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Biomedical subjects

K Shibuya

Publications and source records attributed to K Shibuya.

At least 37 records · Page 2Linked to original sources
PubMed2002

Immunohistochemical and ultrastructural study on effect of fibroblast growth factor on transformation of fibroblasts to regenerated mesothelial cells.

To elucidate the effect of fibroblast growth factor on the phenotypical conversion of fibroblasts to mesothelial cells, both immunohistochemical and ultrastructural examinations were carried out on cultured spheroids that were composed of fibroblasts obtained from the parietal pleura of rats with and without addition of antifibroblast growth factor receptor antibody. In the present study, antifibroblast growth factor receptor antibody was employed to block the effect of the autocrine component of fibroblast growth factor in the culture medium. Phenotypical conversion from fibroblast to mesothelial cells was clearly blocked in the experimental group, to which culture medium had been added with antifibroblast growth factor receptor antibody, whereas the control group, cultured without addition of antifibroblast growth factor receptor antibody, showed phenotypical conversion of fibroblasts that was confirmed by the development of macula adherens, microvilli, and positive expression of cytokeratin. These results indicate the possibility that fibroblast growth factor plays a key role in the process of phenotypic conversion of fibroblasts to regenerated mesothelial cells.

Animals↗
PubMed2002

Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis.

To elucidate the pathology of osteoporosis associated with rheumatoid arthritis (RA), bone mass measurements were performed in 146 female patients with RA and compared with those in 150 age-matched female patients with osteoarthritis (OA) and postmenopausal osteoporosis (OP). Bone mineral density (BMD) was measured at the lumbar spine (L-BMD), the mid-radius (MR-BMD) and the calcaneus (C-BMD) by dual-energy X-ray absorptiometry (DXA), and at the distal radius by peripheral quantitative computed tomography (pQCT). The RA group showed significantly lower BMD at all sites, except L-BMD, than the OA group. Compared with the OP group, the RA group showed a significantly higher L-BMD but no difference at other sites. BMD in RA decreased with disease severity at all sites and lean body mass was highly correlated with L-BMD and C-BMD. Cross-sectional analysis revealed early bone loss at the distal radius and a decrease of L-BMD, MR-BMD, and C-BMD with disease duration. Longitudinal analysis showed that the annual loss of L-BMD, MR-BMD and C-BMD tended to be lower with increasing disease duration. Glucocorticoid administration had no influence on L-BMD, MR-BMD or C-BMD. We concluded that, unlike postmenopausal osteoporosis, osteoporosis associated with RA is characterised by relatively preserved bone mass in the axial bone and marked loss in the peripheral bone. The risk factors for generalised osteoporosis are a long disease duration, severity of disease, and decreased lean body mass.

Absorptiometry, Photon↗
PubMed2002

Deep-seated mycosis as a complication in bone marrow transplantation patients.

Achieving control of opportunistic fungal infections which occur during the course of immunosuppressive therapy is one of the key factors deciding the success or failure of bone marrow transplantation (BMT). A review was conducted of autopsied patients who had undergone BMT at the University of California at Los Angeles Medical Center in the USA between 1985 and 1994. The incidence of complication by deep-seated mycoses was determined, and the causative fungal species and invaded organs were elucidated. Deep fungal infections were found to have occurred in 31.5% (47/149 cases) of the BMT patients, and disseminated disease was found in approximately one-quarter of the infected cases. The findings suggest that BMT patients, who require the use of potent immunosuppressive agents, show increased susceptibility to the development of more serious, and widespread diffuse fungal infections. The most commonly detected causative fungi were Aspergillus species and Candida species. In addition, it was found that the incidence of candidosis had decreased markedly in recent years; conversely, aspergillosis had increased. It was surmised that these findings reflect the development of antifungal agents which are effective against candidosis and have enabled a reduction in the incidence of this disease even in BMT patients, whereas aspergillosis remains difficult to treat. In consideration of these findings regarding the manifestation of deep-seated mycosis in BMT patients, we conclude that in order to increase the success rate of BMT it will be essential to establish safe and effective methods for the prevention and treatment of aspergillosis.

Adolescent↗
PubMed2002

Subepithelial vascular patterns in bronchial dysplasias using a high magnification bronchovideoscope.

BACKGROUND: We have developed a method of high magnification bronchovideoscopy that enables improved observation of subepithelial vascular patterns of the bronchial mucosa. A study was undertaken to investigate the value of high magnification bronchovideoscopy in the detailed examination of dysplasia in the bronchial mucosa of patients with abnormal mucosal fluorescence. METHODS: Thirty one patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light examination was first performed under local anaesthesia and fluorescence bronchoscopy was also carried out using a light induced fluorescence endoscopy (LIFE) lung system. A high magnification bronchovideoscope (XBF 200HM2) was then used to examine the microvascular network in the bronchial mucosa at sites of normal and abnormal fluorescence and the images obtained were compared with pathological diagnoses from bronchial biopsy specimens. Vascular area ratios were calculated using image analysing apparatus. RESULTS: Vascular networks with regular patterns were observed at 20 of 22 abnormal fluorescence sites in biopsy specimens from patients with bronchitis. However, vascular networks with increased vessel growth and complex networks of tortuous vessels of various sizes were observed in 15 of 21 abnormal fluorescence sites in dysplasia specimens. There was a significant difference between bronchitis and dysplasia specimens (OR=25, 95% CI 5.5 to 113, p<0.0001). Mean vascular area ratios from 16 normal bronchial epithelium specimens with normal fluorescence, and 22 bronchitis and 21 dysplasia specimens with abnormal fluorescence were 0.054 (95% CI 0.039 to 0.07), 0.095 (95% CI 0.072 to 0.118), and 0.173 (95% CI 0.143 to 0.203), respectively. The results indicate a statistically significant increase in vascular area in the three groups (p<0.0001). CONCLUSION: Areas of increased vessel growth and complex networks of tortuous vessels in the bronchial mucosa detected using a high magnification bronchovideoscope at sites of abnormal fluorescence may enable discrimination between bronchitis and dysplasia.

Aged↗
PubMed2002

Bronchopleural fistula after lung cancer surgery. Multivariate analysis of risk factors.

BACKGROUND: To elucidate retrospectively the risk factors for bronchopleural fistulae after lung cancer surgery. METHODS: The subjects were 1,177 patients with lung cancer who underwent surgery between 1983 and 1997. Twenty-two clinical factors were examined by logistic analysis. RESULTS: Bronchopleural fistulae were observed in 35 patients (32 males, 3 females) with a mean age of 64 years. Eighteen (51%) of 35 patients died of BPF-related complications. The significant risk factors obtained by univariate analysis were male gender, heavy smoking, current smoking, low level of %FVC, metastases to lymph nodes, squamous cell carcinoma, increased WBC, decreased albumin, advanced postsurgical stage, sleeve lobectomy, and resection of the right lower lobe or middle and lower lobe. The significant risk factors noted by multivariate analysis were heavy smoking (30 or more pack/years), current rather than past smoking, metastases to lymph nodes, decreased albumin (3.5 mg/dl or less), and resection of the right lower lobe or middle and lower lobe. CONCLUSIONS: The above risk factors must be taken into account before surgical techniques followed by adequate perioperative management are selected.

Adolescent↗
PubMed2001

Molecular cloning and characterization of mouse Tspan-3, a novel member of the tetraspanin superfamily, expressed on resting dendritic cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells and play an essential role for triggering T-cell-mediated immune responses. In search for novel cell surface molecules expressed on DCs involved in T cell priming by representational differential analysis, we identified a mouse homologue of Tspan-3 (mTspan-3), a novel member of the tetraspanin superfamily. The mTspan-3 consists of four hydrophobic, putative transmembrane regions, forming a small and a large extracellular loop, with short intracellular amino and carboxil tails. Although the mTspan-3 is expressed on a variety of immune cell types including resting DCs, its expression on DCs is downregulated during activation induced by cross-linking CD40 with anti-CD40 monoclonal antibody. These results suggest that mTspan-3 may be involved in the function of DCs in association with T cell stimulation.

Amino Acid Sequence↗
PubMed2001

Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HLCS) is an enzyme that catalyzes the incorporation of biotin into apo-carboxylases, and its deficiency causes biotin-responsive multiple carboxylase deficiency. The reported sequences of cDNA for human HLCS from liver, lymphocyte, and KG-1 myeloid cell lines differ at their 5' regions. To elucidate variations of the human HLCS mRNA and longer 5' cDNA ends, we performed screening of the human liver cDNA library and rapid amplification of the cDNA ends (RACE). Our results suggest the existence of three types of HLCS mRNA that start at different exons. The first type starts at exon 1, and the second type starts at exon 3, and both are found in various human tissues. The third type, corresponding to the cDNA from the KG-1 cell, starts at exon 2 of the HLCS gene. Various splicing patterns from exons 3-6 were also observed. None of the variations of cDNA found created a new initiation codon. Mutation screening from exons 6-14, therefore, was sufficient to detect amino acid changes in HLCS in patients. Our direct sequencing strategy for screening mutations in the HLCS gene revealed mutations in five Japanese patients and seven non-Japanese patients. Our analyses involving 12 Japanese and 13 non-Japanese patients and studies by others indicate that (1) there is no panethnically prevalent mutation; (2) the Arg508Trp, Gly581Ser, and Val550Met mutations are found in both Japanese and non-Japanese populations; (3) the IVS10+5G-->A mutation is predominant and probably a founder mutation in European patients; (4) the 655-656insA, Leu237Pro, and 780delG mutations are unique in Japanese patients; (5) the spectrum of the mutations in the HLCS gene may vary substantially among different ethnic groups.

Base Sequence↗
PubMed2001

Increased telomerase activity and elevated hTERT mRNA expression during multistage carcinogenesis of squamous cell carcinoma of the lung.

BACKGROUND: Telomerase activation is believed to play a critical role in the immortalization of cells and carcinogenesis. Telomerase activity is undetectable in normal somatic cells (except for those cells undergoing proliferation) but is expressed in the majority of human tumors including lung carcinoma. The expression of hTERT mRNA has been found to be correlated with telomerase activity. In the current study, the authors analyzed telomerase activity and hTERT mRNA expression in preinvasive bronchial lesions using biopsy specimens obtained by fluorescence bronchoscopy. METHODS: The authors studied 150 bronchial biopsy specimens obtained by fluorescence bronchoscopy. The intensity of telomerase activity was determined by the fluorescence-based telomeric repeat amplification protocol method in 74 bronchial biopsy specimens (22 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 23 dysplasia cases, and 14 squamous cell carcinoma cases), and the level of hTERT mRNA was analyzed in another 76 specimens (24 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 20 dysplasia cases, and 17 squamous cell carcinoma cases) by real-time polymerase chain reaction. RESULTS: The mean values (+/- the standard deviation [SD]) of telomerase activity in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 6.2 +/- 7.5, 13.9 +/- 14.8, 18.5 +/- 20.8, and 54.5 +/- 22.3 U/microg protein, respectively. The upper limit of telomerase activity in normal bronchial epithelium or bronchitis was 21 U/microg protein (mean + 2SD). It is interesting to note that, 5 of 15 squamous metaplasia biopsies (33%), 8 of 23 dysplasia biopsies (35%), and all squamous cell carcinoma biopsies (100%) exhibited levels of telomerase activity that were > 21 U/microg protein. The mean levels of hTERT mRNA in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 891 +/- 840, 1936 +/- 1704, 3019 +/- 2607, and 12965 +/- 18008 copies/microg total RNA, respectively. Telomerase activity and hTERT mRNA expression were found to increase in proportion to the severity of histologic change from normal bronchial epithelium or bronchitis to squamous cell carcinoma. CONCLUSIONS: These results suggest that an increase in telomerase activity and hTERT mRNA expression are features of the early stages of the development of squamous cell carcinoma of the lung, with strong telomerase activity and hTERT mRNA expression being prominent during the latter stages.

Adult↗
PubMed2001

In vivo evaluation of the early events associated with liver metastasis of circulating cancer cells.

The mechanism of metastasis formation remains still largely unknown. Many studies underline the importance and complexity of the initial arrest of the circulating tumour cells in the target organ, a key stage in metastasis occurrence. In our study, we evaluated by visual means the metastasis formation using an in vivo microscopy system in a murine model. Moreover, we investigated the involvement of P-selectin in these processes using immunohistochemistry and P-selectin knockout mice. The present study offers direct evidence of distinct pathways for tumour metastasis formation by a lymphoma cell - EL-4 and a solid tumour cell - C26. Off-line analysis of the images and histological data confirmed that mechanical entrapment of the solid tumour cell, which had a bigger diameter than that of the liver sinusoids, promoted metastasis without any detectable involvement of adhesion molecules. On the other hand, we observed that lymphoma cells, in spite of their smaller diameter as compared to the sinusoids, promoted liver metastasis as well, but with the essential participation in their arrest of P-selectin, indicating an adhesion molecule-mediated pathway.

Adenocarcinoma↗
PubMed2001

A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non-hematopoietic tissues.

By contrast to well-defined Fc gamma and Fc epsilon receptors, the structural and functional characteristics of Fc mu receptor are unclear. We have recently described a novel mouse Fc receptor, designated Fc alpha/mu receptor, and its human homologue, which bind both IgM and IgA. Here we show that the Fc alpha/mu receptor is expressed on mature, but not immature, B lymphocytes and acquires the ability to bind IgM and IgA antibodies after stimulation of B lymphocytes. Moreover, stimulation with phorbol 12-myristate 13-acetate increased endocytosis of IgM-coated microparticles mediated by the Fc alpha/mu receptor expressed on pro-B cell line Ba/F3 cells. We also show that the Fc alpha/mu receptor is expressed in secondary lymphoid organs, such as lymph node and appendix, kidney and intestine, suggesting an important role of the receptor for immunity in these organs.

Animals↗
PubMed2001

Isolation and characterization of the UBASH3A gene on 21q22.3 encoding a potential nuclear protein with a novel combination of domains.

In order to identify candidate genes for Down syndrome phenotypes or monogenic disorders that map to human chromosome 21q22.3, we have used genomic sequence and expressed sequence tags mapping to an autosomal recessive deafness (DFNB10) critical region to isolate a novel 2.5-kb cDNA that maps between TFF1 and D21S49. A semi-quantitative reverse transcription/polymerase chain reaction method revealed that UBASH3A gene expression is limited to only a few tissues, with its highest expression in spleen, peripheral blood leukocytes, and bone marrow. The putative 661-amino-acid protein shows considerable homology to a hypothetical protein from Drosophila melanogaster but only domain homologies to other organisms. Both the human and D. melanogaster proteins contain protein-protein interaction domains, viz., SH3 and ubiquitin-associated (UBA) domains, in addition to a novel domain also containing a nuclear localization signal. This is the first protein described containing both UBA and SH3 domains. The gene, thus called UBASH3A, spans 40 kb and is divided into 15 exons. Mutation analysis excluded UBASH3A as being responsible for DFNB10.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Cytokine modulation in acute pancreatitis.

The clinical manifestations of acute pancreatitis (AP) vary significantly from mild to lethal in form, the severity of the disease being largely determined by the actions of various kinds of inflammatory mediators, including cytokines, reactive oxygen species, proteolytic enzymes, and lipids, as well as gaseous mediators. Despite increasing knowledge implicating the involvement of cytokines in the progression of AP, no clinical trials pertaining to cytokine modulation have been performed so far. Progress in intensive care technologies has contributed to the improvement of mortality and morbidity rates in severe AP in the past decade; however, it appears to be reasonable for clinicians to "line up their sights" on the modulation of cytokines as a direct treatment. In contrast to the large body of experimental studies demonstrating the beneficial effects of cytokine modulation on the amelioration of the disease, direct extrapolation from these successful experiments to the clinical situation seems to be extremely difficult.

Acute Disease↗
PubMed2001

Early microcirculatory derangement in mild and severe pancreatitis models in mice.

An in vivo microscopic technique was used to clarify the increase in microvascular permeability and enhanced leukocyte-endothelium interaction of pancreatic microcirculation in experimental pancreatitis of differing severity. Using bovine albumin fluorescein isothiocyanate (FITC) and carboxyfluorescein diacetate succinimidyl ester (CFDASE) as tracers, the change in permeability and the behavior of leukocytes in the acinar microcirculation were quantified during the initial 1, 2, 6, and 12h after the induction of caerulein pancreatitis in mice. Cold stress was added to produce the severe model. It was revealed that the early microcirculatory changes in the pancreas of caerulein pancreatitis included the increased permeability of endothelial lining and an accumulation of extravasated fluid in the perilobular space, which were more severe if cold stress was added. A decrease in flow velocity was also noted 2h after the onset of severe pancreatitis. Leukocyte adherence to the endothelial cells was not observed during the first 12h in either model of severity. In contrast, observation of the hepatic microcirculation revealed a significant number of adherent leukocytes 2h after the induction of severe pancreatitis. These results suggest that during the early course of acute pancreatitis, leukocyte adherence in the pancreatic microcirculation is a secondary event following the increase in pancreatic vascular permeability.

Acute Disease↗
PubMed2001

Laparascope-assisted versus conventional restorative proctocolectomy with rectal mucosectomy.

To assess the advantages of a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis compared with conventional procedures, we retrospectively analyzed the results of the two procedures as follows: Eleven patients including five patients with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) underwent a laparoscope-assisted proctocolectomy and hand-sewn ileal J-pouch anal anastomosis at our department from June 1997 to November 1999. This laparoscope-assisted colectomy (LAC) group was then compared with a group of 13 patients who had undergone conventional ileal pouch anal anastomosis using a standard laparotomy from 1986 to 1997. The median operative time of the LAC group was 8h 23min, which was 81 min longer than that of the standard colectomy (SC) group. The number of days during which eating was prohibited were similar in the two groups but the median postoperative hospital stay was significantly shorter in the LAC group (24.1 days). In the LAC group, the small incisions showed better cosmetic results and there was also a remarkable reduction in the degree of postoperative pain. In conclusion, a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis can be employed widely in patients with FAP and also in selected patients with UC.

Adenomatous Polyposis Coli↗
PubMed2001

Successful resection of a primary liposarcoma in the anterior mediastinum in a child: report of a case.

Primary liposarcomas of the mediastinum are very rare. We report on a 13-year-old girl who presented with a huge mediastinal tumor. The tumor was extirpated by a median sternotomy with a right thoracotomy. The tumor included the superior vena cava in the anterior mediastinum. It therefore probably originated from the anterior mediastinal fat tissue, possibly from the thymus. A pathological examination revealed myxoid liposarcoma. At 35 months postoperatively, the patient has not shown any recurrence.

Adipose Tissue↗