Biomedical subjects

A Siddiqui

Publications and source records attributed to A Siddiqui.

At least 55 records · Page 3Linked to original sources

PubMed1998

The inter-relationship between gonadal steroids and POMC peptides, beta-endorphin and alpha-MSH, in the control of sexual behavior in the female rat.

Estradiol benzoate (10 microg EB) given to ovariectomized-adrenalectomized rats induced sexual receptivity in half the animals and increased alpha-MSH in the preoptic area, ventromedial nucleus (VMN) and arcuate nucleus (ARC), in all the animals, although levels were significantly higher in the VMN and ARC of the receptive (R) subgroup. EB also raised levels of beta-endorphin in the VMN and ARC in the R rats only. POMC expression was not altered. EB did not affect alphaMSH in extra-hypothalamic areas, but addition of progesterone, raised levels in the septum, amygdala, hippocampus and caudate putamen. Only in the VMN, ARC and septum were the steroid-induced increases correlated with onset of sexual behavior.

Animals↗

PubMed1998

Effects of perinatal diazepam exposure on the liver of rats.

Diazepam is routinely used in obstetrics in the treatment of maternal eclampsia or as anesthetic induction during deliveries or cesarean sections. We investigated here the effects of perinatal diazepam treatment on the liver of Sprague Dawley rats. From 15th day of gestation to birth pregnant rats were treated daily in the first experimental group (DZ1) with 2.5 mg DZ/kg b.w., s.c., the second (DZ2) with 5 and the third (DZ3) with 10 mg DZ/kg b.w. After birth respective treatment was continued to the pups till 5th day postnatal. One half of pups from DZ2 and control was sacrificed at 12th day, the other were raised to 120th day and then sacrificed. After fixation in formaldehyde serial paraffin sections were processed with proliferating cell nuclear antigen (PCNA), autofluorescence of lipofuscin and Elastica v. Gieson staining. Livers from 12 day old rats showed increased levels of PCNA marked hepatocytes and lipofuscin containing cells. Livers from 120 day old animals exhibited increased levels of PCNA cells especially with weakly stained nuclei, the number of lipofuscin containing cells were decreased in DZ1 and DZ2 but reached in DZ3 the similar number as control. Statistical analysis showed that quantification of Kupffer cells lacked significance. To conclude livers of 12 day old animals demonstrated a stimulated DNA synthesis and an accumulation of nondegradable residues. Livers from 120 day old rats demonstrated an increase in number of potentially proliferating hepatocytes by increased levels of weakly stained PCNA nuclei. At lower dosage DZ seems to inhibit lipofuscinogenesis, at highest dosage DZ accumulates non-degradable residues. Elastica v. Gieson staining was not suitable to quantify Kupffer cells with certainty.

Animals↗

PubMed1997

The La antigen binds 5' noncoding region of the hepatitis C virus RNA in the context of the initiator AUG codon and stimulates internal ribosome entry site-mediated translation.

Translation initiation of the hepatitis C virus (HCV) RNA genome occurs through an internal ribosome entry site in a cap-independent manner. Here, we have examined the interaction between La antigen and the HCV 5' noncoding region (5'NCR). In this analysis, competitor RNAs derived from HCV 5'NCR carrying deletions and a point mutation were used to identify the site(s) of La antigen binding during UV cross-linking assay. These studies suggest that La antigen recognizes the intact HCV 5'NCR structure. Further, these interactions occurred in the context of the initiator AUG. The latter view is supported by an analysis in which mutants of the HCV 5'NCR RNA with deletion or substitution in the initiator AUG codon failed to compete for La antigen binding to the wild-type 5'NCR. The evidence for the interaction between liver cell-derived La antigen and the HCV 5'NCR is provided by immunoprecipitation of a UV cross-linked species from the S100 fraction of Huh7 cell lysates. The functional relevance of this interaction was demonstrated by the stimulation of the HCV internal ribosome entry site-mediated translation in the presence of La protein. These results suggest an important functional role of La protein in the regulation of internal initiation of translation of the HCV RNA genome.

Autoantigens↗

PubMed1997

Neonatal androgen manipulation differentially affects the development of monoamine systems in rat cerebral cortex, amygdala and hypothalamus.

Neural tissue during perinatal life is sufficiently plastic to respond to the presence of testicular androgens. Here we studied the effect of neonatal androgen manipulation (castration of male and androgenization of female rats) on monoamine neurotransmitter systems in the cerebral cortex and sexually dimorphic regions of brain (hypothalamus and amygdala). Norepinephrine (NE) and dopamine (DA) concentrations in cortex, amygdala and hypothalamus of rats were assayed by HPLC at days 25, 60, 120, 180, 240 and 300. Results show that NE levels in all groups of rats at day 25 were higher in the hypothalamus (5-9 ng/mg protein) compared to the amygdala (0.5-3 ng/mg protein) and the cortex (0.5-1 ng/mg protein). Levels of DA at day 25 in the hypothalamus and the amygdala were comparable (up to 3.5 ng/mg) but higher than in the cortex (1.25-1.75 ng/mg protein). NE and DA concentrations in sham-castrated male and androgen-treated females were higher at day 25 compared to castrated male and control females in both amygdala and hypothalamus; however, levels of NE and DA remained unchanged in the cortex. Pattern of NE concentrations started reversing with increase in age, i.e., NE levels in control females and castrated males increased almost 4-fold in amygdala and 2-fold in hypothalamus by day 300, but there was no significant change in the cortex. Compared to that, NE levels decreased in sham-castrated male (2-fold) and androgen-treated females (3-fold) in amygdala as well as in the hypothalamus (2-fold) in both these groups. A similar pattern of reversal of DA levels was found in both amygdala and hypothalamus, however, at day 300 DA levels were comparable in all the four groups. These studies suggest that androgen manipulation (castration or androgen administration) induces age-dependent short- and long-term effects on the development of noradrenergic and dopaminergic systems in the sexually dimorphic regions of brain, amygdala and hypothalamus, without a significant change in the cerebral cortex.

Amygdala↗

PubMed1997

Transforming growth factor beta 3 (TGF beta 3) accelerates wound healing without alteration of scar prominence. Histologic and competitive reverse-transcription-polymerase chain reaction studies.

BACKGROUND: Transforming growth factor (TGF) beta 3 is a new isoform of the TGF beta superfamily and is presumed to play an important role in wound repair and scarring. OBJECTIVE: To examine the effects of TGF beta 3 on wound healing and on reducing scarring. DESIGN AND INTERVENTIONS: Dermal ulcers were created on the ears of 75 anesthetized young female rabbits. Either TGF beta 3 or vehicle was applied topically to the wounds. Wounds were bisected and analyzed histologically at postwounding day 7. A second group of wounds was treated with topical TGF beta 3 and TGF beta 2 or vehicle at days 0 and 3 and harvested at days 21 through 42 as an excessive scarring model. The third group of wounds was treated with TGF beta 1, TGF beta 2, and TGF beta 3 and vehicle. The granulation tissue was harvested at day 7, and cellular RNA was extracted for performing competitive reverse-transcription polymerase chain reaction. MAIN OUTCOME MEASUREMENT: The amount of new epithelium and granulation tissue was measured in TGF beta 3- and vehicle-treated wounds. The hypertrophic index was calculated for scarring wounds treated with TGF beta 2 and TGF beta 3 or vehicle. Levels of TGF beta 1 messenger RNA were measured in those wounds that were treated with TGF beta 1, TGF beta 2, and TGF beta 3 and in their controls. RESULTS: The use of TGF beta 3 (0.3-0.75 microgram per wound) increased granulation tissue formation by more than 100% (P < .005). Epithelialization showed a biphase, either increasing 30% (P < .04) or decreasing 25% (P < .001) dependent on dose. No significant difference in the hypertrophic index was noted in TGF beta 3-treated wounds compared with controls. Levels of TGF beta 1 messenger RNA increased (7.1- to 14.9-fold) in those wounds treated with TGF beta s compared with controls at day 7. CONCLUSIONS: Exogenous TGF beta 3 displays substantial vulnerary properties in wound healing and may be useful in treating nonhealing wounds. However, the observation that TGF beta 3 can reduce scarring was not confirmed in this study, and the messenger RNA level in response to TGF beta 3 suggests that it behaves similarly to TGF beta 1.

Animals↗

PubMed1997

Perinatal exposure to morphine disrupts brain norepinephrine, ovarian cyclicity, and sexual receptivity in rats.

The effect of perinatal exposure to morphine on the development of catecholaminergic and reproductive function in female rats was investigated. Adult rats received morphine intraperitoneally daily for 40 days. The dose of morphine was progressively increased at 10-day intervals from 5, 7.5, 10 to 15 mg/kg body weight until day 40. The rats were mated between days 38 and 45. Administration of morphine at dose rates of 20 and 30 mg/kg continued during pregnancy. The dose was increased to 40 mg/kg for 10 days postpartum. Results showed that morphine disrupted ovarian cyclicity in 52% of the females. Amongst the remaining females, 43% became pregnant when mated. In the female offspring born to such dams, sexual maturation was delayed and body weight was reduced until weaning. At adulthood, lordosis behavior was inhibited when the female offspring were tested against stimulus males. Plasma estradiol and ovarian estradiol and progesterone levels were reduced. Norepinephrine concentration in the hypothalamus was reduced, whereas it remained unchanged in the amygdala. Dopamine concentrations in both hypothalamus and amygdala were not influenced by perinatal morphine exposure. These results suggest that chronic morphine treatment during perinatal life selectively influences the development of noradrenergic mechanisms in the rat brain and this may in turn be responsible for reduced reproductive activity.

Amygdala↗

PubMed1997

Ischemic tissue oxygen capacitance after hyperbaric oxygen therapy: a new physiologic concept.

In an effort to better understand the effects of hyperbaric oxygen therapy on ischemic tissue, we monitored the real-time changes in subcutaneous tissue oxygen tension before, during, and after exposure to hyperbaric oxygen treatments. We identified an elevation of the tissue oxygen partial pressure to over 300 mmHg during the treatment period (up from a baseline mean of 24 mmHg) in a sustained ischemia rabbit ear model (n = 22 rabbits). There was no sustained change in tissue oxygen tension beyond the period of treatment. This manner of response is consistent with several current theories used to explain the mechanism of action of hyperbaric oxygen therapy. It is also consonant with our opinion that molecular oxygen, when delivered at high pressure, can function both as a respiratory metabolite and as a signal transducer. We also studied the impact of nontherapeutic 100% oxygen at 1 atm on tissue. The sustained peak tissue oxygen tension during such challenges increased in direct proportion to the number of hyperbaric oxygen treatments given. The clinical relevance and extension of these findings are discussed.

Animals↗

PubMed1997

Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid oligomers: I. Synthesis and characterization.

A series of oligomers or low molecular weight polymers of lactic and/or glycolic acid has been synthesized with different molar ratios of lactic to glycolic acid. These oligomers have been characterized with respect to oligomer composition, molecular weight, intrinsic viscosity, crystallinity, melting temperature, and glass transition temperature. The polymerization conditions for the lactic/glycolic acid oligomer syntheses were as follows: 180-220 degrees C, 5 mm Hg, 5 h, and 0.1 wt% of catalyst (antimony oxide) concentration. The polymeric compositions correlated to the feed ratios of lactic to glycolic acid. The molecular weight of the oligomers ranged from 895.8 +/- 48.7 to 1368.0 +/- 0 D with the intrinsic viscosity ranging from 0.0513 to 0.0814 dl g-1. The lactic/glycolic acid oligomers were found to be amorphous. The glass transition temperatures of the lactic/glycolic acid oligomers were lower than physiological temperature.

Biodegradation, Environmental↗

PubMed1996

Sodium benzoate differentially blocks circling induced by D-and L-dopa in the hemi-parkinsonian rat.

D-3,4-Dihydroxyphenylalanine (D-dopa) and L-3,4-dihydroxyphenylalanine (L-dopa) induced circling in rats with a unilateral 6-hydroxydopamine lesion of substantia nigra with similar potency. D-Dopa is not a substrate for aromatic L-amino acid decarboxylase, the enzyme which metabolizes L-dopa to dopamine. This raises the question of how D-dopa has behavioral effect. Two pathways have been suggested to result in conversion of D-dopa to L-dopa, one involving oxidation of D-dopa to dihydroxyphenylpyruvic acid (DHPPA) by D-amino acid oxidase, the other involving transamination of D-dopa to DHPPA. Here we show that sodium benzoate, an inhibitor of D-amino acid oxidase, blocks D-dopa-induced circling while having no effect on circling induced by L-dopa. The results suggest that conversion of D-dopa to L-dopa via DHPPA is highly dependent on oxidase activity and that sodium benzoate effectively inhibits this process in vivo in rat.

Amino Acid Oxidoreductases↗

PubMed1996

Hepatitis B virus transactivator protein, HBx, associates with the components of TFIIH and stimulates the DNA helicase activity of TFIIH.

Human hepatitis B virus genome encodes a protein, termed HBx, that is widely recognized as a transcriptional transactivator. While HBx does not directly bind cis-acting transcriptional control elements, it has been shown to associate with cellular proteins that bind DNA. Because HBx transactivated a large number of viral/cellular transcriptional control elements, we looked for its targets within the components of the basal transcriptional machinery. This search led to the identification of its interactions with TFIIH. Here, we show that HBx interacts with yeast and mammalian TFIIH complexes both in vitro and in vivo. These interactions between HBx and the components of TFIIH are supported by several lines of evidence including results from immunoprocedures and direct methods of measuring interactions. We have identified ERCC3 and ERCC2 DNA helicase subunits of holoenzyme TFIIH as targets of HBx interactions. Furthermore, the DNA helicase activity of purified TFIIH from rat liver and, individually, the ERCC2 component of TFIIH is stimulated in the presence of HBx. These observations suggest a role for HBx in transcription and DNA repair.

Animals↗

PubMed1996

Purification and properties of rat liver nuclear proteins that interact with the hepatitis B virus enhancer 1.

The hepatitis B virus enhancer 1 element plays a fundamental role in the liver-specific regulation of hepatitis B virus gene expression. A central region of enhancer 1, the enhancer core domain, contains at least four cis-acting sequence motifs that are essential for enhancer 1 activity. In this study, we have investigated an essential motif within the core domain previously defined as footprint V (FPV). Transient transfection analyses demonstrate that FPV is capable of independently functioning in a liver-specific manner to activate transcription. Therefore, to further examine the liver-specific properties of FPV-mediated enhancer 1 activity, we have carried out the biochemical purification and characterization of FPV binding activity from rat liver nuclei. This study has conclusively identified hepatocyte nuclear factor 3beta (HNF-3beta), a liver-enriched member of the HNF-3/forkhead gene family, as the predominant purified protein that interacts with the FPV motif. Moreover, a cellular protein(s) that copurified with HNF-3beta specifically interacts with a novel sequence motif that partially overlaps FPV. Since this novel motif contains a palindromic sequence, we have tentatively referred to the protein(s) that binds to this site as palindrome-binding factor (PBF). Additional evidence indicates that HNF-3beta and PBF cooperatively interact with enhancer 1. Therefore, this study supports the hypothesis that FPV-mediated enhancer activity involves a cooperative interplay between HNF-3beta and at least one other enhancer 1-binding protein, PBF.

Activating Transcription Factor 2↗

PubMed1996

The hepatitis B virus transactivator protein, HBx, interacts with single-stranded DNA (ssDNA). Biochemical characterizations of the HBx-ssDNA interactions.

Human hepatitis B virus X protein, HBx, is widely acknowledged as a transcriptional transactivator. While HBx has been shown to increase gene expression in trans, it is generally believed that it does not bind double-stranded DNA. Using several experimental approaches, we show that HBx interacts with single-stranded DNA in a manner that is not sequence-specific. Various heterologous single-stranded DNA (ssDNA) oligonucleotides were able to compete in HBx-ssDNA interactions in gel shift assays. Escherichia coli non-sequence-specific, single-stranded DNA binding protein, E. coli SSB, displaced the HBx-ssDNA interactions, confirming the ability of HBx to interact with single-stranded DNA in a non-sequence-specific manner. We have further characterized the HBx-ssDNA interactions under various biochemical conditions. These include the effects of mono- and divalent cations, the effect of cardiolipin and heparin, pH and temperature dependence, and variations in the incubation time. HBx bound more tightly to d(pyrimidines)25 than to d(purines)25, a property that is characteristic of other single-stranded DNA-binding proteins (SSBs). Collectively the results presented here provide the first evidence of HBx's interaction with ssDNA. The biochemical parameters of these interactions were similar to those of known viral and cellular SSBs.

Base Sequence↗

PubMed1996

Hepatitis B virus X protein partially substitutes for E1A transcriptional function during adenovirus infection.

Lack of an in vitro culture system for human hepatitis B virus has hampered the ability to address fundamental questions regarding the viral life cycle and the effect of viral gene products during productive infection. To study the activity of HBV X protein (HBx) in the context of a viral infectious cycle, we provided HBx in trans during adenovirus infection of liver-derived cells. In hepatoma cells infected with adenovirus mutants deficient in expression of various E1A products, HBx was able to partially substitute for the transcriptional activation function of E1A. HBx also activated adenovirus replication, but to a lesser extent than the activation of transcription. Adenovirus genes transcribed by either RNA polymerase II or RNA polymerase III were activated by HBx during infection. These results suggest that HBx and E1A activate transcription by a similar mechanism and that this viral infection system will be useful for characterization of the functional activities of HBx.

Adenovirus E1 Proteins↗

PubMed1996

A common structural core in the internal ribosome entry sites of picornavirus, hepatitis C virus, and pestivirus.

Cap-independent translations of viral RNAs of enteroviruses and rhinoviruses, cardioviruses and aphthoviruses, hepatitis A and C viruses (HAV and HCV), and pestivirus are initiated by the direct binding of 40S ribosomal subunits to a cis-acting genetic element termed the internal ribosome entry site (IRES) or ribosome landing pad (RLP) in the 5' noncoding region (5'NCR). RNA higher ordered structure models for these IRES elements were derived by a combined approach using thermodynamic RNA folding, Monte Carlo simulation, and phylogenetic comparative analysis. The structural differences among the three groups of picornaviruses arise not only from point mutations, but also from the addition or deletion of structural domains. However, a common core can be identified in the proposed structural models of these IRES elements from enteroviruses and rhinoviruses, cardioviruses and aphthoviruses, and HAV. The common structural core identified within the picornavirus IRES is also conserved in the 5'NCR of the divergent viruses, HCV, and pestiviruses. Furthermore, the proposed structural motif shares a structural feature similar to that observed in the catalytic core of the group 1 intron. The conserved structural motif from these divergent sequences that looks like the common core region of group 1 introns is probably a crucial element involved in the IRES-dependent translation.

Animals↗

PubMed1996

Involvement of the 5-HT1A subtype receptor in the neonatal organization of agonistic behaviour in the rat.

5-hydroxytryptamine (5-HT) interacts with testosterone (T) in the development of a number of neuronal systems controlling sexually dimorphic adult behaviours. In this report, we investigated this interaction on the organization of agonistic behaviour in males, females, androgenized females (250 micrograms/pup of T proprionate on the day of birth), and males castrated on the day of birth. We have shown previously that manipulating 5-HT2 activity over the 2nd week of life modulates adult agonistic behaviour, depending on genetic sex and the presence of T. In this report, we investigated the effects seen in adulthood of a 5-HT1A agonist [8-OH-DPAT, 0.25 mg/kg, intraperitoneally (i.p.)] and antagonist (WAY100135, 0.25 mg/kg, i.p.) given over days 8-16 postpartum. The test for agonistic behaviour was carried out in a neutral territory against a matched conspecific, and introductory, offensive and defensive activities were note. Results show that neonatal administration of the 5-HT1A antagonist WAY100135 increases introductory activity and defense in the presence of neonatal T, independent of genetic sex, because these effects were seen in sham-castrated males and androgenized females. Offence followed a similar pattern, in that it was increased by WAY100135, but only in males. In the case of defence, the effects of the antagonist were reinforced by the action of the agonist (8-OH-DPAT) in both males and females, indicating an inhibitory role of 5-HT1A perinatal activity on defence in the presence of malelike levels of circulating T and a facilitatory role when levels of T are low or negligible. These findings indicate that 5-HT1A activity is involved in the development of agonistic behaviour and the effects are influenced by T. The results also show that the offensive and defensive facets of agonistic activity are controlled differently.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Neonatal organizational effects of the 5-HT2 and 5-HT1A subsystems on adult behavior in the rat.

Males, females, neonatally androgenized females, and neonatally castrated males were treated over the second week of life with 0.25 mg/kg of either the 5-HT2 agonist 1-(2,5-dimethoxy-3-iodophenyl)-2-aminopropane HCl (DOI), the 5-HT2 antagonist ritanserin (Rit), the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), or the 5-HT1A antagonist WAY100135 (WAY). Exploration, anxiety, sociosexual preferences, and sexual behavior were measured in adulthood. Agents acting on 5-HT1A receptors do not appear to affect organization of any of the behavioral systems studied. DOI increased exploratory activity but in females only, which suggests that testosterone antagonizes the stimulatory effect of 5-HT2 activity on exploration. Neonatal ritanserin selectively reduced anxiety in females, and DOI had a similar effect in androgenized females. This indicates that neonatal 5-HT2 activity is anxiogenic in normal females, anxiolytic in androgenized females, and has no effect on anxiety in males. Males and androgenized females both showed a preference for the female teaser that was abolished by the 5-HT2 agonist, DOI. These results point out that 5-HT2 activity selectively suppresses heterosexual preference induced in the presence of neonatal testosterone. DOI also reduced both male sexual behavior in males and female sexual behavior in androgenized females. Thus, the 5-HT2 system antagonizes the action of testosterone in stimulating heterosexual orientation and sexual activity, and this is independent of genetic sex.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Front-line management of pulmonary tuberculosis: an analysis of tuberculosis and treatment practices in urban Sindh, Pakistan.

SETTING: Karachi and Hyderabad, Pakistan. OBJECTIVE: To describe the level and quality of tuberculosis (TB) case management by non-TB control program (TCP) physicians in urban Sindh, Pakistan. DESIGN: We interviewed 152 adults with pulmonary TB confirmed by Karachi's TB control program regarding the initial management of their TB symptoms before entering the TCP. We also surveyed 65 general practitioners (GPs) attending continuing education seminars with a multiple choice test to assess their management of suspected pulmonary TB. We compared both results to guidelines from the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). RESULTS: Eighty percent (122/152) of patients first sought GPs. Only 14% of GPs performed any sputum test. At most, 17 (40%) of the 42 patients recalling their GP's treatment, received the recommended 4-drug regimen. However, 68% (45/65) of surveyed GPs chose correct treatment from a multiple choice format. But their initial laboratory investigations, follow-up, and treatment cessation criteria (9%, 9-31%, and 11% correct, respectively) demonstrated under-utilization of sputum tests and over-reliance on unhelpful tests. CONCLUSIONS: GPs first saw most of these TCP patients, but their weak management likely hinders TB control. A partnership between TB control programs and GPs could improve case management and hasten TB control.

Adolescent↗

PubMed1996

Mucinous (colloid) carcinoma of urinary bladder following long-term cyclophosphamide therapy for Waldenstrom's macroglobulinemia.

Carcinoma of the urinary bladder is a known complication of cyclophosphamide therapy. Almost all such cases have been transitional cell carcinomas. We report here the second example of an adenocarcinoma of bladder and the first purely mucinous (colloid) carcinoma of urinary bladder developing after long-term cyclophosphamide therapy. The patient, a 77-year-old woman, had been treated for Waldenstrom's macroglobulinemia for at least 24 years, during which time treatment for this disease varied from 50 to 100 mg per day. The disease terminated in acute myelogenous leukemia, and she died of severe disseminated intravascular coagulopathy associated with hypermacroglobulinemia. The mucinous (colloid) carcinoma of the urinary bladder was an incidental finding at autopsy.

Adenocarcinoma, Mucinous↗