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Biomedical subjects

A Bhat

Publications and source records attributed to A Bhat.

At least 37 records · Page 2Linked to original sources
PubMed1997

Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells.

The Philadelphia chromosome, detected in virtually all cases of chronic myelogenous leukemia (CML), is formed by a reciprocal translocation between chromosomes 9 and 22 that fuses BCR-encoded sequences upstream of exon 2 of c-ABL. The BCR-ABL fusion creates a gene whose protein product, p210BCR-ABL, has been implicated as the cause of the disease. Although ABL kinase activity has been shown to be required for the transforming abilities of BCR-ABL and numerous substrates of the BCR-ABL tyrosine kinase have been identified, the requirement of most of these substrates for the transforming function of BCR-ABL is unknown. In this study we mapped a direct binding site of the c-CBL proto-oncogene to the SH2 domain of BCR-ABL. This interaction only occurs under conditions where c-CBL is tyrosine-phosphorylated. Despite the direct interaction of c-CBL with the SH2 domain of BCR-ABL, deletion of the SH2 domain of BCR-ABL did not result in an alteration in the complex formation of BCR-ABL and c-CBL, suggesting that another site of direct interaction between c-CBL and BCR-ABL exists or that another protein mediates an indirect interaction of c-CBL and BCR-ABL. Since CRKL, an SH2, SH3 domain-containing adapter protein is known to bind directly to BCR-ABL and also binds to tyrosine-phosphorylated c-CBL, the ability of CRKL to mediate a complex between c-CBL and BCR-ABL was examined.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Coronary artery fistula in children and adults: a review of 25 cases with long-term observations.

We studied 25 patients with coronary artery fistula between 1976 and 1994. Age ranged from 1 to 58 years. Twelve patients were symptomatic; seven had dyspnoea, four had angina, one had palpitation and one had syncope. Coronary arteries in four. Coronary artery fistula drained into right ventricle in 11, right atrium in nine, pulmonary artery in four and left ventricle in two. The Qp/Qs ranged from 1.0 to 2.6 with a mean of 1.39 +/- 0.38. Five patients had associated cardiac anomalies. Two had atrial septal defects, one had patent ductus arteriosus, one had atresia of proximal right coronary artery and in one patient, the right coronary was arising from left coronary artery. Five patients underwent surgery without any operative mortality. Thirteen patients were followed-up medically for a mean period of 6.1 +/- 5.1 years. There were no complications related to coronary artery fistula during follow-up. In one patient coronary artery fistula closed spontaneously.

Adolescent↗
PubMed1997

Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation.

CRKL has previously been shown to be a major tyrosine phosphorylated protein in neutrophils of patients with BCR-ABL+ chronic myelogenous leukemia and in cell lines expressing BCR-ABL CRKL and BCR-ABL form a complex as demonstrated by coimmunoprecipitation and are capable of a direct interaction in a yeast two-hybrid assay. We have mapped the site of interaction of CRKL and BCR-ABL to the amino terminal SH3 domain of CRKL with a proline rich region in the C-terminus of ABL. The proline-rich region was mutated and the effect of this deletion on BCR-ABL transforming function was assayed. Our data show that this deletion does not impair the ability of BCR-ABL to render myeloid cells factor independent for growth. In cells expressing the proline deletion mutation of BCR-ABL, CRKL is still tyrosine phosphorylated and forms a complex with BCR-ABL as demonstrated by coimmunoprecipitation. Our data suggest that the interaction between CRKL and the proline deletion mutant of BCR-ABL is an indirect interaction as CRKL does not interact directly with the proline deletion mutant of BCR-ABL in a gel overlay assay or in a yeast two-hybrid assay. Thus, a direct interaction of CRKL and BCR-ABL is not required for CRKL to become tyrosine phosphorylated by BCR-ABL and suggests that CRKL function may still be required for BCR-ABL function through an indirect interaction.

Adaptor Proteins, Signal Transducing↗
PubMed1991

Premenarcheal anorexia nervosa.

The notions of 'early-onset' and 'prepubertal' anorexia nervosa are reviewed, with particular reference to the role of the pubertal process within the condition. A database of 650 female cases is utilized to identify a small sub-group (n = 30) who developed the condition before the menarche. Many clinical, familial, social and precipitating factors distinguish this group from post-pubertal cases as a whole, and a sub-group of post-menarcheal cases (n = 42) matched for age. An explanation for previous inconsistent findings in 'early-onset' and 'prepubertal' anorexia nervosa is advanced.

Adolescent↗
PubMed1991

Section 136 and African/Afro-Caribbean minorities.

Social, demographic and clinical information was collected retrospectively on all 99 people referred to a South London hospital in 1986 under Section 136 of the Mental Health Act (1983), this being the last complete year before local changes in the procedure for assessment of Section 136 cases were initiated. An over-representation of Afro-Caribbeans was confirmed and this seemed to be accounted for largely by young men under the age of 30 who with Africans had very high rates of previous Section 136 referral, were more likely to be perceived as threatening, incoherent and disturbed but less clearly diagnosed with a mental illness, and were more likely than the Caucasian sample to be living in stable accommodation. The implications of these results are discussed.

Adolescent↗
PubMed1991

A controlled study of the effect of therapies aimed at adolescent and family psychopathology in anorexia nervosa.

Ninety patients with severe anorexia nervosa fulfilling DSM-III-R criteria were assessed in depth in terms of their family developmental psychopathology and then randomly allocated to either one of three treatment groups or to no treatment. In three treatment regimes, a behavioural approach to diet and weight gain was coupled with individual and family psychotherapy directed at the adolescent maturational problems. All three treatment regimes were highly significantly effective at one year in terms of weight gain, return of menstruation, and aspects of social and sexual adjustment. Body weights above those at pubertal onset were achieved for the group mean maximum and one-year follow-up weights for all three treatment groups but not the control group.

Adolescent↗
PubMed1990

Association of muscle strength with functional status of elderly people.

We have studied the association of muscle strength (quadriceps, biceps, handgrip), measured by a portable chair technique, with functional status (Barthel Index, manual dexterity, Mental Test Score, history of falls, fracture, prescribed drugs), in a sample of 92 elderly subjects attending a Local Authority Day Centre and Day Hospital. Anthropometric measurements and hand-grip strength were also measured in 30 young controls. Muscle area, mass and strength were significantly greater in young controls. Elderly men had significantly greater muscle area, mass and strength than elderly women. Muscle strength correlated with several measures of functional status. Using stepwise multiple regression, an independent association of muscle strength with manual dexterity, Barthel Index and receipt of domiciliary services is demonstrated.

Aged↗
PubMed1989

Post-infarction ventricular septal defect: the importance of site of infarction and cardiogenic shock on outcome.

Sixty-eight patients operated upon for post-infarction VSD from 1980-1987 have been reviewed to identify incremental risk factors which influence survival. Univariate and multivariate analysis was performed on 19 parameters and showed the following in decreasing order of importance to be significantly associated with non-survival: (1) operation within 24 h of occurrence of the VSD; (2) inferior infarct preceding the VSD; (3) requirement for inotropic support preoperatively; (4) preoperative cardiogenic shock; (5) a lower mean pulmonary artery pressure; (6) a lower mean wedge pressure; (7) a lower mean systolic pressure. The presence of a graft to the right coronary artery was associated with a better prognosis. Age, sex, diastolic blood pressure, balloon pumping, mean plasma urea, right atrial pressure, extent of coronary disease, number of coronary grafts, grafts to the left coronary system and method of myocardial preservation had no influence on survival.

Aged↗
PubMed1988

Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice.

Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline (median dose 125 mg). The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice. Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment. The effects of the antidepressant were on the core symptoms of depression, and were apparent in all but the most mildly ill patients. The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice.

Adolescent↗
PubMed1984

Serum levels and response to amitriptyline in depressed out-patients.

Serum levels of amitriptyline plus nortriptyline were measured by radioimmunoassay at 1 and 6 weeks in depressed out-patients treated with amitriptyline for 6 weeks. Serum concentrations at 6 weeks were higher in older patients. Serum levels showed no relationship to clinical response at 6 weeks, and a week inverse relationship with response at 2 weeks. Routine monitoring of serum levels appears to be of little value in depressed out-patients treated with amitriptyline.

Adult↗