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Biomedical subjects

M Gupta

Publications and source records attributed to M Gupta.

At least 109 records · Page 6Linked to original sources
PubMed2001

Cytokine modulation with immune gamma-globulin in peripheral blood of normal children and its implications in Kawasaki disease treatment.

Intravenous immune gamma-globulin (IVIG) is used successfully in the treatment of Kawasaki disease, with dose-dependent rapid resolution of symptoms such as fever and irritability and a decrease in ESR, WBCs, and platelets. The mode of action of IVIG in reducing this inflammatory response is not clearly understood. Recently anticytokine antibodies in IVIG have been demonstrated. Serum levels of proinflammatory cytokines have been shown to be elevated in patients with Kawasaki disease. The cytokine interleukin-6 (IL-6) is involved in the de novo production of acute-phase proteins by hepatocytes and cause thrombocytosis and fever in response to tissue injury. Patients receiving parenteral recombinant human IL-6 have dose-dependently experienced fever, malaise, chills, and acute-phase reaction. With high IL-6 concentrations, central nervous system toxicity has also been reported and IL-6 has been thought to mediate endothelial damage. We evaluated the response of stimulated blood cells of 12 normal children to IVIG in the release of the cytokines IL-6, IL-8, TNF-alpha. and IL-6 receptor (sIL-6R). The levels of cytokines IL-6, IL-8, and TNF-alpha (but not sIL-6R) in peripheral blood induced by stimulation with LPS were markedly reduced (P < 0.008) within 3 hr when incubated with IVIG compared to without IVIG. Thus we demonstrated that cells of normal children respond to IVIG in vitro by reducing cytokines such as IL-8, TNF-alpha, and IL-6 without affecting the level of receptor sIL-6R during an acute inflammatory response. We also found significantly higher IL-6 levels in children with Kawasaki disease compared to children with blood culture-negative febrile illnesses. In five children with Kawasaki disease we measured serum IL-6 before and after IVIG and assessed the clinical response to IVIG therapy. Therapy with IVIG was followed by a rapid resolution of symptoms in Kawasaki disease, with a significant decrease in serum IL-6. The attenuation of proinflammatory cytokine responses, especially IL-6, following infusions of IVIG may play an integral role in the rapid resolution of symptoms and decrease in the acute-phase proteins in children with Kawasaki disease. Cells of normal children were found to respond to the IVIG in a manner similar to that of the Kawasaki children.

Blood Cells↗
PubMed2001

Mutations in the alpha-synuclein gene in Parkinson's disease among Indians.

OBJECTIVE: To investigate the prevalence of G88C, G209A and any other mutation(s) in exons 3 and 4 of the alpha-synuclein gene in Indian patients with Parkinson's disease (PD). METHODS: A total of 169 PD patients comprising 18 familial, 3 juvenile, 48 early onset and 100 sporadic cases were included in this study. Genomic DNA was amplified by PCR using primers specific for Exons 3 and 4. Mutations at G88C and G209A were screened following restriction enzyme digestion of the PCR product. Direct PCR product sequencing of entire exons 3 and 4 was carried out for at least one proband each from the 10 familial cases. RESULTS: Neither G88C and G209A mutations nor any other mutation in exons 3 and 4 was found in the PD patients analysed. CONCLUSION: The G88C and G209A mutations do not seem to be the predominant genetic determinant of PD among Indians.

Adult↗
PubMed2001

Indocyanine green augmented transpupillary thermotherapy in the management of choroidal metastasis from breast carcinoma.

PURPOSE: To demonstrate the efficacy of indocyanine green augmented transpupillary thermotherapy (TTT) in the management of choroidal metastasis from breast carcinoma. METHODS: A retrospective study was performed on 4 women aged 39-59 years with solitary choroidal metastasis from breast carcinoma in whom choroidal metastasis was managed using mTT. All patients had undergone indocyanine green (ICG) augmented TTT using a diode laser (810 nm) treatment to these lesions and had a mean post-treatment follow-up of 13.2 months. RESULTS: In all the patients there was a gradual regression of the lesion over a mean follow-up of 13.2 months with retention of good visual acuity. CONCLUSION: Indocyanine green augmented transpupillary thermotherapy is a viable alternative for management of solitary choroidal metastasis from breast carcinoma.

Adult↗
PubMed2001

Localization of tissue transglutaminase in human carotid and coronary artery atherosclerosis: implications for plaque stability and progression.

Although atherosclerosis progresses in an indolent state for decades, the rupture of plaques creates acute ischemic syndromes that may culminate in myocardial infarction and stroke. Mechanical forces and matrix metalloproteinase activity initiate plaque rupture, whereas tissue inhibitors of metalloproteinases have an important (albeit indirect) role in plaque stabilization. In this paper, an enzyme that could directly stabilize the plaque is described. Tissue transglutaminase (TG) catalyzes the formation of epsilon(gamma-glutamyl)lysine isopeptide bonds that are resistant to enzymatic, mechanical, and chemical degradation. We performed immunohistochemistry for TG in atherosclerotic human coronary and carotid arteries. TG was most prominent along the luminal endothelium and in the medium of the vessels with a distribution mirroring that of smooth muscle cells. Variable, often prominent, immunoreactivity for TG was also seen in the intima, especially in regions with significant neovascularization. Additionally, TG was detected in fibrous caps and near the "shoulder regions" of some plaques. A monoclonal antibody to the transglutaminase product epsilon(gamma-glutamyl)lysine isopeptide demonstrated co-localization with TG antigen. Transglutaminase activity was found in 6 of 14 coronary artery atherectomy samples. Cross-linking of TG substrates such as fibrinogen, fibronectin, vitronectin, collagen type I, and protease inhibitors stabilized the plaque. Furthermore, the activation of transforming growth factor-beta-1 by TG might be an additional mechanism for the promotion of plaque stabilization and progression by increasing the synthesis of extracellular matrix components.

Adult↗
PubMed2001

Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase.

Succinate semialdehyde dehydrogenase (ALDH5A1, encoding SSADH deficiency is a defect of 4-aminobutyric acid (GABA) degradation that manifests in humans as 4-hydroxybutyric (gamma-hydroxybutyric, GHB) aciduria. It is characterized by a non-specific neurological disorder including psychomotor retardation, language delay, seizures, hypotonia and ataxia. The current therapy, vigabatrin (VGB), is not uniformly successful. Here we report the development of Aldh5a1-deficient mice. At postnatal day 16-22 Aldh5a1-/- mice display ataxia and develop generalized seizures leading to rapid death. We observed increased amounts of GHB and total GABA in urine, brain and liver homogenates and detected significant gliosis in the hippocampus of Aldh5a1-/- mice. We found therapeutic intervention with phenobarbital or phenytoin ineffective, whereas intervention with vigabatrin or the GABAB receptor antagonist CGP 35348 (ref. 2) prevented tonic-clonic convulsions and significantly enhanced survival of the mutant mice. Because neurologic deterioration coincided with weaning, we hypothesized the presence of a protective compound in breast milk. Indeed, treatment of mutant mice with the amino acid taurine rescued Aldh5a1-/- mice. These findings provide insight into pathomechanisms and may have therapeutic relevance for the human SSADH deficiency disease and GHB overdose and toxicity.

Aldehyde Oxidoreductases↗
PubMed2001

Toxic effects of arsenic (III) on some hematopoietic and central nervous system variables in rats and guinea pigs.

OBJECTIVE: To evaluate the effects of arsenic (III) exposure on porphyrin metabolism and the central nervous system supplemented with data on the effect of hepatic and renal tissues of rats and guinea pigs. METHODS: Rats and guinea pigs were exposed to 10 or 25 ppm arsenic in drinking water for 16 weeks. RESULTS: Following chronic arsenic (III) exposure, delta-aminolevulinic acid dehydratase activity in blood showed a significant reduction as did the total cell counts (RBC and WBC) and reduced glutathione with increased urinary delta-aminolevulinic acid. Zinc protoporphyrin, a sensitive indicator of iron deficiency and impairment of heme biosynthesis, showed a significant increase in arsenic exposure. The hepatic delta-aminolevulinic acid dehydratase and delta-aminolevulinic acid synthetase activity increased in chronic arsenic (III) exposure in rats and guinea pigs. Significant changes in the steady-state level of three major neurotransmitters, dopamine, norepinephrine, and 5-hydroxytryptamine, and monoamine oxidase were observed following chronic arsenic (III) exposure. CONCLUSION: At low doses (10 and 25 ppm in drinking water), the effects of arsenic on hematopoietic indices and whole-brain neurotransmitter concentrations were more prominent in guinea pigs than in rats with some variability in the dose response.

5-Aminolevulinate Synthetase↗
PubMed2001

Percutaneous resection of renal cysts.

Symptomatic renal cysts can be managed endoscopically via retrograde ureterorenoscopy, antegrade percutaneous nephroscopy, or laparoscopy. Although all three methods are minimally invasive and effective, the retrograde approach is limited by the size and location of the cyst. Laparoscopy is also effective but is associated with multiple port sites, extensive dissection, and technical difficulty. We utilize percutaneous trans-parenchymal endocystolysis as a first-line therapy. The technique is described in detail.

Humans↗
PubMed2001

Passive transfer of antibodies protects immunocompetent and imunodeficient mice against lethal Ebola virus infection without complete inhibition of viral replication.

Ebola hemorrhagic fever is a severe, usually fatal illness caused by Ebola virus, a member of the filovirus family. The use of nonhomologous immune serum in animal studies and blood from survivors in two anecdotal reports of Ebola hemorrhagic fever in humans has shown promise, but the efficacy of these treatments has not been demonstrated definitively. We have evaluated the protective efficacy of polyclonal immune serum in a mouse model of Ebola virus infection. Our results demonstrate that mice infected subcutaneously with live Ebola virus survive infection and generate high levels of anti-Ebola virus immunoglobulin G (IgG). Passive transfer of immune serum from these mice before challenge protected upto 100% of naive mice against lethal Ebola virus infection. Protection correlated with the level of anti-Ebola virus IgG titers, and passive treatment with high-titer antiserum was associated with a delay in the peak of viral replication. Transfer of immune serum to SCID mice resulted in 100% survival after lethal challenge with Ebola virus, indicating that antibodies alone can protect from lethal disease. Thus antibodies suppress or delay viral growth, provide protection against lethal Ebola virus infection, and may not require participation of other immune components for protection.

Animals↗
PubMed2001

Function and inhibition sensitivity of the N-terminal segment of surfactant protein B (SP-B1-25) in preterm rabbits.

BACKGROUND: Surfactant protein B (SP-B) is an essential component of pulmonary surfactant, but shorter SP-B sequences may exert equivalent surface activity. METHODS: We synthesised a peptide based on the amino-terminal domain of SP-B (SP-B1-25), a full length SP-B1-78, and a full length palmitoylated SP-C peptide (SP-C1-35) and compared the in vivo function and sensitivity to plasma inhibition of preparations consisting of mixtures of phospholipids with SP-B1-25 or SP-B1-78 and/or SP-C1-35 to Survanta. Preterm rabbits born at 27 days of gestation were treated at birth with surfactant and ventilated for 60 minutes. At 15 minutes half of them received plasma intratracheally. Dynamic compliance was monitored every 15 minutes and postmortem pressure-volume curves were measured to define lung mechanics. RESULTS: Dynamic compliance and postmortem lung volumes were highest after treatment with a surfactant consisting of an SP-B peptide and SP-C1-35 or Survanta. Plasma instillation decreased dynamic compliance and lung volumes sharply, but the most effective activity was by prior instillation of surfactants containing SP-B1-25. CONCLUSION: These experiments suggest that the N-terminal domain of SP-B (SP-B1-25) exhibits in vitro and in vivo surface activity and is relatively insensitive to plasma inhibition.

Analysis of Variance↗
PubMed2001

Comparison of apoptosis and terminal differentiation: the mammalian aging process.

Apoptosis is the ordered chain of events that lead to cell destruction. Terminal differentiation (denucleation) is the process in which cells lose their nuclei but remain functional. Our group examined cell death in three tissues using two different fixatives and a postfixation procedure, involving young (5 months) and old (2 years) guinea pigs. The data reveal that B-DNA and Z-DNA content decreases, whereas single-stranded (ss-) DNA increases, in older tissues undergoing apoptosis (skin and cornea) and terminal differentiation (ocular lens). We speculate that some of the factors that contribute to the aging process might also be responsible for the enhanced amount of damaged DNA in older tissues undergoing cell death. (J Histochem 49:929-930, 2001)

Aging↗
PubMed2001

Effect of supplementation on haemoglobin and serum retinol levels and nutritional status of school children of northern India.

Supplementation study was carried out in 66 children of 10-12 years of age for a period of about 4 months. On the basis of blood analysis, 33 children were taken as deficient having low level of both Hb (<10 g/dl) and serum retinol (< 20 microg/dl). Similar number of children (33) were selected as control purposively who had Hb > 10 g/dl and serum retinol > 20 microg/dl. Average daily consumption of cereals, pulses, vegetables, fruits, milk and milk products, fats and oils, and sugar and jaggery was below the recommended dietary intake in control as well as deficient subjects, however, control children consumed more when compared to deficient children. Among nutrients the daily mean intake of energy, protein, iron, n-carotene and vitamin C were found lower than RDA in deficient subjects as compared to control subjects. Feeding of 100 g/day of cauliflower leaves powder supplements i.e. biscuits and shakarpara improved the Hb, serum retinol, height, weight and nutritional status in deficient subjects. The increase in Hb, serum retinol, weight and height in supplemented group was 14.61, 33.27, 4.48 and 7.06%, respectively. Initially, 27.27% children had normal nutritional status in deficient group, but after supplementation this value was increased to 42.42%. Higher percentage of children having deficiency signs of vitamin A (6.06%), iron (66.67%), B-complex vitamin (9.09%), and symptoms of protein-energy-malnutrition (72.73%) was observed in deficient subjects as compared to control subjects.

Anemia↗