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Biomedical subjects

I Reis

Publications and source records attributed to I Reis.

11 recordsLinked to original sources

Temporal arteritis presenting with scalp ulceration.

We report the case of a 75-year-old-woman who presented with bilateral scalp ulcerations and blindness, accompanied by severe headache and scalp tenderness, due to bilateral temporal arteritis without systemic involvement. A biopsy taken from the border of an ulceration showed evidence of giant cell arteritis. She was treated with oral prednisone, 60 mg per day. The ulcerations healed in a few weeks but the vision loss was irreversible. This case highlights for temporal arteritis the importance of accurate and timely diagnosis as well as the need for prompt therapy with systemic steroids in order to avoid major complications, namely loss of vision. It also demonstrates that scalp necrosis and ulcerations are skin signs associated with a poor prognosis.

Aged↗

Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells.

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by slow-growing plasma cells in the bone marrow (BM). Patients with MM typically respond to initial chemotherapies; however, essentially all progress to a chemoresistant state. Factors that contribute to the chemorefractory phenotype include modulation of free radical scavenging, increased expression of drug efflux pumps, and changes in gene expression that allow escape from apoptotic signaling. Recent data indicate that arsenic trioxide (As(2)O(3)) induces remission of refractory acute promyelocytic leukemia and apoptosis of cell lines overexpressing Bcl-2 family members; therefore, it was hypothesized that chemorefractory MM cells would be sensitive to As(2)O(3). As(2)O(3) induced apoptosis in 4 human MM cell lines: 8226/S, 8226/Dox40, U266, and U266/Bcl-x(L). The addition of interleukin-6 had no effect on cell death. Glutathione (GSH) has been implicated as an inhibitor of As(2)O(3)-induced cell death either through conjugating As(2)O(3) or by sequestering reactive oxygen induced by As(2)O(3). Consistent with this possibility, increasing GSH levels with N-acetylcysteine attenuated As(2)O(3) cytotoxicity. Decreases in GSH have been associated with ascorbic acid (AA) metabolism. Clinically relevant doses of AA decreased GSH levels and potentiated As(2)O(3)-mediated cell death of all 4 MM cell lines. Similar results were obtained in freshly isolated human MM cells. In contrast, normal BM cells displayed little sensitivity to As(2)O(3) alone or in combination with AA. Together, these data suggest that As(2)O(3) and AA may be effective antineoplastic agents in refractory MM and that AA might be a useful adjuvant in GSH-sensitive therapies. (Blood. 2001;98:805-813)

Acetylcysteine↗

Breast cancer and human immunodeficiency virus: a report of 20 cases.

Carcinoma of the breast is the most common malignancy in women in the United States. More than 40% of patients with human immunodeficiency virus (HIV) infection develop cancer during their illness, but breast cancer has seldom been reported. Twenty patients with breast cancer and HIV infection seen at the University of Miami/Jackson Memorial Hospital between January 1988 and August 2000 were retrospectively analyzed. Seventeen patients had a previous or concurrent diagnosis of HIV at the time of the breast cancer diagnosis. Their CD4 count ranged from 13-1126/microL (median, 309/microL). Most patients were premenopausal (16 of 20), with ages ranging from 31-61 years (median, 44 years). All stages of breast cancer were seen: ductal carcinoma in situ (2 patients), stage I (1 patient), stage II (9 patients), stage III (6 patients), and stage IV (2 patients). Ten tumors had estrogen receptors. Four of the 13 patients who underwent axillary lymph node dissection had abnormal lymph node findings, including 2 with follicular hyperplasia and 2 with caseating granulomas. Seven patients received chemotherapy with very poor tolerance. Estrogen receptor-positive patients were treated with tamoxifen. Of the 18 patients who presented with local disease, 7 have died: 2 of breast cancer, 4 of acquired immunodeficiency syndrome, and 1 of cardiac arrest. Nine patients remain free of disease (5 of them > 5 years) and 2 patients are alive with metastatic disease. Breast cancer in the HIV-positive population is similar to that seen in seronegative women. Most of the patients that are long-term survivors were treated with surgery and tamoxifen. The benefits of adjuvant chemotherapy are not clear.

Adult↗

Insertion of the 5' part of BCR within the ABL gene at 9q34 in a Philadelphia-negative chronic myeloid leukemia.

We report a chronic myeloid leukemia patient without evidence of a Philadelphia (Ph) chromosome in whom RT-PCR analysis performed in blast crisis demonstrated the existence of both common b3a2 and b2a2 BCR/ABL fusion transcripts. In situ hybridization studies with BCR- and ABL-specific probes showed location of the BCR/ABL fusion gene on chromosome 9, band q34, instead of at chromosome 22q11, and that it resulted from an insertion of the 5' side of BCR within the ABL gene on chromosome 9. The vast majority of cells showed a BCR/ABL fusion gene on both chromosomes 9, which is equivalent to a double Ph chromosome, thus reinforcing the notion that the critical event in CML is the formation of a functional BCR/ABL fusion gene.

Chromosomes, Human, Pair 9↗

Regional biochemical remodeling in non-infarcted tissue of rat heart post-myocardial infarction.

Changes in the capacities of ATP-synthesizing reactions were analysed in residual non-infarcted myocardium following myocardial infarction. Rats were subjected to left coronary artery ligation (MI; n = 11) or to sham operation (sham; n = 18). Two months later, hearts were excised, rinsed and buffer-perfused isovolumically. In vitro pressure-volume relationships were recorded. After separation into left and right ventricles (LV, RV) and atria (LA, RA), samples were analysed for citrate synthase, glycolytic enzymes (phosphofructokinase, glyceraldehyde-3-phosphate-dehydrogenase, lactate dehydrogenase (LDH) and its isoforms) and the creatine kinase (CK) system [total CK, CK isoenzymes (CKBB, CKMB, CKMM and CKmito) and total creatine]. In residual intact heart, citrate synthase activity and activities of most glycolytic enzymes were unchanged, but LDH activity and anaerobic LDH isoenzymes increased significantly. Total creatine kinae activity (6.5 +/- 0.2 IU/mg protein in sham LV) was decreased by chronic myocardial infarction in LV (5.4 +/- 0.3, with P < 0.05 sham v MI) but not in RV (6.2 +/- 0.2). Significant CK isoenzyme shifts occurred in both ventricles "adult" CKmito (32.5 +/- 1.4% in sham LV) was reduced in LV (22.1 +/- 2.1% with P < 0.05 sham v MI) and in RV (19.2 +/- 2.9%, with P < 0.05 sham v MI), "fetal" CKBB and CKMB increased. Total creatine content was reduced by up to 35% in both ventricles. In sham hearts atria had lower total and mitochondrial CK activity, lower total creatine content and higher CKMB and CKBB activity compared to ventricles; however, myocardial infarction induced changes directionally comparable to the changes observed in ventricles. Thus, 2 months after myocardial infarction changes of the capacities of ATP synthesizing reactions are comparable for all heart chambers, with the exception of total CK activity decreasing only in left ventricular tissue.

Animals↗

Regional changes in creatine kinase and myocyte size in hypertensive and nonhypertensive cardiac hypertrophy.

Several intracellular enzymes have been shown to have altered total activity or isoenzyme composition in cardiac hypertrophy. This study tests the hypothesis that the accumulation of the fetal-type (BB + MB) creatine kinase (CK) isoenzymes in hypertrophied adult myocardium is related to an increase in blood pressure. Consideration was made for the location, size, and hemodynamic load of the myocytes. By using the two-kidney, one-clip (2K1C) rat model of renal hypertension with and without hydralazine treatment, CK (total and isoenzyme), lactate dehydrogenase, and citrate synthase activities and myocyte size were measured. An increased heart weight/body weight ratio occurred in both untreated 2K1C rats (4.15 +/- 0.09) and hydralazine-treated 2K1C rats (4.12 +/- 0.13) as compared with control rats (3.25 +/- 0.10). Blood pressure was high only in untreated 2K1C rats (196 +/- 9 mm Hg), as compared with hydralazine-treated 2K1C rats (142 +/- 6 mm Hg) and control rats (135 +/- 3 mm Hg). Myocytes were isolated from five ventricular regions: left ventricular epicardial and endocardial free wall, left and right halves of the interventricular septum, and right ventricular free wall. Regional differences in normal and hypertrophied myocardium were demonstrated for morphological and biochemical parameters, with the greatest changes occurring in left ventricular endocardium. The shift in CK isoenzyme expression toward accumulating more BB + MB was greater in "hypertensive hypertrophy" (untreated 2K1C rats) than in "nonhypertensive hypertrophy" (hydralazine-treated 2K1C rats). Calculations incorporating isolated myocyte volume showed that the cellular content of total CK remained the same during the hypertrophic process, accounting for a decrease in the tissue activity. Measurement of lactate dehydrogenase and citrate synthase activities suggests that hypertrophied myocardium has relatively higher glycolytic capacity and that this effect is exacerbated in the presence of high blood pressure. We conclude that increased blood pressure is more closely linked to the fetal CK isoenzyme shift than is hypertrophy alone.

Animals↗

Incorporation of [3H]thymidine into mtDNA of ram spermatozoa.

Freshly ejaculated spermatozoa from 6 rams incorporated [3H]-thymidine only after a lag period of 4 h. The thymidine incorporation was dependent on the time after ejaculation regardless of the rate of fructolysis, which was controlled by cold shock. The DNA synthesis period lasted for 3 h followed by a degradation period of 2 h. This synchronized level of labelling of DNA with tritiated thymidine was not due to bacterial contamination, sperm cell mitosis, mitochondrial division, or DNA repair. The fact that the maximal level of the DNA synthesis was dependent upon the external pH of the seminal plasma, in a parabolic fashion with a minimum around pH 6.3, indicated that this activity was of a 'metabolic' type. The sensitivity of the sperm DNA synthesis to 10 micrograms ethidium bromide/ml indicated that it was of a mitochondrial origin.

Animals↗