Thymic hyperplasia: a cause of respiratory distress.
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Humans↗
Biomedical subjects
S Hussain
Publications and source records attributed to S Hussain.
Cortical blindness: an unusual presentation of eclampsia.
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Adult↗
Core LXXLL motif sequences in CREB-binding protein, SRC1, and RIP140 define affinity and selectivity for steroid and retinoid receptors.
An alpha-helical motif containing the sequence LXXLL is required for the ligand-dependent binding of transcriptional co-activators to nuclear receptors. By using a peptide inhibition assay, we have defined the minimal "core" LXXLL motif as an 8-amino acid sequence spanning positions -2 to +6 relative to the primary conserved leucine residue. In yeast two-hybrid assays, core LXXLL motif sequences derived from steroid receptor co-activator (SRC1), the 140-kDa receptor interacting protein (RIP140), and CREB-binding protein (CBP) displayed differences in selectivity and affinity for nuclear receptor ligand binding domains. Although core LXXLL motifs from SRC1 and RIP140 mediated strong interactions with steroid and retinoid receptors, three LXXLL motifs present in the global co-activator CBP were found to have very weak affinity for these proteins. Core motifs with high affinity for steroid and retinoid receptors were generally found to contain a hydrophobic residue at position -1 relative to the first conserved leucine and a nonhydrophobic residue at position +2. Our results indicate that variant residues in LXXLL core motifs influence the affinity and selectivity of co-activators for nuclear receptors.
Adaptor Proteins, Signal Transducing↗
Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension.
Molecular oxygen (O(2)) regulates the expression of a variety of genes. We hypothesized that O(2) tension may regulate iNOS expression in rat liver through the production of reactive oxygen species (ROS) and the reduction of intracellular glutathione (GSH) levels. To investigate this hypothesis, we determined the effects of hyperoxia upon iNOS induction (both at the protein and mRNA level) and the intracellular concentration of GSH in an isolated in vitro perfused rat liver preparation. To study the potential involvement of ROS in the intracellular signaling pathway linking changes in oxygen tension to gene expression, we repeated these determinations in the presence of the thiol antioxidant N-acetyl-L-cysteine (NAC). We found that 95% O(2) tension caused a significant induction of the iNOS protein and mRNA levels paralleled by a significant fall in intracellular GSH concentration. The addition of NAC (1 mM) to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH levels. These results indicate that molecular O(2) regulates the expression of iNOS in rat liver at the transcriptional level, most likely through the production of ROS and the reduction of intracellular GSH levels.
Acetylcysteine↗
Onycholysis as a complication of systemic chemotherapy: report of five cases associated with prolonged weekly paclitaxel therapy and review of the literature.
BACKGROUND: Onycholysis has been reported in association with the use of several noncytotoxic drugs and with chemotherapy in 135 patients. Onycholysis may be precipitated by exposure to ultraviolet radiation. METHODS: The authors studied 91 patients who received paclitaxel and 187 patients who received doxorubicin. RESULTS: Onycholysis occurred in 5 of 21 patients who received > 6 courses of weekly paclitaxel, developing in the summer months in all 5 patients. It did not occur in patients who received fewer weekly paclitaxel courses or those who were treated every 3 weeks. Onycholysis did not occur in 187 patients who received doxorubicin. Review of the literature revealed that onycholysis is nearly exclusively associated with anthracycline and taxane therapy. CONCLUSIONS: Prolonged weekly paclitaxel, other taxanes, and anthracyclines cause onycholysis in some patients, which may be precipitated by exposure to sunlight. Patients receiving these drugs should protect their nails from sunlight.
Adult↗
Monoclonal cryoglobulinemia with extensive gangrene of all four extremities--a case report.
The monoclonal immunoglobulin products of plasma cell neoplasm can give rise to a variety of manifestations including hyperviscosity, amyloidosis, cryoglobulinemia, neuropathy, and renal failure. A 50-year-old woman with monoclonal cryoglobulinemia developed extensive gangrene and ulceration of both hands and feet over several weeks requiring bilateral below-elbow and below-knee amputations. This case illustrates the importance of qualitative properties of paraprotein.
Amputation, Surgical↗
Diagnosis and management of the neonatal cloaca.
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Abnormalities, Multiple↗
Controversy in the treatment of adult long ileocolic intussusception: case report.
Adult intussusception is an unusual cause of intestinal obstruction. In contrast to children, intussusception in adults is usually due to an identifiable cause. We present a case of an 81-year-old female who was diagnosed with a long intussusception on CT scan of the abdomen. Because of the likelihood of neoplasia, a right hemicolectomy was undertaken, after which the patient recovered well. The correct treatment of adult intussusception is not unanimously agreed upon. We present a case of long intussusception in which partial reduction of viable small bowel before the resection was done by applying gentle traction. This provided sufficient small bowel mesentery length, preventing any damage to superior mesenteric vessels and avoiding unnecessary excision of healthy bowel.
Adenoma, Villous↗
PEFR in relation to phases of pregnancy.
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Adult↗
Mycobacterium avium infection of mouse macrophages inhibits IFN-gamma Janus kinase-STAT signaling and gene induction by down-regulation of the IFN-gamma receptor.
Macrophage activation is required to control the growth of intracellular pathogens. Recent data indicate that macrophages become functionally deactivated during mycobacterial infection. We studied macrophage deactivation by examining the expression of a panel of IFN-gamma-inducible genes and activation of Janus Kinase (JAK)-STAT pathway in Mycobacterium avium-infected macrophages. Reduced expression of IFN-gamma-inducible genes-MHC class II gene E beta; MHC class II transactivator; IFN regulatory factor-1; and Mg21, a gene coding for a GTP-binding protein-was observed in M. avium-infected macrophages. Decreased tyrosine phosphorylation and DNA binding activity of STAT1 in M. avium-infected macrophages stimulated with IFN-gamma was observed. Tyrosine phosphorylation of JAK1, JAK2, and IFN-gamma R alpha was also reduced in infected cells. Northern and Western blot analyses showed that a down-regulation of IFN-gamma R alpha- and beta-chain mRNA and protein occurred in M. avium-infected macrophages. The down-regulation of IFN-gamma R and inhibition of STAT1 activation were time dependent and required 4 h of infection for down-regulation of the IFN-gamma R and 8 h for STAT1 inhibition. These findings suggest that M. avium infection inhibits induction of IFN-gamma-inducible genes in mouse macrophages by down-regulating IFN-gamma R, resulting in reduced phosphorylation of IFN-gamma R alpha, JAK1, JAK2, and STAT1.
Animals↗
Manganese scavenges superoxide and hydroxyl radicals: an in vitro study in rats.
The present study was designed to investigate the role of manganese (Mn) as an antioxidant element. In vitro experiments have been conducted to evaluate the ability of Mn in scavenging oxygen free radicals. Superoxide (O*-) and hydroxyl (OH*-) radicals were generated in vitro by using xanthine and xanthine oxidase system and fenton reactions respectively. Different concentrations of Mn (II) and Mn (III) were used in the reaction mixture to evaluate free radical scavenging ability of Mn. The results indicated that Mn scavenged superoxide radicals at nanomolar concentrations whereas hydroxyl radicals were scavenged at micromolar concentrations. In addition, Mn-superoxide dismutase (SOD) activity was measured in different regions of brain in adult male rats treated with MnCl2. The results showed that Mn-SOD activity increased in Mn treated animals. Therefore, the data support the hypothesis that Mn is one of the essential elements which can protect against oxidative damage, however, at higher concentrations Mn can be neurotoxic by generating the free radicals.
Animals↗
Reduced levels of catalase activity potentiate MPP+-induced toxicity: comparison between MN9D cells and CHO cells.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to be toxic by inducing oxygen free radicals in the mammalian nervous system, especially in the nigrostriatal dopaminergic system. The present study was designed to compare the toxic effects of MPP+, the active metabolite of MPTP, in MN9D neuronal cells that exhibit relatively low levels of catalase activity, as compared to CHO cells, which exhibit high levels of catalase activity. The survival of the MN9D cells in the presence of 250 microM MPP+ was less than 10%, whereas CHO cells exhibited 70% survival at the same concentration of MPP+. The ED50 values of MPP+ in MN9D and CHO cell lines were 60-600 microM, respectively. MN9D cells contain less catalase, an enzyme believed to be involved in the detoxification of free radicals compared to CHO cells. The catalase activity was 2 Units/mg protein in MN9D cells and 30 U/mg protein in CHO cells. The catalase activity in CHO cells increased with increasing MPP+ concentrations from 100-500 microM, however, it decreased at 1 mM MPP+. In contrast, catalase activity in MN9D remained the same at all MPP+ concentrations. When the CHO cells were pre-treated with 10-25 mM 3-aminotriazole (3-AT), which inhibits catalase activity, and exposed to MPP+ at various concentrations, they became susceptible to MPP+. It is evident from these data that the differential susceptibility to MPP+ in these two cell lines are due to differences in catalase activity. In addition, the inhibition of constituentive catalase activity in CHO cells by 3-AT treatment enhances their susceptibility. In conclusion, the study demonstrates that catalase activity represents an important defence mechanism in MPTP-induced toxicity.
1-Methyl-4-phenylpyridinium↗
Inhibition of HIV-1 infection by zinc group metal compounds.
Thirty-seven metal compounds were examined for inhibitory activities against infection with human immunodeficiency virus type 1 (HIV-1). Zinc group metal compounds, namely, zinc acetate, zinc chloride, zinc nitrate, cadmium acetate and mercury chloride, showed anti-HIV-1 activities. Cadmium and mercury compounds at 1-10 microg/ml and zinc compounds at 100 microg/ml strongly inhibited HIV-1 infection, although the cadmium, mercury and zinc compounds had severe cytotoxities at 100, 100 and 1000 microg/ml, respectively. They inhibited transcription of HIV-1 RNA and HIV-1 production at concentrations at which they did not affect the growth of HIV-1-producing cells. They had little effect on syncytium formation resulting from cocultivation of uninfected with HIV-1-producing cells. Nor did they affect HIV-1 DNA synthesis following HIV-1 infection. The metal compounds may owe their anti-HIV-1 effects to inhibition of HIV-1 DNA to RNA transcription, rather than inhibition of the adsorption, penetration or reverse transcription step of HIV-1 infection.
Antiviral Agents↗
Contaminated lithium heparin bottles as a source of pseudobacteraemia due to Pseudomonas fluorescens.
Pseudobacteraemia might be responsible for up to 50% of all positive blood cultures and its early recognition is important in order to avoid unnecessary treatment with antibiotics and delay in the search for the true cause of the fever. We describe pseudobacteraemia outbreak of Pseudomonas fluorescens related to contaminated lithium heparin bottles in a paediatric ward. Twelve patients were involved in this outbreak from December 1996-January 1997. All patients had no clinical evidence of sepsis, nevertheless most children were treated with antibiotics. Blood collection bottles were suspected as source of pseudobacteraemia and only lithium heparin bottles were found to be contaminated with P. fluorescences indistinguishable from the blood isolates taken from these children. Withdrawal of these bottles led to the termination of the pseudobacteraemia. Following discussion with the manufacturer, the contaminated batch of lithium heparin bottles was sent back for testing, and replaced with bottles containing dried lithium heparin. A hazard report was sent to the Medical Devices Agency (MDA). In order to minimize the possibility of this problem occurring again, the manufacturer has informed MDA that all lithium heparin solution is to be filtered to 0.2 micron prior to issue, in order to minimize bacterial contamination. Continued monitoring after the pseudobacteraemia showed no isolates of P. fluorescens from the blood of paediatric patients.
Bacteremia↗
Towards the modern management of ectopic pregnancy: a complete audit cycle of practice in a London teaching hospital.
We carried out a complete audit cycle of the management of ectopic pregnancy at a London teaching hospital over 2 years. Case notes of women presenting to St George's Hospital, London in 1995 with ectopic pregnancy were examined and management was assessed. The targets were low rates of rupture, high rates of sonographic diagnosis of ectopic pregnancy, acceptable rates of tubal conservation and laparoscopic surgery. We also considered levels of training of junior doctors in laparoscopic surgery for ectopic pregnancy and the acceptable duration of hospital stay for patients. Recommendations were made, the standards were modified, and the audit repeated for the year 1996. A substantial improvement in the quality of care of women with ectopic pregnancy was achieved. The main improvement was in the ultrasonographic diagnosis of ectopic pregnancy. There was also a reduction in ectopic pregnancies which were ruptured, possibly due to earlier diagnosis. The percentage of cases treated laparoscopically remained stable. More junior doctors performed laparoscopic surgery for the condition. Finally, we confirmed that laparoscopic management of ectopic pregnancy significantly reduces duration of hospital stay, conferring advantages to both patient and hospital.
Journal Article↗
Accumulation of mercury and its effect on antioxidant enzymes in brain, liver, and kidneys of mice.
The effect of mercuric chloride (HgCl2) on the activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and its effect on glutathione (GSH) content were evaluated in different organs (liver, kidneys, and brain) of mice after administration at 0, 0.25, 0.5 and 1.0 mg/kg/day for 14 days. The uptake of mercury shows that the kidneys accumulated the highest levels of mercury compare to brain and liver. The enzyme levels varied in mercury treated organs compare to control. A dose dependent increase of antioxidant enzymes occurred in the liver and kidneys. The increase in enzyme activities correlated with highest mercury accumulation in the kidneys and liver. Mercury is known to generate reactive oxygen species (ROS) in vivo and in vitro, therefore, it is likely that enzyme activities increased to scavenge ROS levels produced as a result of mercury accumulation. Glutathione content increased in liver and kidneys of mercury treated mice compare to control. The results showed that the highest oral dose of mercury significantly increased antioxidant enzymes in kidneys and liver. The increased antioxidant enzymes enhance the antioxidant potential of the organs to reduce oxidative stress.
Animals↗
Undernutrition in children--effect on vecuronium induced neuromuscular blockade.
Sixty children aged one to 12 years requiring anaesthesia including a muscle relaxant were assessed for their nutritional status based on simple anthropometric and biochemical parameters. They were allocated to one of four groups: normal nutrition, mild, moderate or severe malnutrition. The neuromuscular effects of vecuronium bromide 0.1 mg/kg were studied by recording evoked responses to train of four (TOF) nerve stimulation using an accelerograph. In the above nutritional groups, time to onset of 25% depression of T1 was 0.8, 1.4, 1.3 and 2.1 minutes respectively. Maximal depression of TOF response was seen at 2.2, 3.2, 3.7 and 8.4 minutes. The duration of action of the initial dose was 26.5, 24.0, 17.7 and 13.3 minutes and the mean duration of action of top-up doses was 16.2, 14.9, 11.2 and 8.9 minutes respectively. Reversal time with neostigmine 0.05 mg/kg was not significantly different in the four groups. These results demonstrate a statistically significant delay in onset and shortening of the duration of action of vecuronium in the undernourished groups compared with the normal nutrition group when vecuronium is administered to children on a milligram per kilogram basis.
Body Mass Index↗
Autoimmune rheumatic diseases and the heart.
Involvement of the heart is a common finding in autoimmune rheumatic diseases. Although clinically silent changes are common, potentially life-threatening manifestations are well known but early recognition is important if appropriate therapy is to be instituted.
Antiphospholipid Syndrome↗