Immunohistochemical distribution of CA19-9 in normal and tumor tissues of the kidney

The immunohistochemical distribution of CA19-9 in normal and tumor tissue of the kidney was investigated. CA19-9 was detected in the cytoplasm and apical surface of renal proximal tubules, distal tubules and uroepithelium of the renal pelvis. Eight of 28 renal cell carcinomas (29%) expressed CA19-9. CA19-9 was also detected in 2 cases of transitional cell carcinoma and 1 of 4 cases of Wilm's tumor, but not in angiomyolipoma. As the measurement of CA19-9 is widely used to detect gastrointestinal carcinoma, the expression of CA19-9 in normal and neoplastic kidney tissue might have some clinical significance.     

In-vitro Negative Chronotropic and Inotropic Effects of a Novel Dihydropyridine Derivative,CD-832, in the Guinea-pig: Comparison with Calcium-channel Antagonists

The effects of CD-832 (4R-(-)-2-(nicotinoylamino)ethyl-3-nitroxypropyl-1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate), a novel dihydropyridine derivative, on guinea-pig isolated myocardial preparations have been compared with those of Ca²⁺-channel antagonists. All ten compounds induced concentration-dependent negative chronotropic effects on preparations of isolated right atria and negative inotropic effects on isolated right ventricular papillary muscles. The order of potency for the negative chronotropic effect was CD-832 > nicardipine = gallopamil > clentiazem > nifedipine = efonidipine > amlodipine = semotiadil > verapamil > diltiazem; that for the negative inotropic effect was nicardipine = gallopamil > nifedipine > verapamil > CD-832 > diltiazem > clentiazem > efonidipine = semotiadil > amlodipine. The ratio of the EC50 (the concentration of Ca²⁺ antagonist having 50% of the maximum effect) for the negative inotropic effect divided by the EC50 for the negative chronotropic effect, considered to be an index of selectivity for negative chronotropic effect, was higher for CD-832, amlodipine, efonidipine and semotiadil than for the other Ca²⁺ antagonists. The ratio for CD-832, nifedipine, nicardipine, efonidipine, amlodipine, verapamil, gallopamil, diltiazem, clentiazem and semotiadil was 11·4, 0·29, 0·87, 35·4, 37·1, 0·65, 0·87, 0·92, 7·11 and 30·0, respectively. These findings indicate that CD-832 and the newly developed Ca²⁺ antagonists including amlodipine, efonidipine, semotiadil and clentiazem were selective for a negative chronotropic effect rather than for a negative inotropic effect. This ‘chrono-selective’ effect of these drugs might be of benefit in the treatment of cardiovascular disorders.     

Muscular involvement in lysosomal acid lipase deficiency in rats.

We investigated the pathological and biochemical changes of skeletal muscle in rats with lysosomal acid lipase deficiency, which is an animal counterpart of human Wolman's disease. In the affected rats, the acid lipase activity for three different substrates, 4-methylumbelliferyl-oleate (18.9% of the normal control level), [14C]cholesteryl oleate (23.5%), and [14C]triolein (26.9%), was similarly decreased in the lysosomal fraction of skeletal muscle which was obtained by differential centrifugation. Histochemical studies showed that acid phosphatase activity was high in the endomysium and perimysium and in some muscle fibers. Some fibers showed vacuolar degeneration resembling "rimmed vacuoles". Ultrastructural studies demonstrated many membrane-bound lipid droplets in the muscle fibers, especially in the subsarcolemmal space, indicating that a low density lipoprotein (LDL) uptake pathway apparently existed in the muscle cells. However, such lipid accumulation was much greater in the interstitial cells and the endothelial cells. This distribution also suggests that LDL/cholesterol is supplied to muscle cells predominantly through endothelial cells.     

Anti-cholinergic effect of verapamil on the muscarinic acetylcholine receptor-gated K+ channel in isolated guinea-pig atrial myocytes

Summary Effects of verapamil on the acetylcholine (ACh)-induced K⁺ current were examined in single atrial cells, using the tight-seal whole-cell clamp technique. The pipette solution contained guanosine-5-triphosphate (GTP) or guanosine-5-O-(3-thiotriphosphate) (GTP-S, a non-hydrolysable GTP analogue). In GTP-loaded cells, ACh induced a specific K⁺ current, which is known to be mediated by pertussis toxin-sensitive GTP-binding (G) proteins. Verapamil (0.1–100 M) depressed the ACh-induced K⁺ current in a concentration-dependent fashion. In GTP-S-loaded cells, the K⁺ current remained persistently after wash-out of ACh, probably due to irreversible activation of G proteins by GTP-S. Verapamil (0.1–100 M) also depressed the intracellular GTP-S-induced K⁺ current. However, the magnitude of verapamil-depression of the K⁺ current in GTP-S-loaded cells was significantly smaller than that in GTP-loaded cells at concentrations between 1 and 10 M of the drug. From these results, it is suggested that verapamil may block not only the function of muscarinic ACh receptors but also of G proteins and/or the K⁺ channel itself and thereby depress the ACh-induced K⁺ current in isolated atrial myocytes.Supported by grants from the Ministry of Education, Science and Culture of Japan and the Research Program on Ca Signal Control Send offprint requests to Y. Kurachi at the above address     

A comparison of three bioelectrical impedance analyses for predicting lean body mass in a population with a large difference in muscularity

This study tested the hypothesis that, as compared to whole-body bioelectrical impedance (BI) analysis, segmental BI analysis can estimate lean body mass (LBM) more accurately in a population with a large difference in muscularity. In addition to whole-body BI, which determines impedance (Z) between the wrist and ankle, two segmental BI analyses which determine the Z value of every body segment in each of (1) the arms, legs and trunk (distal BI) and (2) the upper arms, upper legs and trunk (proximal BI) were applied to a group of 125 male athletes and 75 non-athletes. The subjects were divided into validation and cross-validation groups. Simple and multiple regression analyses were applied to (length)²/Z (BI index) values for the whole-body and each body segment, to develop the prediction equations of LBM measured using air-displacement plethysmography. In the validation group, the SE of estimation was similar in the whole-body (3.4 kg, 5.4%), distal (3.4 kg, 5.5%) and proximal BI (3.3 kg, 5.2%) analyses. However, the whole-body and distal BI analyses produced systematical errors in the estimates of LBM. Moreover, the residuals in the two methods significantly (P<0.05) correlated with the ratios of BI indices of the upper arms and upper legs to those of the arms and legs, respectively, calculated as variables approximating the relative development of lean tissues at the proximal area of limbs. On the other hand, the proximal BI analysis was validated and cross-validated. Thus, the accuracy of estimating LBM was similar in the whole-body and the two segmental BI analyses. However, the prediction equations derived from the use of the whole-body BI index and a combination of the arms, legs and trunk BI indices produced a systematical error relating to the difference between the limb segments in lean tissue development.     

MALLORY BODY-LIKE STRUCTURES IN THE LUNG

Mallory body-like structures (MBLs), which resemble Mallory body (MB) in the liver, were observed in lungs of 4 cases showing interstitial pneumonitis. MBLs were found in the cytoplasm of especially swollen alveolar epithelial cells. MBLs and MBs had almost similar characteristics morphologically and tinctorially under the light microscopy. MBLs were composed of intermediate type fine fibrils which were positive for anti-keratin antibody. These findings suggested that MBLs were a kind of pathological keratinization of alveolar epithelial cells. Although the origin of MBL containing cells could not be clarified, they were closely related to type 2 alveolar epithelial cells.     

Long term experiment of perfluorochemicals using rabbits

Summary Morphological changes six months to two years after the administration of Perfluorochemicals (PFC) in rabbits injected with a large amount of PFC (67 mg/kg) have already been reported by Ohnishi and Kitazawa (1979, 1980, and 1981). In this paper, the authors report on the persistance of large numbers of foamy cells in the liver, spleen and lymph nodes and many in the kidneys, lung and bone marrow, up to two years after administration. Quantitative analysis of PFC in various organs showed that it was retained. The liver revealed progressive fibrosis surrounding the foamy cells in or around the Glisson's sheath.     

An improved method for the detection of HIV antigen in the blood of carriers

The measurement of HIV antigen levels in sera or plasma of HIV-infected individuals is critical for determining the existence of antigen or infectious virus before seroconversion and for prognosis. Pretreatment of sera or plasma of HIV carriers by heating at 70 degrees C for 10 min at an acidic pH enabled us to estimate antigens efficiently in immune complexes. This procedure will also be useful in determining antigen levels in HIV carriers more precisely.