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Biomedical subjects

A Sheikh

Publications and source records attributed to A Sheikh.

At least 91 records · Page 5Linked to original sources
PubMed1996

A study of the incorrect use of ventilator disconnection alarms.

Pressure-sensitive ventilator disconnection alarms may fail to function correctly when used with discharging compliance ventilators such as the Manley Blease. The increase in gas flow on disconnection generates raised pressure owing to the resistance provided by components of the breathing system. Thirty-four anaesthetists, who were unaware of the nature of the survey, were observed to see if previous recommendations for the correct adjustment of the ventilator alarm were being followed. It was found that 77% of alarms were incorrectly adjusted and would not have alarmed in the event of a true disconnection occurring.

Anesthesia, General↗
PubMed1994

In vitro and in vivo response of hepatocytes from hepatic nodules to the mitoinhibitory effects of phenobarbital.

One of the proposed mechanisms by which phenobarbital (PB) promotes hepatocarcinogenesis in the rat is by differential mitoinhibition. However, our earlier studies indicated that PB inhibited DNA synthesis in vitro in hepatocytes isolated from both surrounding non-nodular liver and hepatic nodules promoted by orotic acid (OA). Since nodules generated by one promoter need not necessarily be resistant to another promoter, the present study was undertaken to determine whether foci/nodules promoted by PB itself are resistant to the mitoinhibitory effects of PB. Accordingly, rats were initiated with diethylnitrosamine (DENA, 200 mg/kg i.p) and promoted with PB (0.07% of PB as its sodium salt) in their drinking water for 16 or 33 weeks. In vitro studies indicated that PB (3-5 mM) inhibited DNA synthesis induced by epidermal growth factor (EGF) in hepatocytes from surrounding non-nodular liver as well as from nodules promoted by PB for 33 weeks. In another experiment, initiated rats exposed to PB for 33 weeks were subjected to either two-thirds partial hepatectomy (PH) or sham hepatectomy. Hepatocytes were labelled with tritiated thymidine in vivo for 48 h. Autoradiographic analysis indicated that in the presence of PB, the hepatocytes from both foci/nodules and the surrounding non-nodular liver responded to PH to the same extent. In addition, they both responded to PH less efficiently as compared to the corresponding controls. Further, initiated rats exposed to PB for 16 weeks when subjected to PH and killed 4 weeks thereafter, the percentage area occupied by gamma-glutamyltranspeptidase-positive foci/nodules in the PB group increased, but to the same extent as in initiated control rats not exposed to PB. The above results raised an interesting possibility that the lack of resistance of the PB-promoted nodules to the mitoinhibitory effects of PB may be because the PB-promoted nodule does not express a resistant phenotype. To examine this aspect, the response of hepatocytes from 33 week PB-promoted nodules to the mitoinhibitory effects of OA was examined. The results indicated that OA (60-120 microM) inhibited EGF-induced DNA synthesis in hepatocytes isolated from both nodules as well as from surrounding non-nodular liver. These results suggest that PB is a mitoinhibitor but may not provide a strong differential growth advantage to foci/nodules in response to a proliferative stimulus. Further, the nodules promoted by PB do not appear to express the resistant phenotype, defined as being resistant to the mitoinhibitory effects of OA and PB.

Animals↗
PubMed1994

Outcome and cost of open- and closed-chest cardiopulmonary resuscitation in pediatric cardiac arrests.

OBJECTIVE: The dismal survival rates of cardiac arrest in children managed with conventional closed-chest cardiopulmonary resuscitation (CC-CPR) have renewed interest in the use of open-chest CPR (OC-CPR). We determined the efficacy of the early use of OC-CPR in children after cardiac arrest. METHODS: A retrospective review of emergency medical services (EMS) and hospital records revealed 27 children who were brought to the emergency department under CPR after blunt trauma. RESULTS: Twelve children had CC-CPR and 15 children underwent OC-CPR. Prehospital resuscitation and transport of both groups of children was excellent by current standards, and OC-CPR was performed within 5 minutes of arrival in the emergency department. CPR was successful with restoration of spontaneous circulation in 17% of children after CC-CPR, whereas 20% of children had restoration of spontaneous circulation after OC-CPR. This difference was not statistically significant. None of the children regained consciousness or survived to discharge. The hospital charges for patients who underwent OC-CPR were significantly higher (P = .005). Less than 30% of the hospital charges were reimbursed in both groups. CONCLUSIONS: OC-CPR does not improve survival in children who sustain cardiac arrest and receive CPR for more than 20 minutes in the field. Under these circumstances OC-CPR is an expensive and futile procedure to undertake.

California↗
PubMed1994

A view of HIV-I infection in Karachi.

A prospective study on the prevalence of HIV-I infection in Karachi, Pakistan was conducted over a period of six years (1986-1992). Over 15,000 individual samples and more than 32,000 donor units of individuals residing in Karachi at the time of sample collection were tested for HIV-I infection by our screening test EIA which revealed a positivity rate of 0.23% and 0.003% in individual and donor units respectively by Western Blot. We divided patients into four groups A, B, C and D based on the most plausible cause of transmission. The largest number of positive patients belonged to group B, who were of either foreign origin or expatriates or Pakistanis settled abroad. They comprised approximately 67% of the total positive cases and were subjected to testing on strong clinical grounds. In individuals of other groups like group A and D, there was history of travel abroad from time to time. The only positive donor unit (group C) belonged to a person who had been living in Middle East for the last 10-12 years. The last group D comprised of samples that were directly sent to us without complete history, except for the fact that they had been travelling back and forth. The large majority of patients fell in 20-50 years age group. Despite the limitations of this study, we conclude that the prevalence of HIV is steadily increasing in our population and so far, we have not been able to find an indigenous case of AIDS in our series.

Adolescent↗
PubMed1993

On the biosynthesis of bovine pancreatic trypsin inhibitor (BPTI). Structure, processing, folding and disulphide bond formation of the precursor in vitro and in microsomes.

The natural gene for bovine pancreatic trypsin inhibitor (BPTI) was expressed by in vitro transcription/translation systems as the 100-residue pre-proBPTI, with a signal peptide for translocation into the endoplasmic reticulum. Expression in the presence of microsomes defined the site of co-translational cleavage of the signal peptide. The resulting proBPTI in the microsomes consists of the 58 residues of mature BPTI, plus an additional 13 residues at the N terminus, including a cysteine residue at position -10, and seven residues at the C terminus. ProBPTI remained in the unfolded, reduced form within microsomes when synthesized under reducing conditions, but folded and formed disulphide bonds rapidly when the disulphide form of glutathione was added. Complete folding could occur within about one minute, even when residue Cys10 was replaced by Ser. The structure of proBPTI was determined by circular dichroism and two-dimensional NMR and found to be that of mature BPTI with flexible extensions on both termini. Its inhibition of the activity of alpha-chymotrypsin was indistinguishable from that of the mature protein. The extensions of the precursor appeared to play only very minor roles in refolding in vitro under conditions where folding and disulphide bond formation are coupled. Under pH and redox conditions thought to reflect those in vivo, complete folding and disulphide bond formation required several hours. Addition of protein disulphide isomerase to in vitro folding experiments caused substantial and similar increases in the rate of formation of the fully folded state for both mature BPTI and proBPTI; the half time for folding to the native state was reduced to approximately two minutes, which is comparable to that occurring in microsomes. The absence of substantial effects of the N and C-terminal extensions on the protein structure, inhibitor activity and refolding leaves their functional roles to be discovered.

Amino Acid Sequence↗
PubMed1993

Effect of orotic acid on in vivo DNA synthesis in hepatocytes of normal rat liver and in hepatic foci/nodules.

One of the proposed mechanisms by which orotic acid (OA) promotes liver carcinogenesis is by differentially mito-inhibiting the normal hepatocytes while permitting the initiated ones to respond to growth stimuli to form foci/nodules. In an attempt to examine this hypothesis, the present study was designed to determine (i) whether OA inhibits DNA synthesis in normal hepatocytes in vivo, and (ii) whether hepatocytes from hepatic foci/nodules are relatively resistant to the mito-inhibitory effects of OA. The results of this study indicate that OA given i.p. as a tablet of 300 mg at the time of partial hepatectomy (PH) almost completely inhibited liver DNA synthesis. Three days later--a time period by which the implanted tablet disappeared--the hepatocytes resumed DNA synthesis. Exposure to OA results in an accumulation of uridine nucleotides and a decrease in adenosine nucleotides. Creation of such an imbalance in nucleotide pools appears to be important for OA to inhibit DNA synthesis. Adenine (a tablet of 300 mg), an agent that inhibits the metabolism of OA to uridine nucleotides, counteracted the mito-inhibitory effects of OA. To determine whether the hepatocytes in foci/nodules are resistant to the mito-inhibitory effects of OA, rats were initiated with diethylnitrosamine (DENA; 150 mg/kg) and promoted by the resistant-hepatocyte model. Fourteen weeks after the administration of DENA, the rats were subjected to PH in the presence of absence of OA (300 mg tablet). The results indicated that, in contrast to hepatocytes in normal or surrounding non-nodular liver, a subpopulation of hepatocyte foci/nodules appear to be relatively resistant to the mito-inhibitory effects of OA. These findings support the hypothesis that differential mito-inhibition is a possible component in the promoting effect of OA. However, whether this is the mechanism by which OA promotes liver carcinogenesis needs to be further investigated.

Adenine↗
PubMed1993

Cytokine-induced suppression and potentiation of hapten-specific immediate hypersensitivity responses.

The ability of subcutaneously (s.c.) injected cytokines (IL-4, IL-5, IL-6, IFN alpha, IFN gamma, GMCSF) to regulate the induction of hapten-specific immediate hypersensitivity (IH) responses was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten-specific IgE antibody forming cell (AFC) response. To induce IH responses, mice were injected in the right pinna with either BPO-BSA (benzylpenicilloyl-bovine serum albumin), BPO-KLH (0.01-1.0 micrograms/ml) or mcAb anti-IgE (0.001 - 1.0 micrograms/ml); and in the left pinna with an equal volume of saline (0.05 ml). Pinnae were measured 5 min to 4 hr later using a micrometer caliper. Treatment of mice with IL-4 or IFN gamma dramatically suppressed the induction of IH responses in dose dependent fashion. In contrast, treatment of mice with IL-6 and IFN alpha increased these responses in dose dependent fashion, while GMCSF and IL-5 had no effect. The suppression obtained with IL-4 and IFN gamma, and the increases seen with IL-6 and IFN alpha, were transient since these cytokines, as well as GMCSF and IL-5, had no effect on IH responses elicited 21 days after the peak of BPO-specific IgE AFC responses. The data suggest that cytokine mediated effects on IH responses occur via changes in serum levels of BPO-specific IgG1 or IgE, through direct or indirect effects of cytokines on mast cells or other cell types, or by affecting the ability of BPO-specific homocytotropic antibodies to bind to mast cell surfaces.

Animals↗
PubMed1992

Orotic acid, nucleotide-pool imbalance, and liver-tumor promotion: a possible mechanism for the mitoinhibitory effects of orotic acid in isolated rat hepatocytes.

This study was designed to determine the possible mechanism by which orotic acid exerts its mitoinhibitory effect on rat hepatocytes in primary culture. Orotic acid inhibited, dose-dependently DNA synthesis in hepatocytes induced by epidermal growth factor, transforming growth factor alpha, hepatocyte growth factor, acidic fibroblast growth factor, or plasma from rats exposed to various liver cell-proliferative stimuli, such as two-thirds partial hepatectomy, lead nitrate, cyproterone acetate, ethylene dibromide, or a diet deficient in choline. Further, orotic acid inhibited DNA synthesis even when added 24 h after the hepatocytes were primed with transforming growth factor alpha. Taken together, these results suggested that the target site may not be at the level of the growth-factor receptor and receptor-mediated early events. In a preliminary experiment, orotic acid inhibited the expression of the ribonucleoside diphosphate reductase gene. Exposure to orotic acid results in an imbalance in nucleotide pools characterized by an increase in uridine nucleotides and a decrease in adenosine nucleotides. It is hypothesized that this imbalance in nucleotide pools inhibits the expression of the ribonucleoside diphosphate reductase gene and, therefore, is a likely target for the mitoinhibitory effect of orotic acid.

Animals↗
PubMed1992

Protein synthesis in Aspergillus nidulans.

In this review of protein synthesis, we have described a system for translation of mRNA using extracts of A. nidulans. This system is useful for characterizing mutants suspected to have defects in protein synthesis and for assessing the toxicity of various antibiotics and their effects on misreading the genetic code. The well developed genetical system of A. nidulans has enabled us to map at least 27 new genes whose mutation disturbs the level of translational accuracy. These mutants could be used to identify new components of translation or new roles for established components. The abundant fidelity mutations themselves could be used to elucidate the mechanism for maintaining the accuracy of protein synthesis. The large number of mutations in the control of fidelity indicate that mutations in other parts of the translation system could be easily obtained. This would be particularly important for initiation where many factors are thought to be needed and yet their exact roles are unknown. A. nidulans appears to have normal eukaryotic ribosomes and translation factors that can be used to study the mechanism of protein synthesis, its regulation, and the maintenance of its high fidelity. If highly purified factors were used, requirements for hitherto undiscovered factors could be seen. Since A. nidulans has typical eukaryotic responses to inhibitors of translation, it could be used to study new inhibitors, their mode of action, and their potency. Among the fungi, A. nidulans could be a worthy competitor to S. cerevisiae in the field of protein synthesis, particularly because so many translation genes have been identified. The system awaits further exploitation.

Aspergillus nidulans↗
PubMed1991

Hygromycin- and paromomycin-resistant mutants of Aspergillus nidulans alter translational fidelity.

Mutants of Aspergillus nidulans resistant to the aminoglycoside antibiotics paromomycin and hygromycin B have been isolated and their growth characteristics are described here. Most paromomycin mutants were cross-resistant to hygromycin and geneticin. All the hygromycin-resistant mutants were slightly cross-resistant to geneticin. Out of the 15 mutants tested 14 had drug-resistant ribosomes in vitro and all 12 of those investigated further had reduced levels of translational misreading. Five new loci have been found--parA on linkage group I, hygA on III, hygB on IV, hygC on V, hygD on VI and parB on VIII. This increases, to at least 12, the number of translational fidelity loci in A. nidulans.

Aspergillus nidulans↗
PubMed1990

Translation of preprochymosin in vitro. Evidence for folding of prochymosin to the native conformation.

1. The cDNA coding for preprochymosin has been sub-cloned into the transcription/translation vector pGEM-3Z, the T7 promoter used to transcribe the gene and the product expressed in an 'in vitro' cell-free system comprising rabbit reticulocyte lysate and dog pancreatic microsomes. 2. Translations in various conditions, and analyses of the translation product in reducing and non-reducing conditions, indicate that oxidizing translation conditions and the cleavage of the N-terminal 'pre-' sequence are essential for generation of a disulphide-bonded translation product. 3. The disulphide-bonded translation product was resistant to proteinases, as expected for a translation product segregated within microsomal vesicles; in the presence of detergent to solubilize the membranes, the product was not readily susceptible to proteolysis, and was converted to a proteinase-resistant core fragment. 4. Segregated prochymosin, synthesized in reducing conditions, was completely degraded by proteinases under similar conditions. 5. Proteinase treatment of purified recombinant prochymosin gave rise to a proteinase-resistant fragment of similar Mr, suggesting that the disulphide-bonded product of translation in vitro was correctly folded. 6. The translocated, disulphide-bonded and folded prochymosin could be converted into pseudochymosin at pH 2.0, and addition of chymosin to the activation mixture resulted in increased pseudochymosin production.

Animals↗
PubMed1989

Comparison of 1.5% enflurane with 1.25% isoflurane in oxygen for caesarean section: avoidance of awareness without nitrous oxide.

We examined the feasibility of administering nearly 100% oxygen throughout the induction-delivery period of general anaesthesia for 113 Caesarean sections. Isoflurane 1.25% was compared with 1.5% enflurane for maintenance of anaesthesia. The level of anaesthesia was monitored by use of the isolated forearm technique. There was a greater amount of isolated forearm movement when enflurane was used. The three main criteria for a satisfactory general anaesthetic technique for Caesarean section were fulfilled, namely no maternal awareness, no undue depression of the fetus and no adverse effect on uterine contractility. Isoflurane and enflurane appear to be suitable anaesthetic agents for facilitating hyperoxygenation during Caesarean section.

Anesthesia, Inhalation↗
PubMed1987

Life threatening complication of high-frequency jet ventilation.

High-frequency jet ventilation is being increasingly used as an alternative to conventional methods of ventilation in both anaesthesia and intensive care. We report a case of severe respiratory obstruction as a complication of high-frequency jet ventilation. Patients with bleeding diathesis, including patients on haemodialysis, may particularly be at risk.

Airway Obstruction↗