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Biomedical subjects

A Siddiqui

Publications and source records attributed to A Siddiqui.

At least 91 records · Page 5Linked to original sources

Modeling plasma lipoprotein-bile lipid relationships: differential impact of psyllium and cholestyramine in hamsters fed a lithogenic diet.

Hamsters fed a lithogenic diet become hyperlipemic with elevated very-low-density lipoprotein (VLDL) and high-density lipoprotein 2 (HDL2) cholesterol pools and develop lithogenic bile in which chenodeoxycholate (cheno) typically predominates. The relationship between these distorted lipoprotein and bile lipid profiles and gallstone induction was investigated in male Syrian hamsters fed for 5 weeks a gallstone-inducing purified diet (5% butter, 0.4% cholesterol) or the same diet supplemented with 5% psyllium or 1% cholestyramine, agents known to alter bile acid metabolism. The gallstone diet essentially doubled plasma cholesterol level, whereas psyllium decreased it to near normal, and cholestyramine to a subnormal level, while correcting the distorted distribution of cholesterol among lipoproteins. Both the gallstone diet and psyllium produced cholesterol-laden livers, in contrast to subnormal values produced by cholestyramine. Fecal bile acid excretion was increased eightfold with cholestyramine and fourfold with psyllium relative to the value produced by the gallstone diet and a literature control value. Supersaturated bile developed with the gallstone diet (lithogenic index [LI], 2.3 +/- 0.6), whereas the LI was decreased by psyllium (1.2 +/- 0.4) and cholestyramine (0.7 +/- 0.3). The gallstone diet decreased the concentration of bile acids in gallbladder bile, but greatly increased the percentage of taurochenodeoxycholic acid, whereas psyllium preferentially decreased all taurine-conjugated bile acid levels and expanded glycocholate output. Cholestyramine greatly decreased the secretion of biliary cholesterol and cheno independent of its conjugation. Accordingly, psyllium increased the glycine to taurine ratio of gallbladder bile fivefold, whereas cholestyramine did not affect this ratio, but increased the cholate to cheno ratio dramatically (25-fold) as compared with a threefold increase with psyllium. This combination of biliary lipid and bile acid alterations induced coordinated responses in the LI and the hydrophobicity index (HI) such that cholesterol gallstones developed in 11 of 12 hamsters fed the gallstone diet, whereas only one of 11 of the psyllium-fed and none of 12 cholestyramine-fed hamsters had cholesterol stones. Thus, psyllium and cholestyramine differentially increased bile acid excretion, which improved the lipoprotein profile and inhibited cholesterol gallstone formation. Both agents operated by different means to decrease biliary cholesterol secretion and the percentage of cheno, which decreased the LI and HI, respectively.

Analysis of Variance↗

Effect of mancozeb on hepatic glutathione S-transferase in rat.

Oral administration of mancozeb (100 or 200 mg/kg body weight) for 7 consecutive days caused an increase in glutathione S-transferase (GST) activity in the liver of newborn, weanling and adult rats. This observed increase in GST activity was higher in weanling than in newborn and adult rats. Evaluation of acute effects at 4 and 20 h following oral administration of 200 mg mancozeb/kg showed a marginal increase in the levels of GST in adult rat liver. However, there was competitive inhibition of GST by the fungicide in vitro.

Animals↗

Regulation of hepatitis B virus gene expression.

Human hepatitis B virus (HBV) mainly infects hepatocytes. HB viral gene expression has been demonstrated to be liver-specific using DNA transfection methods. This liver-specific gene expression is regulated by promoter/enhancer elements. HBV contains two enhancer elements. Enhancer element I has been studied in detail at the DNA-protein level. This is further substantiated by DNA transfections of liver and non-liver cell lines with expression plasmids containing enhancer elements controlling the transcription of reporter genes. Genetic analysis of the enhancer elements defined the minimal sequences which play a key role in the regulation of enhancer function. One of the factors binding in this region is RXR alpha. Using only the DNA binding domain of the liver-specific RXR alpha expressed in E. coli, we demonstrated binding of RXR alpha to the putative retinoic acid receptor response element (RARE) in the HBV enhancer. Our studies implicate a potentially important role of retinoic acid and its receptor in the liver-specific regulation of HBV gene expression and the disease pathogenesis associated with infection.

Base Sequence↗

Tensor fascia lata V-Y retroposition myocutaneous flap: clinical experience.

A modification of the standard tensor fascia lata myocutaneous flap, namely, the tensor fascia lata V-Y retroposition flap, is a reliable, durable, efficient, well-tolerated, and technically straightforward procedure. Indications include trochanteric pressure ulcers, nonhealing, failed hip arthroplasties, and soft tissue defects after regional tumor excisions. In 70 TFL V-Y retroposition flap reconstructions performed, the overall postoperative complication rate was 23%, with 4 total flap failures. Sixty-three percent of complications were treated with local wound care, thus avoiding repeat surgery. Rerotation of this flap is not only possible, but also just as reliable as the initial procedure. The tensor fascia lata retroposition flap offers advantages over many of the other tensor fascia lata flap variations.

Adolescent↗

Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism.

The human hepatitis C virus (HCV) contains a long 5' noncoding region (5' NCR). Computer-assisted and biochemical analyses suggest that there is a complex secondary structure in this region that is comparable to the secondary structures that are found in picornaviruses (E.A. Brown, H. Zhang, L.-H. Ping, and S.M. Lemon, Nucleic Acids Res. 20:5041-5045, 1992). Previous in vitro studies suggest that the HCV 5' NCR plays an important role during translation (K. Tsukiyama-Kohara, N. Iizuka, M. Kohara, and A. Nomoto, J. Virol. 66:1476-1483, 1992). Dicistronic and monocistronic expression vectors, in vitro translation, RNA transfections, and deletion mutagenesis studies were utilized to demonstrate unambiguously that the HCV 5' NCR is involved in translational control. Our data strongly support the conclusion that an internal ribosome entry site exists within the 5' noncoding sequences proximal to the initiator AUG. Furthermore, our results suggest that the HCV genome is translated in a cap-independent manner and that the sequences immediately upstream of the initiator AUG are essential for internal ribosome entry site function during translation.

Base Sequence↗

Age-related effects in the inhibition of oxidative metabolism of xenobiotics by mancozeb.

The effect of po administration of 100 or 200 mg mancozeb/kg body weight for 7 consecutive days on microsomal mixed-function oxidase catalyzed xenobiotic metabolism was investigated in the livers of newborn weanling and adults rats. Mancozeb caused a dose-dependent inhibition in the activities of p-nitroanisole O-dealkylase and aniline hydroxylase, while the activities of aminopyrine N-demethylase and benzo(a)pyrene hydroxylase were unaffected in all the age groups. The inhibition of p-nitroanisole O-dealkylase and aniline hydroxylase, was remarkably higher in adult than in newborn and weanling rats. There was a concentration-dependent decrease in cytochrome P-450 and microsomal protein contents. This study indicates selective age-independent inhibition of hepatic monooxygenases following repeated mancozeb dosing.

Age Factors↗

Retinoid X receptor RXR alpha binds to and trans-activates the hepatitis B virus enhancer.

A retinoid X receptor (RXR) response element was located within the functionally defined hepatitis B virus (HBV) enhancer element. A short segment of the enhancer that contains this region has been shown with genetic analysis to play a key role in the regulation of enhancer function and to represent a major determinant of liver-specific activity. Both the full-length protein and the DNA-binding domain of the liver-specific receptor RXR alpha bound to the putative retinoic acid response element in the HBV enhancer. In vivo, an HBV enhancer-reporter gene construct responds to induction with retinoic acid when cotransfected with an RXR alpha expression vector. A single-base transition (G----A) in the HBV retinoic acid response element leads to a dramatic reduction both in the in vitro binding activity of RXR alpha and the in vivo activity of the HBV enhancer. Thus, retinoic acid and the RXR alpha are implicated as being significant determinants in the liver-specific regulation of HBV gene expression and the resultant disease pathogenesis.

Base Sequence↗

Comparison of gallbladder ejection fraction with histopathologic changes in acalculous biliary disease.

This selective retrospective study was undertaken to establish whether the gallbladder contraction (ejection fraction) calculated during cholescintigraphy correlates with the histopathologic changes in the surgical specimen. The medical records of 243 patients who underwent hepatobiliary scintigraphy were reviewed. Of these, 215 patients had cholecystokinin cholescintigraphy and 100 went on to cholecystectomy. The original histologic slides from 67 gallbladders were available and reviewed by a pathologist who graded each specimen based on presence and severity of changes associated with "chronic" cholecystitis. There was no significant correlation between the severity of histopathologic change and cholecystokinin-induced gallbladder emptying.

Adult↗

Socially available heroin powders--their chemical compositions and reproductive and behavioural effects on female rats.

Morphine is one of such substances which produce very intense euphoria and a prolonged period of relaxation and sedation. These opioids are known to cause modifications in neuroendocrine system during different stages of life, ranging from fetal through postnatal to adult. Heroin, an opioid, is a derivative of morphine and its long-term use, both in males and females, is associated with alterations in sexual behaviour and changes in endocrine functions. In females, hormonal imbalance thus resulted, can lead to amenorrhea and in some cases infertility. In Pakistan, heroin is available mixed with different additives in a variety of forms. Two varieties (S1 and S2) procured from patients visiting Drug Rehabilitating Clinic in the Civil Hospital, Karachi, were analysed for their qualitative and quantitative properties.

Journal Article↗

HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions.

The hepatitis B virus (HBV) X gene product trans-activates viral and cellular genes. The X protein (pX) does not bind independently to nucleic acids. The data presented here demonstrate that pX entered into a protein-protein complex with the cellular transcriptional factors CREB and ATF-2 and altered their DNA binding specificities. Although CREB and ATF-2 alone did not bind to the HBV enhancer element, a pX-CREB or pX-ATF-2 complex did bind to the HBV enhancer. Thus, the ability of pX to interact with cellular factors broadened the DNA binding specificity of these regulatory proteins and provides a mechanism for pX to participate in transcriptional regulation. This strategy of altered binding specificity may modify the repertoire of genes that can be regulated by transcriptional factors during viral infection.

Cyclic AMP Response Element-Binding Protein↗

Functional analysis of a liver-specific enhancer of the hepatitis B virus.

The liver-specific enhancer I of the human hepatitis B virus contains several regions of DNA-protein interaction. Located within this element are also the domains of a promoter controlling the synthesis of the X open reading frame. Functional domains of the enhancer I and the X gene promoter were identified using DNase I protection analysis, deletion mutagenesis, and cell transfections. A unique liver-specific interaction was identified within this element whose binding site includes a direct sequence repeat, 5'-AGTAAACAGTA-3'. The factor(s) binding to this sequence motif was purified by oligonucleotide-affinity chromatography. Binding of this factor appears to play a key role in determining the overall enhancer function. Additionally, the interaction of several purified factors is presented. Cotransfection of liver cells with expression vectors encoding transcriptional factors resulted in trans-activation of the promoter/enhancer function. Based on the results of genetic analysis a model outlining the functional domains of the enhancer/promoter region is presented.

CCAAT-Enhancer-Binding Proteins↗

Regulation of the hepatitis B virus gene expression by the enhancer element I.

Hepatitis B virus (HBV) enhancer is a cis-acting element capable of potentiating transcription with liver cell specificity. To assess the regulatory function of the enhancer during viral gene expression, we employed whole genome transfections in both liver- and non-liver-derived cell lines and compared them with those of enhancerless genome transfections. Using a transient scheme of expression, the effect of enhancer deletion on the transcription of HBV genes was investigated. S1 nuclease analysis showed that deletion of the enhancer sequences did not alter the specificity of the HBV transcripts. Also, the nuclear run-on analysis demonstrated that the influence of enhancer on the HBV gene expression is at the transcriptional level. We further noted that in the absence of the enhancer, synthesis of the pregenomic RNA which originates from the core/pregenomic promoter was markedly affected. This result then implicates an additional role of the enhancer during the replication of HBV.

Carcinoma, Hepatocellular↗

Transcriptional factor C/EBP binds to and transactivates the enhancer element II of the hepatitis B virus.

The human hepatitis B Virus genome (HBV) contains a liver-specific enhancer upstream of the X ORF which has been studied in detail by several investigators. A second liver-specific enhancer element, designated here as enhancer II, has been relatively recently described in the HBV genome, which is located within the core/pregenomic promoter. We have studied the interactions of transcriptional factors with this element and show here that the nuclear factor CCAAT/enhancer binding protein (C/EBP) binds at a unique site within these sequences. Further, using the transient cotransfection scheme of expression with C/EBP encoding vectors and an enhancer II-reporter gene construct, we demonstrate that the enhancer element II responds to increasing amounts of C/EBP by displaying transactivation. Evidence for the functional role of the enhancer element II in transcriptional regulation of the HBV gene expression is presented. A major influence of the enhancer II appears to be on the surface antigen expression.

Base Sequence↗

Heterogeneous effects of ethylenebisdithiocarbamate (EBDC) pesticides on oxidative metabolism of xenobiotics.

Comparative evaluation of the acute effects of ethylenebisdithiocarbamate (EBDC) fungicides, mancozeb and zineb on microsomal mixed function oxidases (MFO) revealed marked substrate-dependent inhibition of oxidative metabolism of aminopyrine, p-nitroanisole and aniline in rats sacrificed 4 hr after oral administration of 100 mg mancozeb or zineb/kg body weight. Mancozeb inhibited p-nitroanisole O-dealkylase and aniline hydroxylase to a greater degree than zineb, whereas the inhibition of aminopyrine N-demethylase by the two fungicides was quantitatively comparable. Interestingly, aryl hydrocarbon hydroxylase (AHH) which exhibited maximum inhibition with mancozeb, remained unaffected following zineb administration. The time-course and dose-dependence of MFO inhibition examined 1 and 4 hr after a single oral dose of 100 mg or 250 mg zineb/kg was expressed as a dose-dependent decline in the rate of xenobiotic biotransformation at 4 hr. In vitro interaction of zineb with MFO resulted in slightly greater inhibition of aminopyrine, p-nitroanisole and aniline while AHH exhibited more pronounced decrease with mancozeb. The magnitude of inhibition of aminopyrine N-demethylase and AHH was independent of the time of preincubation of fungicides with the enzyme. Kinetic studies indicated the non-competitive nature of AHH inhibition. Chronic oral treatment with mancozeb and zineb at a dose of 250 mg/kg for 4 weeks did not modify xenobiotic biotransformations except for a slight induction of aminopyrine N-demethylase by mancozeb.

Animals↗

Prevalence of HIV-infection among blood donors.

Blood donor screening for HIV antibody was carried out at Blood Transfusion Service of Jinnah Postgraduate Medical Centre. Sera of 1655 blood donors were tested by Enzyme linked Immuno-Sorbent Assay (Abbott recombinant HIV-1-EIA) from March, 1987 to December, 1989. Initial reactivity was noted in seven cases, of which three were repeatedly reactive. When these were tested by western blot at National Institute of Health, all were reported negative. Thus no HIV positive blood donor was found in the subject population.

Adult↗