Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 235 records · Page 13Linked to original sources

PubMed1999

Development of a new, simple rat model of early alcohol-induced liver injury based on sensitization of Kupffer cells.

The continuous intragastric in vivo enteral feeding model in the rat developed by Tsukamoto and French has been very useful; however, it requires surgical expertise. Recently, we found that Kupffer cells isolated from rats treated only once with ethanol were sensitized to endotoxin 24 hours later. Accordingly, these experiments were designed to determine if a new, simple animal model of ethanol hepatotoxicity could be developed based on Kupffer cell sensitization. Female Wistar rats were given ethanol (5 g/kg body weight) once every 24 hours intragastrically. Livers were stained with hematoxylin-eosin to assess steatosis, inflammation, and necrosis, and tissue triglycerides, serum transaminases, and plasma endotoxin were measured. Kupffer cells were isolated 0 to 24 hours after one intragastric dose of ethanol daily, and intracellular Ca2+ ([Ca2+]i) was measured using fura-2, while tumor necrosis factor alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western and Northern analysis. Ethanol caused steatosis, necrosis, and inflammation in only a few weeks, and after 8 weeks, serum aspartate transaminase (AST) levels were doubled. Values were similar to levels achieved in the enteral feeding model. Triglycerides were also increased significantly by ethanol as expected, and endotoxin levels were increased to 70 to 80 pg/mL. This latter increase was prevented (<20 pg/mL) by antibiotics implicating endotoxin. In isolated Kupffer cells from untreated control rats, [Ca2+]i increased to 82 +/- 7 nmol/L after addition of lipopolysaccharide (LPS) (100 ng/mL), and levels were elevated about twofold by ethanol given 24 hours earlier (174 +/- 15 nmol/L). In addition, TNF-alpha production by Kupffer cells was increased fourfold in cells isolated from rats treated with ethanol 24 hours earlier. Sterilization of the gut with antibiotics blocked all effects of ethanol on [Ca2+]i and TNF-alpha release completely. Moreover, 4 weeks after ethanol, CD14 in Kupffer cells was elevated about twofold. A new, simple chronic model of ethanol hepatotoxicity has been developed here based on sensitization of Kupffer cells to endotoxin.

Administration, Oral↗

PubMed1999

Pulmonary blood flow distribution after the total cavopulmonary connection for complex cardiac anomalies.

In total cavopulmonary connection (TCPC), the anastomotic portion of the caval veins to the pulmonary artery (PA) is decided empirically based on personal experience. To compare the pulmonary flow distribution from both caval veins in various types of cavopulmonary anastomosis, intrapulmonary ventilation-perfusion distribution after TCPC was studied using lung scanning. We studied 11 patients, 2 to 37 years old, at 30-84 months after TCPC. Lung scanning was performed by administering 185 MBq of xenon-133 saline solution from their upper extremities and, after xenon-133 was washed out, from their lower extremities. Radionuclide counts on both lungs were obtained and intrapulmonary ventilation-perfusion distribution was assessed. In 4 patients whose superior vena cava (SVC)-PA anastomosis was on the right side of the inferior vena cava (IVC)-PA anastomosis, the blood flow distribution of the right and left lungs was 57.4%: 42.6%. In 3 patients whose SVC-PA anastomosis was on the left side of the IVC-PA anastomosis, the blood flow distribution of the right and left lungs was equal in both lungs (right, 53.1%; left, 46.9%). Systemic arterial oxygen saturation increased after TCPC (before TCPC, 85.3% +/- 2.7% and after TCPC, 89.8% +/- 2.3% (P < 0.05) in group R; before TCPC, 86.1% +/- 2.8% and after TCPC, 93.6% +/- 0.6% (P < 0.02) in group L). After TCPC, the value in group L had a tendency to be greater than that in group R (P < 0.04), in spite of the same values of systemic arterial oxygen saturation before TCPC and cardiac index (group R, 2.9 +/- 0.96; group L, 3.4 +/- 0.37). Lung scanning with xenon-133 revealed the distribution of pulmonary blood flow in the patients after TCPC quantitatively, and in the patients whose SVC-PA anastomosis was on the left side of the IVC-PA anastomosis, the right and left balance of the pulmonary blood flow distribution appeared to be more balanced compared with patients whose connection was done the opposite way.

Adolescent↗

PubMed1999

A new method to evaluate ischemic heart disease: combined use of rest thallium-201 myocardial SPECT and Tc-99m exercise tetrofosmin first pass and myocardial SPECT.

We developed a new diagnostic method for simultaneously evaluating myocardial ischemia, myocardial viability and ventricular function in less than 90 minutes by combined use of rest thallium-201 (Tl) SPECT and exercise Tc-99m tetrofosmin (TF) first pass and SPECT. The subjects were 9 healthy controls, 19 angina pectoris patients, and 19 old myocardial infarction patients, in all of whom coronary angiography had been performed. Rest Tl myocardial SPECT was performed first, and was followed by exercise TF myocardial SPECT. We also performed first pass radionuclide angiography by TF during maximum exercise on a bicycle ergometer to assess the left ventricular ejection fraction (LVEF). The total examination time was less than 90 minutes. SPECT diagnosis was performed by semi-quantitative analysis. LVEF below 55% was regarded as abnormal. In the patients with angina pectoris, analysis according to the coronary artery showed that the diagnostic accuracy of SPECT was 85.0% for ischemia in the region of the left anterior descending branch (LAD), 87.5% for the left circumflex branch (LCX) and 77.8% for the right coronary artery (RCA). The accuracy of diagnosis for angina pectoris was 82.1%, as determined by SPECT alone, and rose to 89.3% when the LVEF levels were also taken into consideration. In the patients with old myocardial infarction, the diagnostic accuracy of SPECT was 84.2% for the LAD, 92.3% for the LCX and 85.0% for the RCA. Analysis by patients showed that the accuracy of diagnosis for myocardial infarction was 85.7%, as determined by SPECT alone. The diagnostic accuracy, however, rose to 89.3% when the LVEF levels also were taken into consideration. In conclusion, it was demonstrated that this combined diagnostic method was highly reliable for evaluating ischemic heart disease within a short time.

Aged↗

PubMed1999

Mechanism for abnormal thallium-201 myocardial scintigraphy in patients with left bundle branch block in the absence of angiographic coronary artery disease.

Patients with left bundle branch block (LBBB) often show abnormal images on exercise thallium (T1)-201 scintigraphy without evidence of significant coronary stenosis. We investigated the mechanism for this phenomenon. Six patients with LBBB and without significant coronary stenosis underwent T1-201 SPECT, ECG-gated SPECT imaging with Tc-99m-methoxyisobutyl-isonitrile (MIBI), and atrial pacing stress test. The % count amplitude in Tc-99m-MIBI images was calculated as [(maximal counts) - (minimal counts)]/(minimal counts) x 100. Though all patients had a low count in the septal and inferior wall in T1-201 SPECT images, there was no ischemic production of lactate during an atrial pacing stress test. Nevertheless, gated SPECT images showed attenuated septal activity during systole. In patients with LBBB, the ratios of % count amplitude at the septum to that at the lateral wall at rest (0.47 +/- 0.05, mean +/- SE) were significantly less than the controls (n = 5, 0.83 +/- 0.12, p = 0.014). In conclusion, these results suggest that abnormal T1-201 SPECT images of the septum in patients with LBBB are partially caused by impaired septal wall thickening during systole. Such an abnormal wall motion may reduce blood flow demands to the septum, resulting in reduction of coronary blood flow with little ischemia.

Bundle-Branch Block↗

PubMed1999

Mechanism of L-methionine overproduction by Escherichia coli: the replacement of Ser-54 by Asn in the MetJ protein causes the derepression of L-methionine biosynthetic enzymes.

We derived L-methionine-analogue-resistant mutants from Escherichia coli JM109 strain by mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine and selected the potent L-methionine-overproducing strains by microbioassay using lactic acid bacteria. One of the mutants, strain TN1, produced approximately 910 mg L-methionine/l following the addition of 0.1% yeast extract to fundamental medium containing glucose and ammonium sulfate. The L-methionine biosynthetic enzymes, cystathionine gamma-synthase and cystathionine beta-lyase, of the L-methionine-overproducing mutants were little repressed by L-methionine. To analyse the mechanism of L-methionine overproduction in the mutant strains, the metJ gene coding for the E. coli met repressor, MetJ protein, was cloned and sequenced by the polymerase chain reaction. The same single-amino-acid subsitution (wild-type Ser-->Asn) at position 54 was observed in four independent L-methionine-producing mutants. When the wild-type metJ gene was then introduced into strain TN1 having the mutant metJ gene, the level of enzyme synthesis and the L-methionine productivity in the transformants were found to revert to those of the wild-type. It was therefore considered that only one point mutation in the metJ gene occurred in the L-methionine-producing mutants. These results demonstrate the important role of residue 54 of the MetJ protein in L-methionine overproduction, probably because of the derepression of L-methionine biosynthetic enzymes.

Bacterial Proteins↗

PubMed1999

Technetium-99m HL91 uptake as a tumour hypoxia marker: relationship to tumour blood flow.

Technetium-99m HL91 (HL91) is a potential agent for imaging hypoxic tissue in vivo. To elucidate the relationship between hypoxia and blood flow in a tumour, dual-tracer autoradiography with HL91 and carbon-14 iodoantipyrine (IAP) was performed in a tumour-bearing rat model. The distribution of each tracer was analysed visually and semiquantitatively. In the tumours with central necrotic areas, HL91 uptake was marked around the necrotic areas whereas IAP uptake was marked at the periphery of the tumours, around the areas of marked HL91 uptake. Normalized HL91 uptake (%HL91) was highest in the low normalized IAP uptake (%IAP) fraction in the non-necrotic areas. There was a weak negative correlation between %HL91 and %IAP in the non-necrotic areas (r = -0.322, P<0.0001). In tumours with few or no necrotic areas, HL91 uptake was heterogeneous throughout the tumours, while IAP uptake predominantly occurred at the periphery of the tumours. %HL91 was higher in the inner two-thirds of the tumour than in the outer third. There was again a weak negative correlation between %HL91 and %IAP (r = -0.354, P<0.0001). This study confirmed that high HL91 uptake is related to low blood flow. The marked HL91 uptake around the necrotic region suggests the presence of chronic hypoxia in a tumour.

Animals↗

PubMed1999

Exercise-induced stunning continues for at least one hour: evaluation with quantitative gated single-photon emission tomography.

To elucidate the after-effect of exercise on left ventricular (LV) function, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were evaluated at 1 h after exercise and at rest by technetium-99m tetrofosmin gated myocardial single-photon emission tomography (SPET) using an automated program in 53 subjects. The subjects were grouped as follows: normal scan (n = 16), ischaemia (n = 19) and infarction (n = 18), based on the interpretation of perfusion images. Postexercise LVEF did not differ from resting LVEF in the groups with normal scan and infarction. In patients with ischaemia, postexercise EDV (90+/-17 ml, mean +/-SD) and ESV (44+/-15 ml) were significantly higher than EDV (84+/-15 ml, P = 0.001) and ESV (36+/-14 ml, P<0.0005) at rest. LVEF was significantly depressed 1 h after exercise (53%+/-9% vs 58%+/-9%, P<0.0001). In ischaemic patients with depressed postexercise LVEF, LVEF difference between rest and postexercise showed a significant correlation with the sum of defect scores, which were reversible from exercise to rest perfusion images (r = 0.92, P<0.0001). These results indicate that exercise-induced LV dysfunction (myocardial stunning) continues for at least 1 h in ischaemic patients and that the extent of LVEF depression is determined by the severity of ischaemia.

Blood Volume↗

PubMed1999

Tumor-specific targeting of T helper type 1 (Th1) cells by anti-CD3 x anti-c-ErbB-2 bispecific antibody.

T helper type1 (Th1) or type2 (Th2) cells were induced from naive Th cells obtained from ovalbumin-specific T cell receptor (TCR) transgenic mice. Th1 cells producing interferon gamma (IFNgamma) exhibited stronger antigen-specific cytotoxicity against ovalbumin-(323-339)-peptide-pulsed A20 tumor cells than did Th2 cells. To develop a general method for applying antigen-nonspecific Th1 cells to tumor immunotherapy, we examined the targeting of Th1 cells to tumor cells using a bispecific antibody (bsAb) consisting of anti-(mouse CD3) mAb and anti-(human c-ErbB-2) mAb. When ovalbumin-specific Th1 or Th2 cells were cocultured with c-erbB-2-positive transfectants (CMS7HE), neither type of cell showed significant cytotoxicity or cytokine production in response to tumor cells. However, addition of bsAb resulted in the triggering of both Th1 and Th2 cells. Th1 cells showed higher levels of bsAb-dependent cytotoxicity against CMS7HE tumor cells than did Th2 cells. The targeting of Th1 cells to CMS7HE tumor cells by bsAb also triggered the production of cytokines such as IFNgamma, interleukin-2 and tumor necrosis factor alpha (TNFalpha). The released TNFalpha was demonstrated to be a critical cytolytic factor in bsAb-mediated cytotoxicity by Th1 cells. Finally, Th1 cells were demonstrated to show antitumor activity in vivo against human c-erbB-2-positive tumor cells implanted in nude mice. These results suggest that Th1 cells are useful effector cells for the application to adoptive tumor immunotherapy in conjunction with bsAb.

Animals↗

PubMed1999

Posttraumatic intra-gallbladder hemorrhage in a patient with liver cirrhosis.

We report a case of intra-gallbladder hemorrhage secondary to blunt abdominal trauma in a patient with liver cirrhosis. A 58-year-old man was admitted to a local hospital with persistent right upper quadrant abdominal pain. Anemia was detected, and computed tomography (CT) revealed a high-density mass in the gallbladder lumen. He was transferred to our hospital because a gallbladder tumor was suspected. He had a history of habitual alcohol abuse and had sustained blunt abdominal trauma in the right upper quadrant 29 days before admission to our hospital (4 days before to the admission local hospital). The intra-gallbladder high-density mass depicted on the CT scan, observed as non-shadowing low-level echoes, was deemed to represent a blood clot on ultrasonography (US) performed 31 days after the trauma. US-guided percutaneous transhepatic gallbladder aspiration and cholecystography confirmed the presence of an old blood clot in the lumen. Because of the patient's persistent pain, a cholecystectomy was performed. The distended gallbladder was filled with old clotted blood.

Cholecystography↗

PubMed1999

QT dispersion in patients with Duchenne-type progressive muscular dystrophy.

BACKGROUND: A high degree of QT dispersion is a risk factor for arrhythmic sudden death in patients with myocardial infarction and cardiomyopathy. Duchenne-type progressive muscular dystrophy (DMD) is also associated with the development of ventricular arrhythmias. The purpose of this study was to determine the relationship between QT interval dispersion and ventricular arrhythmias in patients with DMD. METHODS: Sixty-seven patients with DMD were studied. Standard 12-lead electrocardiograms and 24-hour Holter electrocardiograms were recorded, and the QT interval was determined in every lead of the standard electrocardiogram to determine the QT dispersion. QT dispersion was compared with the frequency of ventricular arrhythmias and the severity of skeletal muscle damage on the basis of the Swinyard and Deaver 8-stage scale. RESULTS: QT dispersion in all 67 patients averaged 54 +/- 18 ms. The QT dispersion was 49 +/- 16 ms in stage 5 patients, 61 +/- 22 ms in stage 6 patients, 52 +/- 17 ms in stage 7 patients, and 56 +/- 17 ms in stage 8 patients. Ventricular arrhythmias of Lown grade III or higher were observed in 3 of 35 patients with QT dispersion <60 ms and in 14 of 32 patients with QT dispersion >/=60 ms. Logistic regression analysis demonstrated that QT dispersion is an independent risk factor for ventricular arrhythmias of grade III or higher in patients with DMD. CONCLUSIONS: The incidence of ventricular arrhythmias of Lown grade III or higher was greater in patients with QT dispersion >/=60 ms than in patients with QT dispersion >60 ms. QT dispersion therefore is a risk factor for serious ventricular arrhythmias in patients with DMD.

Adolescent↗

PubMed1999

Cytotoxic and porphyrinogenic effects of diphenyl ethers in cultured rat hepatocytes: chlornitrofen (CNP), CNP-amino, chlomethoxyfen and bifenox.

We studied the cytotoxic and porphyrinogenic effects of four diphenyl ethers (DPEs), chlornitrofen (CNP), CNP-amino, chlomethoxyfen and bifenox, in rat hepatocytes cultured on Matrigel. Cytotoxicity was determined as a decrease in viability measured by the release of lactate dehydrogenase. Of the DPEs examined. CNP-amino was the most cytotoxic, with an LC50 value of 0.36 mM (95% confidence interval, 0.33-0.40 mM). CNP also reduced the viability in a concentration-dependent manner at the concentrations of 0.50 mM or above. In contrast, no concentration-dependent decrease in viability was observed in the chlomethoxyfen- and bifenox-treated hepatocytes at the concentrations up to 1.0 mM. To identify the enzyme involved in the metabolic activation of CNP-amino, inhibition studies were carried out using SKF 525-A (0.050 mM) and methimazole (1.0 mM). SKF 525-A, a cytochrome P450 inhibitor. quickened the onset of cell killing by CNP-amino, while methimazole, an inhibitor of flavin-containing monooxygenase (FMO), partially suppressed the cytotoxicity of CNP-amino. These results suggest that FMO plays an important role in the cytotoxicity induced by CNP-amino, while cytochrome P450 participates in the detoxification, possibly via the ring-hydroxylation. The maximum porphyrin accumulation was observed at 0.13 mM for chlomethoxyfen (18-fold) and at 0.25 mM for CNP and bifenox (17- and 21-fold, respectively). In contrast to these DPEs, the porphyrinogenic effect of CNP-amino was weak, with the maximum accumulation at 0.13 mM (at least fivefold). The predominant species was protoporphyrin IX in all of the DPE-treated cultures. These results suggest that all of the DPEs examined, possibly including CNP-amino, inhibit protoporphyrinogen oxidase, resulting in the accumulation of protoporphyrin IX.

Animals↗

PubMed1999

Undetectable dystrophin can still result in a relatively benign phenotype of dystrophinopathy.

We present here a 28-year-old male patient with Becker muscular dystrophy whose skeletal muscle showed an absence of dystrophin. He has had progressive and predominantly proximal muscular wasting since 5 years of age, but was able to walk until 26 years of age. He showed hypertrophic calves, cardiomyopathy, and an elevated serum creatine kinase level (934 U/1). A skeletal muscle biopsy revealed advanced chronic myopathic changes. Immunohistochemical examination using anti-dystrophin antibodies against C-terminus showed deficiency of the protein. Rod domain and N-terminus were also absent in almost all muscle fibers, but only in a small part of the sample, they were faintly stained. beta-Dystroglycan and utrophin were present only in a small number of muscle fibers. DNA and RT-PCR analysis showed a frame-shift deletion of exons 3-7 in the dystrophin gene. In such an exceptional case as this one, it is important to investigate the factors which determine the severity of dystrophinopathy.

Adult↗

PubMed1999

beta-Methyl-p-(123I)-iodophenyl pentadecanoic acid single-photon emission computed tomography in cardiomyopathy.

beta-Methyl-p-(123I)-iodophenyl pentadecanoic acid (BMIPP) is one of the branched-chain free fatty acids, which has suitable characteristics for myocardial SPECT because of higher uptake and longer retention in the myocardium. Recent advances of BMIPP myocardial SPECT for evaluating cardiomyopathy were reviewed. BMIPP defects were observed in 80% patients with hypertrophic cardiomyopathy (HCM). Moreover, BMIPP uptake was reduced at sites that corresponded with hypertrophic areas, where thallium uptake was increased. The correlations between severity score and septal wall thickness and LV function were better with BMIPP SPECT, suggesting that BMIPP is more suitable for the assessment of myocardial integrity in HCM. The dissociation between BMIPP and thallium defects was not observed frequently in dilated cardiomyopathy (DCM). We carried out BMIPP myocardial SPECT to evaluate the therapeutic effects of co-enzyme Q10 on DCM patients. Hearts to the mediastinum ratio and BMIPP defect scores were significantly decreased after co-enzyme Q10 treatment. BMIPP myocardial SPECT was confirmed to be sensitive in evaluating the therapeutic effect for the perspective of metabolic SPECT imaging. Recently, a lack of myocardial uptake of BMIPP has been found in a small subset of patients (0.3%-1.2%). Cardiac radionuclide imaging using BMIPP and 18F-FDG were performed on patients with type I CD36 deficiency. The percent dose uptake of 18F-FDG was significantly higher than in normal controls. CD functions as a major myocardial long-chain fatty acid transporter and its absence may lead to a compensatory upregulation of myocardial glucose uptake. An increased frequency of CD36 deficiency was demonstrated in cardiomyopathy. Therefore, fatty acid transport proteins and their related gene defects in relation to BMIPP uptake may become an important issue in the future.

Antioxidants↗

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↗