Membrane attack complex of complement and 20 kDa homologous restriction factor (CD59) in myocardial infarction

In order to investigate the mechanism of deposition of the complement membrane attack complex (MAC) in cardiomyocytes in areas of human myocardial infarction, the 20 kDA homologous restriction factor of complement (HRF20; CD59) and complement components (C1q, C3d and MAC) were analysed immunohistochemically using specific antibodies. Myocardial tissues obtained at autopsy from nine patients who died of acute myocardial infarction were fixed in acetone and embedded in paraffin. The ages of the infarcts ranged from about 3.5 h to 12 days. In cases of myocardial infarction of 20 h or less, MAC deposition was shown in the infarcted cardiomyocytes without loss of HRF20. Where the duration was 4 days or more, the cardiomyocytes with MAC deposition in the infarcted areas also showed complete loss of HRF20. Outside the infarcts, HRF20 in the cardiomyocytes was well preserved without MAC deposition. The present study suggests that the initial MAC deposition in dead cardiomyocytes can occur as a result of degradation of plasma-membrane by a mechanism independent of complement-mediated injury to the membrane. Loss of HRF20 from dead cardiomyocytes may not be the initial cause of MAC deposition, but may accelerate the deposition process of MAC in later stages of infarction.     

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.     

Physiological characterization of the renal-sympathetic reflex in rabbits

In urethane-anesthetized and vagotomized rabbits, electrical stimulation of the afferent renal nerve (RN) elicited reflex changes in renal nerve activity (RNA) and arterial pressure (AP). The responses were attributable mostly to excitation of nonmyelinated afferent fibers, although, in about 30% of the animals, they were contributed slightly by myelinated afferents. In about 70% of rabbits, the peristimulus time histogram (PTH) of RNA following stimulation of the RN consisted of a long-lasting inhibitory (I) component occasionally accompanied, during its recovery phase, by a transient excitatory (E) component. In these animals, tetanic stimulation of the RN resulted in a depressor response, either alone or, if an E component was present in the PTH, followed by a slight pressor response. In the remaining rabbits, the PTH was composed exclusively of an E component and tetanic stimulation caused a pressor response. Stimulation of the RN evoked reflex changes in cardiac sympathetic discharges comparable to that of RNA, whereas the change in cervical sympathetic discharges was much smaller. The sympathetic response remained intact after a total transection of the rostral medulla near the ponto-medullary junction; the I component was even augmented. However, it usually disappeared following a transection at the high cervical cord. Bilateral lesions of the nucl. tractus solitarius (NTS) near the obex failed to appreciably affect the response. Among chemical and mechanical stimuli examined, nociceptive stimulation of the kidney elicited a sympathetic response comparable to that following nerve stimulation. In conclusion, the renal-sympathetic reflex in rabbits (1) originates predominantly from nonmyelinated afferent renal fibers activated effectively by nociceptive stimulation applied to the kidney; (2) depends critically on medullary structures other than the NTS; and (3) evokes changes of the same temporal pattern but of nonuniform magnitude in sympathetic discharges to different organs.     

ADRENAL PHEOCHROMOCYTOMA WITH BOTH BENIGN AND MALIGNANT COMPONENTS

A case of adrenal pheochromocytoma Is reported characterized by polygonal basophilic granular cells of benign type, plump eosinophilic granular cells of transitional type, and spindle-shaped cells of malignant type. In the primary tumor the neoplastic cells of each type revealed a distinctive topographical distribution. All gradations between the latter two varieties of cells were found, especially in the vicinity of the transitional cell area. Multiple metastases were present in the liver and lungs, where only anaplastic spindle-shaped cells could be found. Ultrastructurally, the benign cells contained predominantly large, rather light, secretory granules with a coarsely granulated core. In the malignant cells, the number, size, and intensity of granules varied considerably from cell to cell or even within a single cell. In general, the malignant cells had a higher frequency of smaller granules with electron-dense homogeneous cores. Moderate amounts of noradrenalin but not significant dopamine or adrenalin could be demonstrated from a metastatic nodule In liver. We postulate that this adrenal medullary pheochromocytoma was benign originally and underwent malignant transformation shortly before the patient's death. This is based upon the patient's clinical features and the peculiar structures of the primary tumor.     

Cardiac tamponade due to rupture of a subepicardial aneurysm following myocardial infarction

A 71-year-old male died of cardiac tamponade due to cardiac rupture 22 days after onset of acute myocardial infarction. Autopsy revealed rupture of an unusual ventricular aneurysm characterized by abrupt interruption of the myocardium, a narrow neck, a thin fibrous outer wall partially showing myocardial fibers, and lack of adhesion between the epicardium and pericardium. A review of the literature revealed that 11 among 32 autopsy cases of false aneurysm showed a similar morphology to the present case, these being classifiable as subepicardial aneurysm.     

Involvement of opioid receptors in phencyclidine-induced enhancement of brain histamine turnover in mice

Summary When the histamine (HA) turnover in the brain of mice was estimated on the basis of the pargyline-induced accumulation of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, the enhancing effect of phencyclidine (PCP) on the HA turnover was antagonized by a large dose of naloxone. However, a dopamine receptor antagonist haloperidol, which is also a potent receptor antagonist, did not inhibit the effect of PCP on the HA turnover. [abetd-Ala², abetd-Leu⁵]enkephalin, a prototypic opioid agonist, markedly enhanced the HA turnover. The effect of this peptide was demonstrated not only when the HA turnover was determined by the pargyline-induced t-MH accumulation but when it was estimated by the HA depletion induced by -fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. A agonist, SKF-10047, and a agonist, ethylketazocine, had no PCP-like enhancing effect on the HA turnover. These results suggest that PCP enhances the brain HA turnover in mice by stimulating, probably indireclty, endogenous opioid systems. Send offprint requests to K. Saeki at the above address     

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.     

Mental component of health-related quality of life is an independent predictor of incident functional disability among community-dwelling older people: a prospective cohort study

Quality of Life Research - Previous studies have reported a positive association between poor health-related quality of life (HRQOL) and disability mainly in relation to the physical component of...     

Angiosarcoma of the breast: Report of a case and autopsy findings

We report a case of angiosarcoma of the breast and the autopsy findings. The patient was a 35-year-old premenopausal woman who complained of a tumor in her left breast. We found a tumor measuring 55 mm in diameter in the lower external quadrant. The tumor was elastic and soft, smooth surfaced, well-defined and mobile. Dimpling sign or change of skin color were not observed. Clinically it was diagnosed as phyllodes tumor, but tumorectomy revealed primary angiosarcoma of the breast. Further extended surgery was recommended, but the patient refused additional therapy. Histological findings revealed a free surgical margin and neither lymph node metastasis nor distant metastasis were clinically observed. Seven months later, local recurrence in the same breast was recognized and finally radical mastectomy was carried out. Histological findings showed recurrence of angiosarcoma in the left breast but lymph node metastasis was not detected. Two months after mastectomy, metastases to the cervical and thoracic vertebrae were observed and radiation therapy was performed. Sixteen months from onset, she died due to multi-organ failure as general metastases of angiosarcoma. At autopsy, metastases to many organs including the digestive system were observed. The incidence of primary angiosarcoma of the breast is low but its prognosis is poor. This case emphasized the difficulties in clinical diagnosis and treatment for the angiosarcoma of the breast.