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Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 469 records · Page 26Linked to original sources

[Metabolic clearance rate of oxytocin in human subjects].

Oxytocin metabolism seems to occur mainly in the kidney and the liver. Placental cystine amino peptidase (CAP), which inactivates oxytocin by cleavage of the bond between the N-terminal cystine residue and adjacent tyrosine, rises progressively with advancing gestation. The role of CAP in oxytocin metabolism is not clear. To clarify this issue, the authors measure oxytocin metabolic clearance rate(MCR) by the constant infusion of 3mU/min and 6 mU/min synthetic oxytocin in 14 adult subjects: 5 pregnant women (38 approximately 41 weeks gestation), 4 puerperal women and 5 nonpregnant women. Oxytocin MCR (mean +/- SE) during infusion of 3 mU/min was 20.9 +/- 2.6 ml/kg/min in pregnant women; 16.9 +/ 2.4 ml/kg/min in puerperal women; 19.7 +/- 3.3 ml/kg/min in pregnant women. Oxytocin MCR during infusion of 6 mU/min was 22.1 +/- 3.3 ml/kg/min in pregnant women and 22.7 +/- 3.1 ml/kg/min in nonpregnant women. These values were statistically similar. Mean (+/- SE) CAP values were 143.5 +/- 7.8 mU/ml in pregnant women, 60.8 +/- 3.0 mU/ml in puerperal women, and 13.8 +/- 2.7 mU/ml in nonpregnant women. CAP levels in pregnant women were significantly higher than others. 3H-oxytocin degradation was studied in vitro in pooled plasma of pregnant and nonpregnant women. 85% of original 3H-oxytocin was destroyed in pregnant plasma during 1 hour but only below 10% was destroyed in nonpregnant plasma in 2 hours. These results suggest that CAP in pregnant women may not play a role in the inactivation of oxytocin in vivo, thus differing from its role in vitro.

Adult↗

Characterization of mitomycin C-induced gastrointestinal damage. I. In situ recirculation experiment.

The effects of mitomycin C (MMC), an anti-tumor agent, on the intestinal absorption of various drugs in rats were investigated. Based on microscopic observations, preadministration of a single intravenous dose of MMC (3 mg/kg) caused serious degeneration of epithelial cells, villous atrophy, and mitotic arrest in crypts at 48 hr after pretreatment. At this time point, absorption of sulfanilamide, salicylic acid, cephalexin, and L-tryptophan was shown to be significantly decreased by means of an in situ recirculation technique. The histological changes and the decrease in absorption of sulfanilamide, a model for passively absorbed drugs, were shown to depend on the timing of MMC pretreatment. Maximal effects were observed 48 hr after dosing. The MMC-induced reduction in the absorption of drugs was not a result of differences between treated and control animals with respect to pH of the drug solution, binding of drugs with intraluminal macromolecules, or intestinal mucosal blood flow. The absorption of sulfanilamide from the small intestine in the in situ system correlated well with the wet weight of the small intestine regardless of pretreatment dose or route. This suggests that the change in absorptive surface area of the intestinal mucosa may play a major role in the MMC-induced decrease in absorption capacity of the intestine.

Animals↗

Characterization of mitomycin C-induced gastrointestinal damage. II. In vitro everted sac experiment.

The everted gut sac technique was employed to clarify the effects of preadministration of mitomycin C (MMC) on intestinal transport of various drugs. Loss of intestinal tissue weight and increase in mucosal-to-serosal fluxes of passively absorbed drugs were noted in the case of MMC pretreatment, although the extent of the latter effect varied according to the inherent absorbability of each drug. The maximal effect of MMC on intestinal tissue weight and transport of sulfanilamide, a model of a passively absorbed drug, was observed 48 hr after pretreatment. The increase in the transfer of sulfanilamide correlated well with the MMC-induced decrease in intestinal tissue weight. These phenomena may result from the shortened transfer distance from mucosal to serosal fluid and impaired barrier function of the intestinal mucosa. On the other hand, transport of actively absorbed 3-O-methyl-D-glucose was not influenced by MMC pretreatment, which could be explained by an increment in the passive permeation counterbalancing the decrement in the active permeation. The present study also suggested that the measurement of transport of drugs through everted gut sacs might be useful as a simple and qualitative index of gastrointestinal mucosal damage.

3-O-Methylglucose↗

Danazol stimulates the release of follicle-stimulating hormone and inhibits the release of prolactin in vitro studies on rat pituitary cell cultures.

The actions of danazol on the release of gonadotropins and prolactin (PRL) were investigated by using a culture of rat anterior pituitary gland cells. The addition of danazol in the range between 10(-9) M and 10(-5) M elevated the levels of follicle-stimulating hormone (FSH) in a dose-dependent manner. Danazol at 10(-5) M caused a 70% increase in FSH levels over the control. The intracellular contents of FSH was also increased by danazol, suggesting its stimulatory effect on both the synthesis and release of FSH. Danazol had no effect on the release of luteinizing hormone (LH). Danazol diminished the sensitivity of gonadotrophs to luteinizing hormone-releasing hormone (LHRH) in that the LHRH-induced release of both FSH and LH was suppressed. The amount of PRL released into medium was decreased by danazol in a dose-dependent way.

Animals↗

Separation of bone matrix proteins by calcium-induced precipitation.

It was found that significant precipitation occurred immediately after calcium, at a concentration as low as 2 mM, was added to a desalted solution of EDTA extract of adult bovine femur. The maximal yield of the precipitates was observed at a calcium concentration of 30 mM. These precipitates were dissolved in 0.5 M EDTA, desalted, and characterized by Sepharose CL-6B gel filtration chromatography and high performance gel-exclusion chromatography. Results revealed that the precipitates were enriched in a 40 K protein and a higher molecular weight fraction as compared with the original extract of bone proteins. The 40 K fraction was isolated and identified as osteonectin, as judged from amino acid analysis, electrophoresis, and immunodetection. The supernatant after calcium-induced precipitation predominantly contained osteocalcin and a 50 K protein that was tentatively identified as alpha 2HS protein. Osteonectin was purified from the calcium-induced precipitates from the EDTA extract of bovine bone. By calcium titration using fluorescence spectrometry, the isolated osteonectin showed high affinity to calcium ions with an apparent dissociation constant (K0.5) of 8 x 10(-7) M. Thus, the use of calcium to separate bone proteins, especially osteonectin, was proved to be a useful technique. In addition, calcium-induced precipitation of osteonectin suggested a possible in vivo mechanism via which osteonectin might interact with calcium ions and participate in the initial immobilization of calcium to induce the nucleation of calcification in bone tissue.

Animals↗

Comparison of phospholipid N-methylation activity in rat submandibular salivary gland and liver.

Successive phospholipid N-methylation from phosphatidylcholine to phosphatidylethanolamine in submandibular gland and liver microsomes proceeded without the addition of exogenous phospholipid substrate. Methylation activity in the submandibular microsomes showed different susceptibilities to various detergents than the liver enzyme and also partially required Mg2+. However, the three methylation steps could not be distinguished by their Mg2+ requirements. Ca2+ had no effect on the activity. The methylation activity in submandibular gland was much lower than in liver. Chronic administration of isoproterenol, which causes an increase of phosphatidylcholine in membrane phospholipids of salivary glands, decreased methylation activity in the submandibular gland. Thus the increase in phosphatidylcholine in isoproterenol-treated rat salivary glands may not be derived from the phospholipid methylation pathway, but may be due to stimulation of other routes of phosphatidylcholine metabolism.

Animals↗

Fourteen years' experience of management and use of the perinatal data-base system.

Since 1973, we have been recording the data of all obstetric cases in our department in our original data-base system, which was created on the mainframe computer at the Tokyo University Hospital Computer Center. The purposes of this system are mainly for making summaries of patients, for retrieving information of cases to provide data for clinical investigations, and for collecting statistics. The data records consist of 225 items, including different kinds of perinatal information. Our data-base system has been useful in improving perinatal medicine, in clinical investigations, and in our daily work. But after 14 years of experience with it, we recognize the system has problems, namely: 1) How to summarize perinatal data to be used as a substitute for a patient history chart, and 2) How to update the data-base with a little change in format according to improvements of perinatal medicines.

Female↗

The development of sleep-wakefulness cycle and its correlation to other behavior in the human fetus.

Fetal rapid eye movements (REM), breathing movements (BM), and trunk movements (TM) were observed through the use of 3 ultrasonic real-time scanners. Each movement was recorded with the event marker and quantitatively analyzed in relation to the development of the sleep-wakefulness cycle by a computer-assisted system. The results were as follows: The number of REM increased with gestational age. The appearance rate of REM reached a certain level after 32 weeks of gestation. REM-non-REM rhythm was distinguished after 32 weeks. The relationship between REM and BM increased with gestational age. The occurrence of each TM has no correlation to that of REM when it was analyzed in short-term units, but the incidence of TM was high in REM periods. These results demonstrate the course of the development of sleep-wakefulness cycle in human fetuses.

Female↗

Artificial placenta: long-term extrauterine incubation of isolated goat fetuses.

Previously, this group reported on a system of extrauterine incubation of a goat fetus, in which the fetus is surrounded by artificial amniotic fluid and connected to the circuit with an ECMO (extracorporeal membrane oxygenator) by the umbilical arteries and veins. The following is a summary of recent progress using an improved method of catheterization and a new system that included a dialyzer within the circuit. Nine goat fetuses were used in this experiment. Six goats were successfully incubated; the duration of their incubation was 146.5 +/- 61.3 h (mean +/- SD). The longest one was 236 h. Slowly progressive circulatory depression was thought to be the main cause of fetal death. Marked tendencies to bleeding and water retention were not observed in any cases. Stable serum electrolyte levels were maintained.

Animals↗

Insulin action in human thighs after one-legged immobilization.

Insulin action was assessed in thighs of five healthy young males who had one knee immobilized for 7 days by a splint. The splint was not worn in bed. Subjects also used crutches to prevent weight bearing of the immobilized leg. Immobilization decreased the activity of citrate synthase and 3-OH-acyl-CoA-dehydrogenase in the vastus lateralis muscle by 9 and 14%, respectively, and thigh volume by 5%. After 7 days of immobilization, a two-step euglycemic hyperinsulinemic clamp procedure combined with arterial and bilateral femoral venous catheterization was performed. Insulin action on glucose uptake and tyrosine release of the thighs at mean plasma insulin concentrations of 67 (clamp step I) and 447 microU/ml (clamp step II) was decreased by immobilization, whereas immobilization did not affect insulin action on thigh exchange of free fatty acids, glycerol, O2, or potassium. Before and during the clamp step I, lactate release was significantly higher in the immobilized than in the control thigh. Seven days of one-legged immobilization causes local decreased insulin action on thigh glucose uptake and net protein degradation.

Adult↗

Histochemical characteristics of human expiratory and inspiratory intercostal muscles.

The relative occurrence of slow-twitch (ST) and fast-twitch (FTa and FTb) fibers, fiber size, and capillary supply in internal (INT) and external intercostal muscles (EXT), the costal diaphragm (DIA), and vastus lateralis muscle (VAS) was examined post-mortem in eight healthy males. The relative occurrence of ST fibers in INT [64 +/- 3% (SE)] and EXT (62 +/- 3%) was similar but higher than in DIA (49 +/- 3%) and VAS (40 +/- 6%; P less than 0.05). The occurrence of FTa fibers in expiratory INT (35 +/- 3%) was higher than in inspiratory INT and EXT (17 +/- 1%; P less than 0.05) but similar to DIA (28 +/- 6%) and VAS (32 +/- 2%). Accordingly, expiratory INT had fewer FTb fibers (1 +/- 1%) than the others (P less than 0.05). Expiratory INT had a 60% larger fiber area than inspiratory INT and EXT and DIA (P less than 0.05), but the area was similar to that of VAS. The number of capillaries per fiber was higher in expiratory INT (2.3 +/- 0.1) than in inspiratory INT and EXT (1.6 +/- 0.1), DIA (1.9 +/- 0.1), and VAS (1.8 +/- 0.2; P less than 0.05). The results suggest that the occurrence of many large capillary-rich FTa fibers in expiratory INT is bound to function (expiratory vs. inspiratory) rather than to anatomy (INT vs. EXT).

Adenosine Triphosphatases↗

Computer-assisted analysis of fetal behavior in fetal abnormalities.

Fetal behavior was studied in 17 cases of fetal abnormalities including nonimmune hydrops fetalis and in 11 cases of intrauterine growth retardation (IUGR) in comparison to 30 healthy fetuses. Breathing movements, rapid eye movements and trunk movements were observed ultrasonically and analyzed using a computer-assisted system. The cases with central nervous system anomalies showed a markedly different behavioral pattern. In the fetal abnormalities without chromosomal anomalies, the cases without major behavioral disorders were cured by neonatal treatment. IUGR cases with decreased trunk, breathing and REM period were finally diagnosed as having fetal distress by fetal heart rate monitoring. The findings on fetal behavior hint at the possibility of diagnosing abnormalities in neural development as well as in well-being.

Abnormalities, Multiple↗

Differential inhibitory effects of various herb extracts on the activities of reverse transcriptase and various deoxyribonucleic acid (DNA) polymerases.

Forty preparations of the extracts from 28 kinds of Asian herbs were tested for ability to inhibit the activities of murine retroviral reverse transcriptase and human deoxyribonucleic acid (DNA) polymerases. Among the 40 extracts, 35 inhibited reverse transcriptase activity and 29 inhibited DNA polymerase alpha activity. The inhibitory potencies of these extracts were expressed as the 50% inhibition concentrations (IC50), at which the enzyme activities were inhibited by 50%. Very strong inhibitions were observed with the extracts from Millettia pachycarpa (Leguminosae) and Mallotus apelta (Euphorbiaceae) as shown by their low IC50 values for reverse transcriptase (0.4-0.5 micrograms/ml) and DNA polymerase alpha (0.9-1.4 micrograms/ml). Enzyme kinetic analysis revealed that the mode of inhibition of reverse transcriptase by these two extracts was competitive with respect to the template.primer [poly(rA).oligo(dT)] and noncompetitive with respect to deoxythymidine triphosphate (dTTP) substrate. Besides reverse transcriptase and DNA polymerase alpha, DNA polymerase I and ribonucleic acid (RNA) polymerase from E. coli were inhibited by these two extracts. These results indicate that the herb extracts contain as yet unidentified substance(s) which inhibit the activities of reverse transcriptase and cellular DNA polymerases.

Humans↗

Structure-activity correlation of flavonoids for inhibition of bovine lens aldose reductase.

To clarify the structure-activity correlation of flavonoids for inhibition of aldose reductase, about fifty flavonoid compounds were screened. The presence of hydrophobic substituents on the A ring and hydrophilic substituents on the B ring of the flavonoid skeleton was suggested to improve the potency of inhibitory activity. The activities of extracts of Scutellaria baicalensis, Andrographis paniculata and Gutierrezia microcephala are also described.

Aldehyde Reductase↗

[Seasonal fluctuation of flavonol glycosides in Epimedium species].

The seasonal fluctuation of flavonol glycosides in the leaves of Epimedium grandiflorum var. thunbergianum, E. cremeum and E. sempervirens (Berberidaceae) was investigated. The total content of glycosides was shown in the highest quantity at the flowering time, and as the leaves mature it has become stable amount with a little decrease. The suitable period for the harvest of Epimedium leaves was concluded to be two or three months after the flowering time.

Drugs, Chinese Herbal↗

Stimulatory action of prolactin on gonadotropin secretion in vitro.

The action of prolactin (PRL) on the secretion of gonadotropin was investigated by means of a cell culture system of rat anterior pituitary gland. Anterior pituitary glands were removed from Wistar male rats, enzymatically digested and cultured. Luteinizing hormone (LH) release into medium was increased by adding PRL dose-dependently in the range between 10 ng/ml and 1 microgram/ml. This effect of PRL was further augmented by the presence of either gonadotropin-releasing hormone or estradiol. The intracellular LH concentration was also increased by PRL. PRL also caused an increase in follicle-stimulating hormone release into medium dose-dependently. In conclusion, PRL was shown to stimulate the secretion of gonadotropin at the pituitary level, thus suggesting a paracrine mode of PRL action in the anterior pituitary gland.

Animals↗

[Clinical analysis of 24 cases of caudate hemorrhage].

Twenty-four patients with caudate hemorrhage, in whom such definite organic lesions as arteriovenous malformations or ruptured cerebral aneurysms could not be proved, were analyzed. These cases comprise 2.0% of 1202 cases of hypertensive intracerebral hemorrhage diagnosed by computed tomography and experienced from 1976 through 1987. Thirteen patients were male and 11 were female. Their average age was 61 years. Headache (67%) and nausea and vomiting (50%), which were often the initial symptoms, were similar to those of subarachnoid hemorrhage. The main clinical symptoms were signs of meningeal irritation. Ten patients (42%) had transient disturbance of consciousness, and nine (38%) of these were somnolent; only one patient, who had a massive hematoma, was stuporous. When the hematoma extended to the internal capsule, the patient showed motor disturbance (38%). Two patients (8%) had Horner's sign, five (21%) exhibited diminished activity, and one (4%) suffered anosognosia. The volume of the intracerebral hematoma averaged 4.7 ml and was less than 5 ml in 17 patients (71%). In 20 patients (83%), the hematoma was confined to the head of the caudate nucleus. The hemorrhage tended to rupture into the anterior horn of the lateral ventricle, and in nearly all cases (96%), intraventricular hematoma was observed. Seventeen patients (71%) underwent cerebral angiography. There were no instances of dilation of the recurrent artery of Heubner. Twenty patients (83%) were treated conservatively. Continuous ventricular drainage was employed in four patients (17%), and ventriculoperitoneal shunting in three (13%). However, it was judged retrospectively that continuous ventricular drainage had been necessary in only two cases in which disturbance of consciousness was progressed due to acute hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Prognostic factors in acute subdural hematoma and the significance of serum FDP measurement].

Sixty-two cases of acute subdural hematoma were clinically analyzed with special reference to such prognostic factors as age, Glasgow Coma Scale (GCS) score on admission, pupillary signs, decerebration, and initial computed tomography (CT) findings. Intraparenchymal lesions demonstrated by CT were evaluated according to Yamaura's classification. In 19 cases, serum fibrin and fibrinogen degradation products (FDP) were measured at the time of admission. Emergency surgery was performed in 46 cases, and the remaining 16 patients were treated conservatively. The final outcome was judged according to the Glasgow Outcome Scale, and patients were divided into a "good outcome" group (good recovery or moderate disability) and a "poor outcome" group (severe disability, vegetative state, or death). In general, the outcomes proved to be unsatisfactory. Forty-four patients (71%) had a poor outcome, with 32/62 (52%) mortality, and only 18 (29%) had a good outcome. The clinical factors associated with a poor outcome were age over 64 years, a GCS score on admission of less than 7, decerebration, and absence of pupillary reaction to light. Initial CT scans showed brain damage in 46 patients (74%), 39 (85%) of whom had a poor outcome. This indicates that the outcome was significantly related to brain injury complicating the acute subdural hematoma. A high serum FDP level was similarly related to a poor outcome, which suggests that the serum FDP level reflects the degree of both primary and secondary brain injury. Thus, measurement of serum FDP may be valuable both in assessing clinical status and in evaluating the extent of brain injury in acute subdural hematoma.

Acute Disease↗