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Biomedical subjects

M Qureshi

Publications and source records attributed to M Qureshi.

At least 19 recordsLinked to original sources
PubMed2006

Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes.

AIM: To investigate potential role of highly metastatic BL6-10 tumor cell-released exosomes (EXO) in transfer of metastatic activity into poorly metastatic tumor cell line F1. METHODS: The highly metastatic B16 melanoma cell line (BL6-10) was generated in our laboratory. EXO from this cell line were isolated and amount of exosomal recovered proteins was measured using Bradford assay. For phenotypic analysis BL6-10 and F1 melanoma cells were stained with FITC-conjugated anti-MHC I (H-2K(b)), MHC II (Ia(b)) and Met 72 antibodies and analyzed by flow cytometry. C57BL/6 mice (8 per group) were injected (i. v.) with 0.5 x 10(6) F1, BL6-10 and F1(EXO) melanoma cells. Lungs were removed 4 weeks after tumor cell injection, fixed in 10% neutral buffered formaldehyde and embedded in paraffin for histological analysis. RESULTS: Data revealed that BL6-10 cells expressed metastasis marker (Met 72 tumor antigen), while F1 cells did not display this cell surface marker. All mice inoculated with BL6-10 melanoma cells had numerous lung tumor colonies, while mice injected with F1 tumor cells were free of lung metastatic colonies. BL6-10 tumor cells-released EXO also expressed Met 72 tumor antigen as BL6-10 tumor cells, but in less amount. F1 tumor cells can uptake EXO from BL6-10 tumor cells and express acquired exosomal Met 72 tumor antigen. CONCLUSION: The metastatic activity of highly metastatic BL6-10 tumor cells can be transferred to poorly metastatic F1 tumor cells by uptake of highly metastatic BL6-10 tumor-released EXO.

Animals↗
PubMed2004

A clinical trial of creatine in ALS.

BACKGROUND: Mitochondrial dysfunction occurs early in the course of ALS, and the mitochondria may be an important site for therapeutic intervention. Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor function and motor neurons. METHODS: The authors conducted a randomized double-blind, placebo controlled trial on 104 patients with ALS from 14 sites to evaluate the efficacy of creatine supplementation in ALS. The primary outcome measure was maximum voluntary isometric contraction of eight upper extremity muscles, with secondary outcomes including grip strength, ALS Functional Rating Scale-Revised, and motor unit number estimates. Patients were treated for 6 months, and evaluated monthly. RESULTS: Creatine was tolerated well, but no benefit of creatine could be demonstrated in any outcome measure. CI analysis showed that the study, although powered to detect a 50% or greater change in rate of decline of muscle strength, actually made an effect size of greater than 23% unlikely. It was also demonstrated that motor unit number estimation was performed with acceptable reproducibility and tolerability, and may be a useful outcome measure in future clinical trials. CONCLUSION: Any beneficial effect of creatine at 5 g per day in ALS must be small. Other agents should be considered in future studies of therapeutic agents to address mitochondrial dysfunction in ALS. In addition, motor unit number estimation may be a useful outcome measure for future clinical trials in ALS.

Adolescent↗
PubMed2004

Telomere attrition and accumulation of senescent cells in cultured human endothelial cells.

The human umbilical vein endothelial cell (HUVEC) is an important model of the human endothelium that is widely used in vascular research. HUVECs and the adult endothelium share many characteristics including progression into senescence as the cells age. Despite this, the shortening of telomeres and its relationship to the progression into senescence are poorly defined in HUVECs. In this study of several HUVEC lines we show notable consistency in their growth curves. There is a steady decline in the growth rate of HUVECs grown continually in culture and we estimate complete cessation of growth after approximately 70 population doublings. The HUVECs lose telomeric DNA at a consistent rate of 90 base pairs/population doubling and show a progressive accumulation of shortened telomeres (below 5 kilobases). This telomeric loss correlates with the accumulation of senescent HUVECs in culture as assessed by staining for beta-galactosidase activity at pH 6. Although the telomere length of a large population of cells is a relatively crude measure, we suggest that in HUVECs a mean telomere length (as measured by terminal restriction fragment length) of 5 kilobases is associated with entry into senescence. These data demonstrate the strong relationship between telomere attrition and cell senescence in HUVECs. They suggest that DNA damage and subsequent telomere attrition are likely to be key mechanisms driving the development of endothelial senescence in the pathogenesis of vascular disease.

Cell Line↗
PubMed2003

A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis.

OBJECTIVE: To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS. METHODS: A double-blind, placebo-controlled, multicenter randomized clinical trial was conducted. Participants with ALS (n = 296) were randomized (2:1) to receive topiramate (maximum tolerated dose up to 800 mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups. Secondary endpoints included safety and the rate of decline of forced vital capacity (FVC), grip strength, ALS functional rating scale (ALSFRS), and survival. RESULTS: Patients treated with topiramate showed a faster decrease in arm strength (33.3%) during 12 months (0.0997 vs 0.0748 unit decline/month, p = 0.012). Topiramate did not significantly alter the decline in FVC and ALSFRS or affect survival. Topiramate was associated with an increased frequency of anorexia, depression, diarrhea, ecchymosis, nausea, kidney calculus, paresthesia, taste perversion, thinking abnormalities, weight loss, and abnormal blood clotting (pulmonary embolism and deep venous thrombosis). CONCLUSIONS: At the dose studied, topiramate did not have a beneficial effect for patients with ALS. High-dose topiramate treatment was associated with a faster rate of decline in muscle strength as measured by MVIC and with an increased risk for several adverse events in patients with ALS. Given the lack of efficacy and large number of adverse effects, further studies of topiramate at a dose of 800 mg or maximum tolerated dose up to 800 mg/day are not warranted.

Adult↗
PubMed2000

Misdiagnosis of antidepressant discontinuation symptoms.

OBJECTIVE: To demonstrate that when antidepressants are switched, discontinuation symptoms from the first antidepressant may be misdiagnosed as adverse effects of the second antidepressant. METHOD: Single case report. RESULTS: A female patient was switched from paroxetine to dothiepin due to lack of efficacy. Over the next week she developed physical symptoms which she and her doctor regarded as side effects of dothiepin. It was decided to change the dothiepin and a second opinion was obtained regarding a suitable alternative. At that point it was realized that her symptoms represented a paroxetine discontinuation syndrome. The patient was reassured and continued dothiepin. The discontinuation symptoms resolved over the next 3 weeks and her depression subsequently remitted. CONCLUSION: Increased professional awareness of discontinuation symptoms is necessary to prevent misdiagnosis and inappropriate treatment.

Antidepressive Agents, Second-Generation↗
PubMed2000

Differences in breast cancer screening rates: an issue of ethnicity or socioeconomics?

Previous reports suggest that use of preventive measures, such as screening mammography (SM), differs by ethnicity. It is unclear, however, if this is determined directly by ethnicity or indirectly by related socioeconomic factors. We studied self-reported data from 18,245 women aged 40-49 who participated in the Behavioral Risk Factor Surveillance System telephone survey in 1992 and 1993. Of these, 11,509 (63%) reported having obtained mammography within the preceding 2 years for screening purposes only. Using reports of other preventive healthcare behaviors, education level, socioeconomic status, and healthcare access problems as independent variables, bivariate associations were assessed, and a logistic regression model was developed. Models for each ethnic group were developed, with consistent results. Women who engaged in other preventive health measures, such as Pap smear (odds ratio [OR] 8.99, 95% confidence interval [CI] = 7.6-10.7), cholesterol measurement (OR 2.64, 95% CI = 2.3-3.0), and seatbelt use, were more likely to obtain SM. Women with healthcare access or insurance problems (OR 0. 59, 95% CI = 0.5-0.7) and current smokers (OR 0.71, CI = 0.6-0.8) had a lower likelihood of obtaining SM. Ethnicity, alcohol use, marital status, and education level were not significantly associated with women's reports of SM. Although ethnicity apparently does not influence a woman's likelihood of obtaining SM, access to healthcare and insurance and engaging in other healthy behaviors do. Health policy planners should consider the importance of these related factors when developing preventive health programs for women.

Adult↗
PubMed1999

Diversity in expression of glucose-6-phosphate dehydrogenase deficiency in females.

The aims of this study were to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the United Arab Emirates (UAE), to describe the different mutations in the population, to determine its prevalence, and to study inheritance patterns in families of G6PD-deficient individuals. All infants born at Tawam Hospital, Al-Ain, UAE from January 1994 to September 1996 were screened at birth for their G6PD status. In addition, those attending well-baby clinics during the period were also screened for the disorder. Families of 40 known G6PD-deficient individuals, selected randomly from the records of three hospitals in the country, were assessed for G6PD deficiency. Where appropriate, this was followed by definition of G6PD mutations. Of 8198 infants, 746 (9.1%), comprising 15% of males and 5% of females tested, were found to be G6PD deficient. A total of 27 families were further assessed: of these, all but one family had the nt563 Mediterranean mutation. In one family, two individuals had the nt202 African mutation. The high manifestation of G6PD deficiency in women may be due to the preferential expression of the G6PD-deficient gene and X-inactivation of the normal gene, and/or to the presence of an 'enhancer' gene that makes the expression of the G6PD deficiency more likely. The high level of consanguinity which, theoretically, should result in a high proportion of homozygotes and consequently a higher proportion of females with the deficiency, was not found to be a significant factor.

Consanguinity↗
PubMed1999

Review of newer contraceptive agents.

Advances in contraceptive technology have made birth control more effective, convenient, and safe. We review the newer products and some under development, including the latest oral contraceptives, injectable progesterone, subdermal progestin implants, progesterone-releasing IUDs, emergency contraception, and male contraception.

Absorbable Implants↗
PubMed1999

Presenting features in Pakistani patients suffering from the antineutrophil cytoplasmic antibody--classical subtype (c-ANCA) associated vasculitis.

OBJECTIVES: To study the clinicopathological features in c-ANCA positive patients suffering from vasculitis with a view to find out the most common mode of presentation. STUDY DESIGN: Retrospective. SETTINGS: Department of Immunology, AFIP, Rawalpindi, MH Rawalpindi, CMH Rawalpindi, Department of Rheumatology, PIMS, Islamabad, RGH Rawalpindi, FFH, Rawalpindi. SUBJECTS: Seventeen patients suffering from vasculitis and found to be positive for c-ANCA. MAIN OUTCOME MEASURES: Clinico-pathological features at presentation. RESULTS: There were 9 males in age range 11-60 years (mean age 32.5 years) and 8 females in age range 26-42 years (mean age 32.3 years). Common presenting features were a combination of cough, blocked nose and post nasal drip 14/17 (82%) followed by nose bleed and haematuria 11/17 (65%). Six patients were demonstrated to be suffering from Wegener's granulomatosis after biopsy. C-ANCA was detected by indirect immunofluorescence in the titre range of 8-640. The auto antibody levels related to disease activity. CONCLUSION: c-ANCA associated vasculitis is a rare (17 patients in five years) but aggressive form of vasculitis. It must be suspected in patients with persistent respiratory tract related symptoms associated with fever and joint pains which fail to respond to adequate treatment for infections. The c-ANCA estimations can be utilised as sensitive and specific diagnostic and prognostic marker in this form of vasculitis.

Adolescent↗
PubMed1998

Meiotin-1, a meiosis-enriched protein present in normal leptotene chromosomes and lacking in precociously condensed leptotene chromosomes.

During mitotic prophase, chromosomes progressively compact to their metaphase length. In contrast, meiotic chromosomes condense moderately until late in prophase I, then they condense more dramatically (coil) to their fully condensed state. Meiotin-1 is a meiosis-enriched, chromosomal protein. We propose that it delays coiling until after reciprocal genetic exchange. We have used immunoblotting and immunocytochemistry with normal lily cells undergoing meiosis to demonstrate that meiotin-1 is present during the early portions of prophase I, but diminishes at the time when meiotic chromosomes begin to coil. Additionally, we have examined lily meiotic nuclei undergoing the reversible phenomenon of precocious leptotene chromosome condensation (precocious coiling). The leptotene chromosomes that are precociously condensed lack meiotin-1 immunostaining. Furthermore nuclei returning to the normal state of moderate prophase I condensation acquire meiotin-1.

Antibodies, Monoclonal↗
PubMed1997

Torsional constraints on the formation of open promoter complexes on DNA minicircles carrying sigma 54-dependent promoters.

A topoisomer gel retardation assay has been used to examine the topological requirements for the formation of open promoter complexes on DNA minicircles carrying sigma 54-dependent promoters. In the absence of intercalators, individual topoisomers carrying both the nifL and nifF promoters could be resolved as discrete species by electrophoresis, but exhibited anomalous electrophoretic behavior at relatively high negative superhelical density, indicative of a structural transition. In the presence of phosphorylated activator protein NTRC, ATP, and sigma 54 RNA polymerase holoenzyme, discrete topoisomer shifts were detected associated with the formation of open promoter complexes. At the nifL promoter open complexes could be formed on all negatively supercoiled topoisomers examined as well as on nicked circular DNA, but not on the DeltaLk = 0 topoisomer or positively supercoiled DNA. Minicircles carrying the sigma 54-dependent glnAp2 promoter could not be resolved in the electrophoresis system, but using a combination of potassium permanganate footprinting and topoisomerase I relaxation assays, we found in contrast to the nifL promoter, that open complexes were formed not only on negatively supercoiled topoisomers but also on relaxed minicircles and the Delta Lk = +1 topoisomer. These results indicate there is a thermodynamic barrier to the formation of open complexes on DNA minicircles carrying the nifL promoter which is not evident at glnAp2.

Bacterial Proteins↗
PubMed1995

DNA, histone H1 and meiotin-1 immunostaining patterns along whole-mount preparations of Lilium longiflorum pachytene chromosomes.

Meiotin-1 is a chromatin protein found in lily microsporocytes preceding and during meiosis. It reaches peak levels in the leptotene-pachytene interval. Here we report the pattern of immunostaining of meiotin-1 along pachytene chromosomes prepared using a whole-mount, synaptonemal complex spreading technique. Meiotin-1 immunostaining, like immunostaining for histone H1 and DNA, is found all along the lengths of the chromosomes. Unlike histone H1 and DNA immunostaining, there are several patches of particularly intense meiotin-1 immunostaining. The sites of intense staining may be clustered in the in vivo nucleus. The distribution of meiotin-1 along the width of the chromosomes was examined and compared with the pattern of histone H1 and DNA immunostaining. All three were distributed across the width of the chromosome, and did not appear to be preferentially associated with the synaptonemal complex. There was a slight suggestion that histone H1 and meiotin-1 may be located preferentially away from the synaptonemal complex. The temporal and spatial distribution of meiotin-1 in microsporocytes and tapetal cells, and the chemical and physical properties of meiotin-1, are discussed in the context of our hypothesis that meiotin-1 is a protein that functions to limit the degree of chromosome condensation during prophase I of meiosis.

Chromosomes↗
PubMed1993

Acute myeloid leukemia-FAB classification and its correlation with clinico-haematological features.

The French-American and British (FAB) classification of 62 consecutive cases of acute myeloid leukemia was undertaken. AML-M2 was the commonest FAB type (32.26%), followed by M1 and M4 (22.58% each), M5 (8.6%) and M6 and M7 (1.61% each), respectively. One of the patients was diagnosed as AML-MO (not a FAB type). The mean age of M1, M2, M3 and M5 cases was between 25 and 29 years, whereas in M4 patients it was 45.6 years. AML-M2, M4 and M5 were commoner in males, M1 in females and M3 equal in both sexes. Feeling of weakness, easy fatiguability and pallor were invariably present in all FAB types. All the patients of M1 and M5, 85% of M2, 64% of M4 and 50% of M3 presented with fever. Bleeding manifestations were most frequent in M3 cases followed by M5, M1, M4 and M2, respectively. Hepatomegaly and splenomegaly were relatively less prominent features in M3 as compared to other FAB types. Amongst the haematological parameters, anaemia was more severe in M1, leucocytosis in M2 and thrombocytopenia in M3 cases as compared to other FAB types.

Acute Disease↗
PubMed1989

Correction of subclinical ascorbate deficiency in patients receiving dialysis: effects on plasma oxalate, serum cholesterol, and capillary fragility.

Whole blood ascorbate, plasma oxalate, serum cholesterol, and capillary fragility were measured at monthly intervals for 3 mth in 7 patients receiving continuous ambulatory peritoneal dialysis and 4 receiving haemodialysis, to whom ascorbate supplements had not been prescribed for at least 12 mth. Ascorbate supplements, 25 mg/day, were prescribed for the first month and 50 mg/day for the second month; in the final month patients received no supplements. Whole blood ascorbate was below normal in 6/11 patients at the start of the study but was normal in 10/11 patients when taking ascorbate 50 mg/day. No significant changes in plasma oxalate were observed with these doses of ascorbate, and correction of ascorbate deficiency had no effect on serum cholesterol, mean cell volume, or the results of capillary fragility tests. In a supplementary study, ascorbic acid 500 mg/day was administered for 3 wk to 11 patients. This resulted in a significant rise in mean plasma oxalate from 30.3 (SEM 3.5) to 48.4 (SEM 20.3) mumol/l.

Ascorbic Acid↗
PubMed1985

Nuclear matrix-associated DNA methylase.

Previous procedures for the extraction of DNA methylase (EC 2.1.1.37) from nuclei of mouse ascites cells have involved the use of buffers containing 0.2M NaCl. Whilst such 'soluble' methylase accounts for the bulk (70-80%) of DNA methylase activity a further portion of activity is detectable in a 'bound' form firmly associated with 2 M NaCl-resistant nuclear matrix-like structures. This association, which in part requires continuing DNA replication and protein synthesis, can, however, be disrupted in vitro with high concentrations of ammonium sulphate, and the enzymic properties of the 'bound' form of DNA methylase are similar to those described for the 'soluble' form.

Ammonium Sulfate↗