Patterns and problems of alcohol consumption in Japan.

The authors trace the roots of Japan's drinking culture and show how socioeconomic developments, especially in the cities, have led to increased alcohol consumption and associated problems. Measures taken by both the state and nongovernmental bodies to combat alcohol abuse and rehabilitate alcoholics are outlined.     

Evidence for the existence of intraepithelial nerve endings in the junctional epithelium of rat molars: an immunohistochemical study using protein gene product 9.5 (PGP 9.5) antibody

Innervation of the junctional epithelium was investigated in rat molars by means of immunohistochemistry for protein gene product 9.5 (PGP 9.5) at light and electron microscopic levels. In comparison with our previous study on same tissues using neurofilament protein (NFP)-antibody, the PGP 9.5-immuno-staining further disclosed numerous nerve fibers in the gingiva of rat molars and revealed the existence of a well-developed plexus of PGP 9.5-positive nerve fibers. The interproximal portion also contained numerous nerve fibers.
Observation of horizontal sections revealed a denser innervation toward the inner junctional gingival epithelium than the outer marginal epithelium. The nerve fibers, beaded in appearance and extending from the nerve bundles in the lamina propria, penetrated into the junctional epithelial layer and were distributed throughout the junctional epithelium, with some nerves being located near the epithelial surface. Non-neuronal cells showing PGP 9.5-immunoreactivity were absent in the junctional epithelium. In immunoelectron microscopy, the axoplasm of nerves in the gingiva was filled with electron-dense reaction products of PGP 9.5, except for the cell organellae. The nerve fibers were devoid of Schwann cell investment and terminated among the epithelial cells in the junctional epithelium, frequently beneath the epithelial surface. The intraepithelial nerve endings contained various kinds of vesicles including large-cored ones, supporting the presence of peptidergic innervation shown by previous studies. These findings confirmed the usefulness of PGP 9.5-immunohisto-chemistry for the identification of delicated nerve fibers in dental tissue, and suggested the dense network of nerve fibers that may serve as sensory receptor and other functions in the junctional epithelium.     

Effects of Self Washout Structure on the Antithrombogenicity and the Hemolytic Properties of a Centrifugal Pump

Abstract: Antithrombogenicity in an initial type (Nl) of a centrifugal pump (CP) developed in our institute is provided by the central balancing hole of an impeller. A new CP (N2) was modified to obtain better antithrombogenicity, in which the balancing hole was widened to improve self washout flow velocity (Vsf), and an edge of the thrust bearing was rounded off to minimize flow separation. Effects of the modifications were assessed in vitro and in vivo studies. The Vsf of the Nl and the N2 evaluated by a Doppler velocimeter were 12.8 and 22.1 cm/s, respectively. Flow around the thrust bearing, which was visualized by a light cutting method, confirmed less flow stagnation in the N2. The hemolytic indices of the Nl and the N2 were 0.023 and 0.008 mg/dl, respectively. In vivo antithrombogenicity and the hemolytic properties of the N2 and the Nl were investigated without anticoagulation therapy in 3 goats. In each goat the N2 was driven for 1 week and exchanged for the Nl, which was driven for the same period. Red thrombi at the thrust bearing were found in 2 Nls, and 2 small thrombi were on the impeller of another Nl, whereas a thrombus of less than 1 mm³ at the TB was noted in 1 N2. Plasma free hemoglobin was not increased in either CP. These results indicate that the N2 has better antithrombogenicity and hemolytic properties than the Nl.     

An artificial amino acid, 4-iodo-L-meta-tyrosine: biodistribution and excretion via kidney.

We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-(125)I-iodo-L-meta-tyrosine (4-(125)I-mTyr). Results obtained for L-(14)C-Tyr and 3-(125)I-iodo-alpha-methyl-L-tyrosine ((125)I-IMT) were used for comparison. METHODS: In vivo biodistribution studies of 4-(125)I-mTyr were performed in male ddY mice. Urinary excretion of 4-(125)I-mTyr and (125)I-IMT with administration of probenecid was studied. Local distribution of 4-(125)I-mTyr and (125)I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-(125)I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-(125)I-mTyr were compared with those of (125)I-IMT and the parent L-(14)C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK(1) in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na(+)-free medium, and at 4 degrees C. RESULTS: 4-(125)I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of (125)I-IMT. Blood clearance of 4-(125)I-mTyr was faster than that of (125)I-IMT. Three hours after administration, >70% of 4-(125)I-mTyr was excreted via the urine, whereas <5% was found in the feces. Renal autoradiography revealed moderate accumulation of 4-(125)I-mTyr and high accumulation of (125)I-IMT in the renal cortex. Probenecid further reduced accumulation of 4-(125)I-mTyr and (125)I-IMT in the kidney as well as urinary excretion. At 30 min after tracer injection, intact free 4-(125)I-mTyr accounted for >98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-(125)I-mTyr into LLC-PK(1) cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4 degrees C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-(14)C-Tyr and (125)I-IMT showed similar results; however, uptake of (125)I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates. CONCLUSION: The artificial amino acid 4-(125)I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radiolabeled L-Tyr analogs. 4-(125)I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-(125)I-mTyr demonstrates different pharmacologic features than those of (125)I-IMT, particularly in renal handling. 4-(125)I-mTyr may potentially be applied as a new amino acid transport marker.     

Scintigraphic image patterns in dysplastic coxarthrosis: Evaluation with reference to radiographic findings in 210 hips

Little is known about scintigraphic image patterns in the various stages of coxarthrosis. We assessed bone scintigraphy in 159 patients (210 hips) with dysplastic arthrosis of the hip. Scintigraphic images were divided into 5 types related to the radiographic stages of the disease. The scintigraphic images showed little, if any, uptake in the stage of prearthrosis. In the early stage, we found an increase in uptake in the weight bearing area in 30% of cases. In the advanced stage, more than half of the cases had an increase in uptake in the medial side of the joint and in the weight bearing area. In the terminal stage, a marked increase in uptake in the weight bearing area was commonest. Since the osteoblastic reaction intensified, a marked increase in uptake was seen not only in the weight bearing area, but also throughout the entire joint. These types of scintigraphic patterns, which change with the stage of coxarthrosis, seem to reflect the natural course of the disease. All hips with rapid progression of the disease showed a marked increase in uptake of radionuclide the entire joint at earlier stages.     

Study of anticoagulant mechanism of low molecular weight heparin

The binding ability of low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) to factor Xa (F.Xa), thrombin and ATIII was investigated using FR-860- and UF-heparin-Sepharoses. FR-860 could not bind directly to F.Xa. FR-860 bound to thrombin and ATIII with stronger affinity to ATIII than to thrombin. On the other hand, UF-heparin bound to F.Xa, thrombin and ATIII with the strongest affinity to AT III followed by thrombin and F.Xa. AT III mediated the binding between F.Xa and FR-860 and accelerated the reaction between F.Xa and UF-heparin. On the other hand, ATIII did not affect the binding between thrombin and FR-860 or UF-heparin. Diisopropyl fluorophosphate-treated thrombin inhibited the binding between ATIII and FR-860, but not that between ATIII and UF-heparin. These results suggest that the anti-F.Xa activity of FR-860 is mediated by AT III. Furthermore, the difference of antithrombin activity between FR-860 and UF-heparin depends on the capability to form ternary complex of FR-860 or UF-heparin, ATIII and thrombin.