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Biomedical subjects

M Mohammed

Publications and source records attributed to M Mohammed.

At least 19 recordsLinked to original sources

Array comparative genomic hybridization profiling of first-trimester spontaneous abortions that fail to grow in vitro.

OBJECTIVES: Cytogenetic analysis of spontaneous abortion samples can be limited by culture failure. Failure to grow in vitro has traditionally been suspected to be due to in vivo death of tissue associated with spontaneous abortion (SAB) or simply technical factors of growth in culture. METHOD: We used array comparative genomic hybridization (array CGH) to investigate chromosomal imbalances in products of conception that failed to grow in vitro. RESULTS: Our data on 26 cases of SABs that failed to grow in culture are compared and contrasted with published data on cytogenetic findings following in vitro culture. The results revealed abnormalities uncommonly seen by classic cytogenetic methods. These abnormalities include high rates of double aneuploidy and autosomal monosomy. The data taken together suggest that classic cytogenetics of spontaneous abortion may yield normal karyotypes or selected abnormal karyotypes that permit cell proliferation in vitro while Array CGH detects other abnormalities. CONCLUSION: Array CGH is becoming an important clinical assay for unbalanced chromosome abnormalities whether cells grow in culture or not and in cases of analysis on one or few cells.

Abortion, Spontaneous↗

De novo interstitial direct duplication of Xq21.1q25 associated with skewed X-inactivation pattern.

Genotype-phenotype correlation in women with an abnormal phenotype associated with a duplication of the long arm of the X chromosome remains unclear. We report on prenatal diagnosis and follow-up of a girl with an Xq duplication and dysmorphic features. The abnormal phenotype included growth retardation, hypotonia, and nystagmus. In order to improve the resolution of the cytogenetic analysis, we used both conventional and array-based comparative genomic hybridization to perform a global molecular cytogenetic analysis of the genome. These molecular cytogenetic analyses showed a direct duplication Xq21.1 --> q25 without other chromosomal abnormalities. This duplication was originating from the paternal X chromosome. Moreover, a skewed X-inactivation pattern was observed leading to a partial functional disomy of the chromosomal region Xq21.1q25. This report and review of the literature suggest that functional disomy for chromosome X could explain the abnormal phenotype. In prenatal diagnosis, this can have implication for patient management and genetic counseling.

Base Sequence↗

Prognostic indicators of early and late death in children admitted to district hospital in Kenya: cohort study.

OBJECTIVES: To identify clinical indicators of immediate, early, and late mortality in children at admission to a sub-Saharan district hospital and to develop prognostic scores. DESIGN: Prospective cohort study. SETTING: One district hospital in Kenya. PARTICIPANTS: Children aged over 90 days admitted to hospital from 1 July 1998 to 30 June 2001. MAIN OUTCOME MEASURES: Prognostic indicators of mortality. RESULTS: Of 8091 children admitted up to 1 June 2000, 436 (5%) died. Sixty (14%) died within four hours after admission (immediate), 193 (44%) after 4-48 hours (early), and 183 (42%) after 48 hours (late). There were marked differences in the clinical features associated with immediate, early, and late death. Seven indicators (neurological status, respiratory distress (subcostal indrawing or deep breathing), nutritional status (wasting or kwashiorkor), severe anaemia, jaundice, axillary temperature, and length of history) were included in simplified prognostic scores. Data from 4802 children admitted from 1 July 2000 to 30 June 2001 were used to validate the scores. For simplified prognostic scores the areas under the receiver operating characteristic curves were 0.93 (95% confidence interval 0.92 to 0.94), 0.82 (0.80 to 0.83), and 0.82 (0.81 to 0.84) for immediate, early, and late death, respectively. CONCLUSION: In children admitted to a sub-Saharan hospital, the prognostic indicators of early and late deaths differ but a small number of simple clinical signs predict outcome well.

Cause of Death↗

Interferon-alpha induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo.

The ability of interferon-alpha (IFN-alpha) to induce dendritic cell (DC) differentiation in chronic myeloid leukemia (CML) was evaluated. Peripheral blood mononuclear cells from CML patients cultured with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology. Fluorescence in situ hybridization demonstrated that the DCs harbored the bcr/abl translocation. The DCs prepared with IFN-alpha/GM-CSF expressed significantly higher levels of class I and II HLA than those grown in interleukin-4 (IL-4) and GM-CSF. The DCs prepared from newly diagnosed CML patients using IFN-alpha/GM-CSF expressed immunoregulatory proteins at levels comparable to normal DCs. In contrast, DCs cultured from CML patients who did not achieve a cytogenetic response to IFN-alpha expressed significantly lower levels of class I HLA, CD40, CD54, CD80 and CD86 than normal DCs. The expression of CD86 by CML DCs was enhanced when they were cultured with IFN-alpha/IL-4/GM-CSF, or when IFN-alpha/GM-CSF-treated cells were induced to mature by CD40 ligand. The DCs from IFN-alpha failures were less stimulatory than normal DCs in the allogeneic mixed leukocyte reaction. CML patients who had a cytogenetic response to IFN-alpha initially had low numbers of bone marrow DCs that increased significantly with treatment, while nonresponders had more prevalent DCs at baseline that showed no consistent change with treatment. Therefore, IFN-alpha can induce DC differentiation from CML progenitor cells both in vitro and in vivo. The therapeutic activity of IFN-alpha in CML may be due to its ability to stimulate the generation of DCs that can present CML-specific antigens. Resistance to IFN-alpha may result when DC differentiation becomes impaired.

Antigen Presentation↗

Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.

Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. This substitution of threonine with isoleucine was sufficient to confer STI-571 resistance in a reconstitution experiment. In three patients, resistance was associated with progressive BCR-ABL gene amplification. These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance.

Amino Acid Sequence↗

Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans.

Wnt-4, a member of the Wnt family of locally acting secreted growth factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In this article, we show that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry. Furthermore, we elucidate a possible mechanism for human XY sex reversal associated with a 1p31-p35 duplication including WNT-4. Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype. Thus, WNT-4, a novel sex-determining gene, and DAX1 play a concerted role in both the control of female development and the prevention of testes formation. These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway.

Amino Acid Sequence↗

Short-term mortality among middle-aged cataract surgery patients.

PURPOSE: To investigate the short-term mortality of middle-aged patients undergoing cataract surgery in the United Kingdom (UK), to compare this with the expected mortality for the UK population of similar age and to try to identify at-risk groups. METHODS: In a retrospective study, the 5-10 year mortality of all middle-aged patients undergoing cataract surgery between 1989 and 1993 was determined. Expected mortality was calculated from UK Interim Life Tables for 1991. Cox's regression analysis was performed using age, sex and self-assigned ethnic group as variables. RESULTS: From the 709 patients in the study group, there were 86 deaths. This is significantly greater than expected (p < 0.01). Ethnic minority status (hazard ratio = 1.72, confidence interval = 1.12-2.64) and male sex (HR = 1.68, CI = 1.08-2.63) were found to be significantly associated with early mortality (p < 0.05). CONCLUSIONS: This study suggests that, for some middle-aged patients, cataract is associated with a reduced life expectancy and may be a feature of premature ageing, reflecting systemic ill-health. Screening these and younger patients for systemic disease when they present with cataract provides the best opportunity to affect this increased mortality. The findings of this study are particularly relevant for patients from ethnic minority groups.

Adult↗

The effect of wearing the veil by Saudi ladies on the occurrence of respiratory diseases.

It is customary in clinical practice and elsewhere to put on a mask for protection against infection, dust, and so forth. The veil, which is traditionally worn by women in many Muslim countries, especially in Saudi Arabia, may have a similar effect. The study was carried out during 1998-1999 in the eastern province of Saudi Arabia. Adult women were asked to answer a structured questionnaire related to the occurrence of respiratory tract problems and about veil wearing. Veil wearing was practiced by 58% of the sample. Respiratory infections and asthma were significantly more common in veils users (p < 0.00001 and p < 0.0003, respectively). This unexpected finding was probably secondary to infection. More and bigger studies are recommended.

Adolescent↗

The ISO 14001 EMS Implementation Process and Its Implications: A Case Study of Central Japan.

/ This study aims to investigate the ISO 14001 implementation process and its implications for regional environmental management. The region of Central Japan (known as Chubu in Japanese, which literally means center) was chosen for this case study. The study focuses on selected issues such as the: (1) trends and motives of private firms in the implementation of an ISO 14001-based environmental management system (EMS); (2) obstacles during system implementation; (3) role of the system in enhancing environmental performance within the certified organization; and (4) relation between the major stakeholders, local citizens, governments, and firms after adopting the system. To achieve these objectives, a questionnaire survey was mailed to all certified firms in the region. A 58% response was achieved overall. The results show that the main aims behind the adoption of ISO 14001 by firms in the Chubu region are to improve the environmental aspects within the enterprises and to enhance the employees' environmental awareness and capacity. The results have also shown that the ISO 14001-based EMS has had a great effect on a firm's environmental status as certified firms have claimed that natural resources such as fuel, water, and paper consumption have been more efficiently managed after adopting the system. Implementation of the system causes the firms to consider the role of the local people and the government in more effectively involving the local people in the firm's daily environmental activities. It also helps to enhance the environmental awareness among the local people. Adopting the system also promotes a better relation within the enterprises affiliated to the same group, such as more attention given by the parent firms (head offices) towards other firms working for the same group, or branches-mainly small and medium sized enterprises (SMEs)-in the field of EMS. Finally, the results show that firms give serious consideration to their final products' impacts on the environment. In other words, attention is given to life cycle analysis (LCA) among certified firms.

Journal Article↗

Copper resistance & its correlation to multiple drug resistance in Salmonella typhi isolates from south Karnataka.

A study was conducted to ascertain the prevalence of copper resistant Salmonella typhi isolates in south Karnataka. Of the 186 strains studied, 26 (13.97%) were found to be copper resistant. Among the copper resistant strains 19 (73.08%) were found multi drug resistant. All copper resistant strains remained uniformly sensitive to ceftriaxone, ciprofloxacin and norfloxacin. Multiple drug resistance was exclusively associated with E1 phage types.

Copper↗

Long-term adult renal graft outcome after ureteric drainage into an augmented bladder or ileal conduit.

Patients with an augmented or diverted urinary system are considered higher risk recipients in view of increased technical problems and infective complications. We studied the long-term renal graft function and survival in patients with a pretransplant ileal conduit or ileal/caecocystoplasty. Between 1986 and 1997, 14 of 1253 (1.1%) renal transplant recipients had their transplant ureters anastomosed into an abnormal urinary tract. These consisted of ten ileal conduits and four ileal/caecocystoplasties. Median follow up was 42 months (range 1-156). All ten ileal conduits were discharged with a functioning graft. There was one graft loss chronic rejection and one cardiac death. The median creatinine level was 130 mmol/l and 50% have a urinary infection. All the patients with an ileal/caecocystoplasty were discharged with a functioning graft and these are still functioning; median creatinine of 132 mmol/l and 75% have a urinary infection. One- and 3-year graft survival was 93% and 86%. We conclude that the long-term outcome of renal transplantation in carefully assessed patients with an abnormal urinary tract is satisfactory despite a high incidence of urinary infection.

Adult↗

Differentiating between parthenogenetic and "positive development" embryos in turkeys by molecular sexing.

In mated or inseminated turkeys, 5 to 15% of eggs set for incubation show only rudimentary development. Most of these embryos die during the first 24 to 48 h of incubation and contain only unorganized sheets of tissue. This abnormal development is termed "positive development" (PD). Turkey eggs also show incidence of parthenogenesis and the resulting progeny is believed to be always male. As both types of embryos are morphologically similar at the early stage of incubation, it has been speculated that PD embryos may in fact be parthenogens. By identifying the sex at the blastodermal stage with the help of DNA markers, we have differentiated between the PD embryos and parthenogens. Parthenogenetic embryos were obtained from eggs laid by uninseminated or virgin Beltsville Small White (BSW) hens, and the PD embryos were obtained from eggs of inseminated Nicholas and British United Turkeys of America (BUTA) hens. DNA was extracted from blastoderms of parthenogenetic and PD embryos. Turkey W-chromosome specific DNA probe and primers were used to detect females in all samples by Southern blot and polymerase chain reaction (PCR), respectively. No female was detected among the 35 parthenogens examined, whereas there were 3 females among the 11 PD embryos. The presence of both males and females among PD embryos suggests that they are products of fertilization, and that at least these 3 female embryos, if not all the 11 PD embryos, are not of parthenogenetic origin. It is concluded, therefore, that PD embryos result from errors in fertilization or from early embryonic mortality following successful fertilization, and that they are unlikely to be of parthenogenetic origin.

Animals↗

"Pulmonary tongue" a right ventricle phase abnormality in muga studies in patients with pulmonary hypertension.

Pulmonary hypertension (PH) produces strain followed by hypertrophy and later dilatation of the right ventricle (RV) and pulmonary artery. The signs and symptoms are nonspecific. There is a need for a noninvasive sensitive way to diagnose PH. The purpose of this study is to evaluate phase abnormalities in radionuclide MUGA studies of patients with referred diagnosis of PH. In a retrospective analysis of 44 patients who had a radionuclide multigated study (MUGA) and contrast ventriculography (CV), 19 had high mean pulmonary pressure (over 20 mmHg) and a high pulmonary vascular resistance index (over 2.0). In 15 patients, a delayed phase segment in the RV corresponding to the pulmonary infundibulum and pulmonary conus was noted "The Pulmonary Tongue" sign (PT), 12 had PH (True positive) and 3 did not (false positive) on CV. No PT was seen in the remaining 29 patients, only 7 of them had PH (False negative). The sensitivity, specificity and accuracy of the PT sign in detecting PH was 80%, 72% and 77% respectively. The number of patients was too small to calculate the correlation of the grade of PT with the severity of PH. We conclude that "The Pulmonary Tongue" sign on a MUGA study is clinically useful in detecting PH.

Adult↗