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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 271 records · Page 15Linked to original sources
PubMed1999

Expression of CD80 and CD86 on peripheral blood T lymphocytes in patients with systemic lupus erythematosus.

CD80 and CD86 were detected in high amounts on circulating T cells in the peripheral blood of some patients with systemic lupus erythematosus (SLE), using flow cytometry and monoclonal antibodies. Patients with other connective tissue diseases did not have a high percentage of T cells expressing CD80 or CD86 in their peripheral blood. CD80 was expressed mainly on CD4 T cells, whereas CD86 was expressed on CD8 T cells, and these two populations were associated with particular clinical features. These two molecules were expressed on different T-cell populations and might have different roles in the generation and regulation of immune responses. Since high expression of CD86 on T cells was detected much earlier than the appearance of clinical features and a high titer of anti-DNA antibody, it may be a useful parameter for predicting the flare of SLE.

Adult↗
PubMed1999

Levels of IL-12 in the sera of patients with systemic lupus erythematosus (SLE)--relation to Th1- and Th2-derived cytokines.

IL-12 is a cytokine that induces Th1-derived cytokines (interferon-gamma (IFN-gamma) and IL-2). The significance of IL-12 in human autoimmunity is no clear, and the serum levels of IL-12 in SLE are not clearly established. Therefore, we examined the levels of IL-12 in 39 patients with active SLE, with sandwich ELISA. The levels of IL-12 in patients were significantly higher than in normal subjects. Patients with high levels of IL-12 also had high levels of IFN-gamma, while their levels of IL-13 were significantly lower than in patients with normal levels of IL-12. Patients with pulmonary involvement had high levels of IL-12, and steroid therapy decreased the IL-12 level in three patients. In a retrospective study of seven patients, various changes of IL-12 and IL-13 were recognized before disease flare. Thus, in SLE patients, the level of IL-12 was increased and this increase was related to the change of Th1- or Th2-derived cytokines with some organ involvement.

Adult↗
PubMed1999

Primary synovial sarcoma of the lung: report of two cases confirmed by molecular detection of SYT-SSX fusion gene transcripts.

AIMS: Primary pulmonary sarcoma is rare, and frequently creates diagnostic challenges. We describe two cases of primary pulmonary spindle cell sarcoma in which a molecular approach using archival paraffin-embedded tissue was proved to aid diagnosis. METHODS AND RESULTS: Both patients had huge masses replacing the upper and middle lobes of the lung, respectively, without any primary extrapulmonary neoplastic lesions. Microscopically, the lesions showed a solid hypercellular nodular or lobular growth of atypical short spindle cells in variably intersecting fascicles or in a haphazard fashion, together with focal areas displaying a prominent haemangiopericytoma-like pattern. Immunohistochemically, a small number of the tumour cells were positive for epithelial markers such as cytokeratin and epithelial membrane antigen. In both cases, a reverse transcription-polymerase chain reaction using RNA extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX fusion gene transcripts, which are characteristic of synovial sarcoma. CONCLUSION: On the basis of the morphological and molecular findings, these tumours are considered to be rare examples of monophasic synovial sarcoma of the lung. Our molecular assay detecting the SYT-SSX fusion transcripts is useful for the final diagnosis of synovial sarcoma arising at such an unusual anatomical site.

Adult↗
PubMed1999

Inhibitory effect of interleukin-16 on interleukin-2 production by CD4+ T cells.

Signalling through CD4 by human immunodeficiency virus (HIV)-1 envelope glycoprotein (gpl20) and/or anti-CD4 antibodies can promote T-cell activation and anergy. Interleukin (IL)-16 is a competence growth factor for CD4+ T cells that can induce a G0 to G1 cell cycle transition but cannot induce cell division. The receptor of this cytokine is thought to be the CD4 molecule, although the binding epitope of IL-16 differs from that of HIV. We have demonstrated that both HIV-1/gp120 and IL-16 induced CD4+ T-cell dysfunction, as indicated by suppression of mitogen-induced IL-2 production. Two anti-CD4 antibodies with different binding sites on CD4 also showed an inhibitory effect on IL-2 production. These results indicate that promotion of CD4+ T-cell anergy via the CD4 molecule does not depend on the binding sites of the CD4 ligands.

Antibodies↗
PubMed1999

Lobular involvement: prognostic indicator for invasive ductal carcinoma of the breast.

One of the striking microscopic appearances of breast carcinoma is malignant transformation of the epithelium of an entire lobule, although the lobular architecture is still preserved. We termed this pathological feature 'lobular involvement'. An investigation was carried out to determine whether lobular involvement would be a useful prognostic indicator for invasive ductal carcinoma. One hundred and fifty cases of invasive ductal carcinoma were included in this study. The lobular involvement, as well as the conventional prognostic factors, was evaluated to find out the correlation with the overall and relapse-free survivals by univariate and multivariate analyses. The lobular involvement was identified in 31 of 150 patients (20.6%). Of the patients with lobular involvement, two had experienced recurrence (6.5%) and one had died (3.2%). The lobular involvement and lymph node metastases were significantly and independently correlated with the overall and relapse-free survivals. The presence of lobular involvement was statistically correlated with the favorable outcome. Lobular involvement can be assumed as a new prognostic indicator for invasive ductal carcinoma.

Adult↗
PubMed1999

Myoepithelioma of soft tissue.

A myoepithelioma occurred in the subcutaneous tissue of the right shoulder of a 28-year-old man. The well-demarcated nodular tumor (3. 0 x 2.8 cm) was located in the subcutaneous tissue with no adhesion to the deltoid muscle. The tumor was composed of a fascicular proliferation of spindle cells with variable amounts of stroma and showed areas of sheets of epithelioid cells. In most areas, the tumor cells had uniform nuclei, but pleomorphic epithelioid cells were focally present. Mitotic activity was three per 10 high-power fields. No ductular structure was found throughout the tumor. Immunohistochemical and ultrastructural studies confirmed the myoepithelial origin of the tumor cells. The occurrence of myoepithelioma in the subcutaneous tissue has been rarely reported. Even though the tumor showed no aggressive behavior on the 2-year follow-up, it is still too early to comment definitely on the behav- ior of myoepithelioma of the subcutaneous tissue. This case provides further information about soft tissue myoepithelioma.

Adult↗
PubMed1999

Endothelins stimulate expression of cyclooxygenase 2 in rat cultured astrocytes.

Endothelin (ET) is one of the active endogenous substances regulating the functions of astrocytes. In the present study, we examined effects of ET on cyclooxygenase (COX) expression in cultured astrocytes. ET-3 (100 nM) caused transient increases in the expression of both COX2 mRNA and protein, but not those of COX1, in cultured astrocytes. ET-induced COX2 mRNA expression was suppressed by 5 microg/ml actinomycin D, 30 microM BAPTA/AM, inhibitors of protein kinase C (1-100 nM staurosporin and 100 microM H-7), 2 microM dexamethasone, and prolonged treatment with 100 nM phorbol 12-myristate 13-acetate. ET-3 stimulated production of prostaglandin (PG) E2 in cultured astrocytes. The effect of ET-3 on the PGE2 production was diminished by actinomycin D. Indomethacin and NS398, a selective COX2 inhibitor, comparably decreased both the basal and the ET-stimulated PGE2 production. Proliferation of cultured astrocytes was stimulated by 100 nM ET-3, and the increased proliferation was reduced by co-addition of 1 microM PGE2. Treatment with 1 microM PGE2 caused astrocytic morphological changes accompanied by disappearance of stress fibers, a prominent structure of organized cytoskeletal actin in cultured astrocytes. In the presence of 10 nM ET-3, PGE2 did not show an effect on astrocytic actin organization. The present study shows that ET is an inducer of astrocytic COX2 and suggests that ET-induced PGE2 production through COX2 may be involved in the regulation of astrocytic functions.

Animals↗
PubMed1999

Chaotic dynamics in circulation with Tohoku University vibrating flow pump.

For the development of a totally implantable ventricular assist system (VAS), we have been developing the vibrating flow pump (VFP), which can generate oscillated blood flow with a relative high frequency (10-50 Hz) for a totally implantable system. In this study, the effects of left ventricular assistance with this unique oscillated blood flow were analyzed by the use of nonlinear mathematics for evaluation as the whole circulatory regulatory system, not as the decomposed parts of the system. Left heart bypasses using the VFP from the left atrium to the descending aorta were performed in chronic animal experiments using healthy adult goats. The ECG, arterial blood pressure, VFP pump flow, and the flow of the descending aorta were recorded in the data recorder during awake conditions and analyzed in a personal computer system through an A-D convertor. By the use of nonlinear mathematics, time series data were embedded into the phase space, the Lyapunov numerical method, fractal dimension analysis, and power spectrum analysis were performed to evaluate nonlinear dynamics. During left ventricular assistance with the VFP, Mayer wave fluctuations were decreased in the power spectrum, the fractal dimension of the hemodynamics was significantly decreased, and peripheral vascular resistance was significantly decreased. These results suggest that nonlinear dynamics, which mediate the cardiovascular dynamics, may be affected during left ventricular (LV) bypass with oscillated flow. The decreased power of the Mayer wave in the spectrum caused the limit cycle attractor of the hemodynamics and decreased peripheral resistance. Decreased sympathetic discharges may be the origin of the decreased Mayer wave and fractal dimension. These nonlinear dynamic analyses may be useful to design optimal VAS control.

Analog-Digital Conversion↗
PubMed1999

Total vascular resistance and blood flow frequency during left ventricular assistance using a vibrating flow pump.

A vibrating flow pump (VFP) can generate high frequency oscillated blood flow within 10-30 Hz by the oscillation of its central tube. A totally implantable artificial heart using a VFP is being developed as a unique type of blood pump. In this study, left ventricular (LV) assist circulation was performed using a VFP. The total vascular resistance and driving frequency of the VFP were estimated from their relationship. The effect of oscillation on the vascular system was studied by the frequency analysis method and vascular impedance. Adult goats were anesthetized by halothane using an inhaler and a left fourth thoracotomy was performed. The inflow cannula was inserted into the left ventricle, and the outflow cannula was sutured to the descending aorta. The VFP and a centrifugal pump were set in parallel for alternation and comparison. The driving frequency of the VFP was changed and included 15, 20, 25, and 30 Hz. The hemodynamic parameters were continuously recorded during experiments by a digital audio tape (DAT) data recorder. The internal pressure of the left ventricular cavity and aortic pressure were monitored by the pressure manometers continuously. One hundred percent LV assistance was judged by the separation of LV and aortic pressure. The total vascular resistance was decreased by the start of operation of each pump. The decrease during flow using the VFP was not as large as that using a centrifugal pump (CP). The arterial input impedance during oscillated blood flow by the VFP showed a slow curve appearance. It was similar to the frequency characteristics curve of natural heart beats within the lower frequencies. The study of arterial impedance may be important for the estimation of the reflection of the pulsatile wave from the arterial branch, among other things.

Animals↗
PubMed1999

Peripheral vascular resistances during total left heart bypass with an oscillated blood flow.

For development aimed at a totally implantable type ventricular assist device (VAD), the vibrating flow pump (VFP) has been developed at Tohoku University. A transcutaneous energy transmission system (TETS) using amorphous fibers was developed to power the totally implantable VAD system. The VFP works at a high frequency compared to that of a natural heart of a biological system. It is a frequency of 10-50 Hz. In this research, animal experiments with left heart bypass were carried out with healthy adult goats. For comparison between nonpulsatile flow and oscillated flow, a rotary pump (RP) and the VFP were used in the experiments. For the achievement of total left heart bypass, left ventricular approaches were carried out, and blood was pumped from the left ventricle to the descending aorta. Adequate support of the left heart was provided by both pumps. In terms of the results, the vascular resistances tended to decrease during the use of both pumps during 100% bypass driving. When we compared these pumps at the same flow rate, the resistances during RP driving were significantly smaller than those during VFP driving. These results may suggest that the influences of the VFP upon the peripheral vessels may be relatively small compared to those of the RP. This may be an important result when a stable hemodynamic condition is required during artificial circulation. The VFP was considered as a candidate for a totally implantable VAD as a result.

Animals↗
PubMed1999

Relationship between CD4+/CD8+ T cell ratio and T cell activation in systemic lupus erythematosus.

We investigated the relationship between the ratio of CD4+ to CD8+ T cells (CD4/CD8 ratio) and T cell activation, indicated by human leukocyte antigen (HLA)-DR expression, in patients with systemic lupus erythematosus (SLE). We found that the ratio was decreased in SLE patients and that this was significantly related to expression of HLA-DR by CD8+ (but not CD4+) T cells. These findings may assist in understanding the pathogenesis of SLE. In some SLE patients, the CD4/CD8 ratio and HLA-DR expression may be good indicators of therapeutic efficacy.

Adult↗
PubMed1999

Sugar-branched-cyclodextrins as injectable drug carriers in mice.

The purpose of this study was to investigate stable complexation of drug in blood by sugar-branched-beta-cyclodextrins (beta-CDs) such as glucose (glu)- or galactose (gal)-branched-beta-CDs and the pharmacokinetic disposition of drug in sugar-branched-beta-CD complex. Complexation of steroidal drugs in sugar-branched-beta-CDs and their replacement by cholesterol were measured. The complexes of dexamethasone/glucosyl-beta-CDs (dexamethasone/glu-beta-CD or dexamethasone/glu-glu-beta-CD) were not replaced by cholesterol, which is a representative endogenous compound, whereas the complex of dexamethasone/beta-CD was replaced by cholesterol. The same results were obtained in steroidal drugs such as hydrocortisone, triamcinolone, and prednisolone. Thus, the use of glu-beta-CD and glu-glu-beta-CD permitted the stable complexation of the drug in water. Stability constants of dexamethasone/glu-glu-beta-CD and dexamethasone/gal-glu-beta-CD complexes are the same, which means that the sugar moiety of the side chain in beta-CD has little effect on stability constants. After the dexamethasone/gal-glu-beta-CD complex or the dexamethasone/glu-glu-beta-CD complex (dexamethasone: 1 mg/body) was administered intravenously to mice, dexamethasone concentrations in liver tissue and blood were measured. The dexamethasone/gal-glu-beta-CD complex (66.1 +/- 1.7 micrograms as dexamethasone/gram of liver tissue) was distributed to liver tissue significantly more than the dexamethasone/glu-glu-beta-CD (beta-CD) complex (59.9 +/- 1.0 micrograms as dexamethasone/gram of liver) at 30 min after administration (p < .05). Sugar-branched-beta-CD gave a water-soluble and stable complex for dexamethasone and changed the disposition of dexamethasone. Sugar-branched-beta-CDs are potentially excellent carriers for a steroidal injectable formulation.

Animals↗
PubMed1999

Therapeutic effect of an anti-Fas ligand mAb on lethal graft-versus-host disease.

Several anti-Fas ligand (FasL) inhibitory mAb (FLIM) were raised and characterized in this study. One, FLIM58, showed more potent neutralizing activity than Fas-Fc, the previously established artificial neutralizing agent for FasL. Several murine models of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation have been used to show that both FasL and perforin, the major effector molecules of cytotoxic T lymphocytes, are involved in this disease. In our GVHD model, FasL rather than perforin was associated with lethality. Administration of FLIM58 or Fas-Fc reduced the weight loss and mortality caused by GVHD, although other signs of GVHD, such as skin lesions, lymphoid hypoplasia and mononuclear cell infiltration in the liver, did not improve significantly. FLIM58 was more effective than Fas-Fc in reducing mortality. Our results demonstrated that neutralizing agents for FasL are therapeutic for lethal GVHD.

Amino Acid Sequence↗
PubMed1999

Immunohistochemical analysis of PAI-2 (plasminogen activator inhibitor type 2) and p53 protein in early gastric cancer patients with recurrence: a preliminary report.

BACKGROUND: High levels of urokinase-type plasminogen activator (u-PA) were demonstrated in gastric carcinomas along with inhibitors of plasminogen activators (PAI-1 and PAI-2). They may influence the ability to invade and metastasize and therefore be of importance to the risk of recurrence of stomach neoplasms after curative operation. This also appears to be the case for p53 mutations and p53 protein overexpression. METHODS: Six patients, all differentiated cancer cases who developed recurrent disease 5-10 years after curative operations for early gastric cancers (recurrence group), were studied in comparison with 49 patients who had no recurrence more than 10 years after similar surgery (control group). The expression of u-PA, PAI-1, PAI-2 and p53 was compared immunohistochemically in the recurrence and control groups. RESULTS: The expression of PAI-2 was significantly more frequent in the recurrence group, being found in five (83.3%) patients vs eight (16.3%) in the control group. p53 was expressed in five (83.3%) patients in the recurrence group and in 15 (30.6%) in the control group; the rate was again significantly higher in the former. CONCLUSION: The results suggest that PAI-2 and p53 expressed in differentiated early gastric cancers are possible indices of the risk of recurrence.

Adenocarcinoma↗
PubMed1999

Crystallographic studies on a family B DNA polymerase from hyperthermophilic archaeon Pyrococcus kodakaraensis strain KOD1.

A hyperthermostable family B DNA polymerase from the hyperthermophilic archaeon, Pyrococcus kodakaraensis strain KOD1, has been crystallized by the hanging-drop vapor diffusion method at 293 K with 2-methyl-2,4-pentanediol as the precipitant. The diffraction pattern of a crystal extends to 3.0 A resolution, and two full sets of 3.0 A resolution diffraction data for native crystals were successfully collected at 290 K and 100 K upon exposure to synchrotron radiation at KEK-PF, Japan. The crystals belong to the space group, P212121, with unit-cell dimensions of a = 112.8, b = 115.4, and c = 75.4 A at 290 K, and a = 111.9, b = 112.4, and c = 73.9 at 100 K. Structural analysis by means of the multiple isomorphous replacement method is now in progress.

Crystallography, X-Ray↗