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Biomedical subjects

M Mirza

Publications and source records attributed to M Mirza.

At least 19 recordsLinked to original sources
PubMed2006

Sequence variation, linkage disequilibrium and association with Crohn's disease on chromosome 5q31.

Chromosome 5q31 contains a cluster of genes involved in immune response, including a 250 kb risk haplotype associated with Crohn's disease (CD) susceptibility. Recently, two functional variants in SLC22A4 and SLC22A5 (L503F and G-207C), encoding the cation transporters OCTN1 and OCTN2, were proposed as causal variants for CD, but with conflicting genetic evidence regarding their contribution. We investigated this locus by resequencing the coding regions of 10 genes in 24 CD cases and deriving a linkage disequilibrium (LD) map of the 27 single nucleotide polymorphisms (SNPs) detected. Ten SNPs representative of the LD groups observed, were tested for CD association. L503F in SLC22A4 was the only nonsynonymous SNP significantly associated with CD (P=0.003), but was not associated with disease in the absence of other markers of the 250 kb risk haplotype. Two other SNPs, rs11242115 in IRF1 and rs17166050 in RAD50, lying outside the 250 kb risk haplotype, also showed CD association (P=0.019 and P=0.0080, respectively). The RAD50 gene contains a locus control region regulating expression of the Th2 cytokine genes at this locus. Other as yet undiscovered SNPs in this region may therefore modulate gene expression and contribute to the risk of CD, and perhaps of other inflammatory phenotypes.

Base Sequence↗
PubMed2006

An osteopontin splice variant induces anchorage independence in human breast cancer cells.

In malignant tumors, metastasis genes are typically deregulated by aberrant expression or splicing. Osteopontin is expressed at high levels by various cancers and contributes importantly to their invasive potential. In contrast, osteopontin derived from host cells induces cellular immunity and could bolster antitumor protection by cytotoxic T lymphocytes. Here we show that breast cancer cells express multiple splice variants of osteopontin. According to RT-PCR analysis of human breast tissue specimens, the splice variant osteopontin-c is a highly specific marker for transformed cells, which is not expressed in their surrounding normal tissue. The full-length form of osteopontin aggregates in the presence of physiologic amounts of calcium and, in this state, leads to enhanced cell adhesion. Ostensibly, this effect is inhibitory for tumor cell dissemination. The shortest splice variant, osteopontin-c, does not aggregate in the presence of calcium and enhances clone formation in soft agar. According to microarray analysis, osteopontin-c induces the expression of oxidoreductases, consistent with protection from anoikis during anchorage-independent growth. These studies define a third functional domain of osteopontin, beside the C-terminal CD44-binding site and the central integrin-binding site. They also provide evidence for a bifunctional character of osteopontin, with the soluble form supporting invasiveness and the aggregated form promoting adhesion.

Alternative Splicing↗
PubMed2004

Effect of finite doses of propylene glycol on enhancement of in vitro percutaneous permeation of loperamide hydrochloride.

We hypothesised that the depletion of propylene glycol from topical formulations applied at clinically relevant doses (approximately mg/cm2) would limit its penetration enhancement effect. The in vitro percutaneous permeation of a model drug-loperamide hydrochloride-in formulations containing propylene glycol was therefore investigated under finite dose conditions. The flux of loperamide and propylene glycol across dermatomed human skin was measured. The first study examined the effect of topical loading of a gel containing 12% propylene glycol. The second study investigated the effect of propylene glycol content in creams containing 15 and 40%. Both studies showed a correlation between the amount of propylene glycol dosed on the skin and the amount of drug that had permeated. The substantial permeation of propylene glycol and relatively small permeation of loperamide, strongly suggests, that the time dependent permeation of the drug was due to the depletion of propylene glycol at the skin surface and not to the depletion of the drug itself. As often doses applied in in vitro skin permeation experiments do not match the intended clinical dosage-they are usually much greater-this study suggests that the penetration enhancement effect of propylene glycol can be overestimated in in vitro studies.

Administration, Cutaneous↗
PubMed2004

A case of subcutaneous myxopapillary ependymoma presenting as a pilonidal sinus.

We describe a rare neurogenic tumour presenting as a pilonidal sinus. This case illustrates the pitfalls associated with the management of a commonly occurring surgical condition. Pilonidal sinuses are often the province of trainee surgeons and while ependymomas are rare, this example emphasises the need to send the pilonidal sinus tract for histological examination.

Adult↗
PubMed2003

A whole genome screen for linkage in Turkish multiple sclerosis.

Factors exerting recessive effects on susceptibility to complex traits are expected to be over-represented in communities having a higher frequency of consanguineous marriage. Multiple sclerosis, a typical complex trait, is relatively common in Turkey where cultural factors also determine a high rate of consanguineous marriage. Previous genetic studies of multiple sclerosis in Turkey have been confined to the search for associations with candidate genes. In order to exploit the special genetic features of the Turkish population, we performed a whole genome screen for linkage in 43 Turkish multiplex families employing 392 microsatellite markers. Two genomic regions where maximum lod score (MLS) values were suggestive of linkage were identified (chromosomes 13q and 18q23) along with a further 14 regions of potential linkage. Parametric analysis of these data using a recessive model, appropriate for populations with a high frequency of consanguinity, increased the LOD scores in four regions.

Chromosome Mapping↗
PubMed1999

Risky behavior of bus commuters and bus drivers in Karachi, Pakistan.

Buses account for a disproportionate number of road traffic accident fatalities in Karachi, Pakistan and other developing countries. Potentially dangerous bus driving and commuting practices that increase risk of road accidents and the effect of traffic police on bus behavior are evaluated. A total of 250 episodes each of disembarking and embarking commuters, buses stopping and moving on the road at ten of Karachi's highest risk intersections for traffic injuries were observed. Of the disembarking passengers, 33% did not wait for the bus to stop; 54% stepped off in the center of the road and 84% did not look out for traffic. Among the embarking commuters, 38% got on moving buses; 73% climbed on buses filled to their outer foot boards and 83% waited for buses on the street. Males were more likely than females to jump off a moving bus (43% versus 1.6%, P < 0.001), get on a moving bus (49% versus 12%, P < 0.001), and run to catch a bus (45% versus 8%, P < 0.001). At the bus stops, 30% of the buses did not stop completely; 46% stopped away from the stop and 79% stopped in the center of the road. Where traffic police were present buses were more likely to race (9% versus 3%, P = 0.05) and to cut off other vehicles (13% versus 2%, P = 0.001) than where police were absent. Risky behavior is common among both Karachi bus drivers and bus commuters. The traditional efforts to regulate bus traffic through traffic police is ineffective.

Accidents, Traffic↗
PubMed1998

Genetic analysis of inflammatory bowel disease in a large European cohort supports linkage to chromosomes 12 and 16.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a complex disorder of unknown etiology. Epidemiological investigations suggest a genetic basis for IBD. Recent genetic studies have identified several IBD linkages. The significance of these linkages will be determined by studies in large patient collections. The aim of this study was to replicate IBD linkages on chromosomes 12 and 16 in a large European cohort. METHODS: Three hundred fifty-nine affected sibling pairs from 274 kindreds were genotyped using microsatellite markers spanning chromosomes 12 and 16. Affection status of the sibling pairs was defined as Crohn's disease (CD) or ulcerative colitis (UC). RESULTS: Nonparametric statistical analyses showed linkage for both chromosomes. Two-point results for chromosome 12 peaked at D12S303 (logarithm of odds [LOD], 2.15; P = 0.003) for CD and at D12S75 (LOD, 0.92; P = 0.03) for UC. Multipoint analyses produced a peak LOD of 1.8 for CD. Chromosome 16 showed linkage for CD at marker D16S415 (LOD, 1.52; P = 0.007). Multipoint support peaked above markers D16S409 and D16S411 (LOD, 1.7). CONCLUSIONS: These data are consistent with linkage of IBD to chromosomes 12 and 16. The replication of genetic risk loci in a large independent family collection indicates important and common susceptibility genes in these regions and will facilitate identification of genes involved in IBD.

Chromosomes, Human, Pair 12↗
PubMed1998

Interictal SPECT with Tc-99m HMPAO studies in migraine patients.

Migraine is considered to be a functional neurological disorder. For several years cerebral blood flow studies have been fueling the controversy surrounding the pathophysiology of migraine headache. Tc-99m HMPAO SPECT brain imaging was performed during the headache-free period in 44 migraineurs. The findings were compared with those of age 17 and sex-matched controls. The SPECT analysis was performed by using a 360 degrees rotating single head gamma camera system (Toshiba GCA 602A/SA, Japan), equipped with a LEAP collimator, interfaced to a Toshiba computer system, after 20 minutes following the injection of 350-550 MBq of Tc-99m HMPAO. The SPECT images revealed clear interhemispheric asymmetry in the upper frontal and occipital parts of the brain in migraineurs. It is suggested that an impaired regional cerebral vascular autoregulation may exist even during headache-free intervals in patients suffering from migraine.

Adolescent↗
PubMed1995

Prognostic value of serum hyaluronic acid and type I and III procollagen propeptides in extrahepatic biliary atresia.

Although portoenterostomy has greatly improved the prognosis of extrahepatic biliary atresia (EHBA), 10-20% of patients still die before 5 y of age, and the only treatment option is liver transplantation (LT). To investigate whether these patients may be identified at an early stage, when the changes of successful LT are optimal, we have measured serum concentrations of hyaluronic acid (HA), the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP, PINP) in 24 selected patients with EHBA, both before portoenterostomy and then every 6 mo until death (n = 10, age at death = 7-20 mo), LT (n = 6, age at LT = 1.1-4.8 y) or 5 y of age (n = 8). Raised serum HA above 200 micrograms/L before portoenterostomy identified those patients who would die or require LT in the first 5 y of life with a positive predictive value of 88%; after portoenterostomy, longitudinal changes in HA reflected clinical status in each patient. None of the other three markers was of prognostic value, and only PIIINP showed any relationship with clinical status, and then only up to 1.5 y. Interestingly, PINP (but not PICP) tended to be low in all patients before portoenterostomy and may reflect impaired bone collagen metabolism during early skeletal changes in EHBA. This study therefore suggests that measurement of serum HA may be a useful complementary test in EHBA, particularly in identifying, at an early stage, those patients who should be considered for LT.

Age Factors↗
PubMed1995

Studies on the differential morphological alterations in human and goat erythrocytes against ATP depletion and Ca(2+)-induced stresses.

Erythrocyte membranes obtained from goat exhibited Ca2+/calmodulin-insensitive (Ca(2+)-Mg2+)-ATPase activity and the activity levels were significantly lower as compared to those obtained from human erythrocyte membranes. Although Ca2+/ionophore A23187 -treatment enhanced the intracellular Ca2+ levels in both the freshly collected human and goat erythrocytes, negligible loss of ATP was noticed in goat erythrocytes under such conditions. Also, fluoride, a known metabolic inhibitor, caused a lesser ATP depletion in goat erythrocytes compared to that of human. Goat erythrocytes showed remarkable rigidity to shape change and unlike human erythrocytes, did not undergo echinocytic formation as a result of metabolic depletion and Ca2+/ionophore A23187-treatments. These studies suggest the participation of (Ca(2+)-Mg2+)-ATPase -independent mechanism(s) for Ca(2+)-extrusion.

Adenosine Triphosphate↗
PubMed1994

A crosslinked tetrameric alpha 2M that binds but incompletely entraps trypsin.

A crosslinked preparation of alpha-2-macroglobulin was obtained by treatment of the purified human plasma inhibitor with glutaraldehyde at low temperature. The preparation migrated as a 780 KDa polypeptide in SDS-PAGE and with mobility comparable with that of trypsinized native alpha-2-macroglobulin under nondenaturing conditions. Trypsinization of the glutaraldehyde treated alpha-2-macroglobulin further increased its electrophoretic mobility in non-denaturing gels and resulted in the association of the proteinase with the crosslinked inhibitor. Trypsin associated with crosslinked alpha-2-macroglobulin, unlike that associated with native inhibitor was incompletely protected from soybean trypsin inhibition.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

Entrapment of nonproteolytic enzymes in alpha 2-macroglobulin using immobilized trypsin.

Entrapment in human alpha 2-macroglobulin (alpha 2M) of non-proteolytic enzymes was achieved with the help of trypsin covalently attached to Sepharose matrix. While it was also possible to achieve entrapment by the exposure of the alpha 2M: enzyme mixtures to soluble trypsin, use of the immobilized proteinase resulted in improved entrapment yields and also prevented the coentrapment of trypsin. Both soluble and immobilized trypsin transformed alpha 2M to the electrophoretically fast form but the immobilized trypsin required relatively longer incubation to bring about the transformation. Horseradish peroxidase was entrapped in higher yield in alpha 2M compared to the relatively high-molecular-weight invertase. alpha 2M-entrapped peroxidase and invertase appeared highly accessible to their respective substrates, as evident from their relatively unaltered Km values. alpha 2M-associated invertase, in spite of its large dimensions, failed to crossreact with the rabbit anti-invertase antiserum, indicating its physical entrapment rather than any other form of association.

Animals↗
PubMed1993

Studies on griseofulvin: part-ii effects on the liver and kidney of albino rat.

Studies were performed on albino rats to investigate any untoward effects of griseofulvin on their liver and kidneys. Animals weighing between 200-250g were selected and divided into control and test groups. Griseofulvin was administered to the test groups at a dose level of 20 mg/Kg/day for 2, 46 and 8 weeks respectively. Animals wee sacrificed at the end of their respective study periods for collection of blood and removal of the liver and kidneys. Histopathological examination of the liver and kidneys of the treated animals at the end of 4 and 8 weeks of griseofulvin administration showed no cytotoxic changes. It was, therefore, concluded that griseofulvin has no hepatotoxic effects in albino rats at a dose level of 20 mg/Kg/day.

Journal Article↗
PubMed1991

Intermittent vs maintenance medication in schizophrenia. Two-year results.

This is a 2-year, double-blind, placebo-controlled study of 101 patients, evaluating the relative efficacy of intermittent medication (given only when the patient shows early signs of relapse) compared with moderate doses of maintenance medication for stable schizophrenic outpatients. Patients were dropped from the study if they had three prodromal episodes in 1 year or if an episode lasted more than 9 weeks. Fourteen percent of patients given maintenance treatment were dropped from the study compared with 46% of intermittently treated patients. Relapse rates were 16% for patients given maintenance treatment and 30% for intermittently treated patients, a nonsignificant difference. Intermittently treated patients were receiving significantly less medication, but there were no differences found in drug side effects. There appears to be no advantage in using the intermittent approach, but we found that the use of an early intervention strategy reduced the relapse and rehospitalization rates for these patients.

Adult↗