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Biomedical subjects

A Ahmed

Publications and source records attributed to A Ahmed.

At least 55 records · Page 3Linked to original sources
PubMed2002

Determination of antimicrobial activity of Cefaclor on common respiratory tract pathogens in Pakistan.

OBJECTIVE: To determine the antimicrobial activity of Cefaclor against common respiratory tract pathogens isolated from patients in Pakistan. SETTING: Department of Microbiology, Liaquat National Postgraduate Medical Centre, Karachi. METHOD: A laboratory analysis was done on 466 isolates of respiratory tract pathogens collected from 13 laboratories from all over Pakistan. Antibiotic sensitivity test was done by Kirby Bauer disc diffusion method and MIC of Cefaclor was determined by 'E' test. RESULT: Of the 163 Streptococcus pneumoniae, 87 Moraxella catarrhalis and 216 Haemophilus influenzae > 95% isolates were susceptible to Cefaclor. The MIC 90 of all these pathogens were < 2 ug. CONCLUSION: Resistance of respiratory tract pathogens to the 2nd generation Cephalosporin, Cefaclor is very low. MIC 90 of Cefaclor against all three common respiratory tract pathogens is < 2 ug, which indicates that Cefaclor would be effective in more than 90% of cases infected with these bacteria.

Cefaclor↗
PubMed2002

Determination of anti-microbial susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis.

OBJECTIVE: A retrospective study to determine the antibiotic resistance pattern seen in respiratory tract pathogens. MATERIALS AND METHODS: All sputum samples received during one year period (2000) were cultured by standard laboratory technique and antibiotic sensitivity was performed by Kirby Bauer disc method. RESULT: A total of 238 respiratory pathogens were isolated. All three isolates (Haemophilus influenzae, Streptococcus pnuemoniae and Moraxella catarrhalis) were highly resistant against Trimethoprim Sulfamethoxazole. Strep. pnuemoniae was not resistant to Penicillin. Rest of the antibiotics showed good response. CONCLUSION: Strep. pnuemoniae is still very sensitive to Penicillin and all three pathogens were resistant to Timethoprim Sulfamethoxazale.

Anti-Bacterial Agents↗
PubMed2002

Methicillin resistant Staphylococcus aureus: a multicentre study.

OBJECTIVE: To determine the frequency of Methicillin resistance Staphylococcus aureus infection in major cities of Pakistan. SETTING: Various laboratories of the country with one as the central Laboratory. MATERIALS AND METHODS: Seven hundred and ninety two consecutive clinical isolates of Staphylococcus aureus were collected from 8 laboratories all over Pakistan i.e. Karachi, Peshawar, Lahore, Sukkhur, Islamabad, Quetta, and Mirpur, Azad Kashmir. Antibiotic sensitivity was done by Kirby Bauer disc diffusion method and MIC of Vancomycin was determined by 'E' test. RESULTS: Forty two percent of the isolates were found to be Methicillin resistant staphylococcus aureus (MRSA) while no Vancomycin resistance was encountered. CONCLUSION: Methicillin resistant Staphylococcus aureus (MRSA) are seen in the local population with frequencies varying between 2-61% highest incidence is seen in the major cities of the country. Fortunately no Vancomycin resistant Staphylococcus has been isolated from any of the major cities.

Developing Countries↗
PubMed2002

Superstitions regarding health problems in different ethnic groups in Karachi.

OBJECTIVE: To find out the superstitions regarding health problems in different ethnic groups, their implications over the socio-economic development of that group and to what extent can those superstitions be related to their level of literacy. METHODS: The study was a questionnaire-based survey, 20 subjects from each ethnic group were selected by cluster sampling of residential areas where that particular group has its highest concentration, making a total of 100 subjects. RESULTS: It was found that most people (73%) do have some superstitious beliefs. Fifty percent of people believe in them as a part of culture and tradition, another 25% got them from their elders. No significant difference was found between different racial groups (p value = 0.9). According to literacy rate, 73.5% of literate community and 94.1% illiterate community were found to have superstitions. The occupation of the breadwinner of family didn't have a significant impact over the belief in superstitions (p value = 0.6). CONCLUSION: Majority of our population believes in superstitions, which are more common in illiterates. These superstitions not only predict health seeking behaviour of a person but also play a major role in shaping the response of a community to any health intervention program. Without the knowledge of these superstitions, effective community participation cannot be achieved.

Adolescent↗
PubMed2001

Risk factors for squamous cell carcinoma of the oesophagus in women: a case-control study.

Oesophageal cancer rates in women in the UK are more than 3 times higher than in most other European populations. A population-based matched case-control study of histologically confirmed squamous cell carcinoma of the oesophagus in women was carried out in 4 regions in England and Scotland. Interviews were carried out in hospital or at home and topics included: smoking; alcohol; tea and coffee consumption; medical and obstetric history; and diet. Response rates were 62% for cases and 65% for first-chosen controls. There were 159 case-control pairs. Significant results were found for: eating salads (odds ratio (OR) 0.42, 95% CI 0.20-0.92 in the highest quartile of consumption) and a light (as distinct from no) breakfast (OR 0.18, 95% CI 0.07 - 0.48) were protective; quantity of tea was a risk factor and there was a significant positive trend with temperature at which hot drinks were consumed (P = 0.03). Alcohol consumption was unrelated to risk, but there was a significant trend with years of smoking (P = 0.015). A protective effect of aspirin consumption was confined to the English centres (OR 0.08, 95% CI 0.01-0.56). Comparison with a parallel study of adenocarcinoma indicated a common protective effect of a healthy diet but otherwise distinct risk factors.

Aged↗
PubMed2001

Efficient transformation of the yellow fever mosquito Aedes aegypti using the piggyBac transposable element vector pBac[3xP3-EGFP afm].

We report efficient germ-line transformation in the yellow fever mosquito Aedes aegypti accomplished using the piggyBac transposable element vector pBac[3xP3-EGFP afm]. Two transgenic lines were established and characterized; each contained the Vg-Defensin A transgene with strong eye-specific expression of the enhanced green fluorescent protein (EGFP) marker gene regulated by the artificial 3xP3 promoter. Southern blot hybridization and inverse PCR analyses of genomic DNA demonstrated a precise piggyBac-mediated, single copy insertion of the pBac[3xP3-EGFP afm,Vg-DefA] transposon in each transgenic line. For each line, genetic analysis confirmed stability and integrity of the entire transposon construct in the mosquito genome through the G2-G6 generations. Successful establishment of homozygous transgenic lines indicated that in both cases a non-lethal integration of the transposon into the mosquito genome had occurred. The 3xP3-EGFP marker was tested in mosquitoes with different genetic backgrounds. In white-eyed transgenic mosquitoes, the strong eye-specific expression of GFP was observed throughout all stages of development, starting from newly hatched first instar larvae to adults. A similar level and pattern of fluorescence was observed in red-eyed mosquitoes that were generated by crossing the 3xP3-EGFP transformants with the kh(w) white-eye mosquitoes transformed with the Drosophila cinnabar gene. Importantly, the utility of the 3xP3-EGFP, as marker gene for transformation of wild type mosquitoes, was demonstrated by strong eye-specific GFP expression in larval and pupal stages of black-eyed hybrids of the 3xP3-EGFP white-eye transformants and the wild type Rockefeller/UGAL strain. Finally, analysis of the Vg-DefA transgene expression in transformants from two established lines demonstrated strong blood-meal activation and fat-body-specific expression regulated by the Vg 1.8-kb 5' upstream region.

Aedes↗
PubMed2001

Macrophages orchestrate the immune response to tumor cell death.

The mechanisms by which the immune system distinguishes normal developmental cell death from pathological immunogenic cell killing are central to effective cancer immunotherapy. Using HSVtk suicide gene therapy, we showed that macrophages can distinguish between tumor cells dying through classical apoptosis and tumor cells engineered to die through nonapoptotic mechanisms, resulting in secretion of either immunosuppressive cytokines (interleukin 10 and transforming growth factor beta) or inflammatory cytokines (tumor necrosis factor alpha or interleukin 1beta), respectively. Additionally heat shock protein 70 acts as one component of a bimodal alarm signal that activates macrophages in the presence of stressful, immunogenic tumor cell killing. These differential responses of macrophages can also be used to vaccinate mice against tumor challenge, using adoptive transfer, as well as to cure mice of established tumors.

Animals↗
PubMed2001

Transcriptional regulation of the mosquito vitellogenin gene via a blood meal-triggered cascade.

In anautogenous mosquitoes, a blood meal is required for activation of genes encoding yolk protein precursors (YPP). Vitellogenin (Vg), the major YPP gene, is transcribed at a very high level following blood meal activation. It is expressed exclusively in the female fat body, the tissue producing most of mosquito hemolymph and immune proteins. In this paper, we analyzed the upstream region of the Aedes aegypti Vg gene in order to identify regulatory elements responsible for its unique expression pattern. To achieve this goal, we analyzed the gene using transgenic Drosophila and Aedes as well as DNA-binding assays. These analyses revealed three regulatory regions in the 2.1 kb upstream portion of the Vg gene. The proximal region containing binding sites to EcR/USP, GATA, C/EBP and HNF3/fkh is required for the correct tissue- and stage-specific expression at a low level. The median region carrying sites for early ecdysone response factors E74 and E75 is responsible for hormonal enhancement of Vg expression. Finally, the distal GATA-rich region is necessary for extremely high expression levels characteristic of the Vg gene. The present work elucidates the molecular basis of blood meal-dependent expression of this mosquito gene, laying the foundation for mosquito-specific expression cassettes with predictable stage and tissue specificity.

5' Flanking Region↗
PubMed2001

Perfluorosulfonated ionomer-modified polyethylene. A material for simultaneous solid-phase enrichment and enhanced precolumn dansylation of C-21 ketosteroids in human serum.

A new derivatization procedure has been developed where solid-phase catalysis is utilized to facilitate the formation of hydrazones in precolumn labeling of keto-containing compounds. This procedure has been implemented on a solid-phase enrichment and enhanced derivatization (SPEED) device, prepared from porous polyethylene that has been coated with Nafion and dansylhydrazine. The SPEED devices have been optimized using experimental design and characterized for dansylation of C-21 ketosteroids by multivariate data analysis, using progesterone as the model compound. The reaction temperature and the molar ratio between the steroid and the derivatization reagent were found to be the factors most strongly affecting the reaction. Faster reaction kinetics were achieved when the molar ratio between dansylhydrazine and the steroid was increased. Mass spectroscopic analysis showed that the four derivative peaks eluting when derivatized progesterone was separated on an octadecyl silica stationary phase were due to the syn and anti mono- and bis(hydrazones) formed in the reaction. Using optimal reaction conditions, the derivatives mainly constitute the syn and anti conformers of bis-derivatives. In contrast to solution-based acid catalysis, the SPEED device was remarkably insensitive to water in the reaction mixture. A sample volume of 400 microL was found to be the maximum, enabling sample enrichment prior derivatization. Using optimal experimental conditions, picomole amounts of ketosteroids could be derivatized in 10 min at room temperature. Analysis of spiked serum samples containing 0.4-2.0 nmol of progesterone showed overall recoveries of 52-63%. The corresponding 3delta detection limit was 1.3 pmol (n = 4, 100 microL injected), as estimated from calibration curve data.

Dansyl Compounds↗
PubMed2001

Study of the mechanism underlying the difference in motility between the large and small intestine: the "single" and "multiple" pacemaker theory.

The common movement of the small intestine (SI) is peristalsis and of the large intestine (LI) are giant migrating contractions. The mechanism underlying the difference in the type of motility between the SI and LI is yet to be elucidated; the current communication investigated this point. 7 pigs (4 male) were anesthetized, abdomen opened and a balloon-ended catheter was introduced into the right colon through ileotomy. Balloon was filled in increments of 10 ml of saline and the EMG activity of the colonic longitudinal and circular muscle layers was recorded before and after myotomy performed between 2 of the 3 electrodes fixed to the colon. The balloon was then withdrawn, located in the terminal ileum and distended in increments of 2 ml; the ileal EMG activity was registered before and after myotomy done between 2 of the 3 electrodes applied to the ileum. The LI showed slow waves or pacesetter potentials (PPs) and action potentials (APs) which had the same frequency, amplitude and conduction velocity from the 3 electrodes of the same animal. The waves were recorded from the longitudinal and not the circular muscle coat. Upon LI distension, the electric activity increased and was recorded also from the circular muscle. At 40-50 ml distension, the balloon was dispelled to the transverse colon. Electric activity from SI was similar to that of the LI, but was not the same from the 3 electrodes; it diminished aborally. It increased with increasing balloon distension until, at 8-10 ml distension, the balloon moved slowly aborally. Electric waves were recorded proximally but not distally to colonic myotomy, and the balloon moved up to the cut. In the SI, waves were recorded both proximally and distally to the ileal myotomy, and the balloon moved across the cut. The fact that the colonic electric waves displayed the same variables from the 3 electrodes and that they were not recorded distally to the colonic myotomy, would suggest the presence of a "single" colonic pacemaker, probably situated in the cecum. This is in contrast to the hypothesis of the "multiplicity" of the small intestinal pacemakers, which is based on the fact that the electric activity diminished as the waves propagated aborally and on the existence of slow waves distal to the ileal myotomy. The concept of "single" and "multiple" pacemakers explaining the difference in the motility of small from that of large gut needs further studies.

Animals↗
PubMed2001

Secretory leukocyte protease inhibitor, but not alpha-1 protease inhibitor, blocks tryptase-induced bronchoconstriction.

Alpha-1-protease inhibitor (alpha(1)-PI) and secretory leukocyte protease inhibitor (SLPI) are two natural airway serine protease inhibitors. While inhibition of neutrophil elastase is a function common to both alpha(1)-PI and SLPI, we showed previously that they exhibit different patterns of protection against antigen-induced changes in airway function in allergic sheep. Specifically, the protective effect seen with SLPI was similar to the profile of action of synthetic tryptase inhibitors in the model. Based on these data, and the fact that tryptase is a serine protease, we hypothesized that SLPI, but not alpha(1)-PI, would block tryptase-induced bronchoconstriction. To test this, we compared the responses to inhaled tryptase in five sheep without treatment or after treatment with either aerosol alpha(1)-PI (10 mg) or aerosol SLPI (50 mg). The doses of alpha(1)-PI and SLPI selected had been shown to be effective in previous antigen-provocation studies. Treatments were given 30 min before aerosol challenge with tryptase (500 ng). Tryptase alone increased (mean+/-SEM) pulmonary resistance (R(L)) 142 +/- 24% over baseline. Pretreatment with alpha(1)-PI had no effect on the tryptase response (R(L)increased 122 +/- 20%). Pretreatment with SLPI, however, blocked the tryptase-induced response (R(L) increased only 40 +/- 4% P<0.05 vs. tryptase). These are the first studies comparing the inhibitory activity of SLPI and alpha(1)-PI on inhaled tryptase-induced bronchoconstriction. We conclude that, in vivo, SLPI, but not alpha(1)-PI, can block tryptase-induced bronchoconstriction and that this activity may explain the differential effects of these two serine protease inhibitors on antigen-induced airway responses in allergic sheep.

Administration, Inhalation↗
PubMed2001

Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide.

The known responses of vascular endothelial growth factor (VEGF) are mediated through VEGF receptor-2 (VEGFR-2/KDR) in endothelial cells. However, it is unknown whether VEGFR-1 (Flt-1) is an inert decoy or a signaling receptor for VEGF during physiological or pathological angiogenesis. Here we report that VEGF-stimulated nitric oxide (NO) release is inhibited by blockade of VEGFR-1 and that VEGFR-1 via NO negatively regulates of VEGFR-2-mediated proliferation and promotes formation of capillary networks in human umbilical vein endothelial cells (HUVECs). Inhibition of VEGFR-1 in a murine Matrigel angiogenesis assay induced large aneurysm-like structures. VEGF-induced capillary growth over 14 days was inhibited by anti-VEGFR-2-blocking antibody as determined by reduced tube length between capillary connections (P < 0.0001) in an in vitro angiogenesis assay. In contrast, loss of VEGFR-1 activity with a neutralizing anti-VEGFR-1 antibody resulted in an increase in the accumulation of endothelial cells (P < 0.0001) and a dramatic decrease in the number of capillary connections that were restored by the addition of NO donor. Porcine aortic endothelial (PAE) cells expressing human VEGFR-1 but not VEGFR-2 plated on growth factor-reduced Matrigel rearranged into tube-like structures that were prevented by anti-VEGFR-1 antibody or a cGMP inhibitor. VEGF stimulated NO release from VEGFR-1- but not VEGFR-2-transfected endothelial cells and placenta growth factor-1 stimulated NO release in HUVECs. Blockade of VEGFR-1 increased VEGF-mediated HUVEC proliferation that was inhibited by NO donors, and potentiated by NO synthase inhibitors. These data indicate that VEGFR-1 is a signaling receptor that promotes endothelial cell differentiation into vascular tubes, in part by limiting VEGFR-2-mediated endothelial cell proliferation via NO, which seems to be a molecular switch for endothelial cell differentiation.

Cell Division↗
PubMed2001

Vascular endothelial growth factor receptor-2-mediated mitogenesis is negatively regulated by vascular endothelial growth factor receptor-1 in tumor epithelial cells.

Vascular endothelial growth factor (VEGF) receptors are present on nonendothelial cells suggesting that VEGF may mediate nonendothelial effects during organogenesis and tumorigenesis. Here we show that VEGF receptor-1 (VEGFR-1) negatively regulates VEGFR-2-mediated proliferation via nitric oxide (NO) in an epithelial cancer cell line ECV304. Cell proliferation was assessed by [(3)H]thymidine incorporation, fluorescent-activated cell-sorting analysis, and cell number using a Coulter Counter. Total NO generated by the action of nitric oxide synthase was measured by Seivers NOA 280 Nitric Oxide Chemiluminescence Analyser. VEGF (1 ng/ml) stimulated DNA synthesis and increased ECV304 cell number in a manner that was inhibited by a neutralizing anti-VEGFR-2 antibody. In contrast, VEGF (50 ng/ml) stimulated NO release in a manner that was inhibited by functionally neutralizing anti-VEGFR-1 antibody. Blockage of the VEGFR-1 receptor signal with anti-VEGFR-1 stimulated DNA synthesis and increased cell number. Cell-cycle analysis showed that inhibition of VEGFR-1 increased the transition from G(1) to S phase whereas inhibition of VEGFR-2 blocked the VEGF-mediated transition from G(1) to S phase. Finally, the addition of NO donors suppressed both VEGF-mediated proliferation and the increase in growth after blockade of VEGFR-1. Conversely, inhibition of VEGF mediated NO release by nitric oxide synthase inhibitor, L-monomethyl-L-arginine, restored the mitogenic effect of VEGF. These findings identify a dose-dependent reciprocal regulatory mechanism for VEGF via its two receptors. It shows that VEGFR-1 induces cell cytostasis via NO and as such is a suitable target for molecular strategies suppressing tumorigenesis.

Antibodies, Monoclonal↗
PubMed2001

Analysis of the consistency of intraurethral prostaglandin E(1) (MUSE) during at-home use.

OBJECTIVES: To determine the consistency of a successful response to intraurethral prostaglandin E(1) (MUSE), an effective treatment for a proportion of patients with erectile dysfunction, during at-home use in men who had a successful response in the office, to define the factors that correlated with the consistency of the response, and to determine whether patients continued long-term use. METHODS: The study group consisted of men with documented erectile dysfunction who had a successful response (grade 3 or 4 erection) to MUSE during an initial in-office dose. All enrollees completed a home diary assessing the treatment success during at least five medication administrations. Factors such as patient age, vascular risk factor status, and degree of in-office response were prospectively evaluated as correlates of response consistency. Finally, patient follow-up was conducted in an attempt to define how many patients were continuing to use this medication as a long-term treatment modality. RESULTS: Two hundred twelve patients underwent screening and 72 (34%) patients had in-office success. The overall per patient at-home consistency rate was 51%. None of the aforementioned factors correlated with the consistency of the response. At a mean of 9 months after beginning treatment, only 31% of the in-office responders were continuing to use MUSE. CONCLUSIONS: Although MUSE is an appropriate and safe treatment for many patients with erectile dysfunction, the lack of consistency is a significant consideration. Clinicians should pay close attention to patient education in an effort to promote realistic expectations for MUSE therapy. Furthermore, the lack of consistency may significantly lower the patient's interest in continuing this treatment long term.

Adult↗
PubMed2001

Hepatitis C virus and liver transplantation.

Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.

Antiviral Agents↗