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Biomedical subjects

H Tsuji

Publications and source records attributed to H Tsuji.

At least 361 records · Page 20Linked to original sources
PubMed1994

The effect of platelet-activating-factor antagonist TCV-309 on arrhythmias and functional recovery during myocardial reperfusion.

BACKGROUND: We investigated the effects of a platelet-activating-factor antagonist TCV-309, an antagonist of metabolites of ischemia, on arrhythmias and functional recovery during in-situ reperfusion in dogs. METHODS: Open-chest anesthetized dogs were subjected to ligation of the left anterior coronary artery. Ischemia was maintained for 20 min after which reperfusion was allowed. A cardiac surface ECG was recorded continuously with the II limb lead. Monophasic action potential, left ventricular segment shortening measured by sonomicrometer, and left ventricular pressure were recorded simultaneously under atrial pacing (group A, n = 14). In a second group of dogs, TCV-309 (1 mg/kg) was administered before coronary artery occlusion (group B, n = 12). The hearts were constantly paced through the right atrium at 120 beats/min throughout all experiments. Measurements were continuously obtained from before drug administration to 30 min after reperfusion. RESULTS: The 90% repolarization time of monophasic action potentials in group B revealed significant recovery compared with group A until the fifth minute after reperfusion (P < 0.02). Reduction of severe ventricular arrhythmias was observed during reperfusion in group B (P < 0.05). The percentage segment shortening and left ventricular pressure did not differ significantly between the groups. CONCLUSION: The platelet-activating-factor antagonist had beneficial effects on arrhythmias but not on functional recovery during reperfusion after brief coronary artery occlusion in situ in dogs.

Action Potentials↗
PubMed1994

Effects of epidermal growth factor on invasiveness through the extracellular matrix in high- and low-metastatic clones of RCT sarcoma in vitro.

We investigated the invasiveness of tumor cells through the extracellular matrix and the influence of epidermal growth factor (EGF) on tumor cell invasion using in vitro systems in high-[RCT(+)] and low-metastatic [RCT(-)] clones established from poorly differentiated murine RCT sarcoma in C3H/He mice. In the invasion assay using a filter coated with reconstituted basement membrane (Matrigel) in a Boyden chamber, RCT(+) cells were more invasive than RCT(-) cells. The attachment of RCT(+) cells to extracellular matrix components and the degradation of type IV collagen by the cells were significantly greater than with RCT(-) cells. However, there was no significant difference in the migration of cells to the extracellular matrix components between cultured RCT(+) and RCT(-) cells. These findings suggested that the different invasiveness of these clone cells was associated with the difference in the ability of attachment to and degradation of the matrix. The level of laminin receptor expression in RCT(+) cells was about four-fold that in RCT(-) cells and laminin stimulated the type IV collagenolytic activity of RCT(+) cells, suggesting that RCT(+) cell attachment to laminin via laminin receptor on the cell surface induced the production of type IV collagenase by the tumor cells. EGF did not affect the invasiveness of RCT(-) cells. In RCT(+) cells, EGF stimulated the invasiveness through Matrigel, the attachment to extracellular matrix components and the degradation of type IV collagen through high-affinity EGF receptors (EGFR), with Kd of pM order, while the migration to the matrix was not influenced by EGF. These findings suggest that the stimulatory effect of EGF on invasion is related to the acceleration of cell adhesion, and the degradative cascade of the extracellular matrix and high-affinity EGFRs play an important role in the effect of EGF on in vitro invasiveness in this tumor.

Animals↗
PubMed1994

Serum levels of laminin, type IV collagen and type III procollagen peptide as markers for detection of metastasis.

We investigated the clinical usefulness of serum laminin, type IV collagen and type III procollagen peptide (PIIIP) as markers for detection of metastasis in patients with primary or metastatic bone and soft part tumors. The subjects consisted of 28 patients with metastatic bone tumors, 18 with primary bone tumors (benign; 10, malignant; 8), 22 with primary soft part tumors (benign; 12, malignant; 10), 18 with cancer without metastasis (as controls to metastatic bone tumor) and 60 healthy controls. Elevated levels of serum laminin, type IV collagen and PIIIP were not associated with any specific histological subtype, tumor size or location, and were clearly related to evidence of metastasis. Mean serum concentrations of laminin, type IV collagen and PIIIP were significantly higher in patients with metastasis than in patients without metastasis. Positive correlations were observed among serum laminin, type IV collagen and PIIIP levels in tumor patients. The sensitivity values for laminin, type IV collagen and PIIIP in detecting metastasis were 83.7%, 83.3% and 80.5%, respectively, with specificity of 90.0%, 86.1% and 86.1%. When two of the three markers were evaluated in identical blood samples, combined sensitivity and specificity values exhibited further increases as compared to the sensitivity and specificity of each marker. The use of all three markers led to the best combined sensitivity and specificity. These findings suggest that the combination of these markers would be a valuable screening test in predicting metastasis.

Analysis of Variance↗
PubMed1994

CD4+ T cells from collagen-induced arthritic mice are essential to transfer arthritis into severe combined immunodeficient mice.

The role of T lymphocytes in the adoptive transfer of collagen-induced arthritis (CIA) in DBA/1J mice to severe combined immunodeficient (SCID) mice was investigated. Spleen cells from non-immunized, type I collagen (CI) or type II collagen (CII)-immunized DBA/1J mice were injected into SCID mice which lack functional T and B cells. Specific antigenic stimulation of arthritogenic cells was required since only lymphocytes from arthritic CIA mice plus simultaneous administration of CII transferred arthritis to 11 of 12 SCID mice with a marked increase in CII antibody titre. However, CI-immunized or non-immunized DBA/1J mice cells did not induce arthritis in SCID mice. SCID recipients of pre-arthritic CIA lymphocytes presented increase in CII antibody, but showed no clinical signs of arthritis, suggesting that antibodies to CII alone can not induce CIA. Depletion of CD4+ T cells inhibited the transfer of arthritis to SCID mice, with a decrease in CII antibody titre in chimaeras. In contrast, depletion of CD8+ T cells enhanced the onset of arthritis in SCID mice. The results imply that CD4+ T cells are required for the induction of CIA. In addition, CD8+ T cells might have a suppressive role in the etiology of this disease. It is probable that memory CD4+ T cells stimulate production of antibodies to CII and subsequent arthritis. This study clarifies the role of T lymphocytes in the transfer of CIA to SCID mice.

Animals↗
PubMed1994

Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study.

BACKGROUND: The prognostic implications of alterations in heart rate variability have not been studied in a large community-based population. METHODS AND RESULTS: The first 2 hours of ambulatory ECG recordings obtained on original subjects of the Framingham Heart Study attending the 18th biennial examination were reprocessed to assess heart rate variability. Subjects with transient or persistent nonsinus rhythm, premature beats > 10% of total beats, < 1 hour of recording time, processed time < 50% of recorded time, and those taking antiarrhythmic medications were excluded. The associations between heart rate variability measures and all-cause mortality during 4 years of follow-up were assessed. There were 736 eligible subjects with a mean age (+/- SD) of 72 +/- 6 years. The following five frequency domain measures and three time domain measures were obtained: very-low-frequency power (0.01 to 0.04 Hz), low-frequency power (0.04 to 0.15 Hz), high-frequency power (0.15 to 0.40 Hz), total power (0.01 to 0.40 Hz), the ratio of low-frequency to high-frequency power, the standard deviation of total normal RR intervals, the percentage of differences between adjacent normal RR intervals that are > 50 milliseconds, and the square root of the mean of the squared differences between adjacent normal RR intervals. During follow-up, 74 subjects died. In separate proportional hazards regression analyses that adjusted for relevant risk factors, very-low-frequency power (P < .0001), low-frequency power (P < .0001), high-frequency power (P = .0014), total power (P < .0001), and the standard deviation of total normal RR intervals (P = .0019) were significantly associated with all-cause mortality. When all eight heart rate variability measures were assessed in a stepwise analysis that included other risk factors, low-frequency power entered the model first (P < .0001); thereafter, none of the other measures of heart rate variability significantly contributed to the prediction of all-cause mortality. A 1 SD decrement in low-frequency power (natural log transformed) was associated with 1.70 times greater hazard for all-cause mortality (95% confidence interval of 1.37 to 2.09). CONCLUSIONS: The estimation of heart rate variability by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional risk factors.

Aged↗
PubMed1994

Brain hemorrhage in mixed connective tissue disease. A case report.

Mixed connective tissue disease (MCTD) uncommonly develops stroke, although collagen disease is an important condition for stroke. A nonhypertensive woman with MCTD developed massive putaminal hemorrhage. No obvious predisposing factors were revealed by clinical and pathologic examination. MCTD may contribute to the development of brain hemorrhage by some mechanism other than hypertension.

Cerebral Arterial Diseases↗
PubMed1994

Identification and characterization of lysosomal enzymes involved in the proteolysis of phenobarbital-inducible cytochrome P450.

We have studied lysosomal proteases capable of degrading a major form of cytochrome P450 (CYP2B1) which was purified from the liver microsomes of phenobarbital-treated rats. After incubation of CYP2B1 with extracts of triton-filled lysosomes (tritosomes), its proteolysis was measured by a quantitative immunoblot procedure. A CYP2B1 protein band with an apparent molecular mass of 53 kilodaltons (kDa) was degraded to 42-, 38-, and 29-kDa polypeptides after a short period of incubation. These proteolytic fragments disappeared on prolonged incubation. One milligram of tritosomal protein contained enough activity to hydrolyze approximately 67.3 micrograms CYP2B1 protein/min at pH 4.5. Approximately 85% of the hydrolyzing activity was localized in a soluble fraction of the tritosomes. The degradation of CYP2B1 was effectively inhibited by pepstatin A, an aspartic protease inhibitor, but not by phenylmethanesulfonyl fluoride (PMSF), o-phenanthroline and leupeptin. CYP2B1-hydrolyzing activity was coeluted with cathepsin D when the soluble fraction was chromatographed by means of Ultrogel Ac44 gel filtration. Cathepsin D, purified from rat livers, was able to degrade CYP2B1 at pH 4.5 which corresponds to the intralysosomal pH. These results indicate that cathepsin D is responsible for the major CYP2B1-hydrolyzing enzyme activity in lysosomes.

Amino Acid Sequence↗
PubMed1994

Uptake of liposomes surface-modified with glycyrrhizin by primary cultured rat hepatocytes.

Previously, we synthesized 30-stearyl glycyrrhizin (GLOSt) and reported that small unilamellar liposomes containing GLOSt (GLOSt-SUV) accumulated in the liver several times more than the control liposomes (control-SUV). In the present study, to determine the interaction between GLOSt-SUV and hepatocytes, in vitro uptake experiments were achieved with primary cultured rat hepatocytes. The uptake amount of GLOSt-SUV by rat hepatocytes was considerably higher compared to the control-SUV, while GLOSt-SUV showed about a 10-fold higher uptake level than the control-SUV during 2 h of incubation. It was assumed that GLOSt-SUV not only bind to the surface of the hepatocytes but are internalized and degraded in the cells, because at 37 degrees C, GLOSt-SUV were taken up and the level of the degradable marker was lower than the inert marker, and this did not occur at 4 degrees C. Since the uptake of GLOSt-SUV was inhibited by glycyrrhizin (GL), it was suggested that a binding-site for GL is present on the surface of hepatocytes, and GLOSt-SUV are likely to be internalized via this site by the hepatocytes. Furthermore, it was confirmed that the efficacy of GLOSt on liposomes is not affected by the fluidity of the liposomal membrane.

Animals↗
PubMed1994

Effect of body characteristics on the variables of signal-averaged electrocardiograms in healthy subjects.

Late potentials have been reported to be affected by body size or left ventricular mass. To our knowledge, however, the effect of subadipose tissue, which is known to influence QRS amplitudes of the surface ECG on the variables of late potentials, has not been evaluated. The relationships between the variables of late potentials and various obesity indices were assessed in 45 men, aged 24 to 38 years, without structural heart disease and bundle branch blocks. QRS duration (DUR), root mean square voltage in the last 40 ms (RMS), and low-amplitude signals < 40 microV (LAS) were obtained by signal-averaged ECG. Left ventricular mass (LV mass) was determined by echocardiography. The DUR and RMS had no correlation with body height, weight, body mass index (BMI), sum of skin folds (triceps and subscapular), or LV mass. Positive linear correlations were found between LAS and weight (r = 0.48, p < 0.002), BMI (r = 0.54, p < 0.002), sum of skin folds (r = 0.57, p < 0.002), and percent BMI (r = 0.54, p < 0.002). Subadipose tissue may shift the onset of the 40-microV point of LAS to the left with a consequent prolongation of LAS by attenuation of the QRS complex. These data suggest that the use of LAS alone or as a combination in an obese population for the definition of positive late potentials is inappropriate.

Adult↗
PubMed1994

Quantitation of hepatitis C virus RNA in liver tissue as a predictive marker of the response to interferon therapy in chronic hepatitis C.

Recently, factors predicting the response to interferon (IFN) therapy against hepatitis C virus (HCV) have received much attention. To evaluate the usefulness of the quantitation of intrahepatic HCV RNA as a predictive marker of the response to IFN therapy, we compared the amount of intrahepatic HCV RNA with serum levels in 16 patients. Eleven patients who had 10(10) copies/g or more of intrahepatic HCV RNA had increased level of serum alanine aminotransferase (ALT) after IFN therapy, while 4 of 5 patients who had less than 10(10) copies/g of intrahepatic HCV RNA achieved sustained normalization of serum ALT level and were designated as complete responders. Four complete responders possessed significantly less HCV RNA in the liver parenchyma than partial and nonresponders (P = 0.010, Mann-Whitney U-test), but the amount of HCV RNA in the serum was not significantly different between those groups. In conclusion, the results suggest that the quantitation of intrahepatic HCV RNA is a better indicator of the response to IFN therapy than serum HCV RNA.

Adult↗
PubMed1994

An autopsy case of pyruvate kinase deficiency anemia associated with severe hemochromatosis.

We report an autopsy case of pyruvate kinase deficiency anemia with severe hemochromatosis. This anemia is rarely associated with hemochromatosis. In this case, the autopsy findings showed hemochromatosis of the heart, pancreas, liver, kidneys, thyroid gland, adrenal glands, testes and skin. Microscopic examination showed iron depositions in these organs, but not in the bone marrow. A family study showed negative data for iron overload and no known HLA type suggestive of idiopathic hemochromatosis. To explain this rare association, we suggest that this patient's iron overload was an acquired type, which might have mainly been caused by increased iron absorption due to the severe hemolytic anemia.

Adult↗
PubMed1994

Radiation tolerance of the liver in relation to the preserved functional capacity.

The radiation tolerance of the liver was investigated in 12 patients, 11 of them with liver cirrhosis, treated for hepatocellular carcinoma by partial liver irradiation with doses between 50 and 77 Gy. The tolerance was assessed by the complication probability (Lyman's model), which concerned the injured tissue itself, and by a prediction score used for postsurgical liver failure, which concerned the preserved functional capacity, assuming that the > or = 30 Gy volume was equivalent to the resected volume. The prediction score corresponded better with the observed risk of fatal liver failure than the complication probability. The liver volume after radiotherapy correlated largely with the untreated volume and the low-dose volume. Thus the preserved functional capacity gives a better expression of the radiation tolerance than direct measures of the extent of injured tissue.

Aged↗
PubMed1994

Phenotypic differences of CD34-positive stem cells harvested from peripheral blood and bone marrow obtained before and after peripheral blood stem cell collection.

Using two-color flow cytometry, we analyzed the subpopulations of CD34+ stem and progenitor cells in the blood and bone marrow from 10 patients with hematological malignancies. Peripheral blood mononuclear cells (PBMNC) harvested after chemotherapy (high-dose Ara C and VP-16) and rhG-CSF, and BM mononuclear cells, which were obtained before chemotherapy (BMMNCbefore) and after the stem cell collection (BMMNCafter) were isolated by Ficoll-Hypaque centrifugation. The purified cells were stained with FITC-conjugated anti-CD34 antibody and one of the following PE-conjugated antibodies: anti-CD7, CD10, CD11b, CD11c, CD13, CD19, CD33, CD38, CD45RO, CD56, and HLA-DR. CD34+ PBMNC harvested and the CD34+ BMMNCafter expressed CD13 and CD33 more frequently than CD34+ BMMNCbefore but expressed CD10 and CD19 less frequently than CD34+ BMMNCbefore. These data suggested that harvested PBMNC contain more myeloid lineage committed progenitors than BMMNCbefore, which might contribute to the rapid recovery of neutrophils after peripheral blood stem cell transplantation. No significant phenotypic differences of CD34+ cells between harvested PBMNC and BMMNCafter were observed except for the expression of CD11c. CD34+ PBMNC harvested coexpressed CD11c more frequently than both CD34+ BMMNCbefore and CD34+ BMMNCafter, which expression might be associated with commitment to the monocyte lineage.

Adolescent↗
PubMed1994

Cycling of an 85-kDa lysosomal membrane glycoprotein between the cell surface and lysosomes in cultured rat hepatocytes.

We studied the endocytic transport of an 85-kDa lysosomal membrane glycoprotein (LGP85) from the cell surface to lysosomes in cultured rat hepatocytes. Fab' fragments of a monoclonal antibody against LGP85 (YA30 mAb) were conjugated with horseradish peroxidase (HRP) and then used as probes to monitor the endocytic transport of LGP85 from the plasma membrane to lysosomes. Continuous internalization and lysosomal transport of HRP-YA30 mAb Fab' occurred in the hepatic cells, resulting in its accumulation in the dense lysosomal fraction obtained from the cells on Percoll density centrifugation. The endocytic transport of HRP-YA30 mAb continued in the presence of the protein synthesis inhibitor, cycloheximide, indicating that LGP85 is cycled between the cell surface and lysosomes or endosomes, like other lysosomal membrane glycoproteins, lamp-1 and lamp-2, as reported previously [Akasaki et al. (1993) J. Biochem. 114, 598-604]. The half times (t1/2) of internalization and lysosomal transport of LGP85 were 32 min and 2.0 h, respectively. The kinetics of endocytic transport for LGP85 are very similar to those of lamp-1 and lamp-2. LGP85 possesses a short cytoplasmic tail whose amino acid sequence is quite different from those of lamp-1 and lamp-2. Therefore, these results suggested that continuous internalization from the cell surface and lysosomal transport of of endogenous LGP85 occur through a mechanism that can recognize this novel amino acid sequence, probably a Leu-Ile-containing motif, in normal hepatic cells of rat.

Amino Acid Sequence↗
PubMed1994

Protein C deficiency found in a patient with acute myocardial infarction: a single base mutation 157 Arg (CGA) to stop codon (TGA).

Protein C has an important role in the regulatory mechanisms of coagulation and fibrinolysis. In patients with heterozygous protein C deficiency, there is an increased risk for thromboembolic disease, especially in the venous system. We describe a patient with protein C deficiency presenting with an acute myocardial infarction (AMI). Direct sequence analysis of the whole protein C gene detected a single base mutation at exon 7; 157 [Arg(CGA) to stop codon (TGA): 6182 C to T]. Thus, the patient was suspected to have a deficiency of the protein C heavy chain molecule, resulting in both a low protein C antigen and activity level. The mutation was also found in the propositus' son and was confirmed by differential termination of the primer extension (DTPE).

Base Sequence↗
PubMed1994

Preliminary results of bladder-preserving therapy with definitive radiotherapy and intraarterial infusion of chemotherapy.

PURPOSE: For management of muscle-invading bladder cancer (clinical stages T2 to T4), combined treatment of definitive radiotherapy (RT) and intraarterial (IA) administration of chemotherapy was carried out for local cure and bladder preservation. METHODS AND MATERIALS: Between 1987 and 1990, a pilot study (Protocol-1) was initially conducted in 16 patients to investigate the efficacy of chemoradiotherapy where RT was combined with TURB and continuous IA infusion of cisplatin. We then performed a regimen of possible bladder-preservation treatment (Protocol-2) in which 19 patients were treated with combination of TURB, full-dose RT and one-shot IA infusion of cisplatin and methotrexate. In RT small pelvis irradiation was performed with x-rays followed by proton beam boost irradiation to the original tumor site. RESULTS: Among patients treated on Protocol-1, a tumor-free bladder was observed in 50% (2/4) after 50-76 Gy but only 8% (1/14) after 30-40 Gy. In this regimen, planned cystectomy was performed in 10 patients and 13 patients (81%) are alive. Among 19 patients treated on Protocol-2, 17 patients (89%) are alive and 13 patients (68%) retained intact bladders without any recurrence. There were 3 cystectomies performed because of persistent tumors. Using a conformal mode of proton beam irradiation, a total dose of 60-80 Gy was safely administered with acceptable morbidities. CONCLUSION: In the light of good complete response and survival rates achieved in the patients treated on Protocol-2, the combined treatment of definitive RT and IA administration of chemotherapy is considered as an effective bladder-preserving strategy.

Aged↗