Genetic variants of human T-lymphotrophic virus type II in American Indian groups

The human T-lymphotropic virus type II (HTLV-II) is found in many New World Indian groups in North and South America and may have entered the New World from Asia with the earliest migration of ancestral Amerindians over 15,000 years ago. To characterize the phylogenetic relationships of HTLV-II strains infecting geographically diverse Indian populations, we used polymerase chain reaction to amplify HTLV-II sequences from lymphocytes of seropositive Amerindians from Brazil (Kraho, Kayapo, and Kaxuyana), Panama (Guaymi), and the United States (the Navajo and Pueblo tribes of the southwestern states and the Seminoles of Florida). Sequence analysis of a 780-base pair fragment (located between the env gene and the second exons of tax/rex) revealed that Amerindian viruses clustered in the same two genetic subtypes (IIa and IIb) previously identified for viruses from intravenous drug users. Most infected North and Central American Indians had subtype IIb, while HTLV-II infected members of three remote Amazonian tribes clustered as a distinct group within subtype IIa. These findings suggest that the ancestral Amerindians migrating to the New World brought at least two genetic subtypes, IIa and IIb. Because HTLV-II strains from Amazonian Indians form a distinct group within subtype HTLV-IIa, these Brazilian tribes are unlikely to be the source of IIa viruses in North American drug users. Finally, the near identity of viral sequences from geographically diverse populations indicate that HTLV-II is a very ancient virus of man.     

Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress

We have previously shown, using qualitative approaches, that oligodendroglial precursors are more readily damaged by free radicals than are astrocytes. In the present investigation we quantified the oxidative stress experienced by the cells using oxidation of dichlorofluorescin diacetate to dichlorofluorescein as a measure of oxidative stress; furthermore, we have delineated the physiological bases of the difference in susceptibility to oxidative stress found between oligodendroglial precursors and astrocytes. We demonstrate that (a) oligodendroglial precursors under normal culture conditions are under six times as much oxidative stress as astrocytes, (b) oxidative stress experienced by oligodendroglial precursors increases sixfold when exposed to 140 mW/m2 of blue light, whereas astrocytic oxidative stress only doubles, (c) astrocytes have a three times higher concentration of GSH than oligodendroglial precursors, (d) oligodendroglial precursors have > 20 times higher iron content than do astrocytes, and (e) oxidative stress in oligodendroglial precursors can be prevented either by chelating intracellular free iron or by raising intracellular GSH levels to astrocytic values. We conclude that GSH plays a central role in preventing free radical-mediated damage in glia.     

CHESS: comprehensive health enhancement support system for women with breast cancer

The Comprehensive Health Enhancement Support System (CHESS) was developed to assist people dealing with health crises. Needs assessments with patients were conducted in its development and validation studies performed. CHESS provides information, social support, and decision-making assistance via a personal computer and modem that are placed in patients' homes. Women of all ages and varied socioeconomic backgrounds have successfully used this program to empower them to become active participants in their care following a diagnosis of breast cancer.     

Mechanism for improved cardiac performance with arteriolar dilators in aortic insufficiency

To determine how arteriolar dilation improves cardiac performance in aortic insufficiency, we evaluated the acute effects of hydralazine in 10 patients with chronic severe aortic insufficiency. Control measurements of intracardiac and intravascular pressures, cardiac output and left ventricular volumes were obtained at cardiac catheterization. Hydralazine, 0.3 mg/kg i.v. (maximal dose 20 mg), was administered and all measurements were repeated 30 minutes later. A reduction in systemic vascular resistance from 1264 to 710 dyn-sec-cm-5 was associated with significant increases in forward cardiac index (2.9 to 5.1 l/min/m2) and stroke volume index (37 to 55 ml/m2). Left ventricular end-diastolic pressure was reduced from 19 to 12 mm Hg. There was a significant reduction in mean arterial pressure (88 to 83 mm Hg) and a significant increase in heart rate (81 to 94 beats/min). Regurgitant stroke volume was reduced by more than 10 ml/m2 in seven patients and for the group was significantly reduced, from 65 to 53 ml/m2. Regurgitant fraction was reduced in all patients; the overall reduction from 0.64 to 0.48 was highly significant. Ejection fraction increased more than 0.10 in four patients, by 0.08 in an additional patient and for the group increased significantly from 0.50 to 0.57. Left ventricular end-diastolic volume decreased by more than 25 ml/m2 in four patients, by 19 ml/m2 in an additional patient and was decreased significantly, from 208 to 190 ml/m2, for the group. Arteriolar dilators improve cardiac performance in aortic insufficiency by reducing the amount of aortic regurgitation and, in some patients, by substantially improving systolic pump fraction. These data suggest a role for arteriolar dilators in the management of selected patients with aortic insufficiency.     

Cancer of the bladder in spinal cord injury patients

Since 1963, 10 cases of bladder carcinoma have been detected in 1,052 new admissions to our center. A high percentage of these patients had squamous cell carcinoma and/or squamous elements. This relatively high incidence stimulated a prospective study of 81 spinal cord injury patients either maintained on intraurethral catheter drainage for 10 years or an external appliance for 15 years. There were changes of squamous metaplasia in 19 per cent of the cases but no cancer was detected. It remains undetermined if squamous metaplasia is a pre-malignant lesion. However, the incidence of squamous metaplasia and squamous cell carcinoma in paraplegics with chronically infected bladders is not uncommon. Any spinal cord injury patient with hematuria needs a complete bladder evaluation and any long-term paraplegic with chronic infection should undergo cystoscopy and Papanicolaou smears as part of the yearly checkup.     

A confocal microscopic evaluation of the effects of insulin imprinting on the binding of Concanavalin A by Tetrahymena Pyriformis

With confocal microscopy it is possible to study the Concanavalin A (Con A) binding characteristics of the surface and interior of a single cell by viewing optical sections. It was observed in Tetrahymena pyriformis that Con A bound both to the plasma membrane and to intracellular structures. Incubation of cells with a competing sugar a-methylmannopyranoside, decreased binding. Hormonal imprinting with insulin resulted in an increase in binding of Con A to the cell surface and a decrease in intracellular binding. It is possible that the intracellular binding sites may migrate to the plasma membrane.     

Some pharmacological studies on Artemisia herba-alba (Asso.) in rabbits and mice

This clinical research plan was designed to evaluate the predictable and current developments, growth, and stability of the economic status of part-time or full-time African-American practicing surgeons. In many communities throughout the United States, the economic successes of certified or experienced black surgical specialists are inhibited or modified by mistrust, jealousy, professional disengagements, prejudices, and self-hatred by black and white physicians and lay African Americans. Nevertheless, there are subtle and overt evidences of increasing satisfactory and above average associative interprofessional relationships between African-American physicians and surgical specialists. One hundred African-American surgical specialists from thirty-four communities in the United States were interviewed at periodic intervals over a period of three decades. Recommendations for improvements and changes are presented.     

Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin

Glycoprotein 330 (gp330) is a member of a family of endocytic receptors related to the low density lipoprotein receptor. gp330 has previously been shown to bind a number of ligands in common with its family member, the low density lipoprotein receptor-related protein (LRP). To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed. As a result, a 70-kDa protein was selected from human milk and identified by protein sequencing to be apolipoprotein J/clusterin (apoJ). Solid-phase binding assays confirmed that gp330 bound to apoJ with high affinity (Kd = 14.2 nM). Similarly, gp330 bound to apoJ transferred to nitrocellulose after SDS-polyacrylamide gel electrophoresis. LRP, however, showed no binding to apoJ in either type of assay. The binding of gp330 to apoJ could be competitively inhibited with excess apoJ as well as with the gp330 ligands apolipoprotein E, lipoprotein lipase, and the receptor-associated protein, a 39-kDa protein that acts to antagonize binding of all known ligands for gp330 and LRP. Several cultured cell lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize 125I-apoJ. Only cells that expressed gp330 endocytosed and degraded radiolabeled apoJ. Furthermore, F9 cells treated with retinoic acid and dibutyryl cyclic AMP to increase expression levels of gp330 displayed an increased capacity to internalize and degrade apoJ. Cellular internalization and degradation of radiolabeled apoJ could be inhibited with unlabeled apoJ, receptor-associated protein, and gp330 antibodies. The results indicate that gp330 but not LRP can bind to apoJ in vitro and that gp330 expressed by cells can mediate apoJ endocytosis leading to lysosomal degradation.