Relationship of Estrogen and Progesterone Receptor Protein Levels in Carcinomatous and Adjacent Non-Neoplastic Epithelium of the Breast: A Histopathologic and Image Cytometric Study

Background. Results of a previous study demonstrating a correlation between steroid hormone receptor concentrations in benign and tumor tissue in patients with breast carcinoma suggest that receptor levels in breast epithelium undergoing malignant transformation may play a role in determining the receptor levels in the resulting carcinoma. Data used in that study were derived from ligand binding assays and may reflect shortcomings inherent in this methodology, particularly the dilution of receptor proteins from benign and malignant epithelial cells by stromal components. Methods. We performed a correlation study of steroid hormone receptor expression in benign and malignant breast epithelial cells using computerized image cytometry and histologic sections stained for estrogen (ER) and progesterone receptor (PR), avoiding the problems of contribution of stromal cells to the measurements and uncertainty about the histologic composition of the sample. Sections which contained both tumor and non-neoplastic breast elements were obtained from surgical specimens from 50 patients with breast carcinoma. Results. Positive area (PA) scores for ER in benign and malignant epithelium showed direct correlation that was significant (r=0.46, p<0.001), whereas those for PR, although trended in the same direction, did not (r=0.17, p>0.2). PA levels for both receptor proteins were higher in benign breast epithelium with proliferative features, compared to non-proliferative benign epithelium, and in tumors when the associated benign tissue had proliferative changes, but neither of these differences were statistically significant, suggesting that the correlation of ER levels in benign and malignant epithelium was not simply a function of proliferative change. Conclusion. Our results provide support for the concept that ER expression in breast carcinoma depends partially on epithelial cell receptor levels in the breast in which it arises, but not for the analogous hypothesis for PR. When costs and benefits of tamoxifen chemoprevention are weighed for a patient at risk for breast carcinoma, and when cyto- or histopathologic breast tissue specimens are available, it may be reasonable to include breast epithelial ER levels among the factors considered in making the treatment decision.     

Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene

We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.     

A new mtDNA mutation in the tRNA(Leu(UUR)) gene associated with ocular myopathy

We studied a patient with ptosis, ophthalmoparesis, and exercise intolerance who showed in her muscle biopsy ragged-red fibers and combined defects of the complexes I and IV of the mitochondrial respiratory chain. Molecular analysis revealed a T3273C transition in the mitochondrial DNA tRNA(Leu(UUR)) gene. The mutation was heteroplasmic and very abundant in muscle from the proposita, less abundant in her other tissues studied, and still less abundant in blood from her maternal relatives. Single muscle fiber analysis showed significantly higher levels of mutant genomes in ragged-red fibers than in normal fibers. The T3273C mutation affects a strictly conserved base pair in the anticodon stem and was not found in controls, thus satisfying the accepted criteria for pathogenicity.     

Acute peritoneal dialysis as both cause and treatment of hypernatremia in an infant

This report describes a 4-month-old infant with multisystem organ failure who developed severe hypernatremia (sodium 168 mEq/l) due to rapid free water removal associated with acute peritoneal dialysis instituted for fluid overload. The current report describes the pathophysiology of the hypernatremia, and its correction by low-sodium hypertonic peritoneal dialysis without compromising ultrafiltration or supplementing with free water. Although peritoneal dialysis can cause hypernatremia, a modified solute concentration in the dialysate can treat the hypernatremia successfully. Received: 2 January 2001 / Revised: 24 April 2001 / Accepted: 24 April 2001     

Molecular mechanism of monoamine toxicity in Parkinson's disease: hypothetical cell death model

Although there have been experimental approaches to understanding the etiology of Parkinson's disease, the cause of cell degeneration in this neurological disorder remains a mystery. Herein, a hypothetical model is proposed to explain the mechanism leading neurons to die. The model is based on recent experimental evidence and it attempts to dissect the actions of dopamine and metal ions as potential triggers for the activation of an ordered cascade of events of the cell death machinery.     

Epidemiology and impact of rheumatic disorders in the United States Hispanic population

The emergence of a sizable Hispanic population in the US is a relatively recent historical phenomenon, and thus much is still unknown about this group of North Americans. Data from national surveys suggest small differences between Hispanic and non-Hispanic white populations in the age-adjusted prevalence of self-reported arthritic conditions. However, the rate of activity-limitation attributable to arthritis is higher among Hispanic patients. This likely reflects the poorer socioeconomic conditions and lack of health insurance that prevail among Hispanic populations, which may limit their access to rheumatologic care. Osteoporotic vertebral and hip fractures are less frequent, and proximal femoral mineral density is higher, in Hispanic individuals than in non-Hispanic white individuals. The mechanisms for these observations are currently under investigation. There have been no studies of the prevalence of osteoarthritis, rheumatoid arthritis, or systemic lupus erythematosus among Hispanic populations. However, important immunogenetic, clinical, and psychosocial differences between Hispanic and non-Hispanic patients in regard to rheumatoid arthritis and systemic lupus erythematosus have been reported. There is no published information on the prevalence or characteristics of other rheumatic diseases in the US Hispanic population. Emerging evidence suggests considerable underuse of certain health services for arthritis among Hispanic patients, likely due in part to socioeconomic factors. Further research is needed to determine whether biologic, cultural or psychosocial factors contribute to underuse as well. There is clearly a need for data on the prevalence and characteristics of arthritis and other rheumatic and musculoskeletal diseases in this emerging US population.     

Protective effect of melatonin against adriamycin toxicity in the rat

Adriamycin, an anthracyclinic antibiotic frequently used in quimioterapeutic treatments is highly toxic; it inhibits protein synthesis and provokes prooxidant effects. Melatonin has recently been shown to have high antioxidative properties. We tested if melatonin is able to neutralize the oxidative damage induced by a single dose (20 mg/kg, i.p.) of adriamycin preceded (3 days) and followed (7 days) by a low pharmacological dose (50 microg/kg, i.p.) of melatonin. After the administration of a single dose of adriamycin (20 mg/kg i.p.) to male Wistar rats, the reduced to oxidized glutathione (GSH/GSSG) ratio and the glutathione peroxidase (GPx, E.C. 1.11.1.9.) activity in the brain, intestine, heart, kidney, and lung were significantly reduced. When the treatment of adriamycin was preceded and followed by low pharmacological doses of melatonin, the decrease in the GSH/GSSG ratio was significantly reduced but the reduction in GPx activity was not attenuated. A significant increase in lipid peroxidation products was observed in brain, heart, and kidney tissues after a single administration of adriamycin, which was attenuated by pre- and post-treatment with a low pharmacological dose of melatonin. Our results demonstrate that oxidative damage induced by the antitumor drug, adriamycin, can be reduced by low pharmacological doses of melatonin.