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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 199 records · Page 11Linked to original sources

Correlation between myocardial blood flow and tissue succinate during acute ischemia.

This study was performed to clarify the relationship between degree plus duration of myocardial ischemia and tissue succinate or lactate contents, and to assess whether their accumulation might be a metabolic marker of ischemic myocardium. Regional myocardial blood flow (MBF) was measured using the hydrogen gas clearance method in anesthetized open-chest dogs subjected to 10 min or 60 min of myocardial ischemia by coronary ligation. The contents of succinic acid and lactic acid in myocardium corresponding to locations of MBF measurement were quantitatively analyzed by gas chromatography-mass spectrometry. In severely ischemic areas with MBF less than 20 ml/min/100g, significant increases in both succinic and lactic acids were observed 10 min after coronary occlusion. Sixty min of ischemia induced significant increase in the myocardial succinic acid content not only in severely but also in moderately ischemic areas. In contrast, lactic acid was significantly increased only in the severely ischemic area 60 min after coronary occlusion. These results indicate a good correlation between degree plus duration of myocardial ischemia and tissue succinic acid content, suggesting that its accumulation in myocardium may be a reliable and sensitive metabolic marker of coronary ligation ischemia.

Acute Disease↗

[DNA ploidy and proliferating cell nuclear antigen positivity rate as predictive indication of effectiveness of preoperative radiation].

We compared histological effects following radiotherapy in relation to the DNA ploidy pattern and the proliferating cell nuclear antigen (PCNA) positivity rate in 37 patients with rectal cancer who underwent preoperative radiation therapy. Twelve of 23 cases in which the PCNA positivity rate before irradiation was more than 25% showed the effectiveness of radiotherapy (52.2%), against 2 of 6 cases with a rate of less than 25%. Cases in which the rate was more than 25% tended to show more effectiveness. Seventeen of 23 cases in which the PCNA positivity rate was more than 25% showed a decrease in PCNA positivity rate (73.9%). The rate in 6 cases showed no change, and no cases had an increase. In particular, in 12 cases in which the PCNA positivity rate was more than 55%, half showed effectiveness, and the PCNA rate decreased 20% on average. The PCNA positivity rate tended to decrease as a result of irradiation, and especially in diploid cases there were significant differences in the rate before and after irradiation. We suggest that cases in which the PCNA positivity rate is more than 55% with diploid DNA pattern would show most effect. The effects of irradiation could be predicted with biopsy materials and by measuring the DNA ploidy pattern and the PCNA positivity rate.

Adenocarcinoma↗

Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron.

OBJECTIVES: Iron metabolism may be altered in patients with chronic active hepatitis C. In an attempt to evaluate whether excess iron contributes to liver injury, we used phlebotomy for removal of iron from patients with chronic hepatitis C. METHODS: All 10 patients had histochemically detectable iron in the liver and underwent an initial period of weekly or monthly phlebotomy of 200 or 400 ml. A serum ferritin level of 10 ng/ml or less was chosen as the endpoint, and maintenance phlebotomy was performed if the level rebounded. RESULTS: The treatment reduced mean serum alanine aminotransferase activity from 152 +/- 49 to 55 +/- 32 IU/L; this level became normal in five of the 10 patients. Anti-HCV antibodies could be detected in all patients throughout the study. Histologic abnormalities of the liver were unchanged except for disappearance of iron deposits from seven of the patients studied. CONCLUSIONS: Our findings suggest that iron removal may be beneficial for patients with chronic active hepatitis C and histochemical iron in the liver.

Adult↗

Expression of the hepatocyte growth factor receptor in the regenerating rat liver.

The c-met oncogene product is a cell-surface receptor, which ligand is believed to be the hepatocyte growth factor. We studied the expression of c-met oncogene in the regenerating rat liver after either partial hepatectomy or CCl4-induced liver injury. Northern blot analysis showed that after partial hepatectomy the transcripts of c-met decreased at 8 h, reached the minimum at 36 h, and returned to the steady level on the seventh day. In contrast with the hepatectomized liver, the transcripts of c-met increased after CCl4 treatment. These observations suggest that c-met transcription may be regulated differently depending on regeneration signals.

Amino Acid Sequence↗

Inhibitory effects of a bacteria-derived sulfated polysaccharide against basic fibroblast growth factor-induced endothelial cell growth and chemotaxis.

The effects of sulfated polysaccharides on the growth and chemotaxis of endothelial cells promoted by basic fibroblast growth factor (bFGF), a heparin-binding growth factor, and epidermal growth factor (EGF), a non-heparin-binding growth factor, were examined. The binding abilities of these two growth factors to D-gluco-D-galactan sulfate (DS-4152) were the same as to heparin. DS-4152 inhibited the growth and chemotaxis of the cells stimulated by bFGF, and prevented the binding of bFGF to the cells at both its low and high affinity binding sites: the former and the latter are heparin-like molecules and receptor proteins for bFGF, respectively. However, DS-4152 affected neither the binding of EGF to endothelial cells nor the proliferation and chemotaxis of the cells stimulated by the factor. Heparin also inhibited the binding of bFGF to low affinity binding sites to the same degree as DS-4152, but had little effect on the binding of bFGF to high affinity sites and no effects on bFGF-induced endothelial cell growth. Chondroitin sulfate A prevented neither the binding of bFGF to both sites of the cells nor bFGF-induced cell proliferation. We thus concluded that the inhibitory effects of DS-4152 against the growth and chemotaxis of endothelial cells induced by bFGF might be due to the prevention of bFGF binding to its receptor proteins resulting from the binding of DS-4152 to bFGF.

Cell Division↗

Prevalence of hepatitis C virus infection among long-term hemodialysis patients: detection of hepatitis C virus RNA in plasma.

A high prevalence of anti-C100-3 antibodies has been reported in chronic hemodialysis patients. It is, however, unclear whether the results reflect true hepatitis C virus (HCV) infection in these patients, since false-positive results have been reported with this antibody assay. In the present study, plasma from 184 hemodialysis patients (110 males, 74 females) was examined for HCV-RNA by a reverse transcription-polymerase chain reaction method. Anti-C100-3 antibodies, second generation HCV antibodies, and anti-GOR antibodies were also examined by the respective EIAs. The positive rate of anti-C100-3 in the hemodialysis patients was 10.7% (20/184), which was significantly higher than the reported findings in the general population (P < 0.01). Using a second generation HCV antibody assay, the positive rate increased to 22%. HCV-RNA was detected in 15 of 184 patients (8.2%); 5 of 20 C100-3-positive patients (25%), and 10 of 164 C100-3-negative patients (6.1%). Serum alanine aminotransferase and gamma globulin levels were significantly higher in the patients with these HCV markers than those that were negative, while the history of blood transfusion was not related to the rate of the HCV markers. It is concluded that some hemodialysis patients have latent HCV infections that cannot be detected by currently available HCV antibody assays or routine biochemical liver function tests, and that the routes of transmission are not solely through blood transfusion.

Adolescent↗

Correlation of plasma hepatitis C virus RNA levels with serum alanine aminotransferase in non-A, non-B chronic liver disease.

The relationship between plasma hepatitis C virus (HCV) RNA levels, antibody positivity, and hepatocellular damage were studied in 41 patients with non-A, non-B chronic liver disease. The patients were placed into two groups according to the plasma levels of HCV-RNA: plasma HCV-RNA level was estimated as high when detected by a one stage polymerase chain reaction (PCR) and as low when detectable only after a two stage PCR. Anti-HCV (first and second generation assays) and anti-GOR were also measured. The mean alanine aminotransferase (ALT) level of the high HCV-RNA group was 115 +/- 62 IU/l, whereas that of the low HCV-RNA group was 59 +/- 37 IU/l (P < 0.05). Patients with ALT levels above 100 IU/l had invariably a high level of HCV-RNA. There were no differences in clinical features in relation to the presence of anti-GOR or anti-HCV. Circulating HCV-RNA levels but not anti-HCV or anti-GOR antibodies correlated with hepatocellular damage.

Aged↗

The egg nucleus regulates the behavior of sperm nuclei as well as cycling of MPF in physiologically polyspermic newt eggs.

The possible role of the egg nucleus in regulating the behavior of sperm nuclei and the cycling of maturation-promoting factor (MPF) was investigated in the physiologically polyspermic eggs of the newt Cynops pyrrhogaster. Many sperm entered all areas of the egg, but only one sperm pronucleus, the principal sperm pronucleus, moved to the center of the animal hemisphere to form a zygote nucleus with the egg pronucleus. All sperm and egg pronuclei synthesized DNA, but the zygote nucleus completed the synthesis of DNA 0.5-1 hr earlier than the accessory sperm nuclei. Entrance into M phase by the accessory sperm nuclei was delayed to a greater and greater extent with increasing distance of these nuclei from the zygote nucleus. When DNA in the egg nucleus was damaged by uv irradiation, not only were both prophase and M phase in the zygote nucleus prolonged, but also the MPF cycle was delayed. Some accessory sperm nuclei in the animal hemisphere escaped degeneration to form additional bipolar spindles, so that delayed multipolar cleavage occurred. The MPF activity in the vegetal hemisphere was less than 25% of that found in the animal hemisphere at M phase in normally fertilized eggs. The levels of immunologically detectable proteins that contained the sequence PSTAIR in vegetal hemispheres were less than 25% of those in animal hemispheres. These results indicate that the egg nucleus of the Cynops egg is involved in the control of the activation of MPF and that the accessory sperm nuclei in the vegetal hemisphere degenerate as a result of the lack of components that are indispensable for entry into M phase.

Animals↗

Effects of diabetes on cardiac glycogen metabolism in rats.

The effects of diabetes on myocardial glycogen metabolism in rats were examined and compared with those of fasting. Male Wistar rats were divided into three groups: controls, streptozotocin-induced diabetics, and one-week fasted. Isolated rat hearts were subjected to substrate-free 30-min Langendorff perfusion followed by 60-min working heart perfusion with glucose alone or in combination with insulin or insulin plus beta-hydroxybutyrate (BHB). Myocardial glycogen contents were determined before or 30 min after Langendorff perfusion, or 60 min after working heart perfusion. Before Langendorff perfusion, tissue glycogen concentrations in control, diabetic, and fasted hearts were 3.3 +/- 0.2, 10.0 +/- 0.9, and 5.7 +/- 0.5 (mg/g wet weight), respectively. In diabetic rats, the myocardial glycogen concentration was markedly decreased after working heart perfusion of any of the substrate combinations, even those with insulin and BHB. In contrast, myocardial glycogen in control or fasted rats was not reduced after the addition of glucose with insulin, and/or glucose with insulin and BHB. These results suggest that degradation of tissue glycogen occurs in isolated perfused hearts from diabetic rats, while a clearly different response is shown by fasted hearts.

3-Hydroxybutyric Acid↗

Intrahypothalamic, but not hippocampal, administration of muscimol suppresses hyperglycemia induced by hippocampal neostigmine in anesthetized rats.

We investigated the effects of intrahypothalamic or hippocampal injection of GABA receptor agonists on hyperglycemia induced by hippocampal neostigmine. Prior to the injection of neostigmine (50 nmol) into the hippocampus (HPC), muscimol (0.01-1 nmol) or baclofen (1 nmol) was injected into the bilateral ventromedial hypothalamus (VMH). Muscimol suppressed the hyperglycemia in a dose-dependent manner, but baclofen affected it only minimally. In contrast, neither hippocampal muscimol (1 or 2.5 nmol) nor baclofen (1 nmol) suppressed the hippocampal neostigmine-dependent hyperglycemia. Intrahypothalamic muscimol (1 nmol) also decreased the changes in hepatic venous plasma glucagon and epinephrine significantly. These results indicate that intrahypothalamic muscimol suppresses hyperglycemia caused by cholinergic neurons originating from the HPC, indicating existence of the location specificity.

Analysis of Variance↗

Histamine-induced, central nervous system-mediated hyperglycemia is suppressed by atropine in the brain.

We investigated the relationship between histamine and muscarinic cholinergic neurons in central nervous system (CNS)-mediated glucose regulation in anesthetized fed rats. The injection of pyrilamine (5 x 10(-7) mol) into the third cerebral ventricle suppressed the hyperglycemia induced by intraventricular injection of histamine (5 x 10(-7) mol). Ranitidine (5 x 10(-7) mol), however, did not suppress this hyperglycemia. The injection of atropine (5 x 10(-9)-5 x 10(-7) mol) into the third cerebral ventricle suppressed the histamine-induced hyperglycemia in a dose-dependent manner. These findings suggest that histamine induction of CNS-mediated hyperglycemia involves neuronal transmission not only via H1 receptors but also, at least in part, by muscarinic cholinergic neurons.

Animals↗

Activation of GABAA receptor in the brain suppresses neostigmine or histamine-induced central nervous system-mediated hyperglycemia.

We investigated the effect of GABA receptor agonists on the central nervous system (CNS)-mediated hyperglycemia induced by neostigmine or histamine in anesthetized fed rats. The injection of muscimol, GABAA receptor agonist (1, 2.5 nmol) into the third cerebral ventricle suppressed the hyperglycemia induced by intraventricular injection of neostigmine (1 x 10(-8) mol) or histamine (5 x 10(-7) mol). Baclofen, GABAB receptor agonist (1, 2.5 nmol), however, did not suppress these hyperglycemia. Neither muscimol nor baclofen (2.5 nmol) affected plasma glucose levels. These findings suggest that activation of GABAA receptor in the CNS suppresses the hyperglycemia induced by the stimulation of cholinoceptive neuron or histaminergic neuron, but activation of GABAB receptor does not affect them.

Animals↗

Activation of GABAA receptors in hypothalamus modulates PGF2 alpha- or PGE2-induced catecholamine secretion in rats.

We previously reported that injection of PGF2 alpha into the third cerebral ventricle produces hyperglycemia and hyperthermia associated with catecholamine secretion in anesthetized rats. We have also studied the potency of catecholamine secretion induced by injecting PGE2 or PGF2 alpha into the third cerebral ventricle and the effect of the GABA-selective agonist, muscimol, on the catecholamine secretion induced by PGE2 or PGF2 alpha. Administration of 50 micrograms of PGE2 into the third cerebral ventricle increased norepinephrine secretion to a greater extent than the same dose of PGF2 alpha, whereas the latter increased epinephrine secretion to a greater degree. These effects paralleled the potencies of the hyperglycemic and hyperthermic effects of PGF2 alpha and PGE2, respectively. Simultaneous injection of 2.5 nmol of muscimol into the third cerebral ventricle with 50 micrograms of PGF2 alpha or PGE2 completely suppressed epinephrine and norepinephrine secretion induced by PGF2 alpha or PGE2. These findings suggest that central PGF2 alpha and PGE2 stimulate epinephrine and norepinephrine secretion with different potencies, and that brain GABAA receptors suppress catecholamine secretion induced by PGF2 alpha or PGE2.

Animals↗

The inhibitory action of buformin, a biguanide on gluconeogenesis from alanine and its transport system in rat livers.

The effect of buformin, a biguanide, on gluconeogenesis from 10 mM alanine in the presence of 143 nM glucagon were studied using isolated rat liver perfusions. In addition, to investigate possible mechanisms of biguanide action, alanine utilization in isolated rat liver perfusion and [3H]alanine uptake in isolated hepatocytes were observed. Buformin (1.85 mM) strongly inhibited gluconeogenesis from alanine in the presence of glucagon in both normal and streptozocin-induced diabetic rat livers. This inhibition was followed by a decrease in alanine utilization. Both of these inhibitory effects of buformin were dose-dependent. [3H]Alanine uptake was significantly inhibited by buformin. The effect of this agent was similar to but weaker than that of ouabain. However, tolbutamide failed to reduce either alanine utilization or [3H]alanine uptake, although this drug significantly inhibited gluconeogenesis from alanine. These data suggest that biguanides may reduce hepatic alanine utilization via the inhibition of Na+/L-alanine transport activity as one possible mechanism, resulting the inhibition of gluconeogenesis from alanine in the presence of glucagon.

3-Hydroxybutyric Acid↗

An adequate sampling of the prostate to identify prostatic involvement by urothelial carcinoma in bladder cancer patients.

The distribution of any involved prostatic urethra, ducts and acini by urothelial carcinoma was studied to determine an adequate sampling method for detecting prostatic involvement using the maps of 38 cystoprostatectomy specimens. A total of 31 patients had prostatic duct and acini involvement, while 7 had prostatic urethral involvement alone. However, the distribution of the involved prostatic urethra, ducts and acini varied. In 29 of the 31 patients (93.5%) with prostatic duct and acini involvement, urethral carcinoma in situ and/or superficial gland involvement (an involvement of the afferent ducts within a few millimeters of the urethral mucosa) at the 5 and/or 7 o'clock position of the verumontanum portion was identified. In 7 patients with prostatic urethral involvement alone 2 had carcinoma foci at the 5 and/or 7 o'clock position of the verumontanum portion. Furthermore, the frequency of deeper gland involvement (an involvement of true prostatic acini except for superficial glands) was higher in patients with superficial gland involvement at the 5 and/or 7 o'clock position of the verumontanum portion (57.7%) than in patients without such involvement (20.0%). Therefore, this study emphasizes that a transurethral resection biopsy containing prostatic tissue at the 5 and/or 7 o'clock position of the verumontanum portion substantially improves the detection of prostatic duct and acini involvement in bladder cancer patients. Moreover, if the prostatic superficial glands are involved at the 5 and/or 7 o'clock position of the verumontanum portion, the potential involvement of the deeper glands should also be suspected.

Carcinoma in Situ↗

Detection of hepatitis C viral RNA in sporadic acute non-A, non-B hepatitis by polymerase chain reaction. Its usefulness for the early diagnosis of seronegative infection.

To determine the prevalence of hepatitis C viral infection in patients with sporadic non-A, non-B (NANB) acute hepatitis, hepatitis C viral RNA was studied in the plasma of 15 patients by reverse transcription-polymerase chain reaction assay. Plasma samples were sequentially obtained from 15 patients, and polymerase chain reaction was performed with two nested pairs of primers deduced from the 5'-non-coding region of hepatitis C viral sequences. Anti-C100 and anti-GOR antibodies were also measured with an enzyme-linked immunosorbent assay system. Plasma hepatitis C viral RNA was detected transiently in 7 of 15 patients (47%) at an early phase of the clinical course, while anti-C100 antibodies were detectable in only 2 (29%) of hepatitis C viral RNA-positive patients, and in 1 (13%) of the negative patients. Of 7 patients that were positive for plasma hepatitis C viral RNA, 4 (57%) had relapsing or protracted courses. In contrast, in all patients with undetectable hepatitis C viral RNA, hepatitis C viral RNA recovered and remained normal for at least 1 year. Thus, hepatitis C viral infection represents almost half the patients with acute sporadic NANB hepatitis, and detection of hepatitis C viral RNA in an early clinical phase is superior to anti-C100 measurement for diagnosing acute sporadic hepatitis C viral infection.

Adult↗