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Biomedical subjects

F Ahmed

Publications and source records attributed to F Ahmed.

At least 55 records · Page 3Linked to original sources

Campylobacter fetus fetus abortions in vaccinated ewes.

AIMS: To investigate the cause of an outbreak of ovine abortion in 1996 in a flock of 300 two-tooth (rising 2-year-old) ewes vaccinated against Campylobacter fetus fetus infection and to subsequently characterise the strain of C. fetus fetus isolated from aborted foetuses. METHODS: Standard bacteriological methods were used to identify C. fetus fetus isolates which were then antigenically typed and subjected to pulsed-field gel electrophoresis (PFGE) and compared to the vaccine strain. RESULTS: C. fetus fetus was identified as the causal agent of the abortions despite the ewes having been vaccinated before ram introduction and at the time of ram removal. Four isolates cultured from aborted material were indistinguishable when compared using antigenic typing and PFGE, but all differed from the vaccine strain. CONCLUSIONS: Within the limitations of the available typing systems, it is proposed that PFGE may be a useful tool to establish the distribution and strain variation of C. fetus fetus. CLINICAL RELEVANCE: This field case indicates the need for further study of non-vaccine C. fetus fetus strains which cause abortion in vaccinated ewes, and of the importance of these strains to the New Zealand sheep industry.

Journal Article↗

Tracking clinical preventive service use: a comparison of the health plan employer data and information set with the behavioral risk factor surveillance system.

BACKGROUND: There is a need for meaningful and accurate ways of tracking preventive service delivery among different sectors of the US population. OBJECTIVES: To compare methodologies of and clinical preventive service use estimates obtained from 2 data sets: the Health Plan Employer Data and Information Set (HEDIS 3.0) and the Behavioral Risk Factor Surveillance System (BRFSS). METHODS: HEDIS used a combination of mailed-survey, administrative, and medical-record data to measure preventive service use among commercial enrollees of 320 HMOs in 42 states during 1996. BRFSS data are from insured respondents (excluding those reporting Medicare or Medicaid coverage) to a random-digit-dialed telephone survey conducted in the same 42 states during 1996. RESULTS: The median state-specific mammography, Papanicolaou smear, and retinal examination rates reported by HEDIS were consistently and substantially lower than those reported by BRFSS. For mammography, the median HEDIS rate was 72.4%, compared with 81.1% for BRFSS. For Papanicolaou smear and retinal examinations, HEDIS rates were 72.7% and 40.8%, respectively, compared with 91.2% and 61.6% for BRFSS. The median state rates of advice to quit smoking reported by HEDIS were similar to those for BRFSS: 62.1% versus 62.2%, respectively. For each measure, the absolute difference between HEDIS and BRFSS rates varied substantially both within a state and between states. CONCLUSIONS: It does not appear that the BRFSS and HEDIS data can be compared directly to accurately track progress toward national preventive health objectives. This study highlights some of the problems with comparing these data and possible means for addressing the discrepancies.

Adult↗

Pharmacokinetics of orally administered camptothecins.

Phase I trials of oral camptothecins, including camptothecin (CPT) and irinotecan (CPT-11), have reported substantial interpatient variability in systemic exposure, which could result in suboptimal antitumor activity in some patients or enhanced risk for toxicity in others. This investigation evaluates the contribution of intestinal absorption and first-pass metabolism in the disposition of oral CPT and CPT-11, respectively. The transport of CPT in Caco-2 cell lines (validated model of intestinal drug transport) was concentration dependent and saturable (Vmax: 34 x 10(-5) cm/sec and Km: 20 microM), and was temperature dependent with an activation energy (Ea) of 11.7 kcal/mole. Cumulatively, this data was indicative of carrier-mediated intestinal transport. In addition, a reduction of transport in the presence of sodium azide plus deoxyglucose suggested ATP dependence. Thus, variable expression and availability of intestinal transporters could contribute to the observed wide variability in the exposure to oral CPT. CPT-11 is hydrolyzed by the ubiquitous enzyme carboxyl esterase to active SN-38, and first-pass metabolism of oral CPT-11 would include both intestinal and hepatic hydrolysis. Incubation of CPT-11 with S9 fractions of human liver and intestinal tissues resulted in variable rates of formation of SN-38. The mean (+/- SD) specific activities (pmoles/min/mg) were: liver (8.57 +/- 10.4, n = 8), duodenum (5.06 +/- 3.7, n = 4), jejunum (6.44 +/- 2.8, n = 5), ileum (4.81 +/- 2.4, n = 5), colon (1.93 +/- 1.5, n = 6), and rectum (0.82, n = 1). Interestingly, there was a decrease in SN-38 formation by tumor tissue compared to matched normal liver and colon tissues. Therefore variable first-pass metabolism could contribute to the substantial differences in the systemic exposures to CPT-11 and SN-38 in patients receiving oral CPT-11.

Administration, Oral↗

p107 is active in the nucleolus in non-dividing human granulosa lutein cells.

Cells are maintained in a quiescent state by members of the retinoblastoma protein family, pRb and p130. Both are phosphoproteins and hypophosphorylated forms of pRb and p130 bind and repress the activity of E2F transcription factors, thereby preventing entry into the cell cycle. Mitogenic stimulation causes activation of cyclin dependent kinases (cdk) that phosphorylate both pRb and p130, thereby releasing E2F factors which stimulate the transcription of a number of genes that are required for DNA synthesis and for regulating the cell cycle. In non-dividing cells, cdks are maintained in an inactive state by cdk inhibitor proteins such as p27(Kip1). The aim of our study was to determine how E2F complexes are regulated during the differentiation of human primary granulosa lutein cells (GLC) of the corpus luteum (CL). The CL is formed in the ovary after ovulation at the terminal stage of folliculogenesis after completion of maturation and differentiation of Graafian follicles. As shown by flow cytometry GLC are not dividing, being predominantly in the G(0)/G(1) phase of the cell cycle and, consistent with this, they contain the cdk inhibitor protein, p27(Kip1), but not E2F-1 which is normally expressed only in proliferating cells. The GLC do express E2F-4, hypophosphorylated pRb, p130 forms 1 and 2 and, surprisingly, hypophosphorylated p107. p107 is normally present only in dividing cells where it regulates E2F activity during the cell cycle. These forms of pRb, p130 as well as p107, together with E2F-4 are all active in that they can bind an E2F DNA-binding site in a pull-down assay. Immunocytochemistry shows that these proteins are expressed in almost all GLC but have different sub-cellular distribution: p107 is concentrated in nucleoli, while p130 and E2F-4 show relatively even nuclear and cytoplasmic distributions. Both pRb and p130 have been implicated previously in repressing E2F activity in many different cell types during cell cycle arrest in G(0)/G(1). We conclude that p107 is active in human primary GLC but its nucleolar localisation would suggest that it represses ribosomal RNA synthesis rather than E2F activity.

Cell Cycle↗

A study on fatty acid composition of fish oil from two marine fish, Eusphyra blochii and Carcharhinus bleekeri.

Two species of marine fish found in coastal waters of Karachi (Pakistan) were studied, Eusphyra blochii (Hammer-headed Shark) and Carcharhinus bleekeri (Shark) for their fatty acid composition. The isolation, identification and characterization of these fatty acids were carried out by gas liquid chromatography (GLC) and a combination of TLC-GLC technique. A large variation was observed between hammer-headed shark liver oil and shark liver oil. Twenty five individual fatty acids from the oil of marine fish were analyzed among those the palmitic acid was a major saturated fatty acid while stearic acid was the other major constituent. Among unsaturated fatty acids monoenoic e.g. oleic and palmitoleic acids were the major constituents and traces of dienoic and trienoic fatty acids were also found. In addition medicinally important polyunsaturated fatty, acid eicosapentaenoic and docosahexaenoic acids were also identified.

Journal Article↗

Interaction between human topoisomerase I and a novel RING finger/arginine-serine protein.

The N-terminus of human topoisomerase I participates in the binding of this enzyme to helicases and other proteins. Using the N-terminal 250 amino acids of human topoisomerase I and a yeast two-hybrid/ in vitro binding screen, a novel arginine-serine-rich peptide was identified as a human topoisomerase I-binding protein. The corresponding full-length protein, named topors, contains a consensus RING zinc finger domain and nuclear localization signals in addition to the arginine-serine-rich region. The RING finger domain of topors is homologous to a similar domain in a family of viral proteins that are involved in the regulation of viral transcription. When expressed in HeLa cells as a green fluorescent protein fusion, topors localizes in the nucleus in a punctate pattern and co-immunoprecipitates with topoisomerase I. These data suggest that topors is involved in trans-cription, possibly recruiting topoisomerase I to RNA polymerase II transcriptional complexes.

Amino Acid Sequence↗

Caspase inhibitors block the retinal ganglion cell death following optic nerve transection.

Retinal ganglion cells die by apoptosis following axotomy. The molecular mechanisms of the retinal ganglion cell death are not well understood. In the present study using RT-PCR and in situ hybridization techniques we demonstrated that levels of mRNA for Bcl-2 and Bcl-x decreased after axotomy. Bax levels remained high until 4 days after axotomy, decreased by day 7 and remained low up to day 10. CPP32 levels increased at day 7 and remained high after optic nerve cut. We studied whether inhibitors of CPP32/caspase would save the axotomy induced ganglion cell death. DEVD-CHO (Ac-Asp-Glu-Val-aspartic acid aldehyde) and DEVD-FMK (Z-Asp-Glu-Val-Asp-FMK), caspase inhibitors, when administered intraocularly at the time of optic nerve cut, at days 3 and 7 protect about 30-35% the ganglion cells from death. We further demonstrated that the number of reactive microglia decrease in the retina when the inhibitors were given as compared with retina where no inhibitors were given. The present data offers new avenues for studying the complex interactions between the retinal ganglion cell death and the activation of resident microglia/macrophages.

Animals↗

Vitamin A deficiency in Bangladesh: a review and recommendations for improvement.

OBJECTIVE: This article provides a comprehensive review of the change in vitamin A status and the extent of vitamin A deficiency among different population groups in Bangladesh up to the present time. The result of experience with different strategies and interventions designed to improve vitamin A status are then reviewed, leading to a discussion of key options for action, as well as important areas for research and evaluation. DESIGN AND SETTING: All the available data have been examined in detail, including data from nationally representative samples and nationwide surveys, as well as small studies in different population groups. Reports on the effectiveness of different intervention programmes have been used. RESULTS: Over the past three decades a number of studies, which include national nutrition surveys, have been carried out to investigate the prevalence of vitamin A deficiency among different population groups in Bangladesh, and they have demonstrated a significant public health problem. Studies have shown that the prevalence of severe deficiency, based on the prevalence of night blindness in preschool children, decreased from 3.6% in 1982-83 to 1.78% in 1989 and 0.6% in 1996. However, there is still a high prevalence of subclinical vitamin A deficiency, based on the biochemical assessment of serum retinol levels in preschool children, estimated mainly from hospital-based groups. Night blindness and Bitot's spot are also found to exist among school-age children and adolescents. Recent reports indicate that night blindness among rural mothers is as high as 1.4%. Only a limited number of studies, with small sample sizes, are available where serum retinol has been reported for school-age children, adolescents and pregnant women. Nevertheless, these studies confirm the presence of low levels of serum retinol and hence, the existence of subclinical vitamin A deficiency. Furthermore, the dietary intake of vitamin A in each population group has been found to be less than the Recommended Daily Allowance (RDA), indicating a significant risk of deficient intakes of vitamin A. To address the problem of vitamin A deficiency, the government of Bangladesh started the Nutritional Blindness Programme in 1973. The main activities of the programme include vitamin A capsule (VAC) supplementation to children of 6 months to 6 years old, nutrition education to increase the production and consumption of vitamin A rich foods, and training of primary health-care workers on the clinical diagnosis and treatment of vitamin A deficiency, VAC distribution and nutrition education. Since 1988, as a long-term strategy, Helen Keller International has been implementing community home gardening promotion projects. To date, the possibility that foods may be fortified with vitamin A, has not been explored as a possible approach in Bangladesh. CONCLUSION: Although short- to long-term prevention and control programmes are to some extent in place, to improve the situation of vitamin A deficiency, Bangladesh needs a more appropriate mix of interventions for the entire population. More operational research and evaluation are needed if a fully effective programme to alleviate the problem of vitamin A deficiency is to be developed. Finally, to achieve the goal of virtual elimination of vitamin A deficiency will require an integrated approach which brings together appropriate actions at every level, within and across the many sectors of society.

Adolescent↗

Effect of coffee oil and its unsaponifiable fraction on plasma cholesterol level in female rats.

The present study was conducted to identify the cholesterol-raising factor in coffee oil besides the other two well-known diterpenes, cafestol and kahweol. Female rats fed coffee oil for 4 weeks showed significantly higher level of plasma cholesterol (P < 0.01) and triacylglycerols (P < 0.01). Feeding unsaponifiable lipids of coffee oil caused significant decrease in plasma cholesterol; however, increase in triacylglycerol was observed. Rats given beta-sitosterol showed increase in plasma triacylglecerol and decrease in cholesterol levels, an effect similar to that observed with unsaponifiable lipids. beta-sitosterol is the major constituent of unsaponifiable lipids of the coffee oil. These results show that cafestol and kahweol diterpene alcohols are not the only cholesterol-raising factors in coffee oil.

Analysis of Variance↗

Lipopolysaccharide- and cholera toxin-specific subclass distribution of B-cell responses in cholera.

The immunoglobulin subclass responses to homologous lipopolysaccharide (LPS) and to cholera toxin (CT) in adult patients infected with Vibrio cholerae O1 and V. cholerae O139 were studied. LPS-specific antibody-secreting cells (ASC) of both the immunoglobulin A1 (IgA1) and IgA2 subclasses were seen, with the IgA1 ASC response predominating in both V. cholerae O1- and O139-infected patients. For antibodies in plasma, by day 11 after onset of disease, all V. cholerae O1- infected patients responded to homologous LPS with the IgA1 subclass (P = 0.001), whereas fewer (68%) responded with the IgA2 subclass (P = 0.007). About 89% of V. cholerae O139-infected patients responded with the IgA1 subclass (P = 0.003), and only 21% responded with the IgA2 subclass (not significant [NS]). Both groups of cholera patients showed significant increases in LPS-specific IgG1, IgG2, and IgG3 antibodies in plasma. In feces, the response to homologous LPS occurred in both groups of patients with the IgA1 and IgA2 subclasses, with 55 to 67% of patients showing a positive response. V. cholerae O1- and O139-infected patients showed CT-specific ASC responses of the different IgG and IgA subclasses in the circulation, and the pattern followed the order IgG1 > IgA1 > IgG2 > IgA2, with low levels of IgG3 and IgG4 ASC. Plasma anti-CT antibody responses in all subclasses were seen by day 11 after onset of disease. Although there were no increases in CT-specific ASC of the IgG3 (NS) and IgG4 (NS) subtypes, there were significant increases of these two subclasses in plasma (P </= 0.001). The response to CT in the fecal extracts was contributed to by both IgA1 and IgA2 isotypes, with 67 to 75% of the patients responding. Thus, the mucosa-derived ASC and fecal antibodies to LPS and CT were of both the IgA1 and IgA2 subclasses; in plasma, the contribution from IgA2 was lower. Very little difference in the B-cell responses to LPS and CT in the different subclasses was seen in the two groups of cholera patients. Vaccines against O1 and O139 cholera ideally should stimulate antibody subclasses that are likely to offer protection.

Adolescent↗

Single-step method for the determination of the amount of the common deletion in mitochondrial DNA.

A fluorescent-based quantitative PCR assay to measure the percentage of the common deletion in rat mitochondria is reported. The amount of the common deletion is measured relative to the amount of total mitochondrial (mt)DNA. The use of a heterologous competitor construct allows the reaction to be monitored to ensure that exponential accumulation of products occurs. The use of fluorescence-labeled primers provides a safe and sensitive means to quantify products without any adjustment for size. This assay will allow the quantitative determination of the common deletion with one dilution range.

Animals↗

Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus.

We describe a patient with longstanding systemic lupus erythematosus (SLE) in remission who presented with recent onset neurological symptoms. Magnetic resonance imaging, followed by a brain biopsy and in situ hybridization, confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML). The clinical findings in this patient emphasize the importance of considering PML in an individual with SLE and neurological abnormalities.

Adult↗

Reproducibility of medical information obtained via the telephone vs personal interview.

The Motherisk [corrected] Program, a teratogenic information service, conducts patient interviews over the telephone as well as in a clinic setting. In both instances, medical information and exposure history is obtained from the patient, including such items as pregnancy history, drug exposure, alcohol and smoking habits. It occurred on several occasions that the clinic interviewer remarked that the same patient had volunteered information to them, that differed from the information documented on the intake telephone form. The objective of the study was to establish the levels of agreement in the documentation, between these two forms of interviews. Two groups of 100 paired telephone and clinic forms were randomly selected from our data base, 1990-1991 and 1996-1997. These two groups were chosen to assess if there were any differences over a five year time period. Statistical calculations were performed using the Kappa statistic, a method that measures agreement. Kappa scores indicated high reproducibility for both pregnancy and smoking history, good reproducibility for medical history, marginal-good for exposures (although excellent agreement was found for the primary drug of concern) and marginal-good for alcohol information. Overall, agreement was superior in the 1990-1991 group. There were marked differences in consistency, between the information recorded on the telephone form and the clinic form, most specifically relating to secondary exposures and alcohol history. It suggests that a person to person interview yields a more complete medical history than a telephone interview.

Alcohol Drinking↗

MK801-a neuroprotectant in rat hypertensive eyes.

Excitatory synaptic transmission in the mammalian CNS and retina is mainly mediated through l-glutamate. The effect of MK-801, a non-competitive antagonist of the NMDA subtype of glutamate receptor was studied on rat retinal ganglion cells in hypertensive eyes. MK-801 was administered intraperitoneally to the first group, 1 day before the increase, and in the second group, 2 days after the intraocular pressure (IOP) elevation. Phosphate-buffered saline was administered to the control group. Animals were sacrificed 2 and 4 weeks post-IOP increase. The retinal ganglion cells were counted and compared between control (right) and experimental (left) eyes. The data presented here suggests that MK-801 has neuroprotective properties.

Animals↗

High-performance liquid chromatographic quantitation of total and lactone 20(S)camptothecin in patients receiving oral 20(S)camptothecin.

We have developed a sensitive high-performance liquid chromatography (HPLC) assay to quantitate total and lactone forms of 20(S)camptothecin (CPT) in human plasma. Lactone and total CPT were extracted using solid-phase extraction and liquid-liquid extraction, respectively. The extracted lactone samples could be stored without immediate HPLC analysis. The two forms of CPT were quantitated by reversed-phase HPLC with fluorescence detection. The extraction efficiencies were about 100% and 92% for the total and lactone forms, respectively. The lower limit of quantitation was 5.74 nM for the two forms. The method was reproducible with a mean interday and intraday variability of 6% for total CPT and 4% and 6%. respectively, for lactone CPT. The assay could effectively quantitate lactone and total CPT in patients receiving single dose and multiple doses of oral CPT.

Antineoplastic Agents, Phytogenic↗

Blood thrombopoietin levels in clonal thrombocytosis and reactive thrombocytosis.

BACKGROUND: Although the distinction between clonal and reactive thrombocytosis is clinically relevant because clonal thrombocytosis has more thrombohemorragic complications, the differential diagnosis of these two entities can be difficult. Methods such as the detection of unstimulated erythroid or megakaryocyte colony growth are not readily available. Therefore, we measured blood thrombopoietin levels to determine whether these levels can be used to distinguish the two conditions. PATIENTS AND METHODS: Thrombopoietin levels were measured in 73 patients with thrombocytosis (platelet count > 500,000/microL), including 39 patients with clonal thrombocytosis (20 patients with essential thrombocythemia, 15 with agnogenic myeloid metaplasia, 1 patient with polycythemia vera, and 3 with undefined myeloproliferative disorders) and 34 patients with reactive thrombocytosis (17 with malignant tumors, 11 with inflammatory diseases, 4 with sickle cell disease, and 2 with iron deficiency anemia). Seventeen normal volunteers were used as controls. RESULTS: Thrombopoietin levels were significantly higher (P < 0.05) in patients with clonal thrombocytosis (mean +/- SD of 555 +/- 585 pg/mL), including the subgroup with essential thrombocythemia (505 +/- 459 pg/mL), than in patients with reactive thrombocytosis (290 +/- 133 pg/mL) who had similar levels as controls (201 +/- 112 pg/mL). Thrombopoietin levels in patients with clonal thrombocytosis, including essential thrombocythemia, were not correlated with platelet counts. CONCLUSIONS: Thrombopoietin levels may be helpful in distinguishing between clonal thrombocytosis and reactive thrombocytosis. Thrombopoietin is probably responsible for the elevated platelet counts in clonal thrombocytosis including essential thrombocythemia, but not in reactive thrombocytosis. High thrombopoietin levels in patients with clonal thrombocytosis cannot be explained solely by platelet megakaryocyte mass.

Adult↗

A study of adaptive responses in cell signaling in migraine and cluster headache: correlations between headache type and changes in gene expression.

The project was an investigation into whether changes in the expression of G-proteins underlie altered cell signaling in migraine and cluster headache. The basis for this assumption is that altered physiological responses are seen in migraineurs and that differences in cell signaling are detected biochemically in various cell types isolated from peripheral blood. Levels of three G-protein mRNAs--Gs alpha, Gi alpha, and Gq alpha, were quantified in lymphocytes from clinically well-defined migraine and cluster headache patients and correlated with headache type and influence of drug treatment. Gi alpha mRNA was reduced by 50% in all migraine patients compared with control subjects; similarly in patients with or without aura, in patients with a migraine headache at the time of sampling, and patients in a quiescent state. No reduction in the levels of Gs alpha of Gq alpha mRNA were seen in migraine patients. A smaller reduction was seen in cluster headache patients, most marked in those without medication. Levels of Gs alpha mRNA were significantly reduced in cluster headache patients compared with migraine patients. The marked down-regulation of Gi alpha mRNA in migraine, whether quiescent or acute, indicates either an adaptive response to headache in this group of patients or that low levels of Gi alpha mRNA make individuals more susceptible to migraine.

Adolescent↗

S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study.

S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placebo-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F = 4.93; p = 0.033) and month 4 (F = 4.55; p = 0.041). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should be interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study.

Adult↗