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T Shinohara

Publications and source records attributed to T Shinohara.

At least 109 records · Page 6Linked to original sources
PubMed2000

Hepatopulmonary syndrome-discussion of cardiopulmonary parameters.

We report a 70-year-old man with hepatopulmonary syndrome (HPS) in C liver cirrhosis. Hypoxemia worsened markedly, especially on exertion, while the hepatic function was clinically stable. Contrast echocardiography, 99mTc macroaggregated albumin (99mTcMAA) lung scan, and pulmonary angiography were performed. The findings suggested the presence of both intrapulmonary vascular dilatation and substantial right-to-left shunt. The contribution of intrapulmonary vascular abnormalities in patients with severe liver cirrhosis without abnormal chest radiography and spirometry tests when marked hypoxemia is present should be investigated.

Aged↗
PubMed2000

[A tuberculosis outbreak in a mental hospital].

PURPOSE AND METHODS: We experienced a tuberculosis outbreak in a mental hospital and discussed preventive measures for nosocomial tuberculosis infection. RESULTS: There are 18 mental hospitals within the administrative area of Hachioji public health center (PHC). A Total of 18 pulmonary tuberculosis cases were diagnosed in one of these hospitals between December 1995 and November 1998. They were all inpatients and two of them had history of tuberculosis. Fifty-two persons became candidates for isoniazid (INH) chemoprophylaxis as a consequence of the first extraordinary health examination. Chest radiographs of the inpatients had not been taken regularly in this hospital. Our recognition of the tuberculosis outbreak was delayed by omission of not only the case notification from the doctor who had diagnosed tuberculosis but the information from the PHC that had received the application of public subsidy for medical treatment. All cultured bacilli from 8 patients were susceptible to INH, rifampicin, streptomycin and ethambutol. Restriction fragment length polymorphism (RFLP) analysis of 4 strains, which we could have obtained, demonstrated an identical pattern. CONCLUSIONS: To prevent tuberculosis outbreaks in mental hospitals, we should consider these problems as follows; 1) Physical conditions of inpatients should be observed carefully and suitable physical checkups on inpatients with tuberculosis symptoms should be carried out by mental hospitals. 2) The doctor who had diagnosed a patient as having tuberculosis must send the case notification to the nearest PHC. 3) The PHC that received the information should investigate the case carefully and notify all related PHC's. 4) Extraordinary health examinations should be done appropriately by leadership of the PHC. 5) RFLP analysis of the tubercle bacilli is very useful to probe the source and route of infection. 6) Criteria for chemoprophylaxis for more than middle-aged persons should be established.

Adult↗
PubMed1999

Retinal expression of a neo-self antigen, beta-galactosidase, is not tolerogenic and creates a target for autoimmune uveoretinitis.

Recent studies revealing active mechanisms of immune privilege in neural tissues have diminished the putative role of passive tolerance. To examine the significance of Ag localization in the retina on immune privilege, the immune responses of transgenic mice expressing high and low levels of beta-galactosidase (beta-gal) in the photoreceptor cells of the retina were compared with those of normal mice and those of mice expressing moderate levels of beta-gal systemically. Immunization with beta-gal induced experimental autoimmune uveoretinitis indistinguishable from that induced by known photoreceptor cell autoantigens, including destruction of photoreceptor cells, in transgenic mice with high level retinal expression. Retinal expression had no apparent effect on the immune responses to beta-gal, showing that tolerance was not elicited by levels of retinal beta-gal sufficient to serve as a target for autoimmune disease. Mice with systemic expression exhibited reduced lymphoproliferative responses following immunization with beta-gal and did not develop autoimmune disease. T cells prepared from normal mice immunized with beta-gal transferred experimental autoimmune uveoretinitis to the transgenic mice with high level retinal beta-gal expression, but no disease was found in mice with systemic transgene expression under these conditions. The results of our experiments are most consistent with sequestration being the primary mechanism of retinal immune privilege. The results also show that beta-gal can serve as an immunopathogenic neural autoantigen, and that T cells raised by immunization of normal mice with a foreign Ag can be immunopathogenic in certain transgenic recipients.

Adoptive Transfer↗
PubMed1999

beta1- and alpha6-integrin are surface markers on mouse spermatogonial stem cells.

Although spermatogenesis is essential for reproduction, little is known about spermatogonial stem cells. These cells provide the basis for spermatogenesis throughout adult life by undergoing self-renewal and by providing progeny that differentiate into spermatozoa. A major impediment to our understanding of the biology of these stem cells is the inability to distinguish them from spermatogonia that are committed to differentiation. We made use of the known association of stem cells with basement membranes and our spermatogonial transplantation assay system to identify specific molecular markers on the stem cell surface. Selection of mouse testis cells with anti-beta1- or anti-alpha6-integrin antibody, but not anti-c-kit antibody, produced cell populations with a significantly enhanced ability to colonize recipient testes and generate donor cell-derived spermatogenesis. We demonstrate spermatogonial stem cell-associated antigens by using an assay system based on biological function. Furthermore, the presence of surface integrins on spermatogonial stem cells suggests that these cells share elements of a common molecular machinery with stem cells in other tissues.

Animals↗
PubMed1999

Heterogeneity of multiorgan metastases of human lung cancer cells genetically engineered to produce cytokines and reversal using chimeric monoclonal antibodies in natural killer cell-depleted severe combined immunodeficient mice.

Lung cancer is a major cause of cancer deaths, most of which can be attributed to distant multiorgan metastases. To examine the cellular and molecular mechanisms of lung cancer metastasis to distant organs, we have established novel models of human lung cancer (small cell and non-small cell lung cancer) metastasis in natural killer cell-depleted severe combined immunodeficient (SCID) mice. We investigated whether local production of the cytokines responsible for regulation of macrophage function at tumor growth sites affects the pattern of lung cancer metastasis in distant organs. Several lung cancer cell lines were genetically engineered to produce human macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1), and their metastatic potentials were assessed. Interestingly, M-CSF gene transduction had an antimetastatic effect for the liver and lymph nodes, but not the kidneys. In contrast, MCP-1 gene-modified lung cancer cells and their parent cells had identical metastatic potentials. These findings indicate a possible role for cytokines and suggest that lung cancer has metastatic heterogeneity. Examining ways of controlling human lung cancer metastases, we investigated the antimetastatic effect of chimeric monoclonal antibodies (MAbs) against P-glycoprotein and ganglioside GM2 (MH162 and KM966, respectively). Both MAbs, when given on days 2 and 7, inhibited the development of distant metastases of lung cancer in a dose-dependent fashion. Combined use of anti-P-glycoprotein MAb with M-CSF or MCP-1 gene transduction caused complete inhibition of metastasis of H69/VP cells. The antimetastatic effect of these MAbs in vivo was mainly due to an antibody-dependent cell-mediated cytotoxicity reaction mediated by mouse macrophages. These findings suggest that the mouse-human chimeric MAb in combination with cytokine gene transduction may be useful for the eradication of lung cancer metastases in humans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Pathological study on sibling autopsy cases of the late infantile form of neuronal ceroid lipofuscinosis.

We report autopsy cases of two brothers with the late infantile form of neuronal ceroid lipofuscinosis (LINCL) and examine apoptotic cell death in autopsied brains. Both patients showed psychomotor developmental delay, cerebellar ataxia, convulsions, visual disturbance and myoclonus, and they became bedridden around the age of 6-7 years. Macular changes, mimicking cherry-red spots, were observed on funduscopy, but conjunctival biopsy failed to disclose storage materials. In these cases, the autopsies demonstrated severe atrophy with neuronal loss and gliosis throughout the brain and spinal cord, except the hypothalamic neurons and motor neurons in the brain-stem and spinal cord, and autofluorescent lipofuscin-like materials of two types, fine granular deposits and coarse round bodies, were stored in the remaining neurons and glial cells, and in the epithelial cells of various visceral organs. Immunostaining for mitochondrial subunit C visualized the fine granular deposits but not the coarse round bodies. The nuclei of neurons and glia cells were stained by in situ nick end labeling, which was more pronounced in the younger case, although the expression of both bcl-2 and bcl-x was not significantly altered in these cases. It is suggested that immunohistochemistry for subunit C may be useful for diagnosis of NCL, and further investigations are necessary to clarify the relationship between LINCL and apoptosis, especially in severely affected cases.

Atrophy↗
PubMed1999

An unusual autopsy case of a victim stabbed during sadomasochistic prostitution.

A 29-year-old male who lived alone was found dead with his back leaning against the wall of his room. He had been stabbed in his abdomen with a survival-type knife. The victim's mouth was plugged with a pink-colored glove and was sealed with packing tape. His wrists were tightly tied behind his back with the same type of packing tape. The cause of death was diagnosed as hemorrhage from the right common iliac artery and vein. Due to the strange circumstances of the crime scene, the police initially considered the possibility of homicide by a group of assassins. Two months later, the police arrested a male suspect who was a member of a vice racketeer. The victim was characterized as a masochist and bisexual. He often hired the male suspect to perform sadomasochistic activities. On the day of the crime, the victim prepared a survival-type knife and packing tape himself to experience fear and pain more strongly. The victim hoped to use the knife to increase sexual excitement. In this case of sadomasochistic prostitution leading to death, the legal issues of homicide for money, malicious request of injury by the victim and accidental death were involved.

Journal Article↗
PubMed1999

Low rate of apoptosis and overexpression of bcl-2 in Epstein-Barr virus-associated gastric carcinoma.

AIMS: Epstein-Barr virus (EBV) has been demonstrated in about 10% of gastric carcinomas. However, the pathogenetic role of EBV in gastric carcinoma is uncertain. We compared the rate of apoptotic cell death, cell proliferation and the expression of apoptosis-related proteins in gastric carcinomas with or without EBV. METHODS AND RESULTS: Epstein-Barr virus was detected in 40 gastric carcinomas by EBV-encoded small RNA-1 in-situ hybridization. Apoptotic cell death, MIB-1, p53, bcl-2 and bcl-x were examined by the terminal deoxynucleotidyl-mediated dUTP-nick end labelling method and immunohistochemistry. We also included 40 age-, sex- and disease stage-matched EBV-negative cases as a control. The number of apoptotic cells was significantly lower in EBV-positive (20 +/- 15. 1/1000 cells) and bcl-2-positive (17 +/- 12.9/1000 cells) tumours than in EBV-negative (43 +/- 37.1) and bcl-2-negative tumours (38 +/- 32.1, P < 0.001, P < 0.001, respectively). bcl-2 immunostaining was significantly higher in EBV-positive tumours (24 cases) than in EBV-negative tumours (12 cases, P < 0.05). There was no significant difference in bcl-x and p53 expression between EBV-positive and -negative tumours. The number of MIB-1-positive cells in EBV-positive tumours (237 +/- 161/1000) was significantly lower than in EBV-negative tumours (480 +/- 208/1000 cells, P < 0.001). CONCLUSIONS: A low rate of apoptosis and high bcl-2 expression were recognized in EBV-positive gastric carcinomas, suggesting that bcl-2 protein is the main inhibitor of apoptosis in EBV-positive carcinomas. In addition, the low apoptotic and proliferative activities may reflect a low biological activity in EBV-positive gastric carcinomas.

Adult↗
PubMed1999

[Three children with systemic cat scratch disease].

Three girls with systemic cat scratch disease, aged 10, 13 and 9 years, were reported. They presented a prolonged fever and back pain in the early stage of the disease, and had no regional lymphadenopathy. Two of them had hepatosplenic granulomas, one with multiple 5 mm hypoechoic lesions in the liver and spleen, and the other with a single 2.5 cm hypodense lesion in the left hepatic lobe. The latter patient underwent a partial left hepatic lobectomy. All patients had elevated titers of antibodies to Bartonella henselae. Polymerase chain reaction detected B. henselae DNA in tissue specimens of the patient who underwent a hepatic lobectomy. Cat scratch disease should be recognized as a cause of fever of unknown origin because the prevalence of B henselae infection might be higher in Japan.

Adolescent↗
PubMed1999

Cellular immune response to retinal S-antigen and interphotoreceptor retinoid-binding protein fragments in Eales' disease patients.

The role of retinal antigens in Eales' disease was studied in 24 patients and an equal number of healthy controls. Lymphocyte proliferative responses were tested in vitro against native S-antigen, its uveitopathogenic peptides (peptide M and peptide G), yeast histone H3 peptide and uveitopathogenic fragment of interphotoreceptor retinoid-binding protein (IRBP; R16) to establish their role in the pathogenesis of Eales' disease. Out of 24 Eales' disease patients, 6 showed significant proliferative response against S-antigen, its uveitogenic fragments or IRBP. None among the controls showed any response to any retinal antigen used in this study. There was no statistically significant difference in the response to purified protein derivative between patients and controls. These results suggest that retinal antigens may play a role in the etiopathogenesis of Eales' disease. An extraneous agent that could result in exposure of normally sequestered uveitopathogenic antigens of the immune system, leading to an exuberant immune response in the eye may initiate the disease.

Adolescent↗
PubMed1999

Calcinosis cutis and intestinal pseudoobstruction in a patient with adult onset Still's disease associated with recurrent relapses of disordered coagulopathy.

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown origin, characterized by a typical spiking fever, evanescent salmon-colored rash, polyarthralgia, and myalgia. Calcinosis cutis and gastrointestinal involvement have rarely been noted in AOSD. We herein describe a 54-year-old woman who demonstrated repeated disseminated intravascular coagulation (DIC), and adult respiratory distress syndrome (ARDS), associated with AOSD. The patient also revealed a remarkable degree of digital calcinosis cutis and intestinal pseudoobstruction. A connective tissue disease, such as systemic sclerosis, might have been the underlying factor in the latter two symptoms.

Anticoagulants↗
PubMed1999

Antibodies to a microbial peptide sharing sequence homology with betaA3-crystallin damage lens epithelial cells in vitro and in vivo.

Circulating auto-antibodies (Abs) against lens antigens (Ags) are highly prevalent in patients with cataract, but their origin and pathogenic significance are unknown. We hypothesized that Abs raised after exposure to infectious microbes could cross-react with lens Ags. To test this hypothesis, we generated a monoclonal Ab to human betaA3-crystallin. Epitope analysis indicated that the ETQAE sequence in the N-terminus region of betaA3-crystallin was critical for mounting a humoral response. Similar sequences were found in three microbial Ags. Mice injected with a microbial oligopeptide containing ETQAE emulsified with complete Freund's adjuvant (CFA) raised Abs which cross-reacted with betaA3-crystallin and developed lens epithelial cell (LEC) damage in vitro. We also genetically engineered an betaA3-crystallin-expressing E. coli. Mice immunized with the recombinant E. coli developed LEC damage. These results support the hypothesis that exposure to microbes having Ags homologous to self Ags can trigger a humoral immune response that leads to LEC damage in mice.

Amino Acid Sequence↗
PubMed1999

Lens epithelium-derived growth factor: increased resistance to thermal and oxidative stresses.

PURPOSE: To investigate the role of lens epithelium- derived growth factor (LEDGF) in lens epithelial cells subjected to heat or oxidative stress and to determine the localization of LEDGF in lens epithelial cells at different temperatures. METHODS: Mouse lens epithelial cells overexpressing a fusion protein between a green fluorescent protein (GFP) and LEDGF (GFP-LEDGF) were cultured for up to 7 days at various temperatures or for 24 hours in the presence of hydrogen peroxide. Translocation of GFP-LEDGF in the lens epithelial cells was monitored with a fluorescence microscope. Cell survival was determined with the trypan blue dye exclusion test. Expression of heat shock proteins (Hsps) was studied with protein blot analyses using antibody probes. RESULTS: LEDGF was found in the cytosol of lens epithelial cells at 4 degrees C, 15 degrees C, and 28 degrees C, and in the nucleus and nucleolus at 37 degrees C. At 41 C, it was apparent at higher levels in the cytosol, nucleus, and nucleolus. Lens epithelial cells overexpressing LEDGF manifested resistance to thermal and oxidative stress. Levels of Hsp 27, and alphaB-crystallin were elevated in these cells. Depriving lens epithelial cells of LEDGF with anti-LEDGF antibodies reduced nuclear localization of LEDGF and induced cell death. CONCLUSIONS: The overexpression of LEDGF in lens epithelial cells conferred resistance to thermal and oxidative stress. The mechanism of this resistance appears to involve the increased expression of Hsp 27 and alphaB-crystallin.

Animals↗
PubMed1999

[A case of internal hernia through a defect in the falciform ligament treated with laparoscopic surgery].

A 22-year-old male was admitted to our hospital with abrupt onset of upper abdominal pain. Abdominal US and CT revealed dilatation of the small intestine between the abdominal wall and a lateral segment of the liver. After a diagnosis of an internal hernia through a defect in the falciform ligament, emergency surgery was performed. Laparoscopic investigation showed incarceration of the small intestine in a defect of the falciform ligament. After releasing an incarceration, the hernia orifice was opened to prevent relapse. He was discharged on the 4th postoperative day. Internal hernia through a defect in the falciform ligament is extremely rare, with six reported cases including our own in Japan. Characteristic images of abdominal US and CT enable preoperative diagnosis of this condition. Surgery should be performed at an early stage after onset. In patients with no prior history of surgery, laparoscopic techniques may be useful.

Adult↗
PubMed1999

[Rat lens epithelial cell damage and cataract formation induced by immunological response to bovine lens membrane protein].

PURPOSE: To evaluate the correlation of cataractogenesis and immune mechanisms, we investigated the rat lens morphologically and immunologically. METHODS AND RESULTS: Wistar rats were divided into three groups: Group A was immunized with bovine-lens membrane protein (B-LMP) and adjuvant, Group B was immunized with adjuvant only, and Group C was not given any treatment as a control. Titer levels of anti-B-LMP antibody and anti-Rat-LMP antibody were elevated and posterior subcapsular cataract was developed in Group A. In flat preparations, a noncellular part in the lens epithelium was observed in all members of Group A. In this noncellular part, a lens capsule protruding into the lens epithelial cell layer was observed by light microscopy. CONCLUSION: These data suggest that lens epithelial cells may be damaged by immune response, causing the development of cataract.

Animals↗
PubMed1998

Efficient modification of a human chromosome by telomere-directed truncation in high homologous recombination-proficient chicken DT40 cells.

Truncation of human chromosomes at desired sites by homologous recombination techniques enables functional and structural analyses of human chromosomes and development of human artificial chromosomes. However, this targeted truncation has been inefficient. We describe here an efficient method for targeted truncation in the chicken DT40 cells with a high homologous recombination rate. The human chromosome 22 was transferred into DT40 cells, where human telomeric repeat (TTAGGG)n was targeted to the LIF locus on the chromosome. Molecular and cytogenetic analyses showed that the predicted truncation at the LIF locus occurred in all of the targeted clones.

Animals↗