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In situ hybridization of slide-mounted brain sections from rats subjected to acute and chronic phencyclidine treatment was carried out using synthetic oligonucleotides complementary to dopamine D2-receptor and non-N-methyl-D-aspartate (NMDA) glutamate-receptor-subunit (GluR-1) mRNAs. There was no significant difference in either the D2-receptor or the GluR-1 mRNA levels in any brain region of the acute phencyclidine (10 mg/kg)-treated and control groups. However, chronic administration of phencyclidine (10 mg/kg/day, 14 days) significantly decreased the dopamine D2-receptor mRNA level in the caudate-putamen (by 27%, P < 0.01) and significantly increased the GluR-1 mRNA level in the prefrontal cortex (by 29%, P < 0.001). These results suggest that the chronic pharmaco-behavioral effects of phencyclidine may involve expression of both dopamine- and non-NMDA glutamate-receptor mRNAs.

We administered a biological response modifier Picibanil (OK-432), attenuated Streptococcus pyogenes, via the dorsal vein of the penis after 70% hepatectomy in rats, and clarified the scavenging effect of Picibanil on free radicals generated in the regenerating liver. A group of 5 rats was intravenously administered with 25 KE/kg of OK-432 after hepatectomy, while the control group was given saline after hepatectomy. Serum levels of aspartate aminotransferase and alanine aminotransferase and the value of thiobarbituric acid-reactive substances in serum and hepatic tissue after hepatectomy were serially measured, and these values were significantly lower in Picibanil treated animals than in control animals. Free radical production in the regenerating liver was also measured by electron spin resonance spectrometry, and OK-432 injection significantly reduced free radical production. These results suggested that OK-432 reduced hepatocellular damage in regenerating liver by inhibiting lipid peroxidation.

The incidence of nosocomial infections with methicillin-resistant Staphylococcus aureus is of great concern in Japan and the developed world as a whole. Simple typing techniques like coagulase and phage typing are quick and useful for monitoring and evaluating these organisms. In view of this, the current status of antimicrobial susceptibility in Staphylococcus aureus (S. aureus) isolates in Okinawa typed by coagulase and phage typing was studied. Of 508 isolates, methicillin-resistant S. aureus (MRSA) comprised 54.3% (minimum inhibitory concentration (MIC) > or = 16 micrograms/ml). Coagulase type II and phage group III were the most prevalent, comprising 65.2% and 38%, respectively. These were followed by phage non-typable group and coagulase type III with 36.6% and 12.7%, respectively. Compared to a previous study conducted in 1989, there has been an increase of about 17% in the MRSA isolation rate with a concomitant increase of about 11% in the coagulase type II MRSA isolation rate and a decrease of about 27% in the isolation rate of coagulase type III MRSA. Using a panel of 16 antibiotics, coagulase type II MRSA were resistant to all except Arbekacin and Vancomycin. Arbekacin and Vancomycin were the sole antibiotics to which resistance was not expressed by any of the isolates. With regard to the methicillin-sensitive S. aureus (MSSA), coagulase type III and phase group III were the most prevalent, comprising 25.9% and 32.3%, respectively.

An enzyme-linked immunosorbent assay (ELISA) using biotin-labelled oligo-dT primer and digoxigenin (Dig)-dUTP was designed to measure the reverse transcriptase (RT) activity of human immunodeficiency virus type 1 (HIV-1). The ELISA system involves the selective detection step of a newly synthesized cDNA by two specific bindings, biotin-streptavidin binding and alkaline phosphatase (AP)-conjugated anti-Dig-Dig binding, and the enzymatic amplification step to increase coloring generated by AP. This method was used to measure the activity of RT in the culture supernatants of peripheral leukocytes obtained from four anti-HIV-1-positive persons cocultivated with those from four anti-HIV-1-negative persons. RT activity was detected in all of four anti-HIV-1-positive culture supernatants but not in those cultivated with anti-HIV-1-negative supernatants alone. Thus, our improved ELISA for detection of HIV-1 appears to be sensitive enough and useful for routine laboratory work. This non-radioactive method will also be useful for detecting other retroviruses and for screening of RT inhibitors.

The purpose of this study was to determine the aerobic training intensity from the maximal and submaximal running exercise in 21 untrained adult men. To accomplish this, we evaluated the relationship between physiological (oxygen intake and heart rate) and physical parameters (running speed) of training intensity, and determined the training intensity at the submaximal exercise. Oxygen intake and heart rate were measured by a treadmill test. The maximal oxygen intake (VO2 max), and the aerobic threshold (AerT) and anaerobic threshold (AT) were measured to determine respiratory gas exchange. Running capacity was measured by a 12-min running and treadmill test. For the maximal exercise, there was a significant correlation (r = 0.88, P < 0.01) between VO2 max and 12-min running distance (speed). In addition, the oxygen intake and heart rate at AerT and AT in the submaximal exercise were linearly correlated with running speed. Three levels of training intensity at the submaximal exercise were termed: light, moderate, and heavy. Since AerT was the lower limit intensity and AT was the upper limit, we took the middle of their values as the moderate intensity. The end point for the determination of the training intensity at the submaximal exercise was estimated to be 85% VO2 max and 180 beats.min-1.

The contribution of age groups and causes of death to the sex difference in life expectancy (SDLE) at birth in Japan and Scotland was estimated for the period 1965-1990. The purpose was to determine the particular age groups and causes of death responsible for the opposite trend of SDLE in the two countries. SDLE has been widening and narrowing in Japan and Scotland, respectively. The availability of complete and reliable data for these two developed countries facilitated the study. A method of decomposing the total SDLE into age and cause of death components was employed. About 40-60% contribution to SDLE was observed for ages after 65 years. Marked increase in the contribution of the 75+ age group and marked decrease in the contribution of ages 45-64 for Japan and Scotland, respectively, had a major effect on the widening and narrowing of SDLE in the two countries, respectively. The contribution of diseases of the circulatory system was the maximum until 1980 in Japan (< or = 1.8 years or 33.6%; cerebrovascular disease alone < or = 23.4%) and until 1990 in Scotland (< or = 3.1 years or 47.0%; ischemic heart disease alone < or = 42.0%). In Japan, the contribution of malignancy had a marked increased from 0.7 year (12.3%) to 2.0 years (32.6%), particularly for the trachea, bronchus and lung, while there was only a small increase in Scotland from 1.0 year (16.6%) to 1.2 years (19.8%) with an increase in the negative contribution of female breast malignancy. In Japan, the contribution of diseases of the respiratory system increased considerably from 0.5 year (8.5%) to 1.1 years (18.1%) while it decreased in Scotland from 1.0 year (16.5%) to 0.6 year (10.7%). About 60-75% of SDLE is due to the above three groups of causes of death. Malignancy and diseases of the respiratory system had a persistently increased contribution in Japan with resultant widening of SDLE by 0.9 year. Diseases of the circulatory system have always had a high contribution. On the contrary, in Scotland the contribution of diseases of the circulatory system and malignancy was practically unchanged and diseases of the respiratory system had a decrease with a consequent narrowing of SDLE by 0.4 year. Further epidemiological study is necessary to detect and analyze in detail the internal gradients (environmental and genetic-biological) of major contributor diseases to SDLE in Japan and Scotland.

A study of 1,254 laparoscopic cholecystectomies performed at 17 hospitals affiliated with the Liver, Gallbladder, and Pancreas Research Group of the First Department of Surgery at Okayama University was undertaken to assess the current status and safety of this procedure. The data for 336 patients, comprising the initial 20 laparoscopic cholecystectomies performed at each institution, were compared with the data from the remaining 918 patients. Comparison of the two groups revealed the following: 1. the rates of intraoperative conversion to open cholecystectomy were 11.3% and 5.1% (P < 0.05), 2. the complication rates were 5.7% and 3.4%, and 3. the rates of bile duct injury were 2.4% and 1.1%, respectively. Compared with the first group, the bile duct injuries resulting from a lack of experience decreased in the second group, however, the incidence of these injuries occurring during avulsion of the gallbladder in difficult cases increased. These results suggest that the experience acquired during the initial 20 laparoscopic cholecystectomies led to a reduction in the rate of intraoperative conversion to open cholecystectomy, but it did not reduce the rate of complications, and that the risk of bile duct injury was always present.

Chinese ant extract preparations (CAEP) are a Chinese traditional medicine which is mainly used as a health food or drink for the treatment of rheumatism, rheumatoid arthritis, chronic hepatitis, sexual hypofunction, and antiaging in China. The effects on free radicals were examined by electron spin resonance spectrometry using the spin trapping agent 5.5-dimethyl-1-pyrroline-1-oxide (DMPO). Superoxide radicals (3.35 x 10(15) spins/ml) were quenched 50% by the extract at 0.5 mg/ml. The CAEP extract at 0.7 mg/ml inhibited 50% of hydroxyl radicals (52.0 x 10(15) spins/ml) generated by the Fenton reaction. Against DPPH radical, the scavenging action of CAEP was observed at 1.8 mg/ml of the extract and 50% of the DPPH radicals (8.14 x 10(15) spins/ml) were quenched. In vitro tests showed that CAEP inhibited the production of thiobarbituric acid-reactive substances, an index of lipid peroxidation, in rat brain homogenate.

This study was conducted to retrospectively analyzed the outcome of 192 total knee arthroplasties in 132 patients with rheumatoid arthritis (118 women, 14 men). The Okayama Mark II prosthesis, which requires the posterior cruciate ligament (PCL) to be resected, was used in 83 knees (group I), the Mark II prosthesis, which allows the PCL to be retained, was used in 68 knees (group II), and the new Okayama PCL-R prosthesis, which also allows the PCL to be retained, was used in 41 (group III). According to the Japanese Orthopaedic Association knee scoring system, the clinical outcome of groups I, II and III at 1 year after the operation were 64.9, 71.2 and 72.3 points, respectively, and the average flexion angles in each group at 1 year were 78.4, 92.6 and 101.3 degrees. Postoperative flexion in groups III was significantly greater than in groups I and II. These results suggest that postoperative flexion is greater when the posterior cruciate ligament is retained.

Localization of the glycosaminoglycans (GAG) was examined in the synovial membranes of patients with osteoarthritis under light microscopy using a fine cationic colloidal iron staining method combined with enzymatic digestion. Our staining method was very useful for demonstrating the difference in the localization of GAG in regions of the inflammatory site in the osteoarthritic synovial membrane. Hyaluronic acid was mainly located in connective tissues in the surface intercellular and perivascular spaces, chondroitin sulfate A/C in the highly fibrous part of and connective tissue around blood vessels, dermatan sulfate (chondroitin sulfate B) in the subsurface interstitium and vascular endothelial cells and heparan sulfate in part of vascular endothelial cells. No keratan sulfate was detected. GAG is reported to have an important role in cell movement, adherence and aggregation in the inflammatory sites. These findings should be useful for understanding the role of GAG in physiological and pathologic processes of secondary synovitis.

Etoposide (VP-16), one of the topoisomerase II (TopoII) inhibitors, interferes with TopoII by inducing the formation of and stabilizing a cleavable enzyme-DNA complex. VP-16 has been demonstrated to induce apoptosis in murine thymocytes. To clarify the mechanism of action of VP-16, we examined the in vitro effect of a non-cleavable-complex-forming type TopoII inhibitor, ICRF-193 which inhibits the DNA strand breakage induced by VP-16, on murine thymocytes in which apoptosis had been induced with VP-16. DNA fragmentation is characteristic of apoptosis. In the early stages, ICRF-193 decreased DNA fragmentation induced by VP-16, although this inhibitory effect decreased in the later. These data suggest that TopoII inhibitors induce apoptosis in murine thymocytes in two ways: with DNA-strand breaks in the early stage or without them. ICRF-193 itself induced apoptosis in murine thymocytes. The time course of DNA fragmentation caused by ICRF-193 was different from that of VP-16.

In this study, we measured free radicals and thiobarbituric acid-reactive substances (TBARS) in hepatocellular carcinoma and in non-cancerous liver parenchyma. There was a higher concentration of free radicals in malignant tissue than in non-cancerous tissue. In contrast, the level of TBARS was significantly (P < 0.01) lower than non-cancerous liver parenchyma. These paradoxical results suggested that antioxidative enzyme activity and/or inhibition of lipid peroxidation were higher in hepatocellular carcinoma.

Examination was made of the in vitro response of human peripheral blood mononuclear cells (PBNMCs) to phytohemagglutinin (PHA) following treatment with varicella zoster virus (VZV) or herpes simplex virus type 1 (HSV 1). Cell proliferation was determined by colorimetric assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide. The response to PHA was depressed in all cases by virus infection of PBMNCs prior to PHA treatment. When the infection with the viruses was after PHA treatment, PHA response differed. For VZV infection, the response increased in four out of six samples, but was reduced in the other two. The response to PHA was depressed in all six samples by HSV 1 infection.

Many of Helicobacter species have been found to have novel cholesteryl glucosides (CGs). To study the biosynthetic mechanism of CGs, the lipid profiles of H. pylori and H. mustelae grown in serum-supplemented and cholesterol-restricted serum-free media were investigated. In contrast to the serum-supplemented state, helicobacters had less CGs in the serum-free state; a trace amount of CGs and no CG was detected in H. pylori and H. mustelae, respectively. The proportion of total and individual phospholipid also showed significant alteration. Unknown lipids which did not contain phosphate and sugar were detected in the serum-free state, but not in the serum-supplemented state. The CGs were found to be distributed mainly in the membrane fractions, and one of the unknown lipids was found exclusively in the cytosol fraction. Based on these data, it is apparent that the CGs of helicobacters are synthesized by de novo uptake of cholesterol from the media. The unknown lipids detected in the serum-free state may be storage lipids, appearing in response to depletion of nutrients, especially cholesterol, or other factors in the media.

Fas antigen (ag) is a cell surface protein known to trigger apoptosis in a variety of cells upon specific antibody binding. On the other hand, Bcl-2 protein, an oncogene product located at the mitochondrial inner surface, prolongs cell survival by blocking apoptosis. In this study we examined the expression of Fas ag and bcl-2 protein in 17 cases of hepatocellular carcinoma (HCC) to determine their role on HCC. By flow cytometric analysis, mean (SD) value of the expression of Fas ag on hepatocytes derived from normal liver, diseased liver (chronic hepatitis or liver cirrhosis) and HCC was 5.8 (4.7)%, 10.3 (6.9)%, and 24.0 (18.2)%, respectively. Fas ag expression on hepatoma cells was significantly greater than normal and diseased liver cells. The expression of Bcl-2 protein in normal liver, diseased liver and HCC was 4.3 (8.5)%, 0.8 (2.5)% and 2.1 (3.4)%, respectively, and the difference was not significant. These results suggest that induction of apoptosis may be a possible therapy against HCC.

Neuroprotective therapy for Parkinson's disease (PD) is a treatment intended to prevent or reduce neuronal degeneration. Since clinical studies to evaluate such an effect would be prolonged, the choice of agents for use as possible neuroprotective therapy is based on the results of in vitro and animal experiments. Free radicals are currently regarded as the most important factor in the progression of PD. One current possible neuroprotective therapy is reduction of levodopa dose, since levodopa is a source of free radical formation. Dopamine (DA) metabolism inhibition, and administration of the DA agonist bromocriptine that eliminates hydroxyl free radicals have neuroprotective effects experimentally. The other candidates for neuroprotective agents are still under development. However, those whose clinical use is permitted should be considered for use, since patients with long-standing PD cannot wait until the neuroprotective efficacy of these agents is confirmed by clinical study.

The effects of acute exposure to cigarette smoke and systemic administration of nicotine on intestinal propulsion were investigated in rats. The propulsive activity was measured as migration of charcoal powder in the intestine. This activity was suppressed by acute exposure (10 min) to cigarette smoke and by nicotine (0.5 mg/kg x 2, s.c.) administration. This intestinal suppression was more marked in the rats given nicotine than in those exposed to cigarette smoke, whereas the plasma concentrations of nicotine in both rats were similar. These results suggest that acute exposure to cigarette smoke and nicotine administration delay gastric emptying and/or suppress intestinal propulsion, and that some components other than nicotine contained in cigarette smoke may attenuate the suppression of intestinal propulsion induced by nicotine.

Although a strong association has been established between chronic Helicobacter pylori infection and peptic ulcers, the role of H. pylori is not necessarily causative because there are many patients infected with H. pylori who do not develop peptic ulcer. Therefore, we studied the relationship between the gastric mucosal environment and the development of peptic ulcers. We examined 165 endoscopic biopsy specimens from the gastric mucosa of 33 patients with peptic ulcers using the 5-point gastric biopsy method. The follow-up biopsies done within 3 weeks were well correlated with the first biopsy samples. We also reviewed the clinicohistopathological findings of 2250 endoscopic biopsy specimens from 450 patients with active gastric and/or duodenal ulcers. Over 90% of the patients with duodenal ulcer, with or without gastric ulcer, had no fundic gland atrophy, and a high incidence of intestinal metaplasia and pyloric mucosal atrophy was found in the patients with gastric ulcer. These findings suggest that patients with concomitant active gastric and duodenal ulcers exhibit severe atrophic changes in the antral mucosa but not in the fundic mucosa.

We recently reported that stimulation of the arginine vasopressin (AVP) V1-receptor enhanced the pressor response in spontaneously hypertensive rats (SHR). In the present study, we investigated acute changes in systolic blood pressure (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1-receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats (control) to determine whether the pressor effect is specific to SHR or is present in other hypertensive animal models. SBP increased significantly in DOCA rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR. Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP or HR. SBP tended to increase when AVP was administered after injection of OPC-31260. HR increased significantly 15 min after the combined treatment with OPC-31260 and AVP in DOCA rats compared with control rats. SBP did not change significantly when AVP was administered after injection of OPC-21268 in DOCA or control rats, but HR decreased significantly from 1 to 4 min after injection of AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not enhance the pressor response in the DOCA rat, which is a model of volume-dependent hypertension, suggesting that the AVP system, especially V1-receptor, is not as important in the development or maintenance of hypertension in DOCA rats as in SHR.

The results of rotationplasty for patients with osteosarcoma around the knee joint are presented. After an average observation period of 13.3 months, there has been no local recurrence or metastasis. The ankle joints (the new knee joints) of the patients were able to support their body weight with an average range of motion of 75 degrees. All patients could walk well without crutches and without risk of the giving way phenomenon. The average rate of the functional evaluation according to the re-modified system by Enneking was 84.5% (range, 80.0-86.7%). No patient had psychological trouble in accepting the shortened and rotated extremity. The results show that rotationplasty is a useful reconstructive method for the treatment of osteosarcoma around the knee joint.