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Biomedical subjects

M Husain

Publications and source records attributed to M Husain.

At least 91 records · Page 5Linked to original sources

Abnormal temporal dynamics of visual attention in spatial neglect patients.

When we identify a visual object such as a word or letter, our ability to detect a second object is impaired if it appears within 400ms of the first. This phenomenon has been termed the attentional blink or dwell time and is a measure of our ability to allocate attention over time (temporal attention). Patients with unilateral visual neglect are unaware of people or objects contralateral to their lesion. They are considered to have a disorder of attending to a particular location in space (spatial attention). Here we examined the non-spatial temporal dynamics of attention in patients, using a protocol for assessing the attentional blink. Neglect patients with right parietal, frontal or basal ganglia strokes had an abnormally severe and protracted attentional blink When they identified a letter, their awareness of a subsequent letter was significantly diminished for a length of time that was three times as long as for individuals without neglect. Our results demonstrate for the first time that visual neglect is a disorder of directing attention in time, as well as space.

Adult↗

c-Myb function in fibroblasts.

The protooncogene c-myb is a nuclear transcription factor that shares significant sequence homology with two other myb family members, A-myb and B-myb. Recent studies have suggested that c-myb is involved in regulation of the cell cycle via control of intracellular calcium [Ca2+]i concentration. Given the limited cell type expression of the c-myb gene, we set out to investigate whether myb-dependent cell cycle regulation occurs in cells not known to express the c-myb protein. NIH 3T3 fibroblasts were stably transfected with an inducible c-myb dominant negative construct composed of a myb DNA binding domain linked to the Drosophila engrailed transcription suppresser (pGREMEn) and a full-length murine c-myb cDNA sequence. Induced expression of the dominant negative construct was associated with a G1 cell cycle arrest and a failure to increase late G1 intracellular calcium levels. Similar expression studies in mouse embryonic fibroblasts derived from the c-myb knockout mouse have demonstrated lower baseline [Ca2+]i levels than in normal mice fibroblasts that were not further lowered by MEn expression. We conclude that regulation of calcium homeostasis and cell cycle progression via myb-dependent transcription may play an important role in cells not possessing detectable levels of c-myb protein.

3T3 Cells↗

Distractor-dependent frontal neglect.

The effect of distractor load on visual search was examined in a patient with visual neglect following infarction of the right frontal lobe. The spatial extent of his left-sided neglect was modified greatly by changing stimulus attributes. When targets were highly discriminable compared to distractors, or distractor density was low, or when the subject was asked to cancel distractors as well as targets, he was able to direct his search to the extreme left of search arrays and there was little or no evidence of neglect. By contrast, similar changes in distractor load had little or no effect on the neglect of a patient with a fronto-parietal lesion. These findings suggest that distractability towards ipsilesional stimuli may be an important component of neglect in individuals with only frontal lobe injury.

Aged↗

Endometrial ablation by hysteroscopic instillation of hot saline solution.

Current methods of endometrial ablation to treat excessive uterine bleeding use laser or electrosurgical energy sources. These procedures are highly skill dependent, and numerous cases of fluid overload as well as other complications have been reported. A new method of endometrial ablation instills heated 0.9% normal saline at 80 to 90 degrees C. The fluid is recirculated and therefore, it is possible to measure accurately and predetermine the maximum amount of allowable absorption that occurs. Animal data indicate that the procedure is effective and may be safer than current methods of endometrial ablation. Standardization of this new method will require clinical trials, initially with women undergoing hysterectomy, for proper evaluation of the extent of thermal damage in relation to the time and intensity of heat exposure.

Animals↗

The hysteroscopic management of endometrial leiomyomatosis.

Uterine myomata are frequently the cause of abnormal uterine bleeding. They may be removed successfully by hysteroscopy. As a rule, the myomata are single, although on occasion several pedunculated myomas may be present. Three women were diagnosed with extremely large numbers of submucous leiomyomata. Many of the lesions were removed by hysteroscopic resection and many were destroyed with the neodymium:yttrium-aluminum-garnet laser.

Adult↗

Regulation of vascular smooth muscle cell proliferation by plasma membrane Ca(2+)-ATPase.

We have previously shown that reductions in c-Myb-dependent transcription inhibit cell cycle progression and decrease intracellular Ca2+ concentrations in vascular smooth muscle cells (VSMC). We now report that these effects are largely mediated by a 4- to 10-fold increased rate of La(3+)-sensitive 45Ca extrusion, which is associated with 2- to 4-fold increased levels of plasma membrane Ca(2+)-ATPase 1 (PMCA1) mRNA and protein. PMCA4 mRNA, present at much lower concentrations, undergoes similar changes during suppression of c-Myb activity. We also report that PMCA1 expression is regulated during VSMC cell cycle progression, such that levels of PMCA1 are 40% lower at the G1/S interface than at G0. Moreover, transient overexpression of PMCA1a in VSMC elevates the 45Ca efflux rate by approximately 2-fold, decreases resting and peak thapsigargin-releasable Ca2+ concentrations at G1/S by 43% (68 nM) and 52% (160 nM), respectively, and reduces the rate of cell proliferation by over 2.5-fold. These data define a mechanism for c-Myb-dependent Ca2+ homeostasis and support a critical role for PMCA in the regulation of VSMC growth.

Animals↗

c-Myb-dependent cell cycle progression and Ca2+ storage in cultured vascular smooth muscle cells.

Considerable controversy surrounds the role of the c-myb proto-oncogene in vascular smooth muscle cells (VSMCs). Previous investigations using antisense approaches have suggested a relationship between c-myb expression, cell cycle progression, and cytoplasmic Ca2+ concentration ([Ca2+]cyt). However, the ability of certain antisense oligonucleotides to bind and inactivate growth factors allows alternative explanations. To define more specifically the role of c-Myb in cultured VSMCs (SVE and A10 cell lines), we have generated stable cell clones expressing a dominant-negative c-Myb lacking critical elements of the DNA binding domain (delta5-SVE) and transiently transfected cell populations (GRE-MEn-SVE and GRE-MEn-A10) expressing a glucocorticoid-inducible chimeric protein that targets the Drosophila Engrailed repressor domain to c-Myb-responsive promoters. The delta5-SVE clones and GRE-MEn cell populations exhibit a 60% reduction in mean intracellular c-Myb activity, as measured by cotransfection assays with a c-Myb-responsive reporter, a 42% decrease in the mean S phase entry of growth-arrested (G[0]) cells after serum stimulation, and a 36% inhibition of mean cell proliferation over 4 days. These cells also display 28% (34-nmol/L) and 30% (42-nmol/L) reductions in mean [Ca2+]cyt at G(0) and at the G1/S interface, respectively, as well as significant reductions in the peak [Ca2+]cyt responses to thapsigargin (5 micromol/L) and caffeine (10 mmol/L). These latter reductions in operationally defined Ca2+ pools were observed both at different stages of the cell cycle and after transient induction of the dominant-interfering construct, suggesting that c-Myb regulates these releasable Ca2+ stores independent of its effects on cell cycle progression.

Animals↗

AgNOR expression in CNS neoplasms.

Silver colloid staining of nucleolar organiser regions (AgNORs) is used for assessing the proliferative potential of tumours. The present study aimed at evaluating the AgNOR indices in normal and reactive CNS tissue, benign and malignant CNS neoplasms. The study group comprised of tissue from 22 controls and 100 cases (53 benign & 47 malignant neoplasms). The mean AgNOR index of controls was 0.95, benign neoplasms 1.25 and malignant neoplasms 2.12. A statistically significant difference was observed in controls and cases (p < 0.001) and between benign and malignant tumours (p = 0.002). Mean indices for low and high grade astrocytoma also significantly differed (p < 0.001). Using ROC curves cut off values were obtained for differentiation of neoplastic from non neoplastic (AgNOR index 1.10), benign from malignant (AgNOR index 1.75) and low grade (I & II) from anaplastic (Gr III & IV) Astrocytomas (AgNOR index 1.62). A spectrum of gradually increasing AgNOR indices from normal, reactive, benign to low and high grade malignancy indicates the usefulness of this simple technique as a proliferative marker.

Astrocytoma↗

Finger printing of Mycobacterium tuberculosis in patients with intracranial tuberculomas by using in vivo, ex vivo, and in vitro magnetic resonance spectroscopy.

In vivo, ex vivo, and in vitro proton magnetic resonance spectroscopy was performed in 12 patients with intracranial tuberculomas with an aim of detecting the biochemical constituents of Mycobacterium tuberculosis in a granuloma. One dimensional (1D) single pulse and spin-echo sequences and 2D correlative spectroscopy were used for the ex vivo study to confirm the resonances seen on in vivo study. Spectroscopic studies of the perchloric acid and lipid extract of granuloma and M. tuberculosis were performed to look for similarity of resonance. In vivo study showed the presence of lipids at 0.9, 1.3, 2.0, 2.8 ppm, and phosphoserine at 3.7 ppm. All these resonances were confirmed on ex vivo study. In addition, distinct resonances of serine and phenolic lipids were seen on ex vivo and in vitro study of tuberculous granuloma, which have not been observed in other intracranial tumors. Lipid extract of granuloma and M. tuberculosis showed phenolic lipids at 7.1 and 7.4 ppm, a constituent of the cell wall of the bacteria in a tuberculoma. It appears that it may be possible to finger print the biochemicals of the cell wall of M. tuberculosis in a tuberculous granuloma and thus may help in detection and diagnosis of such lesions.

Amino Acids↗

Visual neglect associated with frontal lobe infarction.

Five patients with left-sided visual neglect following focal infarction of the right frontal lobe are presented. Lesion location was assessed using computed tomography or magnetic resonance imaging. The common area of lesion overlap was small, being confined to the dorsal aspect of the inferior frontal gyrus (Brodmann's area 44) and the immediate underlying white matter. This cortical region is part of the homologue of Broca's area in the right hemisphere and is considered to be part of human premotor cortex. The association of neglect with injury to this area suggests it may play an important role in directing attention in visual space.

Aged↗

Nitric oxide synthase (NOS) in schizophrenia: increases in cerebellar vermis.

A high proportion of neurons in the cerebellum and in cholinergic brainstem nuclei stain positive for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd), which is a nitric oxide synthase (NOS). Recent evidence suggests that schizophrenia may involve increased numbers of NADPHd-stained neurons in different areas of the subcortex. This led us to examine the actual concentration of NOS in postmortem brain specimens of cerebellum, and the relevant regions of brainstem tegmentum, to see if NOS concentrations were also increased in schizophrenia. Postmortem brain tissue was obtained at autopsy from schizophrenics and controls who did not have other brain disease. In patients with schizophrenia, NOS concentration was higher.

Aged↗

Visuomotor functions of the lateral pre-motor cortex.

Recent studies have provided new insights into the visuomotor functions of the dorsal and ventral regions of the lateral pre-motor cortex. Anatomical and physiological investigations in non-human primates have demonstrated that these regions have differing patterns of cortical connectivity and distinctive neuronal responses. Brain-imaging techniques and lesion studies have begun to probe the functions of homologous regions in humans.

Animals↗

Diversity of rotavirus strains infecting pediatric patients in New Delhi, India.

Polyacrylamide Gel Electrophoresis (PAGE) of rotavirus can provide information on variation in rotavirus strain prevalent in the community. In the present study 157 samples were collected from children below 5 years of age presenting with acute diarrhoea from May to December, 1990 at Safdarjung Hospital, New Delhi. Seventy-one (45 percent) of these stool samples were positive for rotavirus by ELISA. Sixty-seven samples showed discernible RNA pattern of group A rotavirus by PAGE. It was found that there were seven electropherotypes co-circulating in this 8-month period. Majority of the strains had a IIC pattern, but IIA, IID, IIE, IIG, IE, and IB electropherotype patterns were also seen. The simultaneous co-circulation of multiple group A strains in the community may lead to extensive genomic variation in rotavirus strains.

Acute Disease↗

Classification of rotavirus into G and P types with specimens from children with acute diarrhea in New Delhi, India.

Sixty rotavirus-positive stool specimens from children with diarrhea were classified into G and P genotypes. G typing was done by PCR and then by hybridization with G type-specific (G1 to G4) oligonucleotide probes, whereas nested PCR was performed for P typing. Thirty-nine samples could be classified into both G and P types, of which P8G1 and P4G2 (33% each) genotypes were predominant. The P6 genotype was detected in four children with diarrhea.

Acute Disease↗

Targeting of transgene expression to the vascular endothelium of mice by homologous recombination at the thrombomodulin locus.

We describe a straightforward gene-targeting technique to achieve uniform, stable, and genetically invariant expression of a transgene in the vascular endothelium of mice. To demonstrate the feasibility of this approach, the reporter gene bacterial beta-galactosidase was inserted via homologous recombination into the intronless thrombomodulin locus of murine embryonic stem cells. In this fashion, the lacZ gene is placed under the regulatory control of the endogenous thrombomodulin promoter. The expression of the transgene in adult mice recapitulated the widespread, stable, and high-level expression of the thrombomodulin gene in vascular endothelium. These data indicate that targeting of cDNAs into the thrombomodulin locus serves as a viable strategy to express transgenes in endothelial cells. Analysis of reporter gene expression revealed a heterogeneous pattern of thrombomodulin gene activity in the endothelium of the aorta and its tributaries. We also show that embryonic stem cells with a targeted thrombomodulin locus contribute in a mosaic fashion to the vascular endothelium of chimeric mice. This method for generating animals with a functionally heterogeneous cardiovascular system should provide an experimental technique for studying how localized genetic abnormalities in endothelial cell function lead to the development of vascular diseases.

Animals↗

Developmentally regulated gene expression of thrombomodulin in postimplantation mouse embryos.

Embryonic lethality of thrombomodulin-deficient mice has indicated an essential role for this regulator of blood coagulation in murine development. Here, the embryonic expression pattern of thrombomodulin was defined by surveying beta-galactosidase activity in a mouse strain in which the reporter gene was placed under the regulatory control of the endogenous thrombomodulin promoter via homologous recombination in embryonic stem cells. The murine trophoblast was identified as a previously unrecognized anatomical site where TM expression is conserved between humans and mice and may exert a critical function during postimplantation development. Targeted reporter gene expression in mesodermal precursors of the endothelial cell lineage defined thrombomodulin as an early marker of vascular differentiation. Analysis of the thrombomodulin promoter in differentiating ES cells and in transgenic mice provided evidence for a disparate and cell type-specific gene regulatory control mechanism in the parietal yolk sac. The thrombomodulin promoter as defined in this study will allow the targeting of gene expression to the parietal yolk sac of transgenic mice and the initiation of investigations into the role of parietal endoderm in placental function.

Animals↗

Significance of proliferating cell nuclear antigen in predicting recurrence of intracranial meningioma.

It is well known that the histological appearance of meningiomas often fails to predict accurately the clinical behavior of the tumor. Therefore, attention has turned from tumor histology to tumor biology. Proliferating cell nuclear antigen (PCNA), a cell cycle-regulated protein, has been recently characterized as the cofactor of DNA polymerase-delta, an enzyme required for DNA replication. The rate of synthesis of PCNA directly correlates with the proliferative state of cells. Immunohistochemical labeling of this antigen is now possible with monoclonal antibodies that allow for its demonstration in routinely fixed, paraffin-embedded specimens. In this study, the PCNA labeling index (LI) was determined for 83 meningiomas, including tumors with both benign and malignant clinical courses and with benign, atypical, and malignant histologies, apparent after total or subtotal resections. No statistical difference was found between the LI on recurrence and that found at initial presentation. In addition, stepwise multivariate regression analysis failed to identify any combination of factors (age, gender, race, age of specimen, tumor histology, Simpson grade of resection) that contributes to the predictive strength of the PCNA LI for tumor recurrence. However, for LIs less than 2%, only one of 26 gross totally resected tumors recurred (mean follow up 53 months); for LIs more than 7%, five of 13 gross totally resected tumors recurred (mean follow up 55 months). The difference in recurrence rates between gross totally resected meningiomas with PCNA LIs less than 2% and those with PCNA LIs more than 7% achieved statistical significance with a Fisher's exact probability equaling 0.011. The authors conclude that quantitative PCNA labeling of meningiomas is a promising technique that can provide meaningful prognostic information.

Adult↗