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Biomedical subjects

S Shimizu

Publications and source records attributed to S Shimizu.

At least 91 records · Page 5Linked to original sources

Calf and shin muscle oxygenation patterns and femoral artery blood flow during dynamic plantar flexion exercise in humans.

The effects of dynamic plantar flexion exercise [40, 60, and 80 contractions.min-1 (cpm)] on calf and shin muscle oxygenation patterns and common femoral artery blood flow (Qfa) were examined in six female subjects [mean age 21 (SD 1) years] who exercised for 1 min at 33% of their maximal voluntary contraction at ankle angles between 90 degrees and 100 degrees. Spatially resolved near-infrared spectroscopy was used to measure medial gastrocnemius, lateral soleus (synergist) and anterior tibialis (antagonist) muscle oxygen saturation (SO2, %). Qfa was measured by ultrasound Doppler. The SO2 changed significantly only in the medial gastrocnemius and its decrease (up to about 30%) was independent of the contraction frequencies examined. The increase in Qfa, at the end of exercise, was highest at 80 cpm. When the exercise at 60 cpm was prolonged until exhaustion [mean 2.7 (SD 1.1) min], medial gastrocnemius SO2 decreased, reaching its minimal value [mean 30 (SD 10)%] within the 1st min, and had partially recovered before the end of the exercise with concomitant increases in total haemoglobin content and Qfa. These results suggest that the medial gastrocnemius is the muscle mostly involved in dynamic plantar flexion exercise and its oxygen demand with increases in contraction frequency and duration is associated with an up-stream increase in Qfa.

Adult↗

Video-assisted parathyroidectomy for primary hyperparathyroidism: a new approach involving a skin-lifting method.

BACKGROUND: Recent advances have allowed the performance of parathyroidectomy as an endoscopic procedure. Carbon dioxide (CO2) insufflation can be used to create a working space in the anterior neck, but it has been associated with a number of complications. We have devised a skin-lifting method to overcome these problems. METHODS: Eleven consecutive patients underwent video-assisted parathyroidectomy. Preoperative imaging revealed a solitary adenoma in all 11 cases. A 3-cm oblique incision was made below the clavicle, and a 5-mm incision was made on the lateral neck. After the skin was lifted, video-assisted parathyroidectomy was performed. RESULTS: Surgery required 186 +/- 50 min. No conversions to conventional cervicotomy were needed. Levels of serum calcium and intact parathormone decreased significantly in all patients on postoperative day 1. Laryngeal recurrent nerve paresis and seroma were noted in one patient each. CONCLUSIONS: Our procedure eliminates any potential CO2 problems and offers the advantages of direct manipulation and improved cosmesis. Endoscopic parathyroidectomy should be considered a viable option for the surgical treatment of a solitary adenoma.

Aged↗

Comparison of laparoscopic versus open cholecystectomy in patients with cardiac valve replacement.

To evaluate the benefits and safety of laparoscopic cholecystectomy (LC) in patients with cardiac valve replacement (which frequently leads to cholelithiasis), 12 patients with cholelithiasis associated with cardiac valve replacement were studied. The patients were divided into two groups, of 6 patients each, according to the type of operation performed, open cholecystectomy (OC) or LC. The postoperative course was monitored with respect to laboratory data on postoperative days (POD) 1, 3, and 7. The mean duration of operation, blood loss, days to food resumption, length of hospital stay, and morbidity were compared between the two groups. Significant differences (P < 0.05) were found between the OC and LC groups in white blood cell counts on POD 1 (12 980 +/- 3040/mm3 vs 8300 +/- 1590/mm3), days to food resumption (2.7 +/- 0.4 days vs 1.0 +/- 0.7 days), and length of postoperative stay (15.8 +/- 1.0 days vs 10.8 +/- 1.6 days). There were no complications in the LC group, but 1 patient in the OC group had heart failure postoperatively. Our findings indicate the efficacy and safety of LC in patients with cardiac valve replacement.

Adult↗

Detection of IL-2 receptor gene expression in peripheral blood from renal transplant patients.

Cytokine monitoring is a potentially useful tool in the management of transplant patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy volunteers and patients who underwent laparotomy or renal transplantation. In the patients who underwent laparotomy, IL-1 and TNF expression was detected postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL-2 receptor gene expression was detected in all the renal transplant patients, including those with signs of rejection. No cytokine gene expression was detected preoperatively, pretransplant, or in the healthy volunteers. We were able to discriminate transplantation from laparotomy by the cytokine profile. These results indicate that our method may be a useful tool for the immunological monitoring of transplant patients.

Adult↗

Persistent increase in chromosome instability in lung cancer: possible indirect involvement of p53 inactivation.

Karyotype and fluorescence in situ hybridization analyses have demonstrated the frequent presence of an altered static state of the number of chromosomes (ie, aneuploidy) in lung cancer, but it has not been directly established whether aneuploidy is in fact associated with a persistent increase in the rate of chromosomal losses and gains (ie, chromosome instability, or CIN). The study presented here used a panel of 10 lung cancer cell lines to provide for the first time direct evidence that CIN is a common feature in lung cancer cell lines in association with the presence of significant aneuploidy. In addition, we found that the CIN phenotype correlates well with the presence of p53 mutations. However, human papilloma virus 16-E6-directed inactivation of p53 in a representative non-CIN lung cancer cell line did not result in the induction of CIN, at least up to the 25th generation, suggesting that inactivation of p53 itself is unlikely to directly induce CIN in lung cancer cells. Interestingly, however, significant CIN could be induced in conjunction with the generation of aneuploid populations when the mitotic spindle formation was transiently abrogated in p53-inactivated cells. These results suggest that inactivation of p53 may allow lung cancer cells to go through an inappropriate second division cycle under certain forms of mitotic stresses, which would result in the induction of the CIN phenotype in conjunction with the generation of aneuploidy.

Aneuploidy↗

Infrasternal mediastinoscopic thymectomy in myasthenia gravis: surgical results in 23 patients.

BACKGROUND: Infrasternal mediastinoscopic surgery is a new approach to resection of the anterior mediastinal mass. METHODS: We evaluated this new approach in 23 patients with myasthenia gravis who underwent total thymectomy assisted by infrasternal mediastinoscopy between 1998 and 2000. The results were analyzed with special reference to morbidity and short-term improvement of the disease severity determined according to quantitative myasthenia gravis (QMG) scores. RESULTS: Complete removal of the thymic gland with the pericardial adipose tissue was accomplished through an infrasternal mediastinoscopic approach in 21 of the 23 (91.3%) patients. The remaining 2 patients required conversion to sternotomy, the one for insufficient sternal lifting with vascular tape and the other for invasion of a thymoma to the innominate vein. There was no related mortality and only one complication, a phrenic nerve injury in 1 patient (4.3%). Significant clinical improvement of disease was achieved in the short term and several advantages were apparent. CONCLUSIONS: Infrasternal mediastinoscopic thymectomy is safe and feasible for patients with myasthenia gravis.

Adult↗

Factors Influencing Visual Acuity Following Vitrectomy for Exudative Age-related Macular Degeneration.

Purpose: We investigated the influence of various factors on visual results in patients undergoing surgical removal of choroidal neovascular membranes (CNVM) caused by age-related macular degeneration (AMD).Subjects and Methods: This study was performed in 55 eyes of 55 patients who underwent surgical removal of CNVM for AMD and followed them for 6 months or more. The criterion for surgical eligibility was active subfoveal choroidal neovascular membrane of 0.5 or more disc diameter above the retinal pigment epithelium with visual acuity of 0.3 or worse. We investigated the influence of various factors on the logarithm of the minimum angle of resolution (log MAR) final visual acuity. The factors were age, symptom duration, preoperative log MAR visual acuity, CNVM diameter, mean deviation with visual field analyzer, previous laser treatment, posterior vitreous detachment, findings of indocyanine green angiography, operative complications, and recurrence of CNVM.Results: Better preoperative visual acuity, shorter symptom duration, and smaller CNVM diameter were correlated with better postoperative final visual acuity.Conclusions: Surgical excision of subfoveal CNVM may be the better therapeutic choice in selected cases with AMD.

Journal Article↗

Role of phosphatidylinositol-3 kinase and its association with Gab1 in thrombopoietin-mediated up-regulation of platelet function.

OBJECTIVE: Human blood platelets are easily available physiologic target cells for thrombopoietin (TPO). TPO up-regulates platelet aggregation and alpha-granule secretion induced by various agonists. We investigated the role of phosphatidylinositol 3-kinase (PI3K) and its association with Gab1 in TPO-mediated up-regulation of platelet function. MATERIALS AND METHODS: PI3K inhibitors (wortmannin and LY294002) and a MAP/ERK-kinase (MEK) inhibitor (PD98059) were used to investigate the role of these kinases in TPO-mediated up-regulation of platelet function. To elucidate the molecules associated with PI3K, we performed immunoprecipitation and pull-down experiments followed by immunoblotting. In vitro kinase assay also was performed to detect extracellular signal-regulated kinase (ERK) kinase activity. RESULTS: TPO up-regulated platelet alpha-granule secretion and aggregation induced by thrombin, which was dose-dependently inhibited by preincubation with wortmannin or LY294002. Immunoprecipitation and pull-down experiments revealed that regulatory subunit of PI3K, p85, was rapidly associated with tyrosine-phosphorylated Gab1 via its n- and c-terminal SH2 domains. Pretreatment of platelets with TPO dramatically augmented the thrombin-induced ERK activation, which was almost completely inhibited by LY294002. Furthermore, a MEK inhibitor, PD98059, not completely but significantly inhibited TPO-mediated up-regulation of thrombin-induced alpha-granule secretion. CONCLUSION: TPO induces the association of tyrosine-phosphorylated Gab1 with p85-PI3K. In downstream signaling, ERK is PI3K-dependently activated, which plays a critical role for TPO-mediated up-regulation of platelet function.

Adaptor Proteins, Signal Transducing↗

Stimulation of tetrahydrobiopterin synthesis induced by insulin: possible involvement of phosphatidylinositol 3-kinase.

Although we recently showed that insulin increases the intracellular concentration of tetrahydrobiopterin (BH4), which is one of the cofactors of nitric oxide (NO) synthase, the mechanism of the effect was not elucidated. In the present study, we examined the signaling pathway of the stimulation of BH4 synthesis by insulin in mouse brain microvascular endothelial cells. Extracellular and intracellular BH4 levels were determined as biopterin by using reversed-phase high performance liquid chromatography with fluorometric detection. Measurement of the level of mRNA for GTP cyclohydrolase I (GTPCH), which is the rate-limiting enzyme for de novo BH4 synthesis, was performed by reverse transcription-polymerase chain reaction (RT-PCR). Addition of insulin to endothelial cells caused an increase of not only the intracellular but also the extracellular BH4 level in a time- and a concentration-dependent manner. Insulin also induced an increase of the level of GTPCH mRNA. Moreover, 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTPCH, inhibited the insulin-induced enhancement of BH4 synthesis. The increase in the BH4 level and the induction of GTPCH mRNA by insulin were reduced by wortmannin and LY294002, which are both phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. These results suggest that insulin stimulates BH4 synthesis through the de novo synthetic pathway involving induction of GTPCH, and that the signaling pathway involves the activation of PI3-kinase.

Animals↗

Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat.

Recent experiments have shown that exogenous basic fibroblast growth factor (bFGF) enlarges fracture callus and accelerates the healing of osteotomized long bones. The actions of bFGF are mediated by four different transmembrane receptors (FGFR1-4). Among them, FGFR1 has a high affinity for bFGF, and gain-of-function mutations of the FGFR1 gene cause craniosynostosis in humans. Gene expression for FGFR1 has been analyzed in embryogenesis; however, in skeletal repair, detailed expression of FGFR1 has not been fully established. In the present study, a rat model of closed femoral fracture healing was used to quantify mRNA encoding the FGFR1 and to characterize cells expressing FGFR1 by in situ hybridization. Gene expression for FGFR1 was rapidly upregulated after fracture; its mRNA level on day 1 was 3.4-fold higher than that of unfractured femora. At this stage, a moderate signal for FGFR1 was detected in periosteal osteoprogenitor cells, inflammatory cells near fracture sites, and cells among muscle layers. FGFR1 mRNA reached peak expression when callus remodeling actively progressed (6.8-fold on day 14), and remained elevated even in the later stages of healing (6.3-fold on day 28). During the intermediate stage of fracture healing, a strong signal for FGFR1 was diffusely distributed in mature osteoblasts in the hard callus, and mature osteoclasts also expressed a weak signal for FGFR1. These results suggest that FGF/FGFR1 signaling has multifunctional roles during fracture healing and may regulate both osteoblasts and osteoclasts, contributing to bone formation and callus remodeling.

Animals↗

Serological survey of parapoxvirus infection in wild ruminants in Japan in 1996-9.

The prevalence of parapoxvirus infection was examined in free-ranging wild ruminants in Japan, Japanese serow (Capricornis crispus) and Japanese deer (Cervus nippon centralis), in 1996-9. We collected a total of 151 serum samples from 101 Japanese serows and 50 Japanese deer and tested for antibodies against parapoxvirus by an enzyme-linked immunosorbent assay and an agar gel immunodiffusion test. Overall seroprevalences among Japanese serows were 5/25 (20.0%) in 1996, 4/14 (28.6%) in 1997, 5/32 (15.6%) in 1998 and 2/30 (6.7%) in 1999, respectively. The seroprevalence increased with age but was not affected by sex. No antibodies were detected from any of 50 serum samples taken from Japanese deer. Our results in this study suggest that parapoxvirus infection is widespread among the population of Japanese serows, however, Japanese deer appear to be still free of the disease.

Age Factors↗

Keratosis follicularis squamosa (Dohi): a follicular keratotic disorder well known in Japan.

Keratosis follicularis squamosa (KFS) is a keratinizing disorder, which is well recognized in Japan but rarely reported in other countries. KFS is characterized by asymptomatic small scaly patches with a follicular plug that is scattered on the trunk and thighs. It is easily diagnosed by its characteristic appearance that was originally described in Japanese as "lotus leaves on the water". We report a typical case of KFS and review the mainly Japanese literature. We conclude that KFS is a distinct clinical entity of unknown origin. World-wide recognition of this disease should further clarify the prevalence and pathogenesis of this skin condition.

Adult↗

Characterization of control and immobilized skeletal muscle: an overview from genetic engineering.

To elucidate the molecular basis of muscle atrophy, we have performed the serial analysis of gene expression (SAGE) method with control and immobilized muscles of 10 rats. The genes that expressed >0.5% in muscle are involved in the following three functions: 1) contraction (troponin I, C and T; myosin light chain 1-3; actin; tropomyosin; and parvalbumin), 2) energy metabolism (cytochrome c oxidase I and III, creatine kinase, glyceraldehyde-3-phosphate-dehydrogenase, phosphoglycerate mutase, ATPase 6, and aldolase A), and 3) housekeeping (lens epithelial protein). Muscle atrophy appears to be caused by changes in mRNA levels of specific regulators of proteolysis, protein synthesis, and contractile apparatus assembling, such as polyubiquitin, elongation factor 2, and nebulin. Immobilization has produced a decrease more than threefold in gene expression of enzymes involved in energy metabolism, especially ATPase, cytochrome c oxidase, NADH dehydrogenase, and protein phosphatase 1. Differential gene expressions of selenoprotein W and uroporphyrinogen decarboxylase, which can be involved in oxidative stress, were also observed. Other genes with various functions, such as cholesterol metabolism and growth factors, were also differentially expressed. Moreover, novel genes regulated by immobilization were discovered. Thus, the current study allows a better understanding of global muscle characteristics and the molecular mechanisms of sedentarity and sarcopenia.

Animals↗

bcl-2 Antisense treatment prevents induction of tolerance to focal ischemia in the rat brain.

In the rat, 60 minutes of transient ischemia to the middle cerebral artery results in infarction of the caudate putamen. Ischemic preconditioning with 20 minutes of transient focal ischemia produced tolerance (attenuated infarction volume) to 60 minutes of subsequent focal ischemia administered three days, five days, or seven days later. Western blots from tolerant caudate putamen demonstrated increased bcl-2 expression, maximum at 3 days and persisting through 7 days. Immunocytochemical examination found that bcl-2 was expressed in cells with both neuronal and nonneuronal morphology in striatum after preconditioning ischemia. bcl-2 antisense oligodeoxynucleotides (ODNs), bcl-2 sense ODNs, or artificial cerebrospinal fluid (CSF, vehicle) was infused into the lateral ventricle for the 72 hours between the 20-minute ischemic preconditioning and the 60-minute period of ischemia. Antisense ODN treatment reduced expression of bcl-2 in the striatum and blocked the induction of tolerance by preconditioning ischemia. Sense and CSF treatments had no effect on either bcl-2 expression or tolerance. In this model of induced tolerance to focal ischemia, bcl-2 appears to be a major determinant.

Animals↗

Ridge widening and immediate implant placement: a case report.

Alveolar atrophy may present an anatomical limitation to the placement of endosseous implants. A case is described of severe maxillary alveolar atrophy with immediate implant placement associated with a ridge widening technique in accordance with a split-crest-bone manipulation. Taper-shaped implants were applied in this technique without a barrier membrane. Because this implant was small and tapped into position, it was easier to use and was considered to be appropriate for the ridge widening technique associated with immediate implant placement.

Alveolar Bone Loss↗

Immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelium of patients with pancreaticobiliary maljunction.

OBJECTIVES: Pancreaticobiliary maljunction, an anomalous union of the pancreatic duct with the common bile duct, is a risk factor for biliary carcinoma. We hypothesized that, in patients with pancreaticobiliary maljunction, persistent regurgitation of pancreatic juice into the biliary tract induces oxidative DNA damage. We assessed the expression of an oxidative DNA base-modified product, 8-hydroxy-2'-deoxyguanosine, in gallbladder epithelium. DESIGN: Eleven noncancerous gallbladders from patients with pancreaticobiliary maljunction, 12 gallbladder carcinomas from patients without pancreaticobiliary maljunction and 14 noncancerous gallbladders from patients without pancreaticobiliary maljunction (control) were studied. METHODS: Immunohistochemistry was performed for 4-hydroxy-2-nonenal-modified protein (as a marker for lipid peroxidation), 8-hydroxy-2'-deoxyguanosine and p53 gene product. RESULTS: Stronger cytoplasmic staining of 4-hydroxy-2-nonenal-modified protein was observed in the gallbladder epithelium from patients with pancreaticobiliary maljunction than in epithelium from gallbladder cancer patients or from control subjects with normal gallbladders. Clear, strong nuclear staining of 8-hydroxy-2'-deoxyguanosine was observed in the gallbladder epithelial cells from patients with pancreaticobiliary maljunction. Densitometric quantitation revealed significantly higher expression of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelial cells from patients with pancreaticobiliary maljunction (index 27.3 +/- 3.1) than in cells from patients with gallbladder carcinoma (11.4 +/- 1.5; P < 0.05) or from control subjects with normal gallbladder (6.4 +/- 1.0; P < 0.05). Positivity of p53 was 27% in gallbladder epithelium associated with pancreaticobiliary maljunction, 75% in gallbladder carcinoma epithelium and 0% in control epithelium. CONCLUSIONS: These results suggest that reactive oxygen species are produced in the gallbladder of patients with pancreaticobiliary maljunction and that oxidative DNA injury is related to carcinogenesis in these patients.

8-Hydroxy-2'-Deoxyguanosine↗

Ectopic expression of MAFB gene in human myeloma cells carrying (14;20)(q32;q11) chromosomal translocations.

Chromosome 14q +, which represents a chromosomal rearrangement involving the immunoglobulin heavy chain gene (IgH) locus, is a genetic hallmark of human multiple myeloma (MM). Here, we report the identification of (14;20)(q32;q11) chromosomal translocations found in MM cells. Double color fluorescence in situ hybridization analyses pinpointed the breakpoints at the 20q11 locus in two MM cell lines within a length of at most 680 kb between the KIAA0823 and MAFB gene loci. Among the transcribed sequences in the vicinity of the breakpoints, an ectopic expression of the MAFB gene, which is located at 450 - 680 kb telomeric to one of the breakpoints and encodes a member of the MAF family basic region / leucine zipper transcription factor, was demonstrated to be associated with t(14;20). This finding, together with that of a previous study describing its transforming activity, suggests that the MAFB gene may be one of the targets deregulated by regulatory elements of the IgH gene as a result of t(14;20).

Avian Proteins↗