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Biomedical subjects

S Mochizuki

Publications and source records attributed to S Mochizuki.

At least 91 records · Page 5Linked to original sources

Augmentation with serum thymic factor of suppressive effects on retroviral tumor development in hosts immune to v-onc product.

Inbred adult female rats were immunized against syngeneic ST-FeSV induced sarcoma cells. ST-FeSV was injected subcutaneously into 57 neonates (vaccinated) born from these immunized females and into 60 non-vaccinated syngeneic neonates. Serum thymic factor (FTS) was injected subcutaneously into 10 of vaccinated and 30 of non-vaccinated rats. Sarcomas developed in 40.4% (19/47) of vaccinated (A), 20.0% (2/10) of vaccinated FTS injected (B), 63.3% (19/30) of non-vaccinated FTS injected (C), and 76.7% (23/30) of non-treated (D) rats. By AB immunostaining using antibody to v-fes product (P85), sarcomas developed in 10 of 13 rats of group C tested, and 3 of 6 rats of group D tested were positive, but those in 7 rats of group A and 2 rats of group B tested were all negative. Lung metastasis was observed in rats of all groups except those of B group. All sera of animals that developed sarcomas were positive to P85 in Western blot analysis. These results showed that FTS augmented suppressive effects on sarcoma development in hosts immune to the viral oncogene product.

Animals↗

What time is the "biologic zero hour" of circadian variability?

Most ambulatory blood pressure monitoring (ABPM) studies have used a mechanical clock as the reference time, but there is no biologic background for assuming that midnight by the mechanical clock is zero hour by the biologic clock. The aim of this study was to determine the biologic zero hour as the zero reference time by evaluating the circadian rhythm of blood pressure, heart rate, and activity. Twenty healthy medical students (18 men, 2 women, mean age 26 years old) were recruited and blood pressure, heart rate, and physical activity were monitored simultaneously by an ABPM device every 30 min for 48 h. Four concepts of zero time were selected in this study and analyzed regarding biologic zero hour: 24:00 by the mechanical clock (clock time); the time of awakening, based on a diary (diary time); the time of a sudden increment in physical activity in the morning (activity time); and the middle of the total sleeping time, based on the diary (midsleeping time). The awakening time is a better individual index than the mechanical clock, and the midsleeping time as the zero reference point is better than the awakening time. We assessed the reproducibility of the data regarding the circadian troughs between the first and second day. The reproducibility of the day-to-day variation of the blood pressure and heart rate was poor. The reproducibility of physical activity was fairly good, but the magnitude of activity was small. A 48-h monitoring profile is superior to a 24-h monitoring period.

Adult↗

[Effects of oral amezinium metilsulfate in patients with sick sinus syndrome].

The effects of amezinium metilsulfate (Risumic) were studied in patients with sick sinus syndrome. Four males and 11 females with clinical symptoms were treated with 0.5 mg/kg for 1 to 40 weeks. In all patients, the length of sinus pause observed during 24-hour Holter monitoring was longer than 2.0 sec, and/or the sinus node recovery time in the electrophysiologic study was longer than 2.0 sec. The effects were evaluated by Holter monitoring and standard electrocardiography. The total number of heart beats every 24 hours by Holter monitoring were significantly increased from 78,917 +/- 15,983 (mean +/- SD) to 85,753 +/- 17,849 beats after the treatment. The length of the sinus pause was significantly decreased from 3.89 +/- 1.24 to 2.36 +/- 1.45 sec. Patients with sinus node recovery time of less than 5.0 sec showed the effects especially clearly. The total number of premature ventricular contractions was decreased from 530 +/- 767 to 123 +/- 182 beats. The PQ, QRS and QTc intervals did not change. Only diastolic pressure was slightly increased. Clinical symptoms disappeared in almost all patients and the clinical courses were favorable. Amezinium metilsulfate, which stimulates the intrinsic sympathetic nervous system, increased total heart beat and shortened sinus pause in patients with sick sinus syndrome. Few side effects, such as arrhythmogenecity or increase of blood pressure were observed. These results show that amezinium metilsulfate is useful in the treatment of patients with sick sinus syndrome, if the disease is not so severe as to require implantation of a cardiac pacemaker.

Administration, Oral↗

A study of 46 cumulative breast cancer autopsy cases.

Forty-six cases of breast cancer, autopsied at the Tokai University Hospital, between 1975 and 1993, were studied. Forty of the patients had undergone surgery, and 27 of them had been surgically treated in the Tokai University Hospital. The major causes of death were respiratory failure, cancer-related complications, and hepatic failure. Frequently involved organs were lymph node, lung, liver, and bone. The survival time after surgery ranged from 1 day to 137 months, with the patients being divided into two groups based on survival of more or less than three years after surgery. Frequently observed in individuals surviving less than 3 years were larger tumor sizes, extensive lymph node metastases, advanced stages, and negative reactions for estrogen and progesterone receptors, as compared to individuals surviving for more than 3 years. The patterns of tumor metastasis were also different in two groups. Local recurrences were more frequently observed in short-term survivors whereas disseminated spreading was encountered in the long-term survivors. These findings seem to indicate that not only survival time but also pattern of recurrence are related to the status of the original tumor.

Autopsy↗

Therapeutic effect of egualen sodium (KT1-32), a new antiulcer agent, on chronic gastritis induced by sodium taurocholate in rats.

We investigated the therapeutic effects of egualen sodium (KT1-32), a new antiulcer agent, on chronic erosive and atrophic gastritis induced by 5 months' administration of sodium taurocholate (TCA; 5 mM) in rats. The chronic gastritis was manifested by mucosal surface injuries (erosions), reduced mucosal thickness, reduction of the number of parietal cells, infiltration of inflammatory cells, and proliferation of collagenous fiber. Egualen sodium, (10-100 mg/kg, t.i.d.) administered orally to the rats for 2 weeks after the withdrawal of TCA, dose-dependently and significantly decreased the total length of erosions. The indicators of atrophic gastritis, i.e., reduced mucosal thickness and reduction in the number of parietal cells, were improved dose-dependently by the administration of this agent. Egualen sodium also reduced the inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa in a dose-dependent manner. The reduced staining of neutral gastric mucus was improved by a high dose (100 mg/kg) of egualen sodium. The therapeutic effects of egualen sodium on experimental gastritis were superior to those of sofalcone and sodium guaiazulene 3-sulfonate. These results suggest that egualen sodium may be a promising agent for the treatment of erosive and atrophic gastritis.

Administration, Oral↗

Effect of repeated administration of KT3-671, a nonpeptide AT1 receptor antagonist, on diurnal variation in blood pressure, heart rate, and locomotor activity in stroke-prone spontaneously hypertensive rats as determined by radiotelemetry.

KT3-671, a nonpeptide AT1 receptor antagonist, was administered to 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) daily for 3 weeks. Its effects on systolic, mean, and diastolic arterial blood pressure (SAP, MAP, DAP), heart rate and locomotor activity were investigated with radiotelemetry. A clear diurnal variation in blood pressure, heart rate, and locomotor activity was observed in synchrony with the light cycle. KT3-671 at a daily dose of 10 mg/kg orally (p.o), produced a significant and consistent reduction in blood pressure, preventing the development of hypertension. KT3-671 reduced SAP more than DAP, suggesting that it may affect both vascular tone and cardiac output. Although KT3-671 did not affect diurnal rhythms in heart rate and locomotor activity, it did cause a slight but significant reduction in heart rate. The MAP determined 23 h after the administration of KT3-671 showed a significant reduction from the day 2 of therapy to the day 3 after discontinuation of therapy, suggesting a long duration of antihypertensive action. There was no rebound increase in blood pressure after discontinuation of KT3-671 therapy. These results suggest that KT3-671 may be potentially useful in the therapy of hypertension.

Angiotensin Receptor Antagonists↗

Inhibitory effect of CV4151, a thromboxane A2 synthetase inhibitor, on ventricular arrhythmias induced by coronary artery occlusion in rats.

The purpose of this study was to determine whether thromboxane A2 (TXA2) is involved in the development of ventricular arrhythmias produced by coronary artery occlusion. Ventricular arrhythmias were induced by coronary artery occlusion in 66 male Sprague-Dawley rats. Rats were separated into 4 groups, and saline (n = 19) or CV4151 (a TXA2 synthetase inhibitor)(10 mg/kg, n = 14; 30 mg/kg, n = 15; or 100 mg/kg, n = 18) was injected intravenously 5 min before coronary artery occlusion. The antiarrhythmic effect of CV4151 was assessed in terms of the number of ventricular premature complexes (VPCs), the combined duration of ventricular tachycardia (VT) and ventricular fibrillation (Vf), the incidence of Vf, and the mortality rate within 30 min after occlusion. The total number of VPCs was as follows; control: 1789 +/- 330 beats: 10 mg/kg group: 1289 +/- 302 beats: 30 mg/kg group: 1008 +/- 229 beats: 100 mg/kg group: 986 +/- 275 beats, with no significant differences between groups. The incidence of Vf was significantly reduced in the 30 mg/kg and 100 mg/kg groups, as was the combined duration of VT and Vf and the mortality rate. Our results indicate that the TXA2 synthetase inhibitor CV4151 reduces the incidence of lethal arrhythmias induced by coronary artery occlusion in rats.

Animals↗

Influence of cisapride on the pharmacokinetics and antihypertensive effect of sustained-release nifedipine.

To investigate the clinical significance of interactions between cisapride and sustained-release nifedipine, we compared the plasma nifedipine concentration and blood pressure after administration of nifedipine alone (20 mg) with those obtained after administration of nifedipine cisapride (2.5 mg) in 20 patients with hypertension. The plasma nifedipine level was not altered by cisapride at one hour after administration, but was significantly increased at two (p < 0.01), three (p < 0.01), and four (p < 0.05) hours when compared with the level measured after nifedipine alone. Cisapride significantly decreased the mean blood pressure at three hours (p < 0.05) after administration of nifedipine. The acetaminophen method was used to determine gastric emptying time. The plasma concentration of acetaminophen at 45 minutes after administration was significantly increased by cisapride, suggesting that enhanced gastrointestinal motility might be the basis for the increase in the plasma nifedipine concentration. These results suggest that enhancement of the antihypertensive effect of nifedipine can occur when the drug is prescribed with cisapride, and that caution is needed when using such a combination therapy.

Aged↗

[A case of ectopic familial pheochromocytoma].

This is a report of the occurrence of familial ectopic pheochromocytoma in two brothers, whose father had bilateral adrenal pheochromocytoma. Both brother complained of hypertension. In the first case, a 22-year-old man presented with much higher than normal norepinephrine. Abdominal CT and chest CT scanning and 123I-MIBG scintigraphy revealed an extraadrenal tumor in the chest on the bilateral adrenal grands. Bilateral adrenectomy was performed. In the second case, the 20-year-old brother was found to have an abdominal mass that was diagnosed as ectopic pheochromocytoma originating in the intra-abdominal paraaorta according to abdominal CT scanning and 131I-MIBG scintigraphy. The tumor was resected.

Abdominal Neoplasms↗

Genetic instability as a basis for transformation of human lymphocytes infected with human retrovirus.

T cell lines (Coculture-14, Coculture-5) derived from human T-cell leukemia virus type I (HTLV-I)-seronegative persons acquired interleukin-2 (IL-2)-dependent continuous growth capacity (immortalized) following in vitro HTLV-I infection. They showed structural abnormalities of chromosomes carrying proviral DNA as seen by in situ hybridization. Following ultraviolet (UV) irradiation, Coculture-5 cells achieved IL-2-independent autonomous growth (transformed) resulting in the establishment of UV-1 and UV-5 lines. They showed additional abnormalities of the same chromosomes. Cocultivation of Coculture-5 cells with IUdR-treated UV-1 cells also resulted in autonomous growth of Coculture-5 cells, giving rise to three cell lines. By ABC immunostaining with specific antibodies, expression of proteins coded for growth regulatory genes, including Ki-67, Topo II, Pol alpha, c-MYC, p53, Rb, bcl-3, bcl-2, and BM-1, was found to be variably altered in transformed cells compared with immortalized cells. These results demonstrated chromosomal instability, altered gene product expression of HTLV-I-infected human lymphocytes, and their susceptibility to transformation without exposure to an initiating carcinogen.

Cell Line, Transformed↗

Reduplication of swine spleen lobes.

In a search for the reduplication of the spleen, a total of 227,513 swine from 130 breeders were surveyed at a slaughterhouse (Ozu Health Center, Ehime Prefecture, Japan) between October 1993 and June 1995. They were 6 to 7 months old and their body weight ranged from 95 to 120 kg. Twenty swine had two lobed spleens. Of these, nine were males and 11 were females. The second or sub-lobe was generally smaller than the main lobe but was variable in size. Large ones were similar in size to the main lobe and small ones were approximately 1/4 of the length of the main lobe. One very small lobe was just a protrusion of the main one across the greater omentum. The two lobes were always attached to each other in the central portion, and fat and the greater omentum were always found between the lobes. The splenic artery, vein and nerve were shared between the two lobes. The main lobe was covered with peritoneum from the parietal surface of the stomach while the sub-lobe was covered with visceral peritoneum. Both peritonea joined to the greater omentum at the hilus in ordinary spleens, but at short distance from the hilus in double lobed spleens.

Animals↗

[Therapeutic ratio of fractionated high-dose-rate against continuous low-dose-rate brachytherapy analyzed by simulation model].

In order to establish the standard schedule of 192Ir-HDR brachytherapy, it is necessary to determine the optimal time-dose-fractionation. A new simulation model was used to determine the optimal schedule. This model, which is based on the LQ-model, includes the effect of incomplete repair between fractionations. The fraction surviving after irradiation is expressed as log (surviving fraction) = n (-alpha x -beta x2)-n beta x2 hn (theta), and the change in fractionation will influence the value of hn (theta). From analysis of this model, the therapeutic ratio will approach one if two fractionations (6-hour and 18-hour intervals) or three fractionations (4-hour, 4-hour and 16-hour intervals) in a day are carried out for 6 days. This simulation model will provide an optimal treatment schedule for tumor control, for example, two daily fractionations of 4.6Gy with 6-hour intervals between the daily fractionations (and 18 hours to the first fractionations of the next day), 12 fractionations to 55.2Gy in 6 days or three daily fractionations of 3.3Gy with a 4-hour interval between the daily fractionations (and 16 hours to the first fractionations of the next day), 18 fractionations to 59.4Gy in 6 days. Further clinical study should be carried out to confirm this simulation.

Brachytherapy↗

Double gallbladder of swine.

In research on the reduplication of the pig gallbladder, a total of 297,531 swine from 130 breeders were surveyed at a slaughter house (Ozu Health Center, Ehime Prefecture, Japan) between October 1993 and December 1995. The swine were 6-7 months old and their body weights ranged from 95 to 120 kg. Twenty-nine swine were found to have reduplication of the gallbladder. Of these 19 were females, nine were males and the sex of one was not identified. The second sac was smaller than main one. Eleven cases were diverticulum of a cystic duct (Type I). Diverticulum of the neck of the main gallbladder of six cases also gave rise to the second gallbladder (Type II). A sac attached to the neck of the main gallbladder via a small cystic duct in seven cases was another type of reduplication (Type III). Connection of the second sac to the middle of the hepatic duct via a small cystic duct was seen in three cases (Type IV). The positions of these small sacs to the main gallbladder were right (13 cases), left (II cases) and ventral (three cases). The fundus of one gallbladder were divided and resulted in double sacs (Type V). One second sac was set apart from the main gallbladder and attached to a hepatic duct of lateral left lobe of the liver (Type VI). One specimen of the Type III gallbladder had two additional small sacs as diverticulum of the cystic duct. Compared to occurrences in humans and the Japanese monkey, the ratio of gallbladder reduplication to normal system anatomy in swine was extremely low. It was similar to the ratio of spleen reduplication in swine (1/10,000).

Animals↗

Regional myocardial sympathetic dysinnervation in patients with coronary vasospasm.

The purpose of this study was to assess the presence and location of impaired myocardial sympathetic innervation by using 123I metaiodobenzylguanidine (123I MIBG) in 15 patients with coronary vasospasm induced by intracoronary acetylcholine. The results were compared with those using thallium-201 (Tl-201). We also examined 14 patients with severe coronary stenosis (> 90%) and 8 control subjects without significant coronary stenosis (< 50%) and provokable coronary vasospasm. Regional myocardial sympathetic dysinnervation was detected by 123I MIBG single-photon emission computed tomography (SPECT) in all patients with coronary vasospasm, despite normal uptake during Tl-201 SPECT. This regional uptake-mismatch between 123I MIBG and Tl-201 Spect occurred specifically in the vasospasm group (p < 0.001 vs stenosis and control groups). Moreover, regional myocardial sympathetic dysinnervation was located in the distribution of perfusion in 25 of the 27 vasospasm-induced vessels. Normal uptake of 123I MIBG was observed in the perfused areas in 16 of the 18 non-vasospasm-induced vessels. The sensitivity ans specificity of 123I MIBG for detection of coronary vasospasm were 92% and 88% respectively. In patients with coronary vasospasm, we found regional myocardial sympathetic dysinnervation to be present. Furthermore, we were able to distinguish these patients from patients with critical coronary stenosis by 123I MIBG and Tl-201 SPECT.

3-Iodobenzylguanidine↗

Effects of bidisomide (SC-40230), a new class I antiarrhythmic agent, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats; comparison with mexiletine and disopyramide.

We investigated the antiarrhythmic effects of bidisomide (SC-40230), a new class I antiarrhythmic drug, in early-phase ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats. The effects of bidisomide were compared with those of mexiletine (MXT) and disopyramide (DSP), established class I antiarrhythmic drugs. Drugs were administered intravenously, 5 min before induction of coronary occlusion. Bidisomide (5 mg/kg) reduced the number of premature ventricular complexes and the incidence of ventricular tachycardia and ventricular fibrillation similarly to MXT and DSP in rats with ventricular arrhythmias induced by coronary artery occlusion. In rats with ventricular arrhythmias induced by coronary artery reperfusion following a 5-min coronary occlusion, the antiarrhythmic effects of 5 mg/kg of bidisomide were similar to those of the same doses of MXT and DSP. All three drugs significantly slowed the heart rate. Our results suggest that bidisomide may effectively reduce the severity of life-threatening ventricular arrhythmias that occur during acute coronary syndrome.

Animals↗