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Yasuhiro Suzuki

Publications and source records attributed to Yasuhiro Suzuki.

At least 127 records · Page 7Linked to original sources

Apoptosis and expression of apoptosis-related genes in the mouse testis following heat exposure.

OBJECTIVE: To investigate molecular mechanisms of germ cell apoptosis induced by heat exposure in mice. DESIGN: Controlled laboratory study. SETTING: Departments of Urology and Biochemistry, Yamagata University School of Medicine, Yamagata, Japan. ANIMAL(S): Forty-four male B6D2F1 mice. INTERVENTION(S): Heat exposure, 43 degrees C for 15 minutes. MAIN OUTCOME MEASURE(S): Testicular germ cell apoptosis (percentages of apoptotic tubules and apoptotic cells) was assessed by using DNA nick-end labeling, and expression of Bcl-2 family, Fas-FasL system, and p53 was evaluated by using Western analysis. RESULT(S): Bilateral testicular weights decreased significantly from 3 days after heat exposure. Percentages of apoptotic tubules and apoptotic germ cells increased significantly from 1 day after heat exposure. There were no significant changes in the levels of Bcl-xl, Bad, and Bax after heat exposure. However, Bcl-2 expression level decreased significantly 7 days after heat exposure. In contrast, the expression level of Fas and p53 increased significantly from 1 day to 3 days after heat exposure, respectively. Expression level of FasL elevated significantly at days 1 and 2 but declined from day 3. CONCLUSION(S): Germ cell apoptosis induced by heat exposure is mainly mediated by the Fas-FasL system.

Animals↗

5Alpha-reductase type 2 genes in Japanese males do not appear to be associated with cryptorchidism.

OBJECTIVE: To evaluate the occurrence of mutations of 5alpha-reductase type 2 gene in patients with cryptorchidism or idiopathic azoospermia. DESIGN: Controlled clinical study. SETTING: Yamagata University Hospital, Yamagata and Tokyo Electric Power Company Hospital, Tokyo, Japan. PATIENT(S): Patients with isolated cryptorchidism (n = 48) or idiopathic azoospermia (n = 33) and a control group of males with proven fertility (n = 51). INTERVENTION(S): Collection and analysis of blood, leukocytic DNA, semen, and testicular biopsy. MAIN OUTCOME MEASURE(S): Semen analysis, screening of the 5alpha-reductase type 2 gene within exon 1 using direct sequencing and exons 2-5 using single strand conformational polymorphism analysis. RESULT(S): No mutations were detected in isolated cryptorchid men, idiopathic azoospermic men, or controls within the 5 exons of the 5alpha-reductase type 2 gene. CONCLUSION(S): 5Alpha-reductase type 2 gene abnormalities do not constitute a major factor in the development of cryptorchidism or idiopathic azoospermia.

Adolescent↗

Genetic analysis of influences on survival following Toxoplasma gondii infection.

Survival of mice during the acute stage of Toxoplasma gondii infection was not influenced by the MHC Class I gene, L(d), but was influenced by the MHC Class II genes, Ia and Ie. As unexplained variability was noted in our initial studies of influence of the L(d) gene on survival, influence of the L(d) gene region on survival in the presence of a number of variables was studied. Although route of administration and dose of parasites, and age and gender of the mice markedly influenced outcome of T. gondii infection, the Class I L(d) gene did not modify survival in any of these circumstances. In separate studies, using mice with a differing genetic background, i.e. H-2(b), C57BL/10 mice, presence of Ia or Ie alone diminished survival even though presence of Ia reduced parasite burden. When neither or both the Ia and Ie genes were present together, survival was greater. In separate analyses of our studies of AxB BxA recombinant inbred mice, similar influences of MHC genes on survival and parasite burden following peroral infection were confirmed. Previously undescribed associations of novel genetic loci and survival and parasite burden also were identified. Genetic loci associated with enhanced survival included D8Mit42, D1Mit3, Iapls1-16, D8Mit14, Hoxb, Mpmv29, Pmv45, and Emv-2; genetic loci associated with reduced parasite burden included H-2, D17Mit62, D17Mit83, D17Mit21, D17Mit34, D17Mit47, D18Mit4, and Gln3-5. These studies demonstrate the importance of MHC region genes (but not L(d)) for survival, and the influence of other novel genes, and endogenous and exogenous variables on survival and parasite burden specified by host genes following T. gondii infection.

Age Factors↗

Neurodevelopmental outcome in children with fetal hydrocephalus.

Thirty-eight children with fetal hydrocephalus treated surgically during the neonatal period were analyzed concerning their neurodevelopmental outcome by means of a follow-up study. The mean gestation at diagnosis was 31.1 weeks, and the mean postconceptual age at the first operation was 36.3 weeks. The ages of the patients at the last follow-up ranged from 3.8 to 11.8 years (mean = 7.4 years of age). During the follow-up period, they underwent neurologic examinations and were also evaluated to determine the developmental quotient or intelligence quotient. The relationships between age at diagnosis or the first operation for hydrocephalus and neurodevelopmental outcome, and between the lateral ventricular width/hemispheral width ratio at diagnosis and age at diagnosis or the first operation, and neurodevelopmental outcome were statistically evaluated. The neurodevelopmental outcome in the patients was normal in three patients, borderline intelligence in one patient, mental retardation in seven patients, and motor disturbance in 27 patients (five of whom were intellectually normal). The etiology was a major determinant of the outcome in the children with early postnatal surgical treatment of fetal hydrocephalus. Furthermore, an early onset and a high lateral ventricular width/hemispheral width ratio at diagnosis of hydrocephalus were significantly correlated with a poor intellectual outcome.

Cerebral Palsy↗

A novel MCA occlusion model of photothrombotic ischemia with cyclic flow reductions: development of cerebral hemorrhage induced by heparin.

Intracerebral hemorrhage is the major complication associated with antithrombotic and thrombolytic therapy. Despite efforts directed toward achieving hemorrhagic infarction, an ideal animal model of cerebral hemorrhage has not yet to be established. Using the photothrombotic technique in rabbits, we developed a model of cerebral hemorrhage by inducing cyclic flow reductions in the middle cerebral artery (MCA). Furthermore, the hemorrhage increased 4-fold after infusion of heparin at a dose prolonging activated partial thromboplastin time by about three times that of control animals. The photothrombotic occlusion of the MCA is based on a thrombosis induced by endothelial injury through singlet oxygen produced by Rose Bengal injection and green light irradiation (Acta Neuropathol. 72 (1987) 315; Acta Neuropathol. 72 (1987) 326; J. Pharmacol. Toxicol. Methods. 29 (1993) 165). Using a pulse Doppler flowmeter, spontaneous reperfusion of the MCA after the thrombotic occlusion following cyclic flow reductions was observed within 2 h in the majority of animals. This model is unusual with respect to the development of clinical stroke, because of the MCA cyclic flow reductions. Thus it is different from permanent or ischemia/reperfusion MCA occlusion in rodents and may be suitable for studying hemorrhagic risks associated with the use of antithrombotic agents.

Animals↗

A novel guinea pig model with cyclic flow reductions following thrombotic cerebral ischemia.

Cyclic flow reductions (CFRs), a phenomenon indicated with repeating rethrombosis following thrombolysis in clotted vessel has been observed in coronal, carotid and popliteal arteries in various species when they were occluded with vessel damage, suggesting the presence of CFRs in the acute phase of stroke in man. Although much effort has been directed toward rethrombosis or ischemia-reperfusion injuries in acute strokes, a therapy for CFRs in strokes has not been established because of the lack of ideal animal models. We have established a novel guinea pig model with CFRs in the middle cerebral artery (MCA) using a photothrombotic technique, in which the MCA was spontaneously recanalized within 20 min after the first occlusion with subsequent CFRs. We also investigated the effects of antiplatelet agents and the anticoagulant heparin using this model. All tested antiplatelet agents inhibited CFRs, whereas an anticoagulant did not. These results show that this model is unique with respect to its development of MCA cyclic flow reductions, and may be suitable for investigating mechanisms and therapeutic reagents of CFRs in the MCA.

Animals↗

Antibacterial activities of beta-lactamase inhibitors associated with morphological changes of cell wall in Helicobacter pylori.

BACKGROUND: Recent study has demonstrated that beta-lactamase inhibitors including clavulanate, sulbactam and tazobactam have an vitro antibacterial effect on Helicobacter pylori. Here we describe the relationship between viability and cell profiles of H. pylori exposed to beta-lactamase inhibitors and some antibiotics in a short-time course. MATERIALS AND METHODS: The antibacterial effects of beta-lactamase inhibitors including clavulanate, sulbactam and tazobactam on the bacterial viability of and morphological changes in H. pylori ATCC43504 were examined. RESULTS: The beta-lactamase inhibitors such as clavulanate and sulbactam alone decreased the viable counts of H. pylori, depending on the antibiotic concentrations. Exposure to these beta-lactamase inhibitors resulted in morphological changes of cell shape, cell-wall disintegration and cell lysis. Among these beta-lactamase inhibitors, clavulanate was the most active, causing a decrease in viable counts and morphological changes such as short filamentous to sphaeroplast formation and lysis. One x minimum inhibitory concentration (MIC) of amoxicillin plus 1 x MIC of clavulanate decreased viable counts effectively compared with 1 x MIC of amoxicillin or 1 x MIC of clavulanate alone, and induced morphological changes of cell shape and cell wall. CONCLUSION: Our results suggest that the beta-lactamase inhibitors alone have concentration-dependent antibacterial activities against H. pylori and affect the morphology of the cell shape and the cell wall in vitro.

Anti-Bacterial Agents↗

Impaired liver regeneration in mice by lipopolysaccharide via TNF-alpha/kallikrein-mediated activation of latent TGF-beta.

BACKGROUND & AIMS: Because impaired regeneration after surgical treatment of the liver is influenced by circulating endotoxin, the underlying molecular mechanism was investigated. METHODS: Lipopolysaccharide (LPS) was injected intraperitoneally into mice, followed 24 hours later by 67% partial hepatectomy. We measured serum tumor necrosis factor (TNF) alpha levels as well as proliferating cell nuclear antigen labeling index, transforming growth factor (TGF) beta expression, and plasma kallikrein (PLK) activities in regenerating livers. We also examined the effect of LPS, TNF-alpha, and PLK on latent TGF-beta activation in homotypic and heterotypic cultures of rat or mouse hepatic stellate cells and Kupffer cells. RESULTS: Serum TNF-alpha levels increased after LPS (500 ng/g body wt) injection and after partial hepatectomy, accompanying TGF-beta-mediated suppression of hepatic proliferating cell nuclear antigen labeling index. This suppression was mimicked by a combination of preadministration of 50 ng/g body wt LPS and postoperative administration of 5 ng/g body wt TNF-alpha. In vitro, LPS stimulated Kupffer cells to secrete TNF-alpha, which enhanced PLK activity on the hepatic stellate cell surface through increasing PLK binding, thereby inducing proteolytic activation of latent TGF-beta and its autoinduction. Blockade of TGF-beta, TNF-alpha, or PLK activity prevented LPS-induced impaired regeneration in vivo. CONCLUSIONS: LPS provokes TNF-alpha/PLK-mediated proteolytic activation of latent TGF-beta in hepatic stellate cells, leading to impaired liver regeneration after partial hepatectomy.

Animals↗

Immature dendritic cells (CD11c+ CD3- B220- cells) present in mouse peripheral blood.

It is well known that dendritic cells (DCs) are developed from the peripheral blood of mice when peripheral blood mononuclear cells (PBMCs) are cultured with GM-CSF. We have previously found that immature DCs are present in the blood even in humans. In the present study, we show that CD11c+ CD3- B220- cells in the mouse peripheral blood are immature DCs. The percentage of CD11c+ CD3- B220- cells in the (PBMCs) of normal mice ranges from 0.5 to 2.5%. The CD11c+ CD3- B220- cells in the PBMCs show dendrites, similar in shape to the CD11c+ CD3- B220- cells in the spleen, which are thought to be DCs definitely. However, they have practically no capacity to stimulate the proliferation of allogeneic T cells, and show a lower expression of MHC class II, B7-1 and B7-2 than CD11c+ CD3- B220- cells in the spleen. When the CD11c+ CD3- B220- cells in the PBMCs are cultured with GM-CSF, they show not only the potent ability to stimulate the proliferation of allogeneic T cells but also a higher expression of MHC class II, B7-1 and B7-2. Moreover, they migrate into the spleen when they are injected intravenously. These results suggest that CD11c+ CD3- B220- cells in the PBMCs are immature DCs, and that they migrate into the spleen, where they mature.

Animals↗

Posterior retroperitoneoscopic partial nephrectomy using microwave tissue coagulator for small renal tumors.

BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy remains surgically challenging because of the potential for excessive blood loss, infection, and the development of urinary fistulas. In addition, posterior retroperitoneoscopic partial nephrectomy is not popular because of the limited space for surgical manipulation. We evaluated the usefulness of a microwave tissue coagulator in posterior retroperitoneoscopic partial nephrectomy for small posterior renal tumor. PATIENTS AND METHODS: Posterior retroperitoneoscopic partial nephrectomy was performed without renal pedicle clamping using a microwave tissue coagulator in six patients with small posterior renal tumors. RESULTS: The mean operative time was 136 minutes (range 78-180 minutes), and the blood loss was <20 mL. No serious operative complications occurred, and there was no significant deterioration of renal function. CONCLUSION: Posterior retroperitoneoscopic partial nephrectomy using a microwave tissue coagulator can be a safe and less invasive method for the treatment of small posterior renal tumors.

Aged↗

Tissue-type plasminogen activator has paradoxical roles in focal cerebral ischemic injury by thrombotic middle cerebral artery occlusion with mild or severe photochemical damage in mice.

The role of endogenous tissue-type plasminogen activator (tPA) in focal cerebral ischemic injury (FCII) after middle cerebral artery occlusion was studied using tPA gene-deficient (KO) mice and their wild-type (WT) littermates. The middle cerebral artery was occluded by thrombi induced by three different intensities of photochemical damage, a method that was newly introduced in mice. In both WT and KO mice, the intensity-dependent increase of FCII size was observed. The FCII size in tPA WT mice was smaller than in KO mice in cases of mild damage, whereas the FCII size was larger in WT mice than in KO mice in cases of severe damage. There was no difference in FCII size between WT and KO mice in cases of moderate damage. The number of microthrombi also increased with damage intensity in both WT and KO mice, but was less in WT mice at all intensities of damage. The results support the validity of the model of thrombotic occlusion by photochemical damage in mice, and suggest that endogenous tPA protects FCII through thrombolytic action on transient occlusion of middle cerebral artery with mild damage, but deteriorates on persistent occlusion with severe damage.

Animals↗

Relationship between the shape of passive urethral resistance relation and prostatic histology in patients with benign prostatic hyperplasia.

We assessed the relationship between the type of passive urethral resistance relation (PURR) and prostatic histology in 28 patients with benign prostatic hyperplasia (BPH), who underwent transurethral resection of the prostate. PURR was classified into three types according to pressure-flow plots, and resected specimens were analyzed by quantitative morphometry. Patient age, prostatic volume and the area densities of each histological component did not show significant differences among the three groups. However, there was a trend to correlation between prostates with a high glandular component and urethral compliance. Further studies of larger populations are needed to validate this assumption.

Aged↗

High level of skeletal muscle carnosine contributes to the latter half of exercise performance during 30-s maximal cycle ergometer sprinting.

The histidine-containing dipeptide carnosine (beta-alanyl-L-histidine) has been shown to significantly contribute to the physicochemical buffering in skeletal muscles, which maintains acid-base balance when a large quantity of H(+) is produced in association with lactic acid accumulation during high-intensity exercise. The purpose of the present study was to examine the relations among the skeletal muscle carnosine concentration, fiber-type distribution, and high-intensity exercise performance. The subjects were 11 healthy men. Muscle biopsy samples were taken from the vastus lateralis at rest. The carnosine concentration was determined by the use of an amino acid autoanalyzer. The fiber-type distribution was determined by the staining intensity of myosin adenosinetriphosphatase. The high-intensity exercise performance was assessed by the use of 30-s maximal cycle ergometer sprinting. A significant correlation was demonstrated between the carnosine concentration and the type IIX fiber composition (r=0.646, p<0.05). The carnosine concentration was significantly correlated with the mean power per body mass (r=0.785, p<0.01) during the 30-s sprinting. When dividing the sprinting into 6 phases (0-5, 6-10, 11-15, 16-20, 21-25, 26-30 s), significant correlations were observed between the carnosine concentration and the mean power per body mass of the final 2 phases (21-25 s: r=0.694, p<0.05; 26-30 s: r=0.660, p<0.05). These results indicated that the carnosine concentration could be an important factor in determining the high-intensity exercise performance.

Acid-Base Equilibrium↗

[Breast cancer].

The HER2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab(Herceptin) has recently been available for clinical use in Japan. In this paper, the details of this novel biologic agent are reviewed in conjunction with the results of the clinical trials for breast cancer.

Antibodies, Monoclonal↗

[Trastuzumab (Herceptin)].

The HER 2/neu protein is thought to be a unique and useful molecular target for antibody therapy of cancers overexpressing the HER 2/neu gene. The recombinant humanized anti-HER 2 monoclonal antibody trastuzumab (Herceptin) has been available for clinical use in metastatic breast cancer in Japan since June 2001. Some breast cancer patients have responded to trastuzumab alone. A phase III study showed significant efficacy of combination use with paclitaxel compared with paclitaxel alone. Trastuzumab has some toxicities including infusion reaction and cardiotoxicity. It is very rare that infusion reaction manifests lethally. Although trastuzumab should not be concurrently used with an anthracycline, cardiotoxicity was also identified in patients treated with trastuzumab alone. The cumulative dose of anthracycline has not yet been identified as a risk factor, but patients who have received a high cumulative dose should be treated with special caution. In this article, the details of this novel biologic agent are reviewed from basic and clinical studies.

Animals↗

[Herceptin and its therapeutic strategy in patients with breast cancer overexpressing HER2].

Herceptin (trastuzumab) is a recombinant humanized murine monoclonal antibody that recognizes HER2/neu cell-surface receptors and has been shown to be active both in combination with adriamycin (epirubicin)/cyclophosphamide or taxanes and as a single agent, either in the 1st or 2nd/3rd line treatment of women with metastatic breast cancer with HER2 overexpression by IHC or gene amplification by FISH. Preliminary results of Herceptin with other agents such as vinorelbine, cisplatin and various hormonal agents are also promising, and these combinations warrant further clinical exploration. Large-scale multicenter trials including a European and an international study in adjuvant setting have started for high-risk women with HER2 overexpressing breast cancer, with total planned recruitment of nearly 10,000 women.

Antibodies, Monoclonal↗