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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 217 records · Page 12Linked to original sources
PubMed1999

Preimplantation diagnosis by fluorescence in situ hybridization using 13-, 16-, 18-, 21-, 22-, X-, and Y-chromosome probes.

PURPOSE: Our purpose was to select the proper chromosomes for preimplantation diagnosis based on aneuploidy distribution in abortuses and to carry out a feasibility study of preimplantation diagnosis for embryos using multiple-probe fluorescence in situ hybridization (FISH) on the selected chromosomes of biopsied blastomeres. METHODS: After determining the frequency distribution of aneuploidy found in abortuses, seven chromosomes were selected for FISH probes. Blastomeres were obtained from 33 abnormal or excess embryos. The chromosome complements of both the biopsied blastomeres and the remaining sibling blastomeres in each embryo were determined by FISH and compared to evaluate their preimplantation diagnostic potential. RESULTS: Chromosomes (16, 22, X, Y) and (13, 18, 21) were selected on the basis of the high aneuploid prevalence in abortuses for the former group and the presence of trisomy in the newborn for the latter. Thirty-six (72%) of 50 blastomeres gave signals to permit a diagnosis. Diagnoses made from biopsied blastomeres were consistent with the diagnoses made from the remaining sibling blastomeres in 18 embryos. In only 2 of 20 cases did the biopsied blastomere diagnosis and the embryo diagnosis not match. CONCLUSIONS: If FISH of biopsied blastomere was successful, a preimplantation diagnosis could be made with 10% error. When a combination of chromosome-13, -16, -18, -21, -22, -X, and -Y probes was used, up to 65% of the embryos destined to be aborted could be detected.

Abortion, Spontaneous↗
PubMed1999

Role of interleukin-12 in the development of acute graft-versus-host disease in bone marrow transplant patients.

Interleukin-12 (IL-12) is a crucial cytokine regulating cell-mediated immunity, and may contribute to the development of graft-versus-host disease (GVHD). We investigated serum IL-12 concentrations, interferon gamma (IFN-gamma) production by peripheral blood lymphocytes (PBL) from allogeneic stem cell recipients after IL-12 plus anti-CD3 monoclonal antibody (mAb) stimulation. We also investigated IL-12 production by peripheral macrophages (Mphi) after lipopolysaccharide (LPS) stimulation from allogeneic stem cell recipients and patients receiving donor leukocyte transfusions (DLT) for treatment or prophylaxis of leukemia relapse and Epstein-Barr virus (EBV) lymphoproliferative disease (LPD). PBL from acute GVHD patients produced high IFN-gamma levels after IL-12 plus anti-CD3 mAb stimulation, whereas PBL from patients without acute GVHD produced low levels of IFN-gamma. However, serum IL-12 concentrations were low in both groups. Peripheral Mphi IL-12 production increased in patients who developed acute GVHD compared to patients without acute GVHD. Five patients receiving DLT for treatment or prophylaxis of leukemia relapse developed acute GVHD. IFN-gamma production by PBL stimulated by IL-12 plus anti-CD3 mAb increased, while IL-12 production by peripheral Mphi stimulated by LPS was very high after the development of acute GVHD. However, serum IL-12 concentration remained low. Three patients receiving DLT for EBV-LPD did not develop acute GVHD with no increase of IFN-gamma and IL-12 production. These results indicate that IL-12 may play an important role in the development of acute GVHD after allogeneic stem cell grafting or DLT, and increased IL-12 production by Mphi occurs with various stimuli, including LPS.

Acute Disease↗
PubMed1999

The quantitative and qualitative defect of CD4+ CD45RO+ memory-type T cells are involved in the abnormality of TH1 immunity in atopic dermatitis patients.

Peripheral blood mononuclear cells (PBMCs) obtained from atopic dermatitis (AD) patients produced low levels of IFN-gamma in response to Dermatophagoides farinae antigen (Der f Ag) plus IL-2 or OKT3 MoAb in contrast with PBMCs obtained from healthy donors. The reduced IFN-gamma production in AD patients' T cells appeared to be derived from the defect of CD4+ T cells but not CD8+ T cells. Indeed, from the cytoplasmic staining analysis of cytokines, it was demonstrated that the frequency of IFN-gamma producing CD4+ T cells (TH1 cells) in AD patients was markedly lower than that of healthy donors. From the phenotypic analysis using flow cytometry, it was also found that the number of CD4+ CD45RO+ memory type T cells was significantly reduced in AD patients compared with that of healthy donors. In addition to quantitative defect of memory type CD4+ T cells, functional defect of CD4+ CD45RO+ memory type T cells was also demonstrated in AD patients. Enriched CD4+ CD45RO+ T cells obtained from AD patients, who exhibited greatly reduced delayed-type hypersensitivity (DTH) response in tuberculin test, showed no significant TH1 immunity in terms of IFN-gamma production by stimulation with OKT3 MoAb or purified protein derivative (PPD). Thus, the immunological abnormality of TH1 immunity in AD patients appeared to be induced in concomitant with both the quantitative and qualitative defect of memory type CD4+ T cells.

Antibodies, Monoclonal↗
PubMed1999

Quantitative analysis of cytokine gene expression in the liver.

The relative levels of cytokine gene expression in the liver were analysed, focusing on IL-2, IL-4, IL-5, IL-6 and IFN-gamma compared to those in the spleen and Peyer's patch by using the reverse transcriptase polymerase chain reaction (RT-PCR). The levels of expression of cytokines in the liver mononuclear cells (MNC). especially that of IL-6, were significantly higher than in other organs when mice were reared under specific pathogen-free (SPF) or conventional conditions. Both the spleen and Peyer's patch MNC expressed little of any of the cytokines, except for IL-4 in Peyer's patch MNC. The liver MNC produced significant amounts of IL-6 in the culture supernatant upon concanavalin A stimulation. These findings suggest that the liver is a potent IL-6-producing organ, which may relate to B cell differentiation, liver regeneration and the induction of acute phase proteins.

Animals↗
PubMed1999

In vivo evaluation of the national cardiovascular center electrohydraulic total artificial heart.

We have been developing an electrohydraulic total artificial heart system. The system comprises an intrathoracic pumping unit composed of diaphragm type ellipsoidal blood pumps and an energy converter in addition to an electronics unit. The in vivo performance of the pumping unit was evaluated in a series of animal implantations with 3 calves weighing 62-85 kg. An interatrial shunt 4.5 mm in diameter was made in the atrial septum to compensate left-right imbalance. Two calves died early postoperatively, one of external controller power failure and the other of interatrial shunt stenosis due to thrombus formation. One calf, however, survived over 10 days under stable circulatory conditions. No abnormality was found in the oxygen metabolic condition or in major organ functions. The generation and dissipation of heat from the device was acceptable. This animal died of device malfunction caused by energy converter bearing breakdown. The device demonstrated a good anatomic fit without compromising the great vessels and adjacent tissues. It is concluded that the pumping unit has a sufficient in vivo basic performance although appropriate countermeasures are to be implemented against the detected problems concerning mechanical durability and interatrial shunt patency.

Animals↗
PubMed1999

Cardiac autonomic nervous function during long-term nonpulsatile left heart bypass.

We investigated the changes in cardiac autonomic nervous activities during long-term nonpulsatile left heart bypass (NLHB) by analyzing heart rate variability. A pulsatile ventricular assist device was installed in 3 goats, and pulsatile left heart bypass (PLHB) was conducted for 2 weeks. Then, NLHB was maintained for the following 4 weeks. The segmental data of the R-R intervals (R-Rs) was analyzed by maximum entropy spectral analysis. Changes in evaluated parameters from the last week of PLHB to the 4th week of NLHB were as follows: the mean R-Rs increased from 511 ms to 692 ms; the coefficient of variation of R-R increased from 10.2 to 14.1%; the power of the low frequency band (LF) increased from 747 ms2 to 2,855 ms2; the power of the high frequency band (HF) increased from 512 ms2 to 1,270 ms2; and the ratio of LF to HF increased from 2.6 to 6.5. These results indicated that the cardiac autonomic nervous activity, both sympathetic and parasympathetic, increased during long-term NLHB.

Analysis of Variance↗
PubMed1999

Development of an ultracompact integrated heart-lung assist device.

A novel integrated heart-lung assist device has been developed as a simple to use portable cardiopulmonary support system. The device comprises a centrifugal pump and an artificial lung, which is located around the pump, in an all in one system. The special membrane employed precludes plasma breakthrough in protracted use and enables preprimed setup. Test lungs consisting of the same membrane preserved gas exchange function well after 3 months of preprimed storage. The entire blood contacting surface is treated with covalent heparin bonding to impart good antithrombogenicity. Heparin bonded test lungs could be continuously perfused without systemic anticoagulation as long as 36 days in a venoarterial bypass chronic animal study using goats. The prototype device (diameter, 126 mm; height, 59 mm; membrane area, 0.85 m2; priming volume, 180 ml) demonstrated 9 L/min pump output at a 400 mm Hg pressure head and 180 ml/min oxygen and 110 ml/min carbon dioxide transfer rates at 5 L/min blood flow. We conclude that this device has potential to be the next generation cardiopulmonary support system.

Animals↗
PubMed1999

Diminished vasoconstrictive function caused by long-term nonpulsatile left heart bypass.

We investigated the functional changes of the systemic vascular system due to prolonged nonpulsatile left heart bypass (NPLHB). Three adult goats underwent pulsatile left heart bypass (PLHB). Two weeks later the PLHB was changed to the NPLHB, which was conducted for 4 weeks. The aortic pulse pressure was 39 and 16 mm Hg during the PLHB and NPLHB, respectively. Systemic vascular resistance (SVR) and the plasma norepinephrine level were measured at the end of PLHB (PUL), and in the 1st, 2nd, 3rd, and 4th weeks of NPLHB (NP1w, NP2w, NP3w, and NP4w). At each point, 1 microg/kg norepinephrine was injected, and the elevation of the SVR (deltaSVR) was calculated. The SVR and the plasma norepinephrine level did not change significantly during the entire course. However, deltaSVR decreased during NPLHB and became significantly lower at NP3w and NP4w than that at PUL (NP3w: 839 +/- 164, NP4w: 746 +/- 268, and PUL: 1,239 +/- 324 dyne x s x cm(-5)). These results strongly indicated that prolonged NPLHB significantly diminished the constrictive function of the vascular system.

Animals↗
PubMed1999

Augmentative effect of pulsatility on the wall shear stress in tube flow.

Wall shear stress (WSS) has been considered to play an important role in the physiological and metabolic functions of the vascular endothelial cells. We investigated the effects of the pulse rate and the maximum flow rate on the WSS to clarify the influence of pulsatility. Water was perfused in a 1/2 inch transparent straight cylinder with a nonpulsatile centrifugal pump and a pulsatile pneumatic ventricular assist device (VAD). In nonpulsatile flow (NF), the flow rate was changed 1 to 6 L/min by 1 L/min increments to obtain standard values of WSS at each flow rate. In pulsatile flow (PF), the pulse rate was controlled at 40, 60, and 80 bpm, and the maximum flow rate was varied from 3.3 to 12.0 L/min while the mean flow rate was kept at 3 L/min. The WSS was estimated from the velocity profile at measuring points using the laser illuminated fluorescence method. In NF, the WSS was 12.0 dyne/cm2 at 3 L/min and 33.0 dyne/cm2 at 6 L/min. In PF, the pulse rate change with the same mean, and the maximum flow rate did not affect WSS. On the other hand, the increase in the maximum flow rate at the constant mean flow rate of 3 L/min augmented the mean WSS from 13.1 to 32.9 dyne/cm2. We concluded that the maximum flow rate exerted a substantial augmentative effect on WSS, and the maximum flow rate was a dominant factor of pulsatility in this effect.

Blood Flow Velocity↗
PubMed1999

In vitro metabolism of simazine, atrazine and propazine by hepatic cytochrome P450 enzymes of rat, mouse and guinea pig, and oestrogenic activity of chlorotriazines and their main metabolites.

1. The in vitro metabolism of chlorotriazines, simazine (SIZ), atrazine (ATZ) and propazine (PRZ) in liver microsomes from rat, mouse and guinea pig and the oestrogenic activity of chlorotriazines and their main metabolites have been studied. 2. The formation rates of products in chlorotriazine metabolism were determined by HPLC. The principal reactions catalysed by the cytochrome P450 (P450) system were N-monodealkylation and isopropylhydroxylation in all liver microsomes. As a result, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (M1) (SIZ-M1 for SIZ and ATZ-M1 for ATZ) and 2-chloro-4-amino-6-isopropylamino-1,3,5-triazine (M2) (ATZ-M2 for ATZ and PRZ-M2 for PRZ), and 2-chloro-4-ethylamino-6-(1-hydroxyisopropylamino)-1,3,5-triazine (M3) (ATZ-M3 for ATZ) and 2-chloro-4-isopropylamino-6-(1-hydroxyisopropylamino)-1,3,5-triazi ne (M4) (PRZ-M4 for PRZ) were detected as the metabolites. N-bidealkylation was not found in this system. 3. The formation rates of N-deethylated metabolites (SIZ-M1 and ATZ-M2) were generally higher in mouse than in rat and guinea pig. The formation rates of N-deisopropylated metabolites (ATZ-M1 and PRZ-M2) in guinea pig were the lowest among the three animal species. The formation rates of isopropylhydroxylated metabolites (ATZ-M3 and PRZ-M4) were remarkably low in mouse compared with rat and guinea pig. 4. The enzyme kinetics of chlorotriazine metabolism were examined by Eadie-Hofstee analyses. Some species differences in Michaelis-Menten parameters for each metabolite were observed, and the ranking orders were varied among the metabolites. 5. The binding affinity of chlorotriazines (SIZ, ATZ and PRZ) and their metabolites (M1-4) for recombinant human oestrogen receptor-alpha was assayed using the fluorescence polarization method. The binding affinity of M2 was significantly higher than those of parent compounds and other metabolites, although the oestrogenic activity was remarkably low compared with that of 17beta-oestradiol (E2). 6. These results suggest that the pattern of metabolism of SIZ, ATZ and PRZ by the P450 system differs extensively among rat, mouse and guinea pig, and that M2 may be an activated metabolite of chlorotriazines.

Animals↗
PubMed1999

Inhibition of rat hepatic cytochrome P450 activities by biodegradation products of 4-tert-octylphenol ethoxylate.

1. The effects of some biodegradation products of 4-tert-octylphenol ethoxylate (OPEO), namely 4-tert-octylphenol (OP), 4-tert-octylphenol diethoxylate (OP2EO) and 4-tert-octylphenol monocarboxylate (OPIEC) on the kinetics of cytochrome P450 (P450) -dependent monooxygenases in rat liver microsomes have been studied. 2. Testosterone 16beta-hydroxylase (TS16BH), testosterone 2alpha-hydroxylase (TS2AH) and testosterone 6beta-hydroxylase (TS6BH) activities were extensively inhibited by OP at 100 microM (56.0-90.3%). Inhibition was competitive for all P450-dependent monooxygenases. Ki(s) of TS16BH, TS2AH and TS6BH from Lineweaver-Burk plots were 6.37, 3.38 and 34.8 microM respectively. 3. The activities of acetanilide 4-hydroxylase (AA4H), 7-ethoxycoumarin O-deethylase (ECOD) and bufuralol 1'-hydroxylase (BF1'H) were also effectively inhibited by OP at 100 microM (48.6-56.0%). The inhibition of these P450-dependent monooxygenases was non-competitive, and Ki(s) (50.1-63.90 microM) were higher than those of TS16BH, TS2AH and TS6BH. 4. OP2EO also inhibited AA4H, ECOD, TS16BH, TS2AH, BF1'H and TS6BH activities by 38.7-69.3% at 100 microM, although the inhibition rates were slightly lower than those for OP. K(i)s were 14.4-106 microM, and the inhibition was of mixed type (AA4H and ECOD), competitive (TS16BH, TS2AH and TS6BH) and non-competitive (BF1'H). 5. Testosterone 7alpha-hydroxylase (TS7AH), 4-nitrophenol 2-hydroxylase (4NP2H) and lauric acid omega-hydroxylase (LAOH) activities were only slightly affected by OP and OP2EO. 6. The ability of OP1EC to inhibit P450-dependent monooxygenase activities was generally weaker than that of OP and of OP2EO: Ki >200 microM. 7. These results suggest that OPEO biodegradation products interact with constitutive P450 isoforms, CYP1A2, CYP2A2, CYP2B2, CYP2C11 and CYP3A2 in rat liver in vitro (OP > OP2EO > OP1EC), and that the mechanism of this interaction differs depending on the compound and P450 isoform.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1999

CD45 can act as a negative regulator for the transition from early to late CD4+ CD8+ thymocytes.

The differentiation process from CD4-CD8- double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) stage is accompanied by vigorous proliferation. The resulting DP cells contain a sizable proportion of large cycling cells, but most DP cells are small resting cells. To explore the molecular mechanisms which regulate cell proliferation of DP thymocytes prior to further development, we used TCR-transgenic (Tg) mice with non-selecting MHC (Tg-Neut), which contain almost exclusively DP thymocytes that are not subject to either positive or negative selection. In Tg-Neut, the thymus contained DP cells of relatively large size, which showed higher extracellular signal-regulated kinase activity and enhanced responsiveness to mitogen compared to small DP cells. This indicates that all the large DP cells in the thymus are not positively selected and that they possess proliferative potential. When Tg-Neut mice were backcrossed with CD45 knockout mice (CD454-/- Tg-Neut), the thymus showed an increase of large DP cells and cycling cells, but a decrease of apoptotic cells. Furthermore, Bcl-2 expression and Jun N-terminal kinase activity, which are associated with resistance to apoptosis, were enhanced. These observations suggest that thymocyte proliferation in the DP stage is suppressed by a CD45-related process with regulation of mitogen-activated protein kinase and Bcl-2 unless DP cells receive TCR-mediated signals.

Animals↗
PubMed1999

Viable tissue in an area of severely reduced perfusion demonstrated with I-123 iomazenil brain SPECT imaging of benzodiazepine receptors.

A 70-year-old woman who experienced transient left hemiparesis had 90% stenosis of the right internal carotid artery. CT revealed small low-density areas in the subcortical frontal area. Baseline cerebral blood flow was reduced, and vasoreactivity was poor in the right frontoparietal area according to I-123 IMP brain SPECT with acetazolamide. The distribution of I-123 iomazenil was normal on the delayed SPECT image but reduced in the early SPECT image, mimicking baseline cerebral blood flow. The distribution of I-123 iomazenil SPECT on the delayed image reflected the normal binding potential of the benzodiazepine receptor and thus identified viable tissue in an area of severely reduced perfusion. These findings were confirmed by positron emission tomography.

Acetazolamide↗
PubMed1999

Correlation of sequential MR images of microsphere-induced cerebral ischemia with histologic changes in rats.

OBJECTIVE: To determine the time course of changes in MRI findings of multiple cerebral microembolism, the authors induced experimental multiple microinfarctions in rats using microspheres and then examined sequential MRI and histopathologic findings. The authors also evaluated how the amount of injected embolic materials affected the findings. METHODS: The authors injected 25-microm microspheres (range, 2000-8000 gm) into the unilateral internal carotid arteries of rats. The animals were assessed by MRI and histopathology at 1 day or 8 days after embolization. RESULTS: One day after embolization, multiple high-intensity areas on T2-weighted images were related to the number of injected microspheres and were associated with regions of cerebral edema on histopathologic specimens. On day 8, the high-intensity areas on T2-weighted images observed on day 1 were markedly diminished in the groups receiving up to 6000 microspheres. In the group injected with 8000 microspheres, however, the high-intensity areas were less diminished, and these areas were significantly larger than in the other groups (P < 0.05). CONCLUSIONS: The MRI features of cerebral ischemia or infarction induced by microsphere embolism vary depending on the number of injected microspheres. Recovery from acute cerebral embolism has a threshold based on ischemic cell volume.

Analysis of Variance↗
PubMed1999

Transforming growth factor-beta impairs postburn immunoglobulin production by limiting B-cell proliferation, but not cellular synthesis.

BACKGROUND: Transforming growth factor-beta (TGF-beta) has been shown to be an inhibitor of immunoglobulin (Ig) synthesis and may contribute to decreased Ig synthesis after burn injury. This study investigated the relationship between TGF-beta and Ig synthesis after burn injury. METHODS: Twenty-four BALB/c mice received either a 30% body surface area full-thickness contact burn or no burn. Splenocytes were isolated 8 days after burn and were cultured with 0, 0.05 or 0.5 ng/mL TGF-beta. After culture, total IgG and total IgM were measured by enzyme-linked immunosorbent assay. The number of IgM-secreting cells per 10(5) cells was measured by enzyme-linked immunoabsorbent spot forming assay. Total IgM per IgM-secreting cell (pg/cell) was calculated. RESULTS: Total IgG, IgM, IgM-secreting cells, and B-cell number after culture were decreased by burn injury, and the decrease was exacerbated by the presence of TGF-beta. The total IgM per IgM-secreting cells, however, was significantly increased by TGF-beta at 0.5 ng/mL. CONCLUSION: These data demonstrates that TGF-beta does not specifically impair IgM secretion by committed IgM B cells but appears to decrease B-cell proliferation or clonal expansion.

Animals↗
PubMed1999

Association of vascular endothelial growth factor expression with angiogenesis and lymph node metastasis in nasopharyngeal carcinoma.

OBJECTIVE: Recent experimental evidence indicates that angiogenesis affects tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is considered to be an important regulator of tumor angiogenesis. The present study was designed to examine the role of VEGF on angiogenesis and lymph node metastasis in primary nasopharyngeal carcinomas (NPCs). STUDY DESIGN: Formalin-fixed paraffin-embedded biopsy specimens were obtained from 29 primary NPCs that consisted of 22 differentiated nonkeratinizing carcinomas and seven undifferentiated carcinomas. METHODS: Microvessels were highlighted by staining endothelial cells with von Willebrand factor (VWF) using immunohistochemical techniques, and were counted (per x 400 field) in the most active area of angiogenesis on light microscopy. The expression of VEGF was also studied with immunohistochemistry. Positive ratio for VEGF was graded on a scale of 1 and 2. Scale 1 represents patients with less than the mean value of the positive ratio, and scale 2 represents patients with more than the corresponding value. RESULTS: There was a significant correlation between increased microvessel count and the progression of regional lymph node involvement. The microvessel counts and the progression of N factor were significantly higher in scale 2 patients than in scale 1 patients. CONCLUSION: These results suggest that VEGF plays an important role in lymph node metastasis through induction of angiogenesis in NPCs.

Carcinoma, Squamous Cell↗
PubMed1999

Indocyanine green angiography and pathophysiology of multifocal posterior pigment epitheliopathy.

PURPOSE: To clarify the pathophysiology of multifocal posterior pigment epitheliopathy (MPPE), or bullous retinal detachment (RD)-an unusual manifestation of central serous chorioretinopathy (CSC)-we evaluated indocyanine green (ICG) angiographic findings of patients with MPPE. METHODS: Indocyanine green angiography was performed on 45 eyes of 26 patients with MPPE in our clinic during a 4-year period and compared with clinical and fluorescein angiographic (FA) findings. RESULTS: Ophthalmoscopically, in the posterior pole there were multiple yellowish-white retinal exudations, associated with flat, serous RD and bullous RD in the lower periphery. Fluorescein angiography demonstrated multiple massive leakages from the choroid into the subretinal space. These leakage sites corresponded to the retinal exudations. Indocyanine green angiography showed hyperfluorescence in the posterior pole of the choroid. The hyperfluorescence was first seen in the middle phase and became prominent in the late phase. This finding seems to be due to extravasation from the choriocapillaris. After laser photocoagulation of the leakage sites seen on FA, the leakages stopped and the retinal exudations and RD were resolved. Indocyanine green angiography, however, revealed hyperfluorescence in the posterior pole that was seen in active stage. DISCUSSION AND CONCLUSION: These ICG angiographic findings for MPPE show that hyperpermeability of the choroidal vessels may be the primary causative lesion. This is followed by an intrastromal accumulation of the extravasated choroidal fluid, which may be subclinical. Involvement of the retinal pigment epithelium may be secondary, and then the disease becomes manifest with RD. In MPPE, a severe form of CSC, the retinal pigment epithelium is involved extensively and widely, and prognosis is unfavorable. We conclude that MPPE and CSC represent opposite ends of a common morbid spectrum.

Adult↗