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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 253 records · Page 14Linked to original sources

Identification of atrial-specific myosin heavy chain in cardiac muscle of adult chickens.

The partial amino acid sequence of subfragment-1 of adult chicken atrial myosin was determined by direct protein sequencing. Subfragment-1 was prepared by limited digestion of adult chicken atrial myosin with alpha-chymotrypsin. Ten peptides were then obtained by cleaving this subfragment with cyanogen bromide. The amino acid composition and amino acid sequence of the obtained peptides were subsequently determined. By sequence comparison with the corresponding region of adult chicken ventricular myosin, three peptides, with differing sequences that corresponded to the same position in subfragment-1, were detected. This indicates that at least three isoforms of atrial myosin exist in adult chicken atrial muscle. One of the three peptides was identical to ventricular subfragment-1 while the remaining two peptides were markedly different. Furthermore, four of these ten peptides were completely different from ventricular subfragment-1. These four peptides were presumed to be fragments of atrial-specific myosin heavy chain protein. Results suggest the expression of at least two species of atrial-specific myosin heavy chain in the atrial muscle of adult chickens.

Amino Acid Sequence↗

MRI findings in the liver in biliary atresia patients after the Kasai operation.

To evaluate liver function in biliary atresia (BA) patients after the Kasai operation, magnetic resonance imaging (MRI) was carried out 28 times in 19 BA patients. Sixteen of these were divided into three groups on the basis of the serum level of total bilirubin (t-bil), glutamic pyruvic transaminase (GPT) and gamma-glutamyltransferase (gamma-GTP) in the postoperative follow-up period (2-11 years). In group 1 (n = 7) the t-bil was continuously kept under 1 mg/100 ml. In group 2 (n = 4) the t-bil was continuously kept under 1 mg/100 ml, but GPT and gamma-GTP remained high (GPT > 100 IU/liter, gamma-GTP > 200 IU/ liter) for more than 2 years. In group 3 (n = 5) an increase in the t-bil level reappeared (1-2 mg/100 ml; n = 4, > 2 mg/100 ml; n = 1). The differences between MRI finding in the 3 groups, and the correlation between MRI findings and laboratory data (t-bil, cholinesterase; ChE, GPT and gamma-GTP), which were taken around the time of MRI examinations, were studied. The results were as follows: (1) All 19 patients had normal or high signal areas of various sizes on T1 weighted images (WI). (2) Eighteen of 19 patients had high signal areas of various sizes on T2 WI in the portal system areas and/or liver parenchyma, and these areas were enhanced by gadolinium-DTPA in about half of the patients. (3) Ten of 16 patients had atrophic change over one liver lobe. (4) MRI findings for group 1 and the other groups were significantly different, and MRI findings, except for atrophic change, were correlated with the increase or decrease in laboratory data taken around the time of MRI examinations (p < 0.05). These results indicate that a normal or high signal area on T1 WI shows functional tissue, and that a high signal area on T2 WI shows tissue damaged by inflammation and/or progressive fibrosis. MRI is useful for evaluating liver function, especially in terms of morphological features, in BA patients after the Kasai operation, and will be one method for establishing their prognosis.

Alanine Transaminase↗

Sinus pericranii associated with a cerebellar venous angioma--case report.

A 64-year-old male presented with sinus pericranii associated with a venous angioma draining through a large venous lake. Increased venous pressure and flow in the dural venous lake in contact with the venous sinus may have developed the sinus pericranii. Three-dimensional computed tomography was very useful in determining the site of the transcranial venous anastomotic channels, and magnetic resonance imaging was also very useful in detecting the intracranial vascular anomalies.

Cerebral Veins↗

Relationship between weight change in young adulthood and the risk of NIDDM. The Sotetsu Study.

OBJECTIVE: To investigate the independent effect of weight change in young adulthood on the risk of prevalent NIDDM among middle-aged Japanese men. RESEARCH DESIGN AND METHODS: A case-control study was carried out in 895 male employees aged > or = 30 years of a railway company located in the vicinity of Tokyo. Adjusted odds ratios (ORs) were calculated for prevalent diabetes in each category of weight change (obtained from subjects' medical records) in young adulthood and adulthood. Adjustment for current age, initial BMI, and weight change in each age stratum was performed by the Mantel-Haenszel method or multiple logistic regression analysis. RESULTS: Weight change between 20 years of age and the age at maximum weight was not associated with the risk of NIDDM. Weight gain between 20 and 25 years of age was significantly and positively associated with the risk of NIDDM (OR 3.87 for gains > or = 10.0 kg, 2.53 for gains of 5.0-9.9%, and 3.73 for gains > or = 10.0%). On the other hand, moderate weight gain after 30 years of age was significantly inversely associated with NIDDM (OR 0.44 for gains of 5.0-9.9 kg, 0.15 for gains of 10.0-19.9%, and 0.38 for gains of 20.0-29.9%). CONCLUSIONS: Extreme weight gain between 20 and 25 years of age is a significant predictor of NIDDM, independent of current age, BMI at 20 years of age, and weight change within other age strata.

Adult↗

Fas receptor (CD95)-mediated apoptosis in leukemic cells.

Binding of Fas ligand (FasL) or an agonistic anti-Fas receptor (Fas/CD95) antibody induces apoptosis in Fas-bearing target cells. The involvement of Fas/FasL pathway has been investigated in human acute myelogenous leukemia (AML) cells. Fas/CD95 is expressed on a majority of AML cells, although the intensity of expression is variable. The cross-linking with anti-Fas antibody can induce apoptotic cell death in certain cases of AML. When DNA synthesis and cell cycle progression are enhanced by growth-promoting cytokines, such as interleukin-3 and granulocyte-macrophage colony-stimulating factor, Fas-insensitive AML cells acquire cellular susceptibility toward Fas-mediated apoptosis. Cell cycle analysis reveals that Fas-mediated apoptotic signals can be transduced into cells in G1B compartment and G1A-->G1B transition might support the induction of Fas-mediated apoptosis. In addition, Fas-mediated apoptotic cell death of AML cells is also induced by interleukin-2-activated T cells expressing functional FasL on their surfaces. Activated T cells express a large amount of FasL mRNA, compared with freshly isolated T cells. The Fas/FasL pathway seems to be the major mechanism of T cell-mediated apoptosis in AML cells, although alternative mechanisms can also be operative. The induction of apoptosis in Fas/FasL system might be a novel and effective approach for leukemia immunotherapy.

Animals↗

Effect of repeated exercise on urinary 8-hydroxy-deoxyguanosine excretion in humans.

The purpose of this study was to investigate the effect of repeated exercise on oxidative damage to DNA in 10 well trained long distance runners who participated in an 8-day training camp. The average running distance during the camp was 30 +/- 3 km/day. The amount of urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion was used to estimate the oxidative DNA damage. Urine samples were collected for both a 3-day control period as well as throughout the camp. Blood samples were drawn after overnight fasting both before and after the camp. Urinary 8-OHdG excretion was significantly increased during the camp compared to the control period (265.7 +/- 75.5 vs. 335.6 +/- 107.4 pmol/kg/day, P < 0.05). The content of 8-OHdG in the lymphocyte DNA on the day after finishing the camp did not differ from that before the camp. Plasma TBARS, LDH, CK, CK-MB, and myoglobin significantly rose after the camp (P < 0.05). The plasma beta-carotene levels tended to rise after the camp, while the plasma alpha-tocopherol levels increased significantly after the camp (P < 0.05). These results indicate that repeated exercise augments oxidative stress and the DNA is also injured by exercise-induced reactive oxygen species. However, the oxidative damage to DNA is not accumulated by consecutive exercise, although it is sustained as long as the exercise is repeated.

8-Hydroxy-2'-Deoxyguanosine↗

Effect of endurance exercise on the tissue 8-hydroxy-deoxyguanosine content in dogs.

The purpose of this study was to investigate the effect of endurance exercise on both the tissue and lymphocyte 8-hydroxy-deoxyguanosine (8-OHdG) content. Six dogs ran on a treadmill for 7 hours. Another six dogs were assigned to a sedentary control group. The exercised dogs were sacrificed immediately after exercise and the counterpart of the sedentary group was also sacrificed at the same time. The brain, lung, liver, spleen, kidney, jejunum, colon, diaphragm, heart, splenius muscle, and the medial and lateral portion of gastrocnemius muscle samples were then collected. Lymphocytes were sampled before and after exercise in the exercised dogs. The 8-OHdG content of lymphocyte DNA was found to significantly decrease after exercise (0.57 +/- 0.19 vs 0.33 +/- 0.10/deoxyguanosine (dG) x 10(5), P < 0.05). The colon was the only tissue which showed a significant decrease in the content (0.83 +/- 0.24 vs 0.54 +/- 0.15/dG x 10(5), P < 0.05). No tissue except for the colon showed any significant changes after exercise. These results therefore indicate that, immediately after endurance exercise, an augmented repair mechanism might thus play a role in the decrease of 8-OHdG in the lymphocytes and the colon, while the 8-OHdG generation might be counterbalanced by its repair in other tissues.

8-Hydroxy-2'-Deoxyguanosine↗

Effect of a single bout of exercise and beta-carotene supplementation on the urinary excretion of 8-hydroxy-deoxyguanosine in humans.

We investigated the effects of acute exhaustive exercise and beta-carotene supplementation on urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion in healthy nonsmoking men. Fourteen untrained male (19-22 years old) volunteers participated in a double blind design. The subjects were randomly assigned to either the beta-carotene or placebo supplement group. Eight subjects were given 30 mg of beta-carotene per day for 1 month, while six subjects were given a placebo for the same period. All subjects performed incremental exercise to exhaustion on a bicycle ergometer both before and after the 1-month beta-carotene supplementation period. The blood lactate and pyruvate concentrations significantly increased immediately after exercise in both groups. The baseline plasma beta-carotene concentration was significantly 17-fold higher after beta-carotene supplementation. The plasma beta-carotene decreased immediately after both trials of exercise, suggesting that beta-carotene may contribute to the protection of the increasing oxidative stress during exercise. Both plasma hypoxanthine and xanthine increased immediately after exercise before and after supplementation. This thus suggests that both trials of exercise might enhance the oxidative stress. The 24-h urinary excretion of 8-OHdG was unchanged for 3 days after exercise before and after supplementation in both groups. However, the baseline urinary excretion of 8-OHdG before exercise tended to be lower after beta-carotene supplementation. These results thus suggest that a single bout of incremental exercise does not induce the oxidative DNA damage, while beta-carotene supplementation may attenuate it.

8-Hydroxy-2'-Deoxyguanosine↗

[A case of papillary cystadenocarcinoma of the prostate].

An 86-year-old was admitted to our hospital with the complaint of urinary retension. Ultrasonography and CT scan revealed a large cystic intrapelvic mass which was palpated on the bilateral inguinal portion. When the needle aspiration was performed, we aspirated serous fluid which a concentration of prostate-specific antigen (PSA) was remarkably elevated to 6200 ng/ml. Following hormonal therapy with diethylstilbestrol diphosphate, maximum androgen blockade with Flutaminde and LH-RH analog was performed. But no reduction in the size of the cyst was observed, he died from dyspnea caused by carcinomatosa 91 days later. Autopsy revealed a papillary cystadenocarcinoma of the prostate. Furthermore, we revealed that the cyst is primary and neoplastic changes supervened in this case. Seven cases of papillary cystadenocarcinoma of the prostate in the Japanese literature are reviewed briefly.

Aged↗

[Phase II study of combination chemotherapy with cisplatin, carboplatin and etoposide (CPVP) in unresectable non-small cell lung cancer: analysis of survival time and prognostic factors].

Phase II study of combination chemotherapy with cisplatin, carboplatin and etoposide (CPVP) was conducted in 46 patients with unresectable non-small cell lung cancer. In the previous paper, we showed that CPVP produced a satisfactory response rate without major toxicities. In the present paper, survival time and prognostic factors were analyzed. The median survival time (MST), 1- and 2-year survival of 46 patients (III A4, III B15, IV 27) were 14.1 months, 57.0% and 18.2%, respectively. In prognostic analysis, responders survived significantly longer than non-responders (MST: 15.8 vs 11.0 months, p < 0.05). Large cell carcinoma and stage IV have proven to be indicators of poor prognosis. Females and patients less than 60 years old tended to do better. With regard to the relationship between the time from initiation of treatment to response and survival time, late responders (response after 3 or 4 courses) survived significantly (p < 0.05) longer than early responders (response after 1 or 2 courses). The CPVP regimen is not only practical, but also very effective. It deserves further study to reveal its advantages compared to the other platinum compound containing regimens.

Adult↗

[Pharmacokinetic and clinical evaluation of azithromycin in the pediatric field].

35 children between 9 months and 12 years of ages were given 9.1 to 12.2 mg/kg of azithromycin (AZM) once a day for 3 days. In the treatment of pediatric infectious diseases, we studied pharmacokinetics, efficacy and safetiness of AZM. After administration of 10 mg/kg/day of AZM for 3 days, the elimination half-life was calculated to be 3.8 +/- 16.3 hours (n = 6, mean +/- S.D.). The excretion rate of AZM in the urine within 120 hours of administration was 9.0 +/- 2.3% (n = 5). For the evaluation of efficacy of AZM, we treated 33 cases of children with pharyngotonsillitis, bronchitis, mycoplasma bronchitis, pneumonia, mycoplasma pneumonia, atypical pneumonia, and SSTI. The efficacy rate of these cases were 93.9%. 6 strains of bacteria were identified as causative agents. All strains were eradicated upon the treatment. One case of elevated GOT and GPT and two cases of elevated GPT were observed. No clinical adverse reactions were observed. In conclusion, AZM was useful for the treatment of pediatric infectious diseases were examined.

Anti-Bacterial Agents↗

[A case of necrotizing crescentic glomerulonephritis with arteritis due to secondary amyloidosis following rheumatoid arthritis].

A 47-year-old woman was admitted on August 4th, 1995, because of edema of the lower extremities. She had been suffering from RA for about 20 years and underwent total knee-replacements 5 years previously. On admission, nephrotic syndrome and rapidly progressive glomerulonephritis had developed in association with ileus, melena, diarrhea, dyspnea and hemoptysis. She showed a high titer of serum rheumatoid factor (357.0 IU/ml) and amyloid A protein (83.9 micrograms/ml) with positive antinuclear antibodies (homogeneous and speckled patterns). However, anti-neutrophil cytoplasmic autoantibody (ELISA), immune complexes and anti-glomerular basement membrane antibody (ELISA) were negative. Renal biopsy showed microscopic PN overlapping A-type positive amyloidosis. Although the maintenance of hemodialysis was necessary, aggressive immunosuppressive therapy with steroid pulse therapy and frequent plasma exchange provided a rapid improvement of systemic symptoms possibly due to vasculitis. We suggested that in this case, massive necrotizing crescentic glomerulonephritis with systemic arteritis developed on the basis of secondary amyloidosis due to rheumatoid arthritis. In such a case, even if various serum autoantibodies and immune complexes were negative, plasma exchange was suggested to be effective to remove not only pathogenic autoantibodies but also various serum inflammatory cytokines which may be related with severe vasculitis and glomerulitis, in addition to aggressive steroid therapy which may suppress the invasion of inflammatory cells producing these cytokines.

Amyloidosis↗

A case of membranous glomerulonephritis associated with gastric cancer.

We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.

Glomerulonephritis, Membranous↗

[Bone metabolism and phosphorus metabolism in patients with prostate cancer: paracrine and endocrine effects produced by prostate neoplasm].

We examined whether paracrine factors produced by prostate cancer cells can modulate bone metabolism in proportion to the volume of cancer cells in bone metastasis. Endocrine factors produced by prostate cancer cells affect both phosphate and 1,25-dihydroxyvitamin D metabolisms. Levels of urine pyridinoline (U-Pyr) excretion and serum carboxy-terminal propeptide of type 1 procollagen (P1CP) in patients with bone metastasis were significantly higher than those in patients without bone metastasis (P < 0.05). In patients with bone metastasis (n = 17), serum prostate-specific antigen (PSA) levels were significantly correlated with the levels of U-Pyr and urine deoxypyridinoline (U-dPyr) excretion, serum cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP), and P1CP levels (p < 0.05). However, serum PSA levels were not correlated with U-Pyr, U-dPyr excretions, serum 1CTP and P1CP levels in patients without bone metastasis. Therefore, prostate cancer cells appear to have some paracrine effects on bone cells. In controls (n = 15), serum 1,25-dihydroxyvitamin D levels (1,25-(OH)2D) were inversely correlated with serum phosphorus levels (P < 0.01). In prostate cancer patients with bone metastasis, the ability to regulate the serum 1,25-(OH)2D levels in response to serum phosphorus levels is lost. These results suggest that endocrine factors produced by prostate cancer cells disturb the regulation of serum 1,25-(OH)2D in response to serum phosphorus levels.

Aged↗

A histopathological study on localization of hepatitis C virus RNA in liver of chronic hepatitis C.

By in situ hybridization (ISH) method using digoxygenin (DIG)-labeled RNA probe, we proved the localization and replication of hepatitis C virus (HCV) RNA not only in the hepatocytes but also in the lymphocytes of the 52 liver tissues of chronic hepatitis C. We classified the staining patterns into four groups. The pattern of signal distribution significantly correlated with serum alanine aminotransferase (ALT) level, quantity of serum HCV RNA just before liver biopsy, histological grade of inflammatory activity, and stage of fibrosis by Spearman rank correlation. Moreover, we investigated the relation between the signals in the hepatocytes or lymphocytes and the effectiveness of interferon (IFN) therapy. Therefore, we suggest that ISH is a useful tool to evaluate the activity of chronic hepatitis C associated with serological and histopathological changes and is an important marker to assess the effectiveness of IFN treatment.

Adult↗

Immunohistochemical investigation of pulmonary surfactant in perinatal fatalities.

In order to verify forensic pathological significance of immunohistochemical investigation of pulmonary surfactant, 11 forensic and 16 clinico-pathological cases of perinatal death were comparatively examined. Surfactant appeared in some infants of 31-32 weeks gestation and was usually positive thereafter, indicating maturity of fetal lungs, although it may not have fully developed until about the 36th week of gestation. It was negative in all cases of the hyaline membrane disease except for a full-term infant (secondary respiratory distress syndrome). In usual cases, surfactant coating the expanded alveolar epithelia with its diffuse deposit in the intra-alveolar spaces was considered to indicate duration of hypoxia under persistent respiration (agonal state). Such finding was most intensely observed in asphyxia and in severe respiratory failure from intrinsic causes in the infants over ca. 36 weeks of gestation. With reference to pulmonary micromorphology, the amount of intra-alveolar surfactant seemed to be most closely related to the alveolar septal (interstitial) edema.

Cause of Death↗

Inhibition of natural killer cell activity against cytomegalovirus-infected fibroblasts by nitric oxide-releasing agents.

The addition of nitric oxide (NO)-releasing agents, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC18), or 3-[(+/-)-(E)-ethyl-2'-[(E)-hydroxyimino]-5-nitro-3-hexenecarbam oyl]-pyridine (NOR 4), significantly inhibited natural killer (NK) cell activity against cytomegalovirus (CMV)-infected cells. Inhibition of NK cell activity was due to NO released in the culture medium because the concentration of nitrite in the culture medium correlated with the inhibition of NK cell activity and the addition of an antagonist of NO, [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide] (carboxy-PTIO), to NK assay restored NK cell activity. The mechanism of inhibition of NK cell activity against CMV-infected cells by NO-releasing agents includes (1) inhibition of the production of interferon (IFN)-alpha by CD16 (Leu11b)-depleted cells cultured with CMV-infected cells and (2) inhibition of the activation process of NK cell by IFN-alpha. It is suggested that the production of NO by an inflammatory process may lead to the inhibition of NK cell-mediated cytotoxicity against CMV-infected cells.

Benzoates↗

Dissociation of HSP72 and HSC73 heat shock mRNA inductions after spinal cord ischemia in rabbit.

The inductions of HSP72 and HSC73 mRNAs were investigated with Northern blot and immunohistochemical analyses for up to 7 days of the reperfusion after 5 or 15 min ischemia in rabbit spinal cord. Following 15 min ischemia, HSP72 mRNA was induced at 8 h of reperfusion, while HSC73 mRNA continuously remained at the control level. Immunoreactivity of HSP72 protein was slightly induced at 8 h of reperfusion selectively in motor neurons, and the majority of motor neuron showed selective cell death at 7 days of reperfusion. This study demonstrated selective induction of HSP72 mRNA and the protein in motor neuron cells that eventually showed selective delayed neuronal death after transient ischemia in the spinal cord. This phenomenon was not accompanied by HSC73 induction.

Animals↗