactivity of the induced bactericidal antibodies against target strains showing microheterogeneity. The results indicate that a single immunization with the hexavalent PorA vaccine induced a dose-dependent bactericidal immune response, which is directed mainly against PorA. The epitope specificity of antibodies is directed mostly against loop 1, although loop 4 and as-yet-unidentified epitopes of PorA P1.7,16 are also involved.

Adult↗

Activation of human umbilical vein endothelial cell progelatinase A by phorbol myristate acetate: a protein kinase C-dependent mechanism involving a membrane-type matrix metalloproteinase.

Matrix metalloproteinases play an important role in tumor invasion, angiogenesis and inflammatory tissue destruction. The 72-kd gelatinase A is the most widely distributed. Along with the 92-kd gelatinase B, it plays an important role in basement membrane turnover. Gelatinase A is secreted as progelatinase A and, when activated, can cause extracellular matrix destruction. The physiologic mechanism of this activation is not well understood. Based on the importance of endothelial cells in inflammation and cancer, we sought in this study to systematically study the PMA-induced activation of endothelial cell progelatinase A. Using HUVEC, we demonstrated that PMA-induced activation of progelatinase A in these vascular endothelial cells (a) was protein kinase C-dependent as it was blocked by H-7; (b) occurred through cell-mediated events as PMA was unable to activate progelatinase A in a cell-free system and that low dose tissue inhibitor of metalloproteinases-2, but not tissue inhibitor of metalloproteinases-1, totally inhibited PMA-induced activation; (c) was accompanied by an increase in the membrane-type matrix metalloproteinase (MT-MMP). We also found that the combination of PMA and the cytokine tumor necrosis factor-alpha increased HUVEC secretion and activation of gelatinase B. In conclusion, our data show that PMA activation of vascular endothelial cell progelatinase A is a cell membrane event that is at least partially mediated through a PKC-dependent mechanism and is accompanied by an increase synthesis of MT-MMP. These data suggest a role for MT-MMP in the activation of progelatinase A in vascular endothelial cells.

Cell Membrane↗

Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation.

Immune reconstitution following autologous bone marrow transplantation (ABMT) is characterized by defects in B cell and T cell function and loss of specific antibody. In the late post-transplant period, patients are at risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We examined whether immunizing ABMT patients before bone marrow (BM) harvest enhanced the early recovery of specific antibody. Twelve patients were immunized before BM harvest with Haemophilus influenzae type b (HIB)-conjugate, tetanus toxoid and polysaccharide pneumococcal vaccines. Forty-one comparable ABMT patients not immunized prior to BM harvest were also studied. Following ABMT, both groups of patients were immunized with HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12 and 24 months and with pneumococcal vaccine at 12 and 24 months. Patients immunized before BM harvest had higher HIB antibody concentrations during the first 2 years post-transplant, the differences reaching significance at 3 months (P = 0.0001) and following the 24-month dose (P = 0.048). Tetanus toxoid antibody concentrations were also significantly higher at 3 months (P = 0.001) and 6 months (P = 0.032) in patients immunized before BM harvest. There were no differences in pneumococcal antibody concentrations between the two groups. Immunization of patients before bone marrow harvest resulted in higher anti-HIB antibody concentrations following ABMT and may be an effective strategy to prevent infectious complications.

Adolescent↗

Effect of zinc supplementation on observed activity in low socioeconomic Indian preschool children.

OBJECTIVES: To investigate whether supplementation of zinc in preschool children is associated with improvement in observed activity levels. METHODS: On 2 consecutive days, we performed 5-hour observations with momentary time sampling (instant activity every 10 minutes) in children selected from an ongoing double-blind, randomized trial of zinc supplementation. The study was conducted in Kalkaji, a low-socioeconomic urban population of New Delhi with high diarrheal incidence and rates of malnutrition. A total of 93 children (48 zinc and 45 control) 12 to 23 months of age from an ongoing community-based, randomized, controlled trial received supplements for at least 1 month before study; 71% had received supplementation for more than 120 days. Zinc gluconate (10 mg of elemental zinc) was given daily, with both zinc and control groups receiving vitamins A, B1, B2, B6, D3, and E and niacinamide in addition. RESULTS: Outcomes were percentages of time spent in each of five activity levels and two groups representing high and low movement and overall rating by two activity scores. Children in the zinc group spent 72% more time performing activities in the high-movement group. Among the zinc-supplemented children, the activity rating by the children's activity rating score was 12% higher and by the energy expenditure score was 8.3% higher than in the control group. CONCLUSIONS: In conclusion, zinc supplementation, given along with selected vitamins, was associated with significantly greater activity levels in children. The relationship between the activity increase and locomotor development needs to be investigated, as do the long-term implications of zinc supplementation in terms of developmental status and school performance.

Double-Blind Method↗

Short-term follow up of patients with multibacillary leprosy and HIV infection.

During a period of 9 years, four male patients with HIV and Hansen's disease were detected in Tamil Nadu, South India. The sequence as to which infection came first is not known. All had high-risk sexual behavior with commercial sex workers and a past history of genital ulcer disease. Their spectrum of leprosy was multibacillary. Patient no. 1 had pure neural leprosy of the lepromatous type, which is rare. He also had a single episode of type 1 reaction which did not require steroid therapy. Despite having taken inadequate treatment, patient no. 2 remained clinically and bacteriologically quiescent after 4 years of follow up. He had a low CD4 count of 330 cells/mm3. The third patient completed a full course of multibacillary multidrug therapy, and a year later is clinically and bacteriologically inactive. The fourth patient died of AIDS within 2 months of the dual diagnosis.

Adult↗

Effect of 4-META adhesive on bond strength and marginal seal of amalgam restorations and repairs--an in vitro study.

Amalgam remains unchallenged as a posterior restorative material. But its inability to bond to the teeth leads to some amount of microleakage at the restoration-tooth interface with associated problems such as post operative sensitivity, pulpal complications etc. Also a broken amalgam restoration requires replacement which will further weaken the tooth structure. Recently, 4-META has been introduced which can graft amalgam and composite to enamel, dentin and old amalgam restorations. In this study, the bonding and marginal sealing abilities of 4-META was assessed both at the tooth-amalgam interface and old amalgam fresh amalgam interface.

Bicuspid↗

Antibody responses to polysaccharide and polysaccharide-conjugate vaccines after treatment of Hodgkin disease.

OBJECTIVE: To compare the immunogenicity of polysaccharide-conjugate vaccines with that of polysaccharide vaccines in patients previously treated for Hodgkin disease. DESIGN: All patients were immunized with Haemophilus influenzae type b (HIB)-conjugate and 4-valent meningococcal polysaccharide vaccines. Subgroups of patients were randomly assigned to receive either 23-valent pneumococcal polysaccharide vaccine or a 7-valent pneumococcal-conjugate vaccine that links seven pneumococcal serotypes to the outer membrane protein complex of Neisseria meningitidis. PATIENTS: 144 patients who had completed treatment for Hodgkin disease, which had been diagnosed at least 2 years before the study. MEASUREMENTS: Antigen-specific antibody concentrations before and 3 to 6 weeks after immunization; number of persons who achieved anti-HIB antibody concentrations considered to be in the protective range. RESULTS: The geometric mean anti-HIB antibody concentration increased from 1.79 micrograms/mL before immunization to 54.1 micrograms/mL after; the percentage of persons with antibody concentrations in the protective range increased from 62% before immunization to 99% after. Patients immunized with 23-valent pneumococcal vaccine had a geometric mean pneumococcal antibody concentration after immunization (9.15 micrograms/mL) that was similar to that of healthy controls (10.0 micrograms/mL) for the seven serotypes measured. In contrast, patients who received 7-valent pneumococcal-conjugate vaccine had a significantly lower mean response compared with patients who received 23-valent; their geometric mean antibody concentration after immunization was 4.95 micrograms/mL (P = 0.005). CONCLUSION: A single dose of HIB-conjugate vaccine was immunogenic in patients who had completed treatment for Hodgkin disease diagnosed at least 2 years before immunization. In addition, responses to the 23-valent pneumococcal and 4-valent meningococcal vaccines were equivalent to those seen in healthy controls. Finally, patients had a significantly lower response to a single dose of 7-valent pneumococcal-conjugate vaccine than to 23-valent vaccine.

Bacterial Capsules↗

Expression of the E2F1 transcription factor overcomes type beta transforming growth factor-mediated growth suppression.

Inhibition of cell growth by type beta transforming growth factor (TGF-beta) occurs in mid-G1 and is associated with decreased G1 cyclin-dependent kinase activity and maintenance of the retinoblastoma tumor suppressor protein Rb in an underphosphorylated, growth-suppressive state. A variety of recent experiments suggest that a functional target of Rb is the E2F transcription factor. In addition, the growth-suppressive effects of TGF-beta can be overcome by expression of viral oncogene products that dissociate E2F from Rb and Rb-related polypeptides. These results suggest the possibility that control of E2F may be a downstream event of TGF-beta action. Consistent with that possibility is the observation that E2F1 RNA levels are drastically reduced in TGF-beta-treated cells. We have also used a recombinant adenovirus containing the human E2F1 gene to overexpress the E2F1 product in mink lung epithelial cells that were growth arrested with TGF-beta. We find that overexpression of E2F1 can overcome the TGF-beta-mediated effect as measured by the activation of cellular DNA synthesis. These results suggest that a likely downstream target for the cyclin-dependent kinases, which are controlled by TGF-beta, is the activation of E2F.

Adenoviridae↗

Acute toxicity of the oil dispersant corexit 9554 to marine organisms.

The acute toxicity of a surfactant-based oil dispersant, Corexit 9554, to the early life stages of four marine species was identified using a closed, flow-through exposure system. Standardized, spiked exposures were used in order to impart a measure of reality to the data. The species were taxonomically diverse: a mollusc, the red abalone (Haliotis rufescens); a fish, the topsmelt (Atherinops affinis); a crustacean, the kelp forest mysid (Holmesimysis costata); and a macroalga, the giant kelp (Macrocystis pyrifera). Results indicated the Haliotis test to be most sensitive, followed by the Macrocystis test, and the Atherinops test, with the Holmesimysis test being least sensitive. Median-effect concentration estimates for the four species ranged from 8.0 to 184.3 initial ppm, a > 20-fold difference. Differences in sensitivity of the four tests were likely the result of both internal (morphological, physiological, etc.) and external (life stage, endpoint, etc.) factors.

Animals↗