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Biomedical subjects

A Mahmood

Publications and source records attributed to A Mahmood.

At least 55 records · Page 3Linked to original sources
PubMed2001

Blood stream infections in a medical intensive care unit: spectrum and antibiotic susceptibility pattern.

OBJECTIVE: To determine the type and sensitivity pattern of causative organisms of septicaemia in intensive care unit, to prepare a guideline for empirical antibiotic therapy. SETTING: Department of pathology and adult medical intensive care unit, PNS SHIFA (Naval Hospital), Karachi. METHODS: The study was conducted from January 1997 to June 1999. Blood specimens for culture were drawn from patients who developed symptoms/signs of bacteraemia/septicaemia 48 hours or more after admission in medical ICU. The specimens were inoculated into Brain Heart Infusion broth. Subcultures were done on days 1,2,3,5,7 and 10. The isolates were identified by standard biochemical tests. Antibiotic susceptibility pattern of the isolates was studied by Modified Kirby Baur method. RESULTS: Eighty-six aerobic organisms were isolated. They included Staphylococcus aureus(n = 34), Pseudomonas aeruginosa (n = 13), Escherichia coli and Enterobacter spp(n = 9 each), Klebsiella pneumoniae(n = 8), Acinetobacter spp and Serratia spp(n = 5 each), Citrobacter diversus(n = 2) and Proteus vulgaris(n = 1). On antibiotic susceptibility testing, 48.18% Staphylococcus aureus isolates were methicillin resistant. Susceptibility to other common drugs was also quite low while 100% of these were susceptible to vancomycin and amikacin. In case of gram negative rods more than 80% were resistant to ampicillin and cotrimoxazole. Susceptibility to gentamicin was as low as 25% for Klebsiella pneumoniae to 44.4% in case of Escherichia coli. Susceptibility to the third generation cephalosporins and the quinolone tested (ciprofloxacin) varied between 50-75%. All these isolates except Pseudomonas aeruginosa were susceptible to imipenem and amikacin. CONCLUSION: In view of the isolation of antibiotic resistant organisms, vancomycin in combination with amikacin or imipenem are the drugs of choice for empirically treating blood stream infections in ICU. Infection control procedures and antibiotic control policies can help to tackle this problem.

Adolescent↗
PubMed2001

Age related effects of organochlorine insecticide lindane on intestinal brush border membrane in rats.

The effect of oral administration of lindane (gamma-HCH) has been studied on the intestine in 10-day, 20-day and 100-day old rats. In 10 day-old suckling pups exposed to lindane, there was a significant decrease in the activities of sucrase (29%), lactase (20%) and that of alkaline phosphatase (24%) compared to control. Sialic acid content of the brush borders was significantly decreased (29%) in 10-day old as well as in 20- and 100-day old rats (20 and 25% respectively), while fucose content of the membranes was significantly enhanced in all the age groups upon pesticide treatment. Among the brush border lipids, cholesterol content was significantly increased in all the age groups studied, the maximum increase of 35% being observed in 10-day-old rats. Membrane phospholipids were also increased in 20- and 100-day old animals (22% each) on lindane exposure. The present studies indicated that brush border membranes of suckling rat intestine were more susceptible to pesticide induced changes compared to older animals.

Administration, Oral↗
PubMed2001

Treatment of traumatic brain injury in female rats with intravenous administration of bone marrow stromal cells.

OBJECTIVE: To study the effect of bone marrow stromal cells administered intravenously to female rats subjected to traumatic brain injury. METHODS: We injected marrow stromal cells harvested from male rat bone marrow (n = 24) into the tail vein of the female rat (n = 8) 24 hours after traumatic brain injury; the rats were killed at Day 7 or 14 after treatment. The neurological function of the rats was evaluated using the rotarod test and the neurological severity score. The distribution of the male donor cells in brain, heart, lung, kidney, liver, muscle, spleen, and bone marrow of the female recipient rats was measured by identifying Y chromosome-positive cells using fluorescent in situ hybridization. RESULTS: We found that marrow stromal cells injected intravenously significantly reduced motor and neurological deficits compared with control groups by Day 15 after traumatic brain injury (P < 0.05, analysis of covariance for repeated measures). The transplanted cells preferentially engrafted into the parenchyma of the injured brain and expressed the neuronal marker NeuN and the astrocytic marker glial fibrillary acidic protein. Marrow stromal cells were also found in other organs in female rats subjected to traumatic brain injury without any obvious adverse effects. CONCLUSION: These data suggest that the intravenous administration of marrow stromal cells may be a promising therapeutic strategy that warrants further investigation for patients with traumatic brain injury.

Animals↗
PubMed2001

Effects of endosulfan on intestinal functions in protein-malnourished rats.

In rats fed 18% protein diet, administration of endosulfan (2mg/kg body weight daily for 7 days) significantly decreased the brush border sialic acid and increased the hexoses contents. The intestinal uptake of glucose was increased while that of glycine and calcium was reduced. Brush border enzymes and lipids were not affected. However, in protein malnourished rats (fed 8% protein) exposed to endosulfan, brush border sucrase and peptidase activities were enhanced, while alkaline phosphatase activity was decreased compared to untreated malnourished animals. Membrane sialic acid content was low while fucose and cholesterol levels were augmented in endosulfan fed malnourished animals. The uptake of glucose and glycine was elevated under these conditions. These results Suggest that the nutritional status of the animals has an important bearing on thc susceptibility of intestinal tissue to endosulfan toxicity in rats.

Administration, Oral↗
PubMed2001

Formation of surfactant-like-particle in rat intestine following chronic ethanol feeding.

Ethanol feeding to rats daily for 40 days induces the secretion of surfactant-like-particles in intestine. The isolated lipoprotein particles were enriched with alkaline phosphatase activity and had high phosphatidylcholine content. There was no difference in disaccharidases activities associated with the particles from control and ethanol fed rats. These results suggest that ethanol induced surfactant-like-particles in rat intestine.

Animals↗
PubMed2000

Role of intestinal surfactant-like particles as a potential reservoir of uropathogenic Escherichia coli.

The binding of uropathogenic Escherichia coli is mediated at the tips of pili by the PapG adhesin, which recognizes the Galalpha(1-4)Gal disaccharide on the uroepithelial surface. These receptors have been identified unequivocally in the human and murine urinary tracts but not in intestinal epithelium, yet uropathogenic E. coli strains are commonly found in normal colonic microflora. The gastrointestinal tract from duodenum to rectum elaborates a phospholipid-rich membrane particle with surfactant-like properties. In these studies, we report that purified murine particles contain a receptor recognized by the class I PapG adhesin because: (1) PapD-PapG complexes and class I pili bound to surfactant-like particles in a solid-phase assay, whereas binding was not detected in microvillous membranes derived from the same tissues, (2) purified PapD-PapG complex bound to a glycolipid receptor detectable in lipid extracts from the particles, and (3) soluble Galalpha(1-4)Gal inhibited the adhesin by 72% from binding to surfactant-like particles. The Galalpha(1-4)Gal receptor present in the intestinal surfactant-like particle which overlies the intestinal mucosa could provide one means to establish an intestinal habitat for uropathogenic E. coli.

Adhesins, Escherichia coli↗
PubMed2000

'3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma: synthesis and evaluation in vitro and in vivo.

'3+1' Mixed-ligand [(99m)Tc]oxotechnetium complexes with affinity for melanoma were synthesized in a one-pot reaction. Complexation of technetium-99m with a mixture of N-R(3-azapentane-1,5-dithiol) [R = Me, Pr, Bn, Et(2)N(CH(2))(2)] and N-(2-dialkylamino)ethanethiol [alkyl = X = Et, Bu, morpholinyl] using Sn(2+) as the reducing agent resulted in the formation of '3+1' mixed-ligand technetium-99m complexes [TcO(SN(R)S)(SNX(2))] in high radiochemical yield (60-98%). In vitro uptake studies in B16 murine melanoma cells indicated a moderate tumor-cell accumulation (40%) of compound 1 [R = Me, X = Et] and a higher accumulation (69%) of compound 2 [R = Me, X = Bu] after a 60-min incubation. In vivo evaluation of compounds 1-6 in the C57Bl6/B16 mouse melanoma model demonstrated tumor localization. Compound 2 displayed the highest accumulation with up to 5% ID/g at 60 min after injection. In vivo, 2 also showed a low blood-pool activity and high melanoma/spleen (4.3) and melanoma/lung (1.9) ratios at 1 h. These results suggest that small technetium-99m complexes could be useful as potential melanoma-imaging agents.

Animals↗
PubMed2000

Cardiff depression study. A sib-pair study of life events and familiality in major depression.

BACKGROUND: An excess of both depression and undesirable life events in first-degree relatives of probands with depression as compared with controls has been reported. This association may have reflected a familial factor in common. AIMS: To examine the familiality of life events and depression and whether there may be a common familial factor influencing vulnerability to depression and the experiencing of life events. METHOD: In a sib-pair design, 108 probands with depression and their siblings were compared with 105 healthy controls and their siblings for psychopathology and life events. RESULTS: The lifetime relative risk of depressive disorder in the siblings of depressed subjects as compared with siblings of controls was 9.74, although these groups did not differ in the life events measures. Several categories of events showed significant sibling correlations, but this was due to the same event affecting both members of the pair. CONCLUSIONS: Although depressive disorder was strongly familial, the familial effects on life events were largely explained by shared experiences. There was no evidence for a common factor influencing both depression and life events.

Adolescent↗
PubMed2000

Bacteriology of surgical site infections and antibiotic susceptibility pattern of the isolates at a tertiary care hospital in Karachi.

OBJECTIVE: To study post surgical infections and sensitivity of the Isolates so that recommendations can be made for their prevention and empirical antibiotic treatment. SETTING: Swabs/pus specimens from the patients developing surgical site infections at PNS Shifa, Karachi were processed in the Department of Pathology during January, 1998 to September, 1999. METHODS: One hundred and twenty-nine swabs/pus specimens from various types of surgical sites suspected to be infected on clinical grounds were processed, by standard methods and antibiotic susceptibility testing of all the isolates was done by using Modified Kirby Baur disc diffusion technique. RESULTS: Of the one hundred and fifty-three organisms isolated, the most common was Staphylococcus aureus (50.32%), followed by Pseudomonas aeruginosa (16.3%), Escherichia coli (14.37%), Klebsiella pneumoniae (11.76%), miscellaneous gram negative rods (5.88%) and Streptococcus pyogenes (1.30%). About 50% of the Staphylococcus aureus isolates were found to be methicillin resistant. In case of Pseudomonas aeruginosa and Escherichia coli more than 60% of the isolates were found resistant to Gentamicin. The resistance to third generation cephalosporins and the quinolone ciprofloxacin was also quite high. Other isolates also showed a very high level of antibiotic resistance. CONCLUSION: In addition to the economic burden for antibiotic treatment, such infections for multi-resistant organisms are a serious threat to our surgical patients. To prevent these happenings, there is an urgent need to adopt basic principles of asepsis and sterilisation and to make judicious use of prophylactic and therapeutic antibiotics.

Adolescent↗
PubMed1999

Expression of nestin after traumatic brain injury in rat brain.

We tested the hypothesis that traumatic brain injury upregulates expression of nestin, an embryonic cell intermediate filament protein. Brain from rats (n=24) subjected to controlled cortical impact injury and sham operated (n=3) and normal (n=3) rats were processed for dual label immunohistochemical study to identify cellular expression of nestin. Our results show that in normal noninjured animals, nestin is expressed slightly and localized only in a few endothelial and subventricular cells. In contrast, at 1-4 weeks postinjury nestin is strongly expressed in astrocytes and microglia. The expression of nestin in astrocytes and microglia after traumatic brain injury support the hypothesis that injured cerebral tissue expresses developmental proteins, and that these proteins may promote recovery after injury.

Animals↗
PubMed1999

Apoptosis and expression of p53 response proteins and cyclin D1 after cortical impact in rat brain.

We measured the temporal profile and cellular identification of apoptosis in rat brain after cortical contusion injury. Double staining immunohistochemistry was also used to investigate the relationship between apoptotic cell death and selective protein expression associated with DNA damage and repair (p53, Bax, MDM2, WAF1, Gadd45, PCNA) and cell cycle protein, Cyclin D1, in male Wistar rats 48 h after injury. Cortical contusion was induced in male Wistar rats with a pneumatic impactor device. The animals were sacrificed at different times after trauma (1, 2, and 14 h and 1, 2, 4, 7 and 14 days; n=4 per time point). Sham-operated rats (n=4) and normal rats not subjected to any surgical procedure (n=4) were used as controls for temporal profile determination. Additional 11 rats were used for study of protein expression. Coronal brain sections were analyzed using an in situ terminal deoxynucleotdyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL), hematoxylin, and immunohistochemical double staining methods. Apoptotic cells were observed as early as 2 h after the impact. Apoptotic cell death peaked at 2 days, gradually tapering off afterward, although scattered apoptotic cells were detected at 2 weeks after the impact. The number of apoptotic cells at 2 days far exceeded their number at other times (p=0.009). Apoptotic cells were observed primarily in the cortex adjacent to the site of injury. In addition, apoptotic cells in conjunction with few injured cells were present in the ipsilateral hippocampus and localized to the granule layer of dentate gyrus. Our data indicate that DNA fragmentation is present in nearly all neurons subacutely after cortical contusion and persists for at least 2 weeks thereafter. Apoptosis is also present in neurons localized to the hilus of the dentate gyrus at a site remote from the area of injury suggesting a selective role for apoptosis in promoting secondary brain damage and dysfunction after traumatic brain injury. Using double staining, we were able to show that a great majority of apoptotic cells (>95%) were neurons and the rest were astrocytes and endothelial cells. Proteins associated with DNA damage and repair (p53, Bax, MDM2, WAF1, Gadd 45, PCNA) were expressed in the cytoplasm of normal cells of naive and sham rats. These proteins were translocated to the nuclei of apoptotic and injured cells at 48 h after cortical contusion. Cyclin D1 was not present in apoptotic cells. The differential expression of proteins associated with DNA damage, repair and the cell cycle protein Cyclin D1 in the contused brain suggest a potential role for these proteins in cell survival and apoptosis after cortical contusion.

Animals↗
PubMed1999

Fluorescent labelling of closely-spaced aldehydes induced in DNA by bleomycin-Fe(III).

PURPOSE: To test the ability of FARPhC and FARP, two novel fluorescent reagents, to label aldehyde-containing sites (principally abasic sites) generated in DNA by the radiomimetic drug bleomycin, and to use fluorescent energy transfer from FARPhc (donor) to FARP (acceptor) to quantitate such closely-spaced sites. MATERIALS AND METHODS: FARPhc, 7-hydroxycoumarin-3-carboxylic acid (((((amino-oxymethyl) carbonyl) hydrazino) carbonylethyl) amide) was synthesized with a protocol similar to the one recently reported for FARP (a fluorescein-based probe). RESULTS: Both FARPhc and FARP form stable oxime bonds with the open-chain aldehydes generated upon acidic depurination of DNA. Plasmid DNA exposed to bleomycin-Fe(III)-ascorbate undergoes extensive strand breakage, and upon subsequent reaction with FARPhc and/or FARP it becomes fluorescently labelled, indicating the generation of aldehyde-containing sites. The binding of the probes to calf thymus or plasmid DNA results in significant fluorescent energy transfer among closely-spaced fluorophores, as revealed by the fluorescence increase following digestion of fluorescently labelled samples with nuclease P1. The fluorescent quenching is most evident when both FARPhc and FARP are used simultaneously to trap aldehyde sites. When single-stranded oligonucleotides engineered to contain either one or two closely spaced bleomycin binding sites are exposed to bleomycin and then fluorescently labelled, the oligonucleotides demonstrate significantly increased fluorescent energy transfer with two binding sites indicating a dependence of aldehyde site generation and clustering on the local sequence of a single strand. CONCLUSIONS: A new detection method for DNA damage induced by bleomycin following fluorescent labelling of aldehyde group-containing sites (FLAGS) and their clustering via fluorescent energy transfer is demonstrated. The method is applicable to any form of DNA. This work may lead to a general approach for the quantification of multiply damaged sites in DNA, a subset of DNA lesions that may have major biological significance.

Aldehydes↗
PubMed1999

Expression of cell cycle proteins (cyclin D1 and cdk4) after controlled cortical impact in rat brain.

We measured the expression of Cyclin D1 and its kinase cdk4, 48 h after induction of cortical contusion in the rat. Brain from rats (n = 6) subjected to controlled cortical impact injury and sham-operated (n = 3) and normal (n = 2) rats were processed for dual label immunohistochemical study to identify cellular expression of these cell cycle proteins. Antibodies against neurofilaments 68 and 200 and glial fibrillary acidic protein were employed to identify neurons and astrocytes, respectively, whereas microglia were identified using histochemical detection of IB4-isolectin. Double staining for DNA fragmentation detection, using terminal deoxynucleotdyl transferase mediated biotinylated deoxyuridine triphosphate nick end 3 'OH labeling (TUNEL) and antibodies for expression of Cyclin D1 and cdk4 was also performed. Cyclin D1 and cdk4 were selectively expressed in morphologically intact or injured neurons throughout the rat brain. Apoptotic cells were not immunoreactive to Cyclin D1 and cdk4. The selective expression of cell cycle proteins observed in nonapoptotic postmitotic neurons suggests a role for these proteins in the survival of cells after cortical contusion.

Animals↗
PubMed1999

Binding of pili from uropathogenic Escherichia coli to membranes secreted by human colonocytes and enterocytes.

PapG adhesins mediate the binding of uropathogenic Escherichia coli. Although receptors for these adhesins have not been demonstrated in intestinal epithelia, the colonic microflora includes strains of uropathogenic E. coli. We now report that surfactant-like particles secreted by the human intestine contain receptors for PapG adhesins and may provide an intestinal habitat for uropathogenic bacteria.

Adhesins, Escherichia coli↗
PubMed1999

Functional role of sialic acid in IgG binding to microvillus membranes in neonatal rat intestine.

A close parallelism exists between sialylation and endocytotic activity of the small intestine during postnatal development in rats. Thus, the binding of 125I-labelled IgG to microvillus membranes and its relationship to membrane sialic acid has been studied in suckling rat intestine, during (a) postnatal development; (b) cortisone-induced precocious maturation, and (c) after desialylation of brush borders by neuraminidase treatment. Neuraminidase-treated membranes exhibited low (42%, p < 0.001) IgG binding. The observed decrease in IgG binding to desialylated membranes was associated with a decrease in the value of affinity constant, (-Ka = 0.4 x 10(6) M-1 in control and 0.23 x 10(6) M-1 in desialylated membranes). The number of IgG-binding sites (2.3 nmol/mg protein) was unchanged under these conditions. A similar decrease (50%) in IgG binding to brush borders was also observed in cortisone-injected pups. This was associated with reduced sialic acid (37%) content of the membranes compared to the controls. The value of -Ka was reduced from 0.4 x 10(6) M-1 in the control to 0.3 x 10(6) M-1 in the hormone-injected pups. The number of binding sites (n) was decreased from 2.2 to 1.4 nmol/mg protein under these conditions. Low concentrations of calcium (0.1-1.6 mM) in the incubation medium enhanced IgG binding (p < 0.001) to brush borders in pups but there was no change in binding of IgG to the membranes at 2 mM Ca2+ concentration compared to controls. Addition of Zn2+ or Mg2+ did not affect IgG binding under these conditions. These findings suggest a functional role of Ca2+ and sialic acid residues of the membrane glycans in IgG-receptor interactions in suckling rat intestine.

Animals↗