Studies on the mechanisms underlying beta-adrenoceptor-mediated relaxation of rat abdominal aorta.

Mechanisms underlying beta-adrenoceptor (beta-AR)-mediated vascular relaxation were studied in the isolated rat abdominal aorta. In the endothelium-denuded helical preparations, a non-selective beta-AR agonist isoprenaline elicited a concentration-dependent relaxation. In the absence of beta-AR antagonists, isoprenaline-induced relaxation was not practically affected by an adenylyl cyclase inhibitor SQ 22,536 (300 microM), but was strongly diminished by high-KCl (80 mM). Isoprenaline-induced relaxation in the presence of SQ 22,536 was significantly diminished by iberiotoxin (IbTx, 0.1 microM), but was not affected by 4-aminopyridine (4-AP, 3 mM). Isoprenaline-induced relaxation was not also affected by SQ 22,536 (300 microM) even in the presence of CGP20712A (a beta(1)-selective antagonist) and ICI-118,551 (a beta(2)-selective antagonist) (0.1 microM for each), but was strongly diminished by high-KCl. By contrast, SQ 22,536-resistant, isoprenaline-induced relaxation in the presence of CGP20712A plus ICI-118,551 was not affected by IbTx (0.1 microM), but was inhibited significantly by 4-AP (3 mM). These results suggest that in rat abdominal aortic smooth muscle: 1) both beta(1)-/beta(2)-AR- and beta(3)-AR-mediated relaxations substantially involve cAMP-independent mechanisms; 2) beta(1)-/beta(2)-AR-mediated, cAMP-independent relaxant mechanisms are partly attributed to the large-conductance, Ca (2+)-sensitive K(+) (MaxiK, BK) channel whereas beta(3)-AR-mediated relaxant mechanisms are attributed to K(v) channel.     

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

Evidence for a defect in urinary concentrating ability in primary aldosteronism and its reversal by adrenal surgery

Of 15 patients with primary aldosteronism, 7 had idiopathic adrenal hyperplasia (IHA) and 8 had aldosterone-producing adenoma (APA). In order to determine any renal problems involved in the treatment, the renal clearance of these patients was analyzed and the results compared with those obtained from 12 patients with essential hypertension. With water diuresis or under antidiuresis status, levels of urine volume, Cosm and CH2O in patients with APA were greater (p less than 0.05-p less than 0.001) than those of patients with essential hypertension, while the fractional tubular sodium delivery of the former patients was lower than that of the latter patients (p less than 0.001 or less than 0.05). A similar tendency was observed in clearance studies in patients with IHA, although to a lesser extent. Adrenal surgery for patients with APA normalized these values, but administration of trilostane (3 beta-hydrosteroid dehydrogenase inhibitor) to patients with IHA failed to improve these values. These results indicate that impaired urinary concentrating ability as well as reduced urinary diluting capability is a common feature of primary aldosteronism. Such impaired renal function was improved only in patients with APA after adrenal surgery.     

Papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma

 We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically positive for vimentin, α-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100, thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation may contribute to the stromal response in the slow growth of the papillary carcinoma. Received: 29 August 1996 / 26 May 1997     

Pulmonary lesions of acquired immunodeficiency syndrome--analysis of 24 Japanese autopsy cases with AIDS]

The pulmonary lesions were studied in 24 autopsy cases of Japanese patients with AIDS. The major pathological findings were opportunistic infections, which were the major clinical symptoms in some patients. The pathogens identified were as follows; Pneumocystis carinii (PC) in 10, cytomegalovirus (CMV) in 14, atypical mycobacterium in 5, cryptococcus in 2, candida in 2, and nocardia in 1. PC pneumonia was prominent in 8 cases and was the cause of death. In such patients, the lung were heavy and appeared parenchymatous. Histological examination revealed numerous protozoa in the foamy material in the alveolar spaces, associated with swelling of the alveolar lining cells and edematous thickening of the alveolar septa. In some cases, only hyaline membrane formation was prominent without foamy material in the alveolar spaces. Immunostaining with anti-PC monoclonal antibody or in-situ hybridization with oligopeptide demonstrated pathogens in the hyaline membranes. Many cases with PC pneumonia had concomitant opportunistic infections such as CMV, Herpes simplex virus, and atypical mycobacterium. Extrapulmonary infection of PC was seen in only one case. CMV infection was found in 14 cases; 7 had innumerable inclusion bodies, and in some cases the lesions were most prominent around the bronchioles. Of the 5 cases of atypical mycobacterial infection, 2 were caused by M. kansaii (MK) and 3 by M. avium intracellulare (MAI). Both lesions of MK infection showed necrosis and cavitation. One of three cases of MAI infection showed cavitation. Around the cavitary lesions, numerous cytomegalic inclusion bodies were identified in the mesenchymal cells, which may have been the cause of necrosis and cavitation of the lesions. MAI infection was systemic and pronounced in the lymph nodes, spleen, and intestinal mucosa. Neoplastic lesions comprised 2 cases of Kaposi's sarcoma and 4 of extranodal non-Hodgkin lymphoma in other organs. Lung involvement was seen in only one case of Kaposi's sarcoma although very small in size. The lesion was situated along the pulmonary vein and appeared hemorrhagic macroscopically. Pulmonary lesions in AIDS are complicated, and many of opportunistic pathogens were identified in single patients.     

Prefrontal cerebral activity during a simple “rock, paper, scissors” task measured by the noninvasive near-infrared spectroscopy method

We conducted a noninvasive near-infrared spectroscopy (NIRS) study using the game of rock, paper, scissors (RPS) as a simple neurocognitive task for the prefrontal cortex (PFC) in 15 healthy volunteers. We employed an opposite “to lose” RPS task coupled with a normal “to win” RPS task, since the former requires inhibition of behavior, one of the most important functions of the prefrontal cortex. During the NIRS examination, subjects had to present one of the three RPS hands in response to hands displayed randomly on a computer screen every 1.5 s, and were required to show hands that lose to the computer, or that beat the computer. We measured the relative concentrations of oxyhemoglobin (oxy-Hb) using the prefrontal probes of the NIRS system during the tasks. The increases in oxy-Hb during the “to win” RPS task were small, but were quite large and laterally dominant during the “to lose” RPS task. The difference between the two tasks might have been due to the participants’ cognitive conflict with losing on the RPS. We conclude that losing is better than winning on the RPS as a sensitive indicator in the NIRS examination of PFC.     

Hepatic infarction with portal thrombosis

A case of hepatic infarction with portal thrombosis is reported. A 63-year-old woman with liver cirrhosis and esophageal varices was admitted for treatment of the esophagel varices. Endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) were performed. Two months later, she experienced right hypochondralgia and right flank pain. Serum transaminase levels were suddenly elevated, and computed tomography scans of the liver showed multiple small nodular lesions. Her condition worsened, and she died of hepatic failure. Autopsy revealed splenic and portal vein thrombosis, multiple hepatic infarction, and evidence of chronic pancreatitis. We believe that liver cirrhosis and chronic pancreatitis were the main risk factors for the portal thrombosis, and the treatment for esophageal varices appeared to have triggered the thrombosis. The hepatic infarction was caused by the portal thrombosis.     

Measurements of active and passive force of horizontal muscles in strabismus

A precision device was developed for quantitative measurement of the active and passive forces of the horizontal muscles in several different types of strabismus. The device consists of a tension gauge for measuring isometric muscle tension (active force) and passive length-tension (passive force), and a circular-motion guide mechanism. In normal subjects, the active force showed nearly linear changes with the eye position, as was reported in past studies. A similar relationship between the active force and the eye position was observed also in strabismus patients in our study. Normal subjects showed a stronger force in the medial than the lateral rectus muscle. Among strabismus patients, those with normal retinal correspondence (NRC)-intermittent exotropia showed a force closest to that of the normal controls. However, the force of the lateral rectus muscle was significantly greater in those with constant exotropia than in the normal controls. The active force of the medial rectus muscle was significantly smaller in those with dual retinal correspondence (DRC)-intermittent exotropia and constant exotropia. Conversely, the active force of the medial rectus muscle was significantly greater in those with esotropia, compared with the normal group. As for the passive force, there was no significant difference between the temporal passive force and the nasal passive force in the normal and esotropic groups, but the temporal passive force was significantly greater in the esotropic group. The magnitude of the force was greater in both directions when traction was applied against the muscle having the stronger active force. These results suggest that the lateral rectus muscle force is relatively stronger in patients with DRC-intermittent exotropia due to a weakness of the medial rectus muscle force, and that the absolute strength of the lateral rectus muscle force is increased in patients with constant exotropia, but in NRC-intermittent exotropia the muscle forces are almost normal. Those with esotropia are considered to have an absolute increase in the medial rectus muscle force.