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Biomedical subjects

Y Kawabata

Publications and source records attributed to Y Kawabata.

At least 19 recordsLinked to original sources

Immunohistochemical detection of ubiquitin-positive intracytoplasmic eosinophilic inclusion bodies in diffuse alveolar damage.

AIMS: To clarify the relationship between ubiquitin-positive pneumocytes and intracytoplasmic eosinophilic inclusion bodies (IB) in patients who died of diffuse alveolar damage (DAD). METHODS AND RESULTS: Eighteen patients with DAD were studied, in whom hyaline membranes were present in one or more out of five sections from each lobe of the lungs and 15 patients with no DAD. Light microscopy revealed hyaline membrane in over 25% of lobes from 18 patients with DAD. The cytoplasm of pneumocytes from six of 18 cases of DAD contained IB. Immunohistochemically, all IBs were characteristically positive for both ubiquitin (Ub) and cytokeratin KL-1. Cytoplasmic granules were also Ub+ in four cases of DAD without IB. IB+ or Ub+ pneumocytes were undetectable in non-DAD patients. We evaluated DAD severity based on hyaline membrane formation; the mean score in DAD with IB (3.60; n = 6) was significantly higher than that in Ub- (2.92; n = 8). Ub+ pneumocytes were found with or without IB among those cases with high DAD scores. CONCLUSIONS: These findings suggest that disordered proteolysis in the Ub-mediated proteasome system leads to the accumulation of abnormal ubiquitinated protein, which includes cytokeratin, in pneumocytes. This is the first report to suggest that Ub+ pneumocytes are associated with disease severity in patients with DAD.

Adolescent↗

Interpretation of scintigraphic findings of oral malignant tumours with a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI).

OBJECTIVES: The purpose of this study was to investigate the usefulness of a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI) for the diagnosis of malignant tumours of the head and neck. METHODS: Scintigraphy with Tc-99m-MIBI was performed in 19 patients with malignant tumours of the head and neck. Factors of the early and delayed static scans (hot, warm or cold uptake), the early and delayed retention indexes, the blood flow index and the tumour retention index were obtained from Tc-99m-MIBI scintigraphy. Tumour retention indexes were classified into three grades; slightly (>0.9), moderately (0.9-0.8) and severely (0.8>) decreased. Grade of tissue differentiation of tumour (well, moderately or poorly differentiated) and tumour size (T1 approximately T4) were examined using the excised tumour. Scintigraphic indexes and tumour characteristics were compared. RESULTS: The early static scan and tumour size showed a correlation with the blood flow index. However, the delayed static scan did not show any relationship with blood flow index and tumour size. The tumour retention index had a tendency to decrease in malignant tumours, and showed a significant correlation with the grade of tissue differentiation of the tumour. CONCLUSIONS: The tendency of the tumour retention index to decrease in Tc-99m-MIBI scintigraphy showed the malignancy of tumour and would be useful for the diagnosis of malignant tumours of the head and neck.

Adult↗

Thallium-201 chloride (Tl-201) accumulation and Na+/K+-ATPase expression in tumours of the head and neck.

OBJECTIVES: The purpose of this report was to evaluate the relationship between the tumour retention index of thallium-201 chloride (Tl-201) scintigraphy and the Na+/K+-ATPase expression in tumours of the head and neck. METHODS: Tl-201 scintigraphy was performed in 146 patients (129 with malignant tumours, ten with benign tumours and seven with inflammation). The tumour retention index was obtained from the early and delayed dynamic Tl-201 scans. The Na+/K+-ATPase expression was evaluated immunohistochemically in 61 of 129 patients with malignant tumour. Furthermore, another 22 patients with benign tumour were evaluated immunohistochemically as a benign control. Comparison of the correlations between the grade of histopathological differentiation of tumour, the tumour retention index of Tl-201 scintigraphy and the Na+/K+-ATPase expression was performed. RESULTS: The grade of histopathological differentiation of tumour, the tumour retention index of Tl-201 scintigraphy and the expression of Na+/K+-ATPase showed a good correlation indicating that Na+/K+-ATPase plays an important role in transportation for Tl-201 to go through the tumour cell membrane. CONCLUSIONS: Na+/K+-ATPase is one of the most important factors for Tl-201 accumulation in tumour.

Adenocarcinoma↗

Scintigraphy for interpretation of malignant tumours of the head and neck: comparison of technetium-99m-hexakis-2-methoxyisobutylisonitrile (Tc-MIBI) and thallium-201-chloride (Tl-201).

OBJECTIVES: The purpose of this study was to compare the usefulness of technetium-99m-hexakis-2-methoxyisobutylisonitrile (99Tc(m)-MIBI) and thallium-201-chloride (Tl-201) as scintigraphic agents. METHODS: Dynamic and static scintigraphic imaging with 99Tc(m)-MIBI and Tl-201 were performed on patients with a variety of malignant and benign tumours. Factors of the grade of the static scan, the blood flow index, the early and delayed retention indexes, and the tumour retention index were obtained from the scintigraphy. In addition to these factors, the grade of tissue differentiation and tumour size were evaluated to clarify the difference between 99Tc(m)-MIBI and Tl-201 for the diagnosis of malignant tumours of the head and neck. RESULTS: 99Tc(m)-MIBI accumulation depended upon the blood flow index in the early static scan, but this accumulation did not correlate with tumour size. The accumulation in most subjects decreased in the delayed static scan, and the tumour retention index had a tendency to decrease with the grade of tissue differentiation. Tl-201 accumulation depended upon the blood flow index in the early static scan similar to 99Tc(m)-MIBI, and the accumulation correlated with tumour size, unlike 99Tc(m)-MIBI. The tumour retention index had a tendency to increase with the grade of tissue differentiation. Thus, the tumour retention indexes showed opposite behaviours between 99Tc(m)-MIBI and Tl-201, but they both accurately determined tumour malignancy. CONCLUSIONS: There was no major difference between 99Tc(m)-MIBI and Tl-201scintigraphy with respect to accuracy of diagnosis of malignant tumours of the head and neck. However, 99Tc(m)-MIBI was superior to Tl-201 for small-size tumours and Tl-201 was useful for large-size tumours.

Adenocarcinoma↗

Expression of permeability-glycoprotein (P-gp) and uptake of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (99Tcm-MIBI) in malignant tumour of the head and neck.

OBJECTIVES: The purpose of this study is to estimate the role of permeability-glycoprotein (P-gp) in the technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (99Tc(m)-MIBI) scintigraphy. METHODS: 71 patients with squamous cell carcinoma (39 patients with well differentiated, 19 with moderately differentiated and 13 with poorly differentiated tumour) were examined. Eighteen of these patients underwent 99Tc(m)-MIBI scintigraphy (early and delayed scans). The tumour retention index, obtained from the ratio of the accumulation of the delayed scan to that of the early scan, was divided into three groups. The immunohistochemical evaluation of P-gp expression was performed in all 71 patients. Levels of the P-gp expression were classified into three grades (score 0, 1 and 2). Correlations among the tumour retention index, the P-gp expression and the tumour tissue differentiation were evaluated. RESULTS: 17 of 18 patients showed a decreasing of the tumour retention index ranging from 0.70 to 0.93 (mean+/-SD=0.850+/-0.071). The tumour retention index showed a statistical correlation with the P-gp expression and the tumour tissue differentiation (chi-squared=7.802>7.779, P=0.10 and 16.835>14.860, P=0.005, respectively). Moreover, there was a statistical correlation between the P-gp expression and the tumour tissue differentiation (chi-squared=14.863>14.860, P=0.005). CONCLUSION: There is a possibility that the P-gp expression is high in the high-grade malignant tumours and P-gp causes the decrease of tumour retention index.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A trial for histopathological subclassification of papillary cystadenoma lymphomatosum by 99Tcm-pertechnetate in a patient with multiple bilateral lesions of the parotid glands.

OBJECTIVES: The purpose of this report was to evaluate the possibility of subclassification of papillary cystadenoma lymphomatosum (PCL) with 99Tc(m)-pertechnetate. METHODS: A patient with multiple bilateral PCLs in the parotid glands was examined by using 99Tc(m)-pertechnetate. RESULTS: All PCLs of the present case, which were diagnosed as the subtype-II histopathologically, showed similar radioactive indexes in scintigraphy (the mean radioactive index = 3.62), although tumours were different in size. The mean radioactive index corresponded well with that from four cases of subtype-II of our previous report (the mean radioactive index = 3.84). CONCLUSIONS: The results of the present report suggest a possibility of histopathological subclassification of PCLs into subtypes by 99Tc(m)-pertechnetate scintigraphy.

Adenolymphoma↗

Temperature and pressure effects on the bending modulus of monolayers in a ternary microemulsion.

We performed small-angle neutron scattering and neutron spin echo experiments on a ternary microemulsion composed of ionic surfactant AOT, water, and decane. Thermal fluctuations of monolayers have been investigated as a function of temperature and pressure. The amphiphilic monolayers become more flexible with increasing temperature and more rigid with increasing pressure. These results are consistent with the microscopic picture that the head-head repulsion of the AOT molecules is enhanced at high temperature while an attractive interaction between the hydrophobic tails of the AOT molecules increases at high pressure.

Journal Article↗

Non-invasive monitoring of gingival crevicular fluid for estimation of blood glucose level.

Development of a non-invasive method for measuring the blood glucose level is an urgent necessity, and putting such a method into practical use will enable some of the physical and mental stress that patients with diabetes have to endure to be removed. To realise a non-invasive blood glucose monitor, the gingival crevicular fluid (GCF) was measured. A GCF-collecting device was developed that was designed to be disposable, biocompatible and small enough to be inserted in the gingival crevice for collection of a sub-microlitre sample of GCF. Also, a high-sensitivity glucose testing tape incorporated in the device was developed. Red laser light in a portable optical device measured the colour density of the testing tape. Standard glucose solutions were used to investigate the measurement accuracy of the GCF glucose monitor and showed a correlation coefficient of R = 0.99 (n = 20) between the optical density and the glucose levels. The GCF glucose monitor was evaluated on healthy Swedish and Japanese adults (n = 10) and both GCF glucose levels (GCFLs) and blood glucose levels (BGLs) were measured in conjunction with meal loads. The GCFLs were about 1/10-1/560 lower than the BGLs. No difference in the range of GCFLs between the Swedish and the Japanese subjects was observed. Therefore it was concluded that physique, body mass index and life-style, such as dietary habit, did not significantly influence the GCFLs. Further, the correlation coefficients of all the subjects were 0.70 and 0.88 with each group. It was suggested that GCF could be used as a method of non-invasive blood glucose measurement.

Adult↗

[Solitary hemangioma of the rib; report of a case].

A case of solitary hemangioma which occurred in the rib. Tumor located in the right seventh rib, incidentally taken X-ray film demonstrated bone tumor, but she had no symptoms. Four years after, chest pain occurred and taken X-ray film, tumor size was inceeced. Computed tomography (CT) showed an expansile, well demarcated lesion, with thin corices and fine trabeclae. Chest wall, from the sixth rib to the eighth rib resection was performed and surgical margin was 4 cm. This case were diagnosed hemangioma of the rib. Hemangiomas of the bone are rare benign vascular tumors that account for less than 1% of all bony neoplasms. These lesions are most often occurring in the vertebral column or in the skull. The localization to the ribs is even more rare, with only sporadic case reports in the literature.

Aged↗

The presence and longevity of peripherally expanded donor-derived TCRalphabeta+ mature T lymphocyte clones after allogeneic bone marrow transplantation for adult myeloid leukemias.

There are two major pathways for T-cell regeneration after allogeneic bone marrow transplantation; thymus-dependent T-cell differentiation of T-cell progenitors, and peripheral expansion of mature T cells in the graft. In order to learn to what extent the peripheral expansion of donor-derived mature T lymphocytes contributes to reconstitution of the TCRalphabeta+ T-cell repertoire after allogeneic bone marrow transplantation for adult myeloid leukemias, we pursued the fate of donor-derived T-cell clones using the amino-acid sequences of the complementarity-determining region 3 (CDR3) of the TCR-beta chain as a clonal marker. Clonal expansion of TCRalphabeta+ T lymphocytes with specific TCRBV subfamilies was identified in donor blood. Identical T-cell clones were not found in blood from recipients before transplantation. The donor-derived T-cell clones were identified in the circulating blood from recipients a few months after allogeneic bone marrow transplantation, and they remained in the blood for 18 months after transplant in two recipients, and for 56 months in one. These results suggest that the peripheral expansion of mature T lymphocytes in the graft makes a significant contribution to post-transplant T-cell regeneration during the early period of transplantation in humans, and that mature T cells can survive in recipients for several years. Further investigation will be required to explore which antigens drive the expansion of T-cell clones in donors and recipients, and the mechanisms of maintaining homeostatic balance between the thymus-dependent pathway and the peripheral expansion of mature T cells in post-transplant T-cell regeneration.

Adult↗

Dermatofibrosarcoma protuberans with COL1A1 (exon 18) -PDGFB (exon 2) fusion transcript.

BACKGROUND: Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor B-chain (PDGFB) gene has been described in dermatofibrosarcoma protuberans (DFSP). Various exons of the COL1A1 gene have been shown to be involved in the fusion with exon 2 of the PDGFB gene. Objectives We examined the breakpoint of the COL1A1 gene using the tumour specimen from the patient with DFSP. METHODS: Reverse transcriptase-polymerase chain reaction (PCR) was performed using cultured DFSP tumour cells. Nucleotide sequence analysis was carried out using the PCR product to identify the breakpoint. RESULTS: The COL1A1-PDGFB fusion transcript was detected from the tumour specimen. Sequence analysis revealed that exon 18 of the COL1A1 gene was fused with exon 2 of the PDGFB gene. CONCLUSIONS: This study identified a novel COL1A1 breakpoint, namely, exon 18 of the COL1A1 gene.

Adult↗

Clinical applications of CD34+ cell-selected peripheral blood stem cells.

Peripheral blood stem cells (PBSC) are increasingly used for stem cell transplantation after high dose chemotherapy. CD34+ cell selection has also been done for use in autologous transplantation studies Bone marrow (BM) may contain tumor cells at the time of harvesting, and on re-infusion, these cells could contribute to a subsequent relapse. Similarly, tumor cell contamination of PBSC collections has been found in a number of studies. Therefore, purging contaminating tumor cells may prevent cases of relapse. As most tumor cell types do not express CD34 antigen, one of the most widespread applications of CD34+ cell selection is likely to be in tumor cell purging. Similarly, CD34+ cell selection has aided allogeneic transplantation studies. Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in cases of allogeneic transplantation. As aGVHD is mediated by donor T cells, removal of T cells from the graft by CD34+ cell selection may ensure prophylaxis against aGVHD. Further, high-dose immunosuppression followed by CD34+ cell-selected stem cell rescue is theoretically reasonable as a therapeutic tool for patients with autoimmune disease resistant to conventional therapy. However, patients given T cell-depleted transplantation have an increased risk of opportunistic infection as well as malignancies related to immunosuppression; therefore, close monitoring is warranted. We describe here clinical applications of CD34+ cell-selected PBSC for a variety of diseases, with special emphasis on the efficacy as well as drawbacks of this novel technique.

Antigens, CD34↗

Distinct TCRAV and TCRBV repertoire and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation.

Acute graft-versus-host disease (GVHD) is a disorder involving the skin, gut and liver that is caused by mismatches of major and/or minor histocompatibility antigens between the HLA-identical donor and recipient. If T lymphocytes infiltrating GVHD lesions recognize antigens expressed in these organs, T cell clones should expand in inflammatory tissues. We previously reported that recipients of allogeneic bone marrow grafts have clonally expanded TCRalphabeta(+) T lymphocytes soon after transplantation, which leads to a skew of TCR repertoires. To establish whether or not the same antigens cause clonal expansion of T lymphocytes in both blood and GVHD tissues, we examined the usage of TCR alpha and beta chain variable regions (TCRAV and TCRBV) and determined the complementarity-determining region 3 (CDR3) of T lymphocytes clonally expanded in circulating blood and GVHD lesions. We found that the repertoires and CDR3 diversity of TCRAV and TCRBV differed between the GVHD lesions and circulating blood, suggesting the selective recruitment of antigen-specific T cells into GVHD tissues. We also found that the usage of TCRAV and TCRBV by the clonally expanded T lymphocytes and their CDR3 sequences differed between the GVHD tissues and blood. These results suggest that the antigen specificity of TCRalphabeta(+) T lymphocytes clonally expanded in blood and GVHD lesions is different.

Acute Disease↗

Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly recognized point mutation in the COL3A1 gene.

Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutation within the COL3AI gene, resulting in the disorder of type III procollagen. The diagnosis is confirmed by demonstrating the synthesis of abnormal type III procollagen molecules from cultured dermal fibroblasts or by identifying the mutation in the COL3A1 gene. The authors report a case of EDS IV caused by a novel point mutation in the COL3A1 gene in a 16-yr-old female. Recurrent haemoptysis and cavitary formation of the lung were evidence of pulmonary involvement. However, extrathoracic manifestations of EDS IV were mostly absent. To the best of the authors' knowledge, all previously reported Ehlers-Danlos syndrome IV patients with respiratory disease had the characteristic findings or histories of Ehlers-Danlos syndrome IV. In the present case, connective tissue friability was suspected due to tissue laceration observed in the biopsied lung specimen, and the diagnosis was made beginning from this pivotal finding.

Adolescent↗

Steroid treatment based on the findings of transbronchial biopsy in idiopathic interstitial pneumonia.

This study was performed to find the rationale for administering steroids to patients with idiopathic interstitial pneumonia (IIP), which was unlikely to be usual interstitial pneumonia (UIP) but was not surgically biopsied. Among IIP patients in the file of the departments, nine patients who met the following criteria were selected for this study ("non-UIP" group): 1) transbronchial lung biopsy showed dense mononuclear cell infiltration in thickened alveolar septa; 2) chest radiograph and computed tomography showed irregular linear, reticular or ground-glass opacities with alveolar consolidation without honeycombing in the lung base; and 3) spirometry was performed before and after steroid therapy. Ten patients with pathologically confirmed nonspecific interstitial pneumonia ("NSIP" group) were also selected for the comparison. Baseline values and percentage increase of vital capacity (VC) after steroid therapy were plotted. Steroids improved VC in both groups of patients. After 1 yr of steroid therapy, percentage increase of VC in "non-UIP" was 28.8+/-7.7%, which was not significantly different from that in NSIP (30.0+/-11.7%). One "non-UIP" patient and one NSIP patient died after 6.4 and 4.3 yrs of follow-up, respectively. Patients with idiopathic interstitial pneumonia presenting cellular interstitial pneumonia in transbronchial lung biopsy, in addition to radiographic findings not typical for usual interstitial pneumonia, could expect a beneficial effect of steroids without undergoing surgical biopsy.

Aged↗

Dynamical fluctuation of the mesoscopic structure in ternary C12E5-water-n-octane amphiphilic system.

Dynamical fluctuations of the bicontinuous microemulsion and lamellar structures in ternary C12E5-water-n-octane amphiphilic system are studied by means of neutron spin echo (NSE) spectrometry. The decay rates of the time correlation of the concentration were analyzed in terms of three theories: (1) A. G. Zilman and R. Granek, Phys. Rev. Lett. 77, 4788 (1996), (2) M. Nonomura and T. Ohta, J. Chem. Phys. 110, 7516 (1999), and (3) R. Granek and M. E. Cates, Phys. Rev. A 46, 3319 (1992), in the first of which a Langevin equation for membrane plaquettes and in the latter two of which time-dependent Ginzburg-Landau equations for the order parameters are considered. The result shows that the intermediate correlation functions I(q,t) for the ranges of 0<t<15 ns and 0<q<0.2 A (-1) are well fitted to a stretched exponential function in time, I(q,t)=exp[-(Gammat)(2/3)], for the bicontinuous microemulsion and the lamellar phases of the same systems with the relaxation rate Gamma increasing as q(3) in agreement with theory (1) from which the bending modulus of the membrane kappa was estimated. For more restricted ranges of 0<t<5 ns and 0.05<q<0.15 A (-1) the NSE result can be expressed by an exponential function in time in agreement with theory (2) determined exclusively by hydrodynamic interactions and for extended range of 0<t<10 ns and 0.03<q<0.15 A (-1) by a nonexponential function in agreement with theory (3), from both of which the effective viscosities eta(0) and eta(eff) of the system were estimated. The effective viscosity from the nonexponential eta(eff) is five times greater than that from the simple exponential eta(0) that is almost the same as the literature value. The implication of this result is discussed in terms of the effective viscosity eta(eff) that takes into account the renormalization of the bending modulus of the membrane.

Journal Article↗

Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells when tested alone or in combination with sulindac sulfide.

Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of carcinogenesis. To provide a better understanding of the effects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29. For comparison, we included the compound sulindac sulfide (SS), because sulindac compounds are well-established colon cancer chemopreventive agents. We found that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of SS. SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. These affects of SAMC were accompanied by induction of jun kinase activity and a marked increase in endogenous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of SS with SAMC enhanced the growth inhibitory and apoptotic effects of SS. These findings suggest that SAMC may be useful in colon cancer prevention when used alone or in combination with SS or other chemopreventive agents.

Antineoplastic Agents↗