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Biomedical subjects

Y Shibata

Publications and source records attributed to Y Shibata.

At least 73 records · Page 4Linked to original sources
PubMed2001

Diversity and molecular anatomy of gap junctions.

In animal tissues, most cells are connected via intercellular cytoplasmic channels called gap junctions. Various electron microscopy techniques have made a crucial contribution to our understanding of the function and structure of gap junction channels. Tracer studies and freeze-fracture replica observations indicate that the connexon, the unit gap junction channel, is a pair of hemichannels apposed in the narrow intercellular gap between neighboring cell membranes. Recent advances in cellular biology have shown that connexon hemichannels are composed of hexamers of connexin proteins. Purification of the gap junction membrane and cDNA cloning analysis indicate the diversity of the connexin protein family, which contains more than 18 members, and their tissue- and cell type-specific distributions. Defects in some connexin genes may cause various hereditary diseases, such as X-linked Charcot-Marie-Tooth disease (Cx32), nonsyndromic autosomal deafness (Cx26), and cataract (Cx50). Analysis of gene knockout mice indicates that certain types of connexin play important roles in differentiation and development at crucial times in specific tissues and cell types.

Animals↗
PubMed2001

Spontaneous esophageal perforation related to a duodenal ulcer with pyloric stenosis: report of a case.

This report describes a case of spontaneous esophageal perforation that was considered to be etiologically related to a duodenal ulcer with pyloric stenosis. The patient was a 54-year-old Japanese man who presented following the sudden onset of severe abdominal pain and dyspnea after an episode of vomiting. He had a history of duodenal ulcer. Computed tomography revealed an extremely dilated stomach containing abundant food residue, intraabdominal effusion, bilateral pleural effusion, and mediastinal emphysema, findings that strongly suggested esophageal perforation. Esophagoscopy confirmed perforation of the lower esophagus. Laparotomy revealed marked contamination, including food residue in the abdominal cavity, and a severely dilated stomach attributed to pyloric stenosis caused by a duodenal ulcer. A 2-cm longitudinal perforation was found on the right side of the lower esophagus. Because the patient's general condition was too poor to tolerate a one-stage operation (primary closure of the perforation, gastrectomy, and reconstruction), we initially performed decompression gastrostomy and control of the esophageal leakage with T-tube placement. Following the T-tube was removed 1 month later, distal gastrectomy and reconstruction of the gastrojejunostomy (Billroth II method) could be safely performed.

Digestive System Surgical Procedures↗
PubMed2001

Magnetic resonance imaging findings and postoperative neurologic dysfunction in elderly patients undergoing coronary artery bypass grafting.

BACKGROUND: Small cerebral infarctions are common in elderly patients, but the association between the magnetic resonance imaging finding and neurologic dysfunction after coronary artery bypass grafting has not been evaluated. METHODS: We determined, prospectively, whether varying degrees of abnormal findings on magnetic resonance images of the brain increased the incidence of preoperative cognitive decline, postoperative neuropsychological dysfunction, and stroke in 421 elderly patients (> or = 60 years) undergoing coronary artery bypass grafting. RESULTS: Control patients (almost normal or leukoaraiosis, n = 212) had rates of postoperative neuropsychological dysfunction (7%) and stroke (1.4%); the small infarctions group (some small infarctions, n = 126) had rates of 13% and 5.6%, respectively; whereas patients with multiple infarctions (multiple small infarctions or broad infarctions, n = 83) had rates of 20% and 8.4%, respectively (p = 0.004, p = 0.013). In the group with multiple infarctions, 49 patients (59%) were asymptomatic and 21 patients (25%) had cognitive decline. Stepwise logistic regression analysis demonstrated that the significant predictors of multiple small infarctions or large infarctions were history of cerebrovascular disease, renal insufficiency, cognitive decline, and cerebral arteriosclerosis. CONCLUSIONS: Multiple infarctions significantly increase the risk of neurologic dysfunction after coronary artery bypass grafting. Routine screening for preoperative cognitive decline should be performed to detect underlying ischemic cerebral disease in elderly patients.

Aged↗
PubMed2001

Time-resolved hole-burning study on myoglobin: fluctuation of restricted water within distal pocket.

We have studied the equilibrium fluctuation dynamics of Zn-substituted myoglobin and its His64-->Leu (H64L) mutant in the pH range from 5 to 9 by using time-resolved transient-hole-burning (TRTHB) spectroscopy. In the H64L mutant, we have observed a largely reduced width of the absorption spectrum and only a slight temporal shift of the hole-burning spectrum. These observations both reflect the suppressed conformational fluctuation in the mutant. On the other hand, the pH-dependent change in the absorption spectrum could not be solely explained by the change in the protonation state of His64 induced by the pH change. These results suggest that although the fluctuation dynamics observed by the TRTHB experiment of the native sample mainly reflects the conformational motion around His64, the interconversion process of His64 between its protonated and unprotonated states has a minor contribution. Instead, we have proposed a tentative interpretation that the motion of the water molecule around His64 is the main source of the observed dynamics in the TRTHB technique.

Animals↗
PubMed2001

Regulation of the epithelial-mesenchymal transformation through gap junction channels in heart development.

Analyses of mice lacking the gap junction protein, connexin45 (Cx45), have provided new insights into the essential roles of gap junction channels in early embryogenesis. Of great surprise is the function of Cx45 in the endothelium, where it is essential for synchronized activation of the transcription factor Nfatc1. This laterally synchronized regulation model extends the generally accepted vertical model, in which interactions between the endocardium and the myocardium induce endocardial cushion formation through the epithelial-mesenchymal transformation.

Animals↗
PubMed2001

GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1.

GM-CSF gene targeted (GM(-/-)) mice are susceptible to respiratory infections and develop alveolar proteinosis due to defects in innate immune function and surfactant catabolism in alveolar macrophages (AMs), respectively. Reduced cell adhesion, phagocytosis, pathogen killing, mannose- and Toll-like receptor expression, and LPS- or peptidoglycan-stimulated TNFalpha release were observed in AMs from GM(-/-) mice. The transcription factor PU.1 was markedly reduced in AMs of GM(-/-) mice in vivo and was restored by selective expression of GM-CSF in the lungs of SPC-GM/GM(-/-) transgenic mice. Retrovirus-mediated expression of PU.1 in AMs from GM(-/-) mice rescued host defense functions and surfactant catabolism by AMs. We conclude that PU.1 mediates GM-CSF-dependent effects on terminal differentiation of AMs regulating innate immune functions and surfactant catabolism by AMs.

Animals↗
PubMed2001

Adenomatoid odontogenic tumour: immunohistochemical demonstration of transferrin, ferritin and alpha-one-antitrypsin.

Three cases of adenomatoid odontogenic tumour (AOT) were examined by morphological and immunohistochemical methods, to define the nature of tumour cells and to determine the correlation between the occurrence of extracellular eosinophilic amorphous material and epithelial tumour cells. The epithelial tumour cell components observed in this study were divided into three cell types (cell type I: small compact cells in a solid nodule and pseudoglandular cells in a duct-like structure; cell type II: peripheral elongated cells and spindle-shaped cells in a cribriform pattern; and cell type III: metaplastic squamous cells). The mesenchymal components consisted of eosinophilic amorphous material and calcified material. Immunohistochemically, the type I cells reacted positively with antibodies to transferrin, ferritin and alpha-one-antitrypsin (alpha1-AT), whereas the type II cells constantly indicated intense expression only for transferrin and alpha1-AT. All types of epithelial tumour cells reacted negatively with lactoferrin, alpha-one-antichymotrypsin, S-100 protein, S-100alpha subunit and S-100beta subunit. Moreover, the eosinophilic amorphous material and calcified material examined were positive for the antibody against alpha1-AT. These materials expressed immunophenotypes similar to those of the epithelial tumour cells, except for metaplastic squamous cells. The present study showed that iron-binding proteins and proteinase inhibitor might be related to the pathogenesis of AOT. Furthermore, we indicated that the formation of eosinophilic amorphous material was associated with type I and type II cells.

Adolescent↗
PubMed2001

Arthroscopic debridement for dialysis shoulders.

PURPOSE: To arthroscopically treat "dialysis shoulder," severe shoulder pain in patients on long-term hemodialysis. This pain occurs only at rest such as during hemodialysis or while sleeping and is temporarily alleviated by assuming the sitting position or moving the shoulder joint. Limitations in range of motion and pain with overhead activity or the arm in the forward flexed position are not the patient's chief complaints. Although frozen shoulder and impingement syndrome may be observed as complications, pain at rest is the most characteristic. TYPE OF STUDY: Clinical research on arthroscopic debridement to treat dialysis shoulder. METHODS: We performed arthroscopic debridement of 36 dialysis shoulders in 29 patients. Only complete debridement in the glenohumeral joint and subacromial bursa was performed, without invasion to the bone and ligaments. RESULTS: The pain improved in 34 shoulders in 27 patients (94%) a mean of 29.8 months after surgery, showing satisfactory results. In this group, the mean Japan Orthopaedic Surgery Association shoulder score (maximum 100 points) was 66.4 points before surgery but increased to 86.6 points postoperatively, statistically significant by 2-group t test. CONCLUSIONS: We decided before beginning the study that no postoperative rehabilitation would be necessary. There were no complications and no need for further surgery, with all but 2 of the patients being satisfied with their postoperative condition.

Activities of Daily Living↗
PubMed2001

Phenotypic and suppressor analysis of defecation in clk-1 mutants reveals that reaction to changes in temperature is an active process in Caenorhabditis elegans.

Mutations in the Caenorhabditis elegans maternal-effect gene clk-1 affect cellular, developmental, and behavioral timing. They result in a slowing of the cell cycle, embryonic and postembryonic development, reproduction, and aging, as well as of the defecation, swimming, and pharyngeal pumping cycles. Here, we analyze the defecation behavior in clk-1 mutants, phenotypically and genetically. When wild-type worms are grown at 20 degrees and shifted to a new temperature, the defecation cycle length is significantly affected by that new temperature. In contrast, we find that when clk-1 mutants are shifted, the defecation cycle length is unaffected by that new temperature. We carried out a screen for mutations that suppress the slow defecation phenotype at 20 degrees and identified two distinct classes of genes, which we call dsc for defecation suppressor of clk-1. Mutations in one class also restore the ability to react normally to changes in temperature, while mutations in the other class do not. Together, these results suggest that clk-1 is necessary for readjusting the defecation cycle length in response to changes in temperature. On the other hand, in the absence of clk-1 activity, we observe temperature compensation, a mechanism that maintains a constant defecation period in the face of changes in temperature.

Animals↗
PubMed2001

Dendritic cells activate antitumor immunity for malignant intracranial germ cell tumor: a case report.

We report a 22-year-old male patient with a history of intracranial malignant germ cell tumor (GCT) who had undergone tumor resection twice, followed by radiation and chemotherapy. The tumor had rapidly recurred along the entire ventricular wall with extensive invasion into the brain parenchyma. The serum level of human beta-chorionic gonadotropin (beta-hCG) was 232.3 ng/ml on admission. Although tissue samples of the recurrent tumor could not be obtained, the previous histological diagnosis of germinoma and elevated serum beta-hCG levels suggested recurrence of malignant GCT. The patient declined chemotherapy but accepted dendritic cell (DC)-based immunotherapy. DC inoculation five times resulted in rapid tumor shrinkage and a significant decrease in the serum level of beta-hCG. Here we discuss the effectiveness of immunotherapy using DCs for recurrent intracranial malignant GCTs.

Adult↗
PubMed2001

Spermatid-specific expression of Iba1, an ionized calcium binding adapter molecule-1, in rat testis.

Postnatal development of mammalian seminiferous tubules can be divided into three phases: spermatogonial mitosis, spermatocyte meiosis, and a postmeiotic phase in which drastic morphological changes occur in spermatids (spermiogenesis). In an attempt to elucidate the molecular mechanisms involved in spermiogenesis, we have applied a differential display method to identify genes that are developmentally up-regulated during rat testis development. One of the cDNA fragments isolated by differential display turned out to be iba1, an ionized calcium binding adapter molecule-1, that contains two EF hand-like motifs. Expression of iba1 mRNA in the rat testis was detected first at 4 wk in postnatal development and then increased up to adulthood. Using the antibody against a synthetic peptide corresponding to the N-terminal Iba1 protein, we discovered that Iba1 protein was not detectable by immunohistochemistry in spermatogonia, spermatocytes, and round spermatids in adult rat testis but was specifically expressed in the cytoplasm of elongate spermatids (steps 10-19) as well as in residual bodies that are ultimately engulfed by Sertoli cells. In situ hybridization, on the other hand, revealed that iba1 mRNA is present in round spermatids as well as early elongate spermatids (steps 1-12) but not in late spermatids, suggesting that iba1 mRNA undergoes post-transcriptional regulation. Because Iba1 protein is specifically expressed in the cytoplasm of elongate spermatids, which is finally engulfed as residual bodies into Sertoli cells, we suggest that Iba1 may be involved in the final stage of spermiogenesis (i.e., in elimination of the residual cytoplasm from spermatids).

Aging↗
PubMed2001

Comparison of histological compositions and apoptosis in canine spontaneous benign prostatic hyperplasia treated with androgen suppressive agents chlormadinone acetate and finasteride.

PURPOSE: Chlormadinone acetate and finasteride are androgen suppressive agents clinically used for benign prostatic hyperplasia but their mechanism for inducing prostatic atrophy differs. We investigated the effect of these androgen suppressive agents on prostatic histology and apoptosis using the spontaneous canine benign prostatic hyperplasia model. MATERIALS AND METHODS: Animals were treated with oral chlormadinone acetate or finasteride for 25 weeks. The prostatic volumes were analyzed every 5 weeks. Prostatic androgen and estrogen concentrations, histological composition and apoptosis were determined at the end of treatment. Apoptosis was measured by in situ labeling of 3' hydroxy ends of the DNA breaks using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method. RESULTS: There was a similar volume reduction effect with 0.3 mg./kg. chlormadinone acetate daily and 1 mg./kg. finasteride daily. Chlormadinone acetate decreased testosterone and dihydrotestosterone but finasteride decreased only dihydrotestosterone in the prostate gland. The concentration ratio of estradiol-to-total androgen in the prostate was significantly increased in finasteride treated canines. Chlormadinone acetate and finasteride decreased the epithelial and stromal components. The extent of apoptosis observed in the prostate was significantly higher in the chlormadinone acetate group compared to that of the control and finasteride groups. CONCLUSIONS: Although a similar effect of chlormadinone acetate and finasteride was observed in the induction of prostatic regression and composition of the histological components, the sustained increase in apoptosis was observed only in chlormadinone acetate treated canines. We suggest that different intraprostatic endocrine environments created by chlormadinone acetate or finasteride, which have different intraprostatic testosterone levels and estradiol-to-androgen ratios, may be responsible for the different outcomes in the extent of apoptosis.

Androgen Antagonists↗
PubMed2001

Implications of excessive fibrinolysis and alpha(2)-plasmin inhibitor deficiency in patients with severe head injury.

OBJECTIVE: To evaluate the involvement of the fibrinolytic system, especially focused on alpha(2)-plasmin inhibitor, in patients with head injury. METHODS: This study consisted of 47 patients with isolated blunt head trauma in whom blood sampling could be initiated within 3 hours after injury. Patients were divided into two groups according to Glasgow Outcome Scale score status at 3 months after injury. In Group 1 patients (n = 26), the outcome was characterized as good recovery or moderate disability; in Group 2 patients (n = 21), the outcome was characterized as severe disability, vegetative state, or death. RESULTS: Concentrations of thrombin-antithrombin III complex were greater than 100 microg/L in 39 of 47 patients, and concentrations in Group 2 patients were elevated significantly beyond the concentrations in Group 1 patients. Activities of alpha(2)-plasmin inhibitor in Group 2 were significantly lower than in Group 1 (P < 0.0001). In Group 1 patients, alpha(2)-plasmin inhibitor activity was greater than 60%, while in all but four Group 2 patients, the inhibitor was reduced to less than 60% of normal activity within 3 hours of injury. All patients with alpha(2)-plasmin inhibitor activity less than 60% showed a marked bleeding tendency and/or severe brain edema. Using sandwich enzyme-linked immunosorbent assay, fibrinogen degradation product and fibrin degradation product were measured separately. A significant correlation was apparent between thrombin-antithrombin III complex and fibrinogen degradation product, as well as between the complex and fibrin degradation product. Marked decreases in alpha(2)-plasmin inhibitor were noted only in patients with thrombin-antithrombin III complex concentrations exceeding 500 microg/L. CONCLUSION: Fibrinolysis and fibrinogenolysis may be involved according to the degree of coagulation activation in the pathophysiology of severe head injury. Decreased activity of alpha(2)-plasmin inhibitor indicated poor prognosis and may be an exacerbating factor in the acute phase of head trauma.

Antithrombin III↗
PubMed2001

Gastrointestinal stromal tumour of the rectum.

Gastrointestinal stromal tumour (GIST) has been immunohistochemically defined as the tumour lacking differentiation towards either leiomyomatous tumour or schwannoma. We report a 75-year-old man who underwent an abdominoperineal resection of a large submucosal tumour of the rectum. The excised specimen was revealed to be an elastic soft tumour, 8 x 7 x 6 cm in size, which histologically consisted of spindle-shaped cells without nuclear atypia. The mitotic count was fewer than 2 per 10 high-power fields. The tumour cells were positive for staining of CD34 and c-kit protein, while the lesions were negative for alpha-smooth muscle actin, HHF-35, neuron-specific enolase, and S-100 protein. The diagnosis of GIST was confirmed by immunohistochemical examination of the tumour. From these findings, the present case is thought to be potentially malignant, and a long-term follow-up observation is needed for the case.

Aged↗
PubMed2001

Th1 adjuvant N-acetyl-D-glucosamine polymer up-regulates Th1 immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice.

Treatment of mice with heat-killed (HK) Mycobacterium bovis BCG or 1- to 10-microm chitin particles (nonantigenic N-acetyl-D-glucosamine polymers) is known to induce innate immune responses, including gamma interferon (IFN-gamma) production, which plays a Th1 adjuvant role. However, HK BCG further induces prostaglandin E2-releasing spleen macrophages (Mphi) (PGE2-Mphi), which potentially inhibit Th1 adjuvant activities. We found that chitin particles did not induce PGE2-Mphi formation. To further assess whether chitin has Th1 adjuvant effects, interleukin-10 (IL-10)-knockout (KO) mice and their wild-type (WT, C57BL/6) controls were immunized with a 30-kDa MPB-59 mycobacterial protein mixed with chitin. Immunization with MPB-59 alone induced Th2 responses, characterized by increases in total serum immunoglobulin E (IgE) and specific serum IgG1 levels and spleen Th2 cells producing IL-4, IL-5, and IL-10. No IFN-gamma-producing spleen Th1 cells, specific serum IgG2a, or delayed-type hypersensitivity (DTH) footpad reactions were detected. On the other hand, chitin-MPB-59 immunization significantly increased spleen Th1 responses, DTH reaction, and serum IgG2a levels along with decreases of Th2 responses. The magnitude of these Th1 adjuvant effects was greater in IL-10-KO mice than in WT mice. In contrast, immunization with HK BCG-MPB-59 showed little or no Th1 adjuvant effect. These data indicate that chitin has a unique Th1 adjuvant effect on the development of Th1 immunity against a mycobacterial antigen. IL-10 down-regulates the adjuvant effect of chitin.

Acetylglucosamine↗
PubMed2001

IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice.

Intratracheal administration of interleukin-10 (IL-10) has been reported to inhibit allergic inflammation but augment airway hyperresponsiveness (AHR). In the present study, airway and smooth muscle responsiveness to methacholine (MCh) were compared in wild-type (WT) and IL-10-deficient (IL-10-KO) mice to investigate the role of endogenous IL-10 in AHR development. Naive WT and IL-10-KO mice exhibited similar dose-dependent increases in airway resistance (Raw) to intravenous MCh. Sensitization and challenge with ragweed (RW) induced a twofold increase in responsiveness to intravenous MCh in WT mice, but hyperresponsiveness was not observed in similarly treated IL-10-KO mice. Likewise, tracheal rings from RW-sensitized and -challenged WT mice exhibited a fourfold greater responsiveness to MCh than IL-10-KO tracheal preparations. Measurements of airway constriction by whole body plethysmography further supported the Raw and tracheal ring data (i.e., AHR was not observed in the absence of IL-10). Interestingly, factors previously implicated in the development of AHR, including IL-4, IL-5, IL-13, IgA, IgG1, IgE, eosinophilia, and lymphocyte recruitment to the airways, were upregulated in the IL-10-KO mice. Treatment with recombinant murine IL-10 at the time of allergen challenge reduced the magnitude of inflammation but reinstated AHR development in IL-10-KO mice. Adoptive transfer of mononuclear splenocytes to IL-10-sufficient severe combined immunodeficient mice indicated that lymphocytes were an important source of the IL-10 impacting AHR development. These results provide evidence that IL-10 expression promotes the development of allergen-induced smooth muscle hyperresponsiveness.

Adoptive Transfer↗
PubMed2001

Cerebral vasoreactivity and internal carotid artery flow help to identify patients at risk for hyperperfusion after carotid endarterectomy.

BACKGROUND AND PURPOSE: Hyperperfusion syndrome is a rare but potentially devastating complication after carotid endarterectomy (CEA). The aim of this study was to investigate whether preoperative measurement of cerebral vasoreactivity (CVR) and intraoperative measurement of internal carotid artery (ICA) flow could identify patients at risk for hyperperfusion after CEA. METHODS: For 26 patients with unilateral ICA stenosis >/=70%, cerebral blood flow (CBF) and CVR were investigated before and 1 month after CEA, with resting and acetazolamide-challenge single-photon emission CT. CBF on the first postoperative day was also measured. ICA flow was measured before and after reconstruction by electromagnetic flowmeter during surgery. RESULTS: Ipsilateral CBF on the first postoperative day significantly increased relatively (56.6+/-53.2%) as well as absolutely (37.9+/-8.8 to 57.7+/-18.0 mL/100 g per minute) in the reduced CVR group (CVR <12%) but not in the normal CVR group (CVR >/=12%) (10.3+/-15.5% and 40.6+/-7.9 to 43.9+/-5.7 mL/100 g per minute, respectively). One month later, this difference almost disappeared. Two patients showed ipsilateral CBF increase of >/=100%. A significant association of intracerebral steal with hyperperfusion (CBF increase >/=100%) on the first postoperative day was also observed. ICA flow increase after reconstruction significantly correlated with CBF increase on the first postoperative day in the reduced CVR group but not in the normal CVR group. The threshold of ICA flow increase for hyperperfusion was estimated to be 330 mL/min in the reduced CVR group. CONCLUSIONS: Single-photon emission CT with acetazolamide challenge and ICA flow measurement during surgery could identify patients at risk for hyperperfusion after CEA, in whom careful monitoring and control of blood pressure should be initiated even intraoperatively.

Acetazolamide↗