GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.

Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.     

Family Functioning and Social Support in the Adaptation of Caregivers of Children With Sickle Cell Syndromes

Objective: To examine moderating effects of family functioningand social support on the relationship of child-related stressorsto caregivers' psychological adaptation in a sample of caregiversof children with a chronic illness. Method: Participants were 67 caregivers of children and adolescentswith sickle cell syndromes. We conducted MANOVAs and subsequenteffect size calculations to determine if family functioningwould buffer the effects of caring for difficult-to-manage childrenwith this illness. Results: Findings supported a moderator effect of family functioningon the association of children's externalizing behavioral problemsto caregivers symptoms of hostility. Greater levels of cohesiveand adaptive family functioning buffered the potential detrimentaleffects of caring for children perceived as hard to manage.No significant associations were obtained between measures ofcaregivers' psychological adaptation and the severity of theirchildren's disease. Conclusions: We make recommendations for family systems interventions,particularly for caregivers of children with behavior problems.     

Retroviruses and schizophrenia in Jamaica

Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon called “an epidemic of schizophrenia,” with the inference that a novel virus, likely to be perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Islands, is perinatally transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/ HTLV-I associated myelopathy). We therefore examined inpatients at the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population, indicating that HTLV-I and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics.     

Comparative assessment of chordal preservation versus chordal resection during mitral valve replacement

Left ventricular function often deteriorates after mitral valve replacement for mitral regurgitation. It has been postulated that disruption of the mitral valve apparatus at operation is a major mechanism of postoperative dysfunction. The hypothesis tested in this investigation was that chordal preservation results in more favorable left ventricular function. Sixty-nine patients with isolated mitral regurgitation who underwent mitral valve replacement were studied before and 6 months after operation by treadmill exercise testing, catheterization, echocardiography, and radionuclide angiography. Nine patients underwent mitral valve replacement with preservation of the entire mitral apparatus and five with preservation of the posterior leaflet and attached chordae. The remaining 55 had mitral valve replacement with complete excision of the native valve. Preoperatively, there were no differences among groups in age, gender, exercise capacity, cardiac index, rest or exercise ejection fraction, fractional shortening, or pulmonary artery pressures. There were four perioperative deaths (7%) and eight late deaths among the 55 patients with chordal resection but no early or late deaths of patients whose chordae were preserved (p = 0.05). In patients in whom the chordae were excised, exercise capacity, left ventricular systolic dimensions, and cardiac index did not improve after mitral valve replacement, and left ventricular function deteriorated, as evidenced by a reduction of both the resting and exercise ejection fractions (from 46% +/- 13% to 31% +/- 13%, p = 0.0001, and from 49% +/- 12% to 37% +/- 14%, p = 0.0007, respectively) and fractional shortening (from 34% +/- 10% to 26% +/- 14%, p = 0.0001). In contrast, exercise capacity improved after mitral valve replacement in patients in whom the entire apparatus was spared (by 4 +/- 3 minutes, p = 0.05), left ventricular systolic dimensions decreased (from 44 +/- 8 to 36 +/- 9 mm, p = 0.03), and left ventricular function was maintained or improved, as evidenced by preservation of the resting ejection fraction (preoperative, 50% +/- 14%; postoperative, 54% +/- 11%; p = no significant difference), exercise ejection fraction (46% +/- 16% versus 52% +/- 9%, p = no significant difference), fractional shortening (from 31% +/- 9% to 28% +/- 9%, p = no significant difference), and an increase in the cardiac index (from 2.0 +/- 0.3 to 2.7 +/- 0.5 L/min/m2, p = 0.05). No statistically significant differences between posterior chordal resection only and preservation of the entire apparatus were found.(ABSTRACT TRUNCATED AT 250 WORDS)     

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF. There by demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (K_D 451-709 pM; receptors/cell 2306-413645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.