Biomedical subjects
Publications and source records attributed to M Ahmad.
BK destroying activity was observed in rat isolated heart perfusates. BK was optimally degraded at pH 8.4 in rat heart. The results indicated that myocardial kinin degradation was due to ACE and a serine protease. These results suggest that bradykinin may have some cardioprotective role during myocardial ischaemia at acidic pH.
Consanguineous marriages in two population samples, one rural and one urban, from Swat (Pakistan) were studied. The frequency of consanguineous marriages was found to be 37.13% and 31.11%, and mean inbreeding coefficients were calculated as 0.0168 and 0.0162, for the rural and urban populations respectively. The most frequent type of marriage was between first cousins, in both samples. Among first cousin marriages, those with father's brother's daughter were predominant. Mean inbreeding coefficient was higher for higher socioeconomic groups in both samples. Differences by ethnic and educational groups were also found. Contrary to previous studies, a significant increase in the incidence of consanguineous marriages over the years has been observed. The incidence of premature mortality was significantly higher only in the offspring of first cousin marriages. Significantly higher incidence of morbidity in the offspring of consanguineous marriages was also observed.
Cryptochrome 1 (CRY1) is a flavin-type blue type receptor of Arabidopsis thaliana which mediates inhibition of hypocotyl elongation. In the work described in this report it is demonstrated that CRY1 is a soluble protein expressed in both young seedlings grown either in the dark or under light, and in different organs of adult plants. The functional role of CRY1 was further investigated using transgenic Arabidopsis plants overexpressing CRY1. It is demonstrated that overexpression of CRY1 resulted in hypersensitivity to blue, UV-A, and green light for the inhibition of hypocotyl elongation response. Transgenic plants overexpressing CRY1 also exhibited a dwarf phenotype with reduced size in almost every organ. This was in keeping with the previous observation of reciprocal alterations found in hy4 mutant plants and is consistent with a hypothesis that CRY1 mediates a light-dependent process resulting in a general inhibitory effect on plant growth. In addition, transgenic plants overexpressing CRY1 showed increased anthocyanin accumulation in response to blue, UV-A, and green light in a fluence rate-dependent manner. This increase in anthocyanin accumulation in transgenic plants was shown to be concomitant with increased blue light-induction of CHS gene expression. It is concluded that CRY1 is a photoreceptor mediating blue light-dependent regulation of gene expression in addition to its affect on plant growth.
In a screen for early-flowering mutants, a number of mutants that were early flowering under both short and long days were isolated. One such mutant, pef1, was selectively insensitive to both red and far-red light in the inhibition of hypocotyl elongation response; a classic phytochrome phenotype mediated by both PHYA and PHYB. The pef1 mutant seedlings could not be phenotypically rescued by biliverdin, a precursor of the phytochrome chromophore, nor did they fail to complement any previously identified elongated hypocotyl (hy) mutants. Difference spectra and Western blot analysis showed normal concentrations of PHYA photoreceptor apoprotein, which appeared photochemically active. It was concluded that the pef1 mutant is defective in both PHYA- and PHYB-mediated signaling pathways, and may represent a lesion in an early step of the phytochrome signal transduction pathway. Additional pef mutants deficient specifically in PHYB-mediated responses were also identified by this screen.
The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.
Enicostema littorale a useful medicinal herb was subjected to phytochemical as well as pharmacological investigations. A secoiridoid glycoside, swertiamarin, was isolated and identified on the basis of UV, IR, Mass and NMR spectroscopic measurements. However, pharmacological studies on the blood pressure of rats and ileum of Guinea-pig could not provide significant results.
This retrospective study audited all the extrahepatic biliary operations performed through a subcostal muscle splitting incision between January, 1979 and June, 1995. Of the 400 patients subjected to biliary surgery 340 (85%) were females and 60 (15%) males. One hundred and eighty (45%) patients presented with symptoms of acute and 220 (55%) with chronic cholecystitis. Most (95%) of the operations were performed electively. Simple cholecystectomy was performed in 320 (80%) patients and 72 (18%) had common bile duct exploration for stones. Of these 67 had choledochoduodenostomy and 5 a polythene tube drainage of common bile duct. The overall morbidity of the procedure was 13.5% of which 3.5% were procedure related complications and 10.0% general complications. Only two deaths occured during the study giving a mortality of 0.5%. This technique has greatly reduced the hospital stay, the amount of blood loss during operation and post operative pain. No patient had incisional hernia or wound dehiscence and all the patients were back to work early. The results of this study suggest that this incision may be used with advantage elsewhere.
The possible relationship between coffee exposure during pregnancy and the teratopharmacological effects on the developing neonates was evaluated in albino mice. The body weight of pups of treated dams was significantly affected after birth and as the pups grew, their weight gains were lower compared to controls. This effect was time- and dose-dependent and the perinatal treatment was more effective (F(6) = 5.06, p < 0.02) than the prepartum treatment (F(6) = 3.12, p < 0.05). Body hair appearance and eye opening were delayed in all treated groups and again, the perinatal treatment was more effective and dose-dependent. Almost all indices for "locomotor behavior" were affected by all doses of coffee but only in the perinatally treated groups and the effects were neither time- nor dose-dependent. In the "tube restraint test", the latency to the first bite was decreased and the number of bites was increased in the offspring, while in female offspring the effect was opposite. The body weight of female offspring remained low even in young adult animals (F(6) = 9.89, p < 0.005). The brain weight in males was unaffected but in females it was decreased but only at the dose of 2 mg/kg. The liver and kidney weights of both sexes decreased at the lower doses. The protein content of these organs was also significantly affected by coffee treatment. These results suggest that coffee intake during pregnancy should be limited since it produces significant and long-lasting teratopharmacological and behavioral alterations in the offspring.
Polyclonal antibodies (Ab's) were raised against a 43-kDa component of a protein complex that has ligand recognition sites similar to those of brain N-methyl-D-aspartate (NMDA) receptors. The Ab's were used to immunopurify from brain synaptic membranes a 60-kDa glycine (Gly), glutamate (Glu) and thienylcyclohexylpiperidine (TCP)-binding protein and to screen a rat hippocampal cDNA expression library. A 1.85-kb clone, pGlyBP, coding for a protein of 470 amino acids (52.7 kDa) was identified. Northern blot analyses performed on poly(A+) RNA from brain revealed hybridization of the labeled cDNA probes to transcripts of 1.9 kb. E. coli transformed with the pGyBP expressed a protein that was recognized by the anti-43 kDa Ab's and had recognition sites for Gly, Glu and TCP. The cloned protein has 2 glycosylation sites, 3 hydrophobic domains, 4 cysteine-rich motifs (C-X2-C-X16-20-C-X5-11), and 2 regions homologous to the NR1 receptor protein.
The Arabidopsis HY4 gene, required for blue-light-induced inhibition of hypocotyl elongation, encodes a 75-kDa flavoprotein (CRY1) with characteristics of a blue-light photoreceptor. To investigate the mechanism by which this photoreceptor mediates blue-light responses in vivo, we have expressed the Arabidopsis HY4 gene in transgenic tobacco. The transgenic plants exhibited a short-hypocotyl phenotype under blue, UV-A, and green light, whereas they showed no difference from the wild-type plant under red/far-red light or in the dark. This phenotype was found to cosegregate with overexpression of the HY4 transgene and to be fluence dependent. We concluded that the short-hypocotyl phenotype of transgenic tobacco plants was due to hypersensitivity to blue, UV-A, and green light, resulting from over-expression of the photoreceptor. These observations are consistent with the broad action spectrum for responses mediated by this cryptochrome in Arabidopsis and indicate that the machinery for signal, transduction required by the CRY1 protein is conserved among different plant species. Furthermore, the level of these photoresponses is seen to be determined by the cellular concentration of this photoreceptor.
The arabidopsis thaliana HY4 gene encodes CRY1, a 75-kilodalton flavoprotein mediating blue light-dependent regulation of seedling development. CRY1 is demonstrated here to noncovalently bind stoichiometric amounts of flavin adenine dinucleotide (FAD). The redox properties of FAD bound by CRY1 include an unexpected stability of the neutral radical flavosemiquinone (FADH.). The absorption properties of this flavosemiquinone provide a likely explanation for the additional sensitivity exhibited by CRY1-mediated responses in the green region of the visible spectrum. Despite the sequence homology to microbial DNA photolyases, CRY1 was found to have no detectable photolyase activity.
PURPOSE: To study the attenuation and scattering effects of ocular implants, made from different materials, on the dose distributions of a 6 MV photon beam, and 6, 9, and 12 MeV electron beams used in orbital radiotherapy. METHODS AND MATERIALS: Central axis depth-dose measurements were performed in a polystyrene phantom with embedded spherical ocular implants using film dosimetry of a 6 MV photon beam and electron beams of 6, 9, and 12 MeV energy. The isodose distributions were also calculated by a computerized treatment planning system using computerized tomography (CT) scans of a polystyrene phantom that had silicone, acrylic, and hydroxyapatite ocular implants placed into it. RESULTS: Electron beam dose distributions display distortions both on the measured and calculated data. This effect is most accentuated for the hydroxyapatite implants, for which the transmissions through ocular implants are on the order of 93% for the 6 MV photon beam, and range from 60% for 6 MeV electrons to 90% for 12 MeV electrons. CONCLUSION: We studied the effect of ocular implants of various materials, embedded in a polystyrene phantom, on the dose distributions of a 6 MV photon beam, and 6, 9, and 12 MeV electron beams. Our investigations show that while 6 MV photons experience only a few percent attenuation, lower energy electron beam with 60% transmission is not a suitable choice of treating tumors behind the ocular implants.
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Cytokine activation of vascular cell adhesion molecule-1 (VCAM-1) gene expression by endothelial cells is an important feature in a variety of vascular inflammatory responses. Cytokines transcriptionally activate the VCAM-1 promoter in endothelial cells at least in part through two closely linked NF-kappa B enhancer motifs, kappa L-kappa R (positions -77 and -63). However, cytokine activation of the dimeric NF-kappa B transcriptional factor (p50+p65 subunits) occurs in almost all cell types, whereas VCAM-1 gene expression exhibits a cell type-specific pattern of expression. Tumor necrosis factor-alpha markedly transactivated a transiently transfected minimal kappa L-kappa R motif-driven VCAM-1 promoter, p85VCAMCAT, in passaged human vascular endothelial cells but not in the human epithelial cell line, HeLa suggesting that cell type-specific factors may function through the kappa L-kappa R motif. Both cell types exhibited similar inductions of NF-kappa DNA binding activity and transcriptional activity. However, co-transfection of HeLa cells with p65 and p50 expression vectors demonstrated that the minimal VCAM-1 promoter was effectively transactivated by p65 alone but that additional co-expression of p50 blocked this activity. Furthermore, cytokine activation of the minimal VCAM-1 promoter in HeLa cells was recovered by inhibition of p50 expression using antisense oligonucleotide. These studies suggest that the NF-kappa B(p50+p65 heterodimer) does not support transactivation of the VCAM-1 promoter with the p50 subunit potentially playing a significant inhibitory role in suppressing cytokine activation of VCAM-1. In addition, p65 associated transcriptional factors other than NF-kappa B may serve as positive, cytokine-inducible, cell type-specific regulators of VCAM-1 gene expression.
Mineralocorticoid hormones such as aldosterone modulate cellular ion homeostasis at least in part through the regulation of Na+, K(+)-ATPase (NAKA) gene expression. While aldosterone acts at the transcriptional level through its ligand-inducible mineralocorticoid receptor (MR), tissue specific and other transcriptional factors may interact with the MR to modulate this regulatory response. cAMP also regulates NAKA alpha 1 gene expression which at the transcriptional level is mediated, in part, through a cAMP response element (CRE) present on a highly conserved, 48 base pair enhancer region, the PUC-1 core, of the rat NAKA alpha 1 subunit gene promoter. We have tested the hypothesis that the MR interacts with cAMP induced transcriptional factors to modulate the NAKA alpha 1 gene expression. In transient transfection studies a PUC-1 core attached to an enhancerless SV40 promoter driven reporter gene (pB1CAT) was induced by 8-bromo-cAMP in HeLa cells. Co-transfected MR expression vector inhibited the 8-bromo-cAMP inducible activity of pB1CAT. DNA binding studies suggested that the PUC-1 core binds both CREB/ATF proteins as well as the glucocorticoid hormone class of steroid receptors. These results suggest that the MR suppresses cAMP-mediated activation of PUC-1 core driven CAT activity possibly through a direct interaction with CREB/ATF transcriptional factors. This in turn suggests that the interaction of two distinct signal transduction systems, aldosterone and cAMP, may define the mineralocorticoid responsiveness of the Na+, K(+)-ATPase alpha 1 gene.
Water samples from Ganga river were collected from 3 different locations viz. Kachla, Fatehgarh and Kannauj (U.P.). High performance liquid chromatography analysis of samples by liquid-liquid extraction procedure showed the presence of some pesticides like DDT, alpha-BHC, aldrin, dieldrin etc. DDT, alpha-BHC, DDD, aldrin and dieldrin were present at concentration ranges of 3.33-5.33 ppb, 1.73-3.01 ppb, 0.88-2.41 ppb, 1.17-2.81 ppb and 0.49-4.11 ppb, respectively. The organophosphorus pesticides like dimethoate and methyl parathion were also detected at the concentration levels of 0.41-0.56 ppb and 0.16-0.50 ppb, respectively. The organic substances in the test samples were extracted by XAD-resin and liquid-liquid extraction procedures, and the extracts were assayed for mutagenic potential by the Ames Salmonella/microsome test. The test samples exhibited a remarkable degree of mutagenicity with TA98, TA100 and TA97a strains with the probable role of contaminating pesticides in the river water.
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This paper reports the characterization of novel mutations within the Arabidopsis thaliana HY4 gene, which has previously been shown to encode a protein (CRY1) with characteristics of a blue-light photoreceptor. Several point mutations were identified within the amino-terminal domain of CRY1--this region of CRY1 has high homology to photolyase and is likely to be involved in blue-light-mediated electron transfer. Mutations were found within the region of homology to the known chromophore binding domains of photolyase. Point mutations within the 200 amino acid carboxy-terminal extension distinguishing CRY1 from photolyase, likewise disrupt function of the protein. CRY1 was originally defined as the photoreceptor responsible for blue-light-mediated inhibition of hypocotyl elongation and we now report that anthocyanin accumulation in germinating seedlings is an additional phenotype under the control of this photoreceptor--this is shown to be mediated in part by modulation of mRNA levels of chalcone synthase, one of the anthocyanin biosynthetic enzymes. The effect of the novel mutations on both inhibition of hypocotyl elongation and anthocyanin biosynthesis have been evaluated, and it is demonstrated that mutations with less severe effects on hypocotyl elongation show a similarly reduced effect on anthocyanin biosynthesis. These results are consistent with the cryptochrome photoreceptor mediating multiple regulatory pathways by the same primary mode of action.