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Biomedical subjects

S Iqbal

Publications and source records attributed to S Iqbal.

At least 19 recordsLinked to original sources
PubMed2006

The association between demolition activity and children's blood lead levels.

Urban renewal efforts are a priority for many American cities. As efforts to reconstitute urban centers increase, the demolition of old, deteriorated structures has accelerated. Recent studies have identified demolitions as a potential source of environmental lead exposure. We conducted a study examining the relationship between demolition activity and blood lead levels of children residing in neighborhoods where demolition activity occurred. A retrospective cohort study was conducted in St. Louis City, Missouri. The study period was January 1, 2002 to December 31, 2002. Data were obtained from the Missouri Childhood Lead Poisoning Prevention Program's (CLPPP) lead surveillance system and St. Louis Demolition Permit Database. Children were considered exposed to a demolition if they had a blood lead test within 45 days of any demolition on a census block. Exposure was classified as both a dichotomous (yes/no) and a categorical (none/one/multiple) variable and was analyzed separately. Linear regression models were developed to determine effects of demolitions on blood lead levels. A total of 1196 children 6-72 months of age living in 395 census blocks were included. 314 (26.3%) were exposed and 882 (73.7%) were unexposed to a demolition. In an adjusted model, exposure to multiple demolitions was found to have significant effects on children blood lead levels (coefficient=0.281; 95% CI=0.069, 0.493; P-value=0.010). Age of the child, race, and age of housing where children's resided were also significant predictors. This study suggests that multiple demolitions within a census block may significantly increase children's blood lead levels. The findings may be useful to municipal planners in older cities where demolitions are being used as an urban renewal tool.

Child, Preschool↗
PubMed2006

Enzyme exposure in the British baking industry.

OBJECTIVES: Enzymes are commonly used in the baking industry, as they can improve dough quality and texture and lengthen the shelf life of the final product. There is little published information highlighting exposure to enzymes (other than fungal alpha-amylase) in the baking industry, therefore the purpose of this study was to identify antibodies and develop assays for the measurement of a variety of such enzymes in samples of airborne flour dust. METHODS: Polyclonal antibodies to bacterial amylase, glucose oxidase and amyloglucosidase were identified and developed into ELISA assays. The assays showed limited cross-reactivity with other enzymes commonly used in the baking industry. RESULTS: We measured levels of airborne enzymes in 195 personal air samples taken from a sample of 55 craft baking establishments. We were able to detect amyloglucosidase in 9% (16/184) of the samples, fungal alpha-amylase in 6% (11/171), bacterial alpha-amylase in 7% (13/195). However, we were unable to detect glucose oxidase in any of the samples. Measurements for protease enzymes were not carried out. Median levels in detectable samples of amyloglucosidase, fungal alpha-amylase and bacterial amylase were similar at 10.3, 5.3 and 5.9 ng/m(3), respectively. These figures represent the total enzyme protein (active and inactive) measured. CONCLUSIONS: There are few data in the literature regarding sensitization and exposure-response relationships to these enzymes, and indeed there is often a lack of information within the industry as to the precise enzyme content of particular baking ingredients. As a precautionary measure, all enzymes are regarded as having the potential to cause respiratory sensitization. Consequently, exposures need to be controlled to as low a level as reasonably practicable, and future investigation may highlight the importance of measuring a variety of enzyme exposures and standardizing these methodologies to inform approaches to adequate control.

Air Pollutants, Occupational↗
PubMed2005

Disruption and aberrant expression of HMGA2 as a consequence of diverse chromosomal translocations in myeloid malignancies.

Chromosomal translocations that target HMGA2 at chromosome band 12q14 are seen in a variety of malignancies, notably lipoma, pleomorphic salivary adenoma and uterine leiomyoma. Although some HMGA2 fusion genes have been reported, several lines of evidence suggest that the critical pathogenic event is the expression of truncated HMGA2 isoforms. We report here the involvement of HMGA2 in six patients with myeloid neoplasia, dysplastic features and translocations or an inversion involving chromosome bands 12q13-15 and either 7p12, 8q22, 11q23, 12p11, 14q31 or 20q11. Breaks within or very close to HMGA2 were found in all six cases by molecular cytogenetic analysis, leading to overexpression of this gene as assessed by RT-PCR. Truncated transcripts consisting of HMGA2 exons 1-2 or exons 1-3 spliced to intron-derived sequences were identified in two patients, but were not seen in controls. These findings suggest that abnormalities of HMGA2 play an important and previously unsuspected role in myelodysplasia.

Adenoma↗
PubMed2005

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.

The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target..

Cell Transformation, Neoplastic↗
PubMed2004

Sengers disease: a rare association of hypertrophic cardiomyopathy and congenital cataracts.

Hypertrophic cardiomyopathy is an uncommon childhood cardiac disease and can be primary or secondary. Several systemic diseases are known to be associated with this entity. Senger's disease is a mitochondrial disorder causing congenital cataracts lactic acidosis and skeletal and cardiac myopathy. Diagnosis should be kept in mind when routine neonatal eye screening reveals absent red reflex. The authors report a case of Sengers disease and discuss the underlying pathogenetic mechanisms.

Blood Chemical Analysis↗
PubMed2003

Corticosteroids for hospitalised children with acute asthma.

BACKGROUND: Systemic corticosteroids are used routinely in the management of children with severe acute asthma. There is a lack of consensus regarding the agent, dose and route of corticosteroid administration. OBJECTIVES: To determine the benefit of systemic corticosteroids (oral, intravenous, or intramuscular) compared to placebo and inhaled steroids in acute paediatric asthma. SEARCH STRATEGY: All controlled trials were identified from the Cochrane Airways Review Group Register, hand searching of respiratory journals, reference lists and contacts with experts and pharmaceutical companies. SELECTION CRITERIA: Studies were included if they described a randomised controlled trial (RCT) involving children aged 1-18 years with severe acute asthma who received oral, inhaled, intravenous or intramuscular corticosteroids. Only studies in which patients required hospital admission were included. DATA COLLECTION AND ANALYSIS: Two reviewers using a standard form extracted all data. All data, numeric calculations and graphic extrapolations were independently confirmed. MAIN RESULTS: Seven trials were included with a total of 426 children studied (274 with oral prednisone vs. placebo, 106 with intravenous steroids vs placebo and 46 with nebulised budesonide vs prednisolone). A significant number of steroid treated children were discharged early after admission (>4 hours) with an OR of 7.00 (95% CI: 2.98 to 16.45) and NNT of 3 (95%CI: 2 to 8). The length of stay was shorter in the steroid groups with a WMD of -8.75 hours (95% CI: -19.23 to 1.74). There were no significant differences between groups in pulmonary function or oxygen saturation measurements. Children treated with steroids in hospital were less likely to relapse within one to three months with OR 0.19 (95%CI: 0.07 to 0.55) and NNT of 3 (95%CI: 2 to 7). The single small study that compared nebulised budesonide to oral prednisone failed to demonstrate equivalence or a difference between each therapy. REVIEWER'S CONCLUSIONS: Systemic corticosteroids produce some improvements for children admitted to hospital with acute asthma. The benefits may include earlier discharge and fewer relapses. Inhaled or nebulised corticosteroids cannot be recommended as equivalent to systemic steroids at this time. Further studies examining differing doses and routes of administration for corticosteroids will clarify the optimal therapy.

Acute Disease↗
PubMed2003

High resolution sequence-based DPB1 typing identified two novel DPB1 alleles, DPB1*9401 and DPB1*9501, from a Kenyan population.

Two novel DPB1 alleles, DPB1*9401 and DPB1*9501, were identified from a Kenyan population during sequence-based HLA-DPB1 typing. Molecular cloning and sequencing of multiple clones confirmed that one of the new DPB1 alleles is identical to DPB1*0402 at exon 2 except for a single nucleotide substitution (CGG -->TGG), changing codon 70 from Arg to Trp. The new allele has been named DPB1*9401. This is the first report of polymorphism at codon 70 of HLA-DPB1 alleles. New codon combinations have been identified in another novel DPB1 allele named DPB1*9501. The extensive diversity at DPB1 locus of this East African population is being revealed by high resolution sequence-based DPB1 typing.

Amino Acid Sequence↗
PubMed2003

Cytotoxic drug contamination on the outside of vials delivered to a hospital pharmacy.

We recently carried out a study of two UK hospital pharmacy units preparing cytotoxic drugs using isolators that showed low level contamination on floor surfaces and disposable gloves worn by staff. It has been suggested that this level of contamination may be related to some level of contamination on the drug vials as delivered from manufacturers rather than leakage from the isolators. We have investigated the level of cytotoxic drug contamination on the external surfaces of the drug vials as delivered to a hospital pharmacy stores. We monitored 30, randomly chosen vials for the drugs cisplatin, carboplatin, cyclophosphamide, ifosfamide and methotrexate using well-established methods. A 0.5 m2 floor area directly in front of the shelves used for storing the cytotoxic drugs was also wipe sampled and the disposable gloves worn while wiping the vials for each drug were also analysed. A significant number of vials had a quantifiable level of external contamination. Levels of contamination up to 344 ng/vial were found. Levels of glove and floor contamination for some drugs were found to be comparable with values found in our study of the clean rooms where the isolators were situated and the pharmacy staff prepared the cytotoxic drugs.

Antineoplastic Agents↗
PubMed2003

Thorium concentration in Pakistani diet.

To evaluate radiation doses due to ingestion of thorium activity by members of the public, baseline analytical data on thorium concentration in a typical Pakistani diet was generated. Food samples were collected from major districts/ cities of the country using the market basket method, and typical daily diets were prepared. Thorium concentration was determined by instrumental neutron activation analysis. It was found to vary from 1.6 ng g(-1) to 12 ng g(-1). The median value was 4.6 ng g(-1). This leads to median daily thorium intake of 2.7 microg d(-1). The geometric mean was 2.6 microg d(-1), which was 13% less than the ICRP value. Based on these measurements the average intake of 232Th activity was 10 mBq d(-1), and the average annual and committed effective doses for adults were estimated to be 8.8 x 10(-7) Sv y(-1) and 4.4 x 10(-5) Sv, respectively.

Diet↗
PubMed2002

MIB-1 assessments in breast cancers.

The variability of MIB-1 measurements in breast cancer was assessed in histological sections from core and excision biopsies taken simultaneously in 13 cases and sequentially (with an intervening period of 2-3 weeks) in 17 cases. Results showed no significant differences in values between cores and sections, whether taken simultaneously or sequentially. Individual pairs of cores and sections occasionally demonstrated substantial differences. The mean ratio of MIB-1 scores between cores and sections was 0.97 [95% confidence interval (CI)=0.68-1.38]. However 95% confidence intervals for ratios within individuals were 0.14-6.68. Although the two samples can be equivalent on an average over numerous patients, they cannot be taken as equivalent within individuals. Severe heterogeneity complicates the assessment of MIB-1 in individual breast cancers and limits utility in monitoring changes in proliferation with treatment.

Journal Article↗
PubMed2001

Identification of four new translocations involving FGFR1 in myeloid disorders.

The 8p11 myeloproliferative syndrome (EMS) is associated with three translocations, t(8;13)(p11;q12), t(8;9)(p11;q33), and t(6;8)(q27;p11), that fuse unrelated genes (ZNF198, CEP110, and FOP, respectively) to the entire tyrosine kinase domain of FGFR1. In all cases thus far examined (n = 10), the t(8;13) results in an identical mRNA fusion between ZNF198 exon 17 and FGFR1 exon 9. To determine if consistent fusions are also seen in the variant translocations, we performed RT-PCR on four cases and sequenced the products. For two patients with a t(8;9), we found that CEP110 exon 15 was fused to FGFR1 exon 9. For two patients with a t(6;8), we found that FOP exon 5 (n = 1) or exon 7 (n = 1) was fused to FGFR1 exon 9. To determine if FGFR1 might be involved in other myeloid disorders with translocations of 8p, we developed a two-color FISH assay using two differentially labeled PAC clones that flank FGFR1. Disruption of this gene was indicated in a patient with a t(8;17)(p11;q25) and Ph-negative chronic myeloid leukemia in association with systemic malignant mast cell disease, a patient with acute myeloid leukemia with a t(8;11)(p11;p15), and two cases with T-cell lymphoma, myeloproliferative disorder, and marrow eosinophilia with a t(8;12)(p11;q15) and ins(12;8)(p11;p11p21), respectively. For the patient with the t(8;11), the chromosome 11 breakpoint was determined to be in the vicinity of NUP98. We conclude that 1) all mRNA fusions in EMS result in splicing to FGFR1 exon 9 but breakpoints in FOP are variable, 2) two-color FISH can identify patients with EMS, and 3) the t(8;17)(p11;q25), t(8;11)(p11;p15), t(8;12)(p11;q15), and ins(12;8)(p11;p11p21) are novel karyotypic changes that most likely involve FGFR1.

Chromosomes, Human, Pair 11↗
PubMed2001

Determinants of prognosis and response to therapy in colorectal cancer.

Identification of the molecular determinants of 5-fluorouracil (5-FU) and irinotecan (CPT-11) efficacy and toxicity is critically important for the development of more efficient and less toxic treatment strategies for patients with colon cancer. We have identified molecular predictors of response to chemotherapy with 5-FU and survival in patients with advanced colorectal cancer. Low gene expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) are associated with response and survival. Preliminary data suggest that gene expression levels of topoisomerase I, p21, bcl-2, and ICE may be predictive of response to therapy with CPT-11. Increased toxicity seen in patients treated with CPT-11 may be explained by polymorphism in the UGT1A1 gene, which is responsible for glucuronidation of the active metabolite of CPT-11.

Antimetabolites, Antineoplastic↗
PubMed2001

New drugs in breast cancer.

The 1990s have seen the emergence of several classes of new efficacious drugs which have become established as treatment for breast cancer. Thus, aromatase inhibitors, taxanes and herceptin have all emerged as potentially valuable therapeutic agents for treatment of advanced breast cancer. Bisphosphonates have found a place in preventing skeletal complications in breast cancer patients with bone metastasis. Tamoxifen has a new role in chemoprevention in patients at high risk of breast cancer. This paper summarises these results.

Anthracyclines↗
PubMed2000

Fusion of H4/D10S170 to the platelet-derived growth factor receptor beta in BCR-ABL-negative myeloproliferative disorders with a t(5;10)(q33;q21).

We have studied a patient who presented with clinical features suggestive of chronic myeloid leukemia in accelerated phase. BCR-ABL transcripts were undetectable by reverse transcription-PCR, but a novel reciprocal translocation, t(5;10)(q33;q21.2), was seen by standard cytogenetic analysis. Chromosome band 5q33 contains the gene encoding the platelet-derived growth factor beta receptor (PDGFbetaR), the receptor tyrosine kinase that is disrupted by the t(5;7), t(5;12), and t(5;14) in myeloid disorders, resulting in the fusion of PDGFbetaR to HIP1, TEL/ETV6, and CEV14, respectively. Southern analysis with PDGFbetaR cDNA revealed novel bands in patient but not control DNA after digestion with several restriction enzymes, indicating that this gene is also targeted by the t(5;10). Fluorescence in situ hybridization analysis of chromosome 5 indicated that a small inversion at 5q33 had taken place in addition to the interchromosomal translocation. The site of the chromosome 10 breakpoint fell within YAC 940e4. Because all PDGFbetaR fusions described thus far result in splicing to a common exon of this gene, we performed 5'-rapid amplification of cDNA ends PCR on patient RNA. Several clones were isolated in which PDGFbetaR fused in frame to H4/D10S170, a previously described ubiquitously expressed gene that is fused to the ret protein tyrosine kinase to form the PTC-1 oncogene in approximately 20% of papillary thyroid carcinomas. The presence of H4-PDGFbetaR chimeric mRNA in the patient was confirmed by reverse transcription-PCR; reciprocal PDGFbeta1R-H4 transcripts were not detected. We conclude that t(5;10)(q33;q21.2) is a novel translocation in BCR-ABL-negative chronic myeloid leukemia and that this abnormality results in an H4-PDGFbetaR fusion gene. This finding further strengthens the association between myeloproliferative disorders and deregulated tyrosine kinases.

Amino Acid Sequence↗
PubMed2000

Role of thrombomodulin in cancer biology.

Effects of malignancy on haemostasis have long been recognized. The role of coagulation factors, anticoagulants and fibrinolytic agents in cancer biology have emerged more recently. Thrombomodulin is a naturally occurring anticoagulant, expressed by numerous epithelial and lymphovascular tumour cells. It may have a role in tumour metastasis.

Journal Article↗