We analyzed the isolation of enterobacteria at Showa University Hospital in 2001 and compared the site of isolation and its antibiotic resistance with data of 1991-1992 or 1997-1998. The identification and antibiotic susceptibility tests were performed by Microscan Walk Away (Dade Behring, USA) . Escherichia coli and Klebsiella pneumoniae were most frequently isolated. Although the number of Escherichia coli isolates from the respiratory tract increased, the susceptibility pattern was similar to that of 1991-1992. As for Klebsiella pneumoniae and Klebsiella oxytoca, the sites of isolation and the susceptibility patterns were similar to those of 1997-1998. It should be noted that 23 strains of ESBL-producing Escherichia coli, 19 strains of ESBL-producing Klebsiella pneumoniae and 4 strains of ESBL-producing Klebsiella oxytoca were isolated. A total of 399 strains of Serratia marcescens were isolated. The ratio of met allo-β-lactamase-producing Serratia marcescens was 3% in 1997-1998. In this survey, 42 strains of imipenem resistant Serratia marcescens, which is considered to be metallo-β-lactam ase producing Serratia marcescens, were isolated; this accounted for 10% of the Serratia marcescens. Analysis of the genome digestion pattern using pulsed field gel electrophoresis revealed that 30 of the 42 strains of imipenem-resistant Serratia marcescens were identical, indicating an outbreak. After containment of the outbreak, the ratio of imipenem-resistant Serratia marcescens decreased to 3%. We also isolated Enterobacter cloacae and Enterobacter aerogenes 417 and 144 strains, respectively; both bacteria were resistant to ampicillin, cefazolin, and cefmetazole. The most alarming finding of the present survey is the emergence of ESBL-producing bacteria.

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It has been reported that induced heat shock protein (HSP) is a factor in the acquisition of tolerance to stress. In the present study we investigated whether HSP70 is induced in the rat liver by warm ischemia preconditioning as well as by heat shock, and the time course of HSP70 immunostaining histologically. The expression of HSP70 in the nuclei of hepatocyts in the pericentral region was oberved. Only a few immunostainings of HSP70 were seen in the periportal area. HSP70 induced by warm ischemia was detected earlier than by heat shock. A short time period of warm ischemia was enough to induce HSP70. After subsequent warm ischemia, reperf usion time was shorter, ischemic preconditioning time was longer, and the expression of HSP70 was observed earlier therefore maintaining homeostasis. According to the tolerance acquisition by the induced HSP, it is speculated that occlusion of hepatic blood flow by Pringle's maneuver is associated with the protection of the liver.

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The purpose of this study was to investigate responses of arterial contractility to high intensity focused ultrasound (HIFU) and histological changes of the artery with various intensities. We constructed a prototype transducer which provides both color flow image and HIFU sonication. HIFU was sonicated to deep femoral arteries in the left thigh of Sprague-Dawley (SD) rats (female, 250-300g) through the skin, where the blood flow was visualized by color imaging. Peak intensities used were 530, 1080, 2750, and 4300 w/cm². The duration of HIFU sonication was 5 seconds; subsequently, 5-sec. sonications were perfomed 5 times on the left thigh across the vessel with spacing of 1.0mm. Blood flow occlusion was accomplished by HIFU exposure of 4300 w/cm² intensity, but the flow was preserved with intensities of 530, 1080 and 2750 w/cm². Peak systolic velocity (PSV) s of blood flow measured by Doppler velocimetry increased in sonicated arteries with HIFU of 1080 and 2750 w/cm² intensity and correlated with HIFU intensity. HIFU exposure of 530 w/cm² intensity did not change blood flow velocity. Histological studies have demonstrated vacuolar degeneration with HIFU exposure of 2750 and 4300w/cm² intensity. HIFU exposure of 1080 w/cm² increased PSV but did not induce histological changes in the vessel wall. In conclusion, the response of the artery to HIFU exposure grades with intensity is in such a way that vascular contraction without tissue degeneration occurs as a first step; subsequently, histological changes diminish vascular diameter and finally occlude the blood flow. It is suggested that these phenomena are probably caused mainly by thermal effects, but cavitaion might have an influence particularly on vascular contraction.

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We performed immunohistochemical analysis of human prostatic carcinoma using Ki-67, p53 and bcl-2. and determined them relationship to pathological and clinical findings on prostatic carcinoma. The subjects consisted of 50 prostatic carcinoma patients who underwent radical prostatectomy. We stained the tissue immunohistochemically with Ki-67, p53 and bcl-2 in operative specimens during radical prostatectomy. We evaluated the proliferative ability about Ki-67 after calculating the labeling index (Ki-67 positive cell/total cell ×100) . Bcl-2 staining was considered positive when tumor cells showed distinct cytoplasmic staining in>5% of cells. On the other hand, p53 staining was considered positive when tumor cells showed distinct nuclear staining in>5% of cells. As Ki-67 labeling index elevated significantly in non organ confined (invasion over capsel (+) ) and had a mutual relationship with the Gleason Score, our results suggest that Ki-67 immunostaining may be useful in predicting the proliferation of human prostate carcinoma. Howerer a higher Ki-67 index was obcerved in patients with lymphnode metastasis than in patients without. Bcl-2 and p53 did not show any significant correlaton with pathological findings.

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1α, 25-dihydroxyvitamin D3 [1, 25 (OH) 2D3], the most active metabolite of vitamin D3, exerts antiprolif erative and differentiating effects on some human prostate cancer cell lines. However, the induction of severe hypercalcemia has limited its clinical use. Several analogs, that retain the antiproliferative effects of 1, 25 (OH) 2D3 but do not induce hypercalcemia, have been synthesized. One of these analogs, 22-oxa-calcitriol (OCT), can induce differentiation in human prostate cancer cells and does not induce hypercalcemia in animal models. This report demonstrates that OCT inhibited proliferation of human prostate cancer cells. Flow cytometry analysis showed that OCT treatment resulted in accumulation of human prostate cancer cells in the GO/G1 phase of the cell cycle. Western blot analysis and quantitative real-time PCR showed that OCT up-regulated insulin like growth factor binding protein 3 (IGFBP-3) and p27Kipl, a cyclin dependent kinase inhibitor, in the human prostate cancer cells. These results suggest that the growth inhibitory effect of OCT on human prostate cancer cells in dependent on IGFBP-3 and p27Kipl.

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This study was carriedout to examine the usefulness of a Two-Step Test (ratio of the maximum length of two steps to height) that was conceived to conveniently predict ability to walk based on the relations hips of 10 m-walking velocity, 6-minute walking distance, history of falling, and degree of independence in daily life. Subjects were 108 healthy volunteers (38 males and 70 females, average age 59.0±12.6) and 108 patients that visit hospitals regularly for rehabilitation (56 males and 52 females, average age 64.0±10.6) : 216 subjects in all, with an average age of 60.3±11.3. Significant positive relationships between two-step values and 10 m-walking velocity, r=0.90, p<0.001, and 6-minute walking distance, r=0.89, p<0.001, were revealed. For the relationships between two-step values and risk of falling or degree of independence, the two-step value was 1.39±0.22 for the group without anxiety, 0.73 (0.27 for those with anxiety of falling and 0.63±0.28 for those with a history of falling; increased the two-step value decreased gradually with the risk of falling. Furthermore, the two-step value was 1.26±0.20 for the group of subjects able to go out transport facilities independently, 0.76±0.23 for those able to walk in the neighborhood independently, 0.52±0.20 for those able to walk independently indoors, and 0.46±0.15 for those needing help to walk indoors; as the independence of daily life became more limited, the more the two-step value decreased. Based on the above, in addition to predicting 10 m-walking velocity or 6-minute walking distance, the Two-step Test is useful for conveniently predicting the risk of falling and the degree of independence in daily life.

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It is well known that many stressors affect areas of the circulation system such as the heart and blood vessels through neuronal and humoral mechanisms. However, the effect of stress on blood fluidity as an important factor of the circulation system is not clarified yet. Elevation of blood fluidity increases vessel resistance by Poiseuille's low and enhances blood coagulation. Elevated blood fluidity increases blood pressure and a risk of thrombosis. Therefore we studied the effects of restraint stress on blood fluidity of rats by MC-FAN (micro channel array flow analyzer) which mimics capillary vessels. Aspirin (0.5 mg/kg, ip) enhanced the blood fluidity. This result indicates the reliability of MC-FAN. Restraint stress in a small box for 6 hours reduced blood fluidity of male Wistar rats. Phentolamine as an α-blocker (0.5 mg/kg, ip) enhanced blood fluidity. These results indicate that restraint stress might reduce blood fluidity at least partly through the noradrenaergic system.

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To study the role of central nervous systems (noradrenergic, dopaminergic and serotonergic) in the formation of cold stress-induced analgesia [CSIA], quantitative changes in mono amines (noradrenarine [NE], dopamine [DA], serotonine [5-HT] ) and metabolites in the brain and spinal cord were measured by coulometric HPLC. CSIA was evaluated by the Tail flick latency method after exposure to environment at 4°C for 0.25, 0.5, 1 or 2 hrs. The quantitative changes in mono amines and the metabolites were measured in the brain (hypothalamus, midbrain-thalamus, medulla-pons) and the spinal cord (cervical cord, thoracic cord, lumber cord) of a cold stressed rat. CSIA was formed by exposure for 0.25 hr to cold stress. CSIA induced by 1 or 2 hrs exposure was significantly greater than that induced by 0.25 hr exposure. The noradrenergic nervous system in the medulla-pons, as well as activity of the serotonergic nervous system in the spinal cord was increased by exposure for 0.25 and 0.5 hr to cold stress. These findings suggest that the noradrenergic and/or serotonergic nervous system in the brain and the spinal cord may play a significant role in the formation of analgesia induced by short-term cold stress but not long term cold stress.

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This study investigates the effects of eight Kampo medicines, Sho-saiko-to, Dai-saiko-to, Oren-gedoku-to, Sanmotsu-ogon-to, Juzen-taiho-to, Kihi-to, Toki-shakuyaku-san, Choto-san on fasting-induced tissue LPO (lipid peroxide) and NO (nitric oxide) formation in the liver, kidney, heart, and brain of mice. Six-week-old male CDF₁ mice were used for the experiment. Measurements were made on amounts of LPO, SOD (superoxide dismutase), GSH-Px (glutathione peroxidase) and NO caused from fasting stress. Before experimenting with the Kampo medicines, we investigated the effect of fasting on LPO formation in the liver, kidney, and brain in mice. LPO formation in the liver, kidney, and brain by the fasting stress showed a maximum level after the second day of fasting. The increases of NO in the liver, kidney, and heart showed the same results. Therefore, in this experiment, the activities in LPO, SOD, GSH-Px, NO were measured from mice organs after 2 days of fasting. The mice had oral administration of the Kampo medicines once a day for four days, before the removal of the organs. Under fasting conditions, the elevation of LPO in liver tissues could be suppressed by the use of, Dai-saiko-to, Oren-gedoku-to, Sanmotsu-ogon-to, Juzen-taiho-to, Kihi-to, Choto-san. For kidney and brain tissues, elevations of LPO were suppressed by all eight Kampo medicines. In heart tissues, elevations of LPO were suppressed by all Kampo medicines except Choto-san. Because effects of Kampo could not be seen on the antioxidant enzymes SOD and GSH-Px, it can be concluded that suppression of the LPO comes from the antioxidants contained in the Kampo. We have shown that fasting-induced NO formation in organs of mice is suppressed to various degrees by treatment with eight Kampo medicines. These findings suggest that Kampo medicines reduce the effect of NO radicals. From these results it can be said that these Kampo medicines have antioxidative effects and can reduce radical-induced injury in various disease states.

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