Biomedical subjects
Publications and source records attributed to T Takagi.
The step-down method can be an alternative method of ovulation induction in women with PCOS. This protocol can induce ovulation with a smaller dose of FSH and with lower incidence of excessive ovarian enlargement in comparison with the traditional fixed-dose administration method.
The number of polypeptides constituting the oligomeric structure of canine phospholamban (a putative regulator of Ca(2+)-ATPase of cardiac sarcoplasmic reticulum) stable even in the presence of sodium dodecyl sulfate was estimated through determination of the molecular weight of the oligomer. Owing to the small molecular size, the low UV-absorptivity and the limited availability, the molecular weight determination required very sophisticated application of the following technique, used as the only recourse: low-angle laser light scattering measurement combined with high-performance gel chromatography. The molecular weight of phospholamban oligomer was found to be 30,400 and the number of subunits was concluded to be five after correction for the dependence of the apparent molecular weights on the protein concentration.
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The suppression of heart rate variation reflects cardiac autonomic nervous dysfunction and is known to be associated with a poor prognosis or sudden death in diabetic patients. We investigated consecutive changes in the heart rate variation in 51 alcoholics using the coefficient of variation of R-R interval (CVRR). To correct for age effects, a ratio of CVRR to the standard predicted value (CVP) was calculated. On the whole, CVRR/CVP was suppressed on admission and on the 7th day of abstinence and increased on the 30th day. However, alcoholics could be divided into two groups by their CVRR/CVP on the 30th day: one group with transient autonomic dysfunction whose CVRR/CVP was more than 0.8 (n = 32), and the other group with persistent autonomic dysfunction whose CVRR/CVP was less than 0.8 (n = 19). Withdrawal hypertension occurred more frequently (63% vs. 19%) and mean systolic pressure (159 +/- 24 mmHg vs. 138 +/- 17 mmHg) was higher in the latter group than in the former, suggesting that persistent autonomic damage might, at least in part, contribute to withdrawal hypertension. To investigate further the relationship between the persistent autonomic damage and other complications, the CVRR/CVP on the 30th day of abstinence was analyzed in an additional 85 alcoholics (total n = 136). Persistent suppression of the CVRR/CVP was more frequently found in alcoholics with leg paresthesia (64%, n = 22), the Wernicke-Korsakoff syndrome (73%, n = 11), or diabetes mellitus (69%, n = 68), than in alcoholics without these complications (31%, n = 35).(ABSTRACT TRUNCATED AT 250 WORDS)
Heterotopic bone formation induced by demineralized bone matrix gelatin (BMG) in bupivacaine-HCl-treated skeletal muscle was examined histologically. BMG was obtained by dehydrating diaphyseal shafts of femora and tibiae of male, 4-week-old Sprague-Dawley (SD) rats, cutting it into chips, and demineralizing and extracting the chips with various solutions. The BMG was implanted into the rectus abdominis muscle of male, 5-week-old SD rats, bupivacaine-HCl was injected at the same site, and the resulting plaques of tissues were examined histologically on days 5, 10, 15 and 20 after BMG implantation. Heterotopic bone formation occurred in all animals. The bupivacaine-treated group had more degenerated and injured muscle fibers, and more osteocytes than the control group. Electron microscopy showed that the basement membrane of muscle fibers was discontinuous and that many mononucleated cells resembling activated satellite cells were present on day 5. Many fibroblasts, undifferentiated mesenchymal cells and myogenic cells were seen in the area around the BMG. In new bones there were few osteocytes on day 10, but their numbers were increased on days 15 and 20 after implantation, especially in the bupivacaine-treated group. The population of osteocytes that increased rapidly may have included mononucleated cells similar to activated satellite cells.
To elucidate the cytotoxic mechanism of tumor necrosis factor (TNF), we isolated TNF-resistant sublines of L929 cells. As compared with L929 cells, TNF-resistant cells retained similar number and affinity of TNF-binding sites, and showed a similar growth rate. TNF stimulated arachidonate release from L929 cells, while no stimulation was observed at all in TNF-resistant cells tested. The cytotoxic action of TNF on L929 cells was inhibited by indomethacin, suggesting that prostaglandin may be involved in the action. Therefore, TNF-stimulated prostaglandin production was examined in L929 and TNF-resistant sublines. The amount of PGE2 produced by L929 cells was increased more than 5-fold after the addition of TNF, whereas the amount of PGE2 did not change in the resistant sublines following addition of the factor. TNF-stimulated arachidonate release and PGE2 production were reversed by islet-activating protein (IAP)-treatment of L929 cells. These results suggest that arachidonate release and subsequent prostaglandin production are important for the cytotoxic action of TNF and that these processes are mediated by GTP-binding protein (G protein) that is coupled to the TNF-receptor.
Synthetic alpha-human atrial natriuretic peptide (hANP) was infused continuously at a rate of 80 ng/kg/min for 20 min into normal volunteers and patients with chronic renal failure (CRF) receiving hemodialysis. Blood pressure (BP) decreased significantly both in normals and in patients with CRF. The magnitude and the duration of the decrease, however, were greater in patients with CRF. The plasma aldosterone concentration (PAC) decreased significantly in normals and only minimally in patients with CRF. The half time (T1/2) of plasma hANP in patients with CRF (M +/- SE: 4.5 +/- 0.5 min) was longer than that in normals (1.8 +/- 0.2 min). Moreover, the metabolic clearance rate in patients with CRF (64 +/- 7 ml/kg/min) was less than in normals (150 +/- 20 ml/kg/min). Thus, the T1/2 in plasma of hANP in patients with CRF was noticeably longer than in a normal control group. These findings suggest that hANP suppresses PAC regardless of electrocyte imbalances and/or volume change induced by kidney dysfunction and that the kidney may be important in degrading hANP.
Since thyroid hormones have been reported to increase the synthesis of rat atrial natriuretic hormone and its mRNA accumulation, we further investigated the mechanism of stimulation of rANH synthesis by T3 using cultured rat atrial myocytes. T3 (10(-9)-10(-7) mol/l) increased cellular content and secretion into the medium of immunoreactive rANH in a dose-dependent manner. However, the ratio of secreted/cellular rANH was not altered by the addition of T3. Furthermore, in both cellular and secreted rANH, the larger molecular form (gamma-rANH) apparently predominated over the smaller one (alpha-rANH), and this profile was not influenced by T3 (10(-7) mol/l). Although T3 (10(-9)-10(-7) mol/l) also increased cellular rANH mRNA accumulation, the ratio of cellular rANH/rANH mRNA was not changed. Moreover, using actinomycin D, we found that T3 (10(-7) mol/l) did not affect the degradation of rANH mRNA. From these findings, we suggest that T3 has no specific effects on the translational and posttranslational processes and the release of rANH, but that T3 stimulates rANH synthesis in the pretranslational levels, probably in the transcriptional level of rANH gene.
We examined whether human left ventricular (LV) wall vibration at the first heart sound emission (LVvibr) could be a potential source of information about the left ventricular physical properties, as has been demonstrated by experimental forced vibration studies. LV posterobasal wall vibration in 51 subjects characterized by functional murmur (n = 13), mitral stenosis (n = 8), hypertrophic cardiomyopathy (HCM, n = 8), ischemic heart disease with old myocardial infarction (n = 12) and without prior infarction (n = 10), was detected with a miniature intraesophageal vibration sensor. Peak frequency, sharpness and peak power of LVvibr in patients with functional murmur and mitral stenosis were linearly related to the Q-vibration interval. HCM patients showed a higher peak frequency and sharper configuration in the power spectrum. However, differing from previous reports, we found no characteristic difference in configuration of power spectrum in patients with ischemic heart disease. These results suggest that human LVvibr possibly includes information demonstrated by experimental forced vibration analysis.
Maternal plasma concentrations of immunoreactive endothelin (ir-ET) during pregnancy, labour and after birth were measured by radioimmunoassay. Concentrations of ir-ET in the umbilical artery, umbilical vein, amniotic fluid and neonatal urine were also examined. The mean (+/- S.E.M.) plasma ir-ET concentration in early pregnancy (4-7 weeks) was 13.7 +/- 0.5 pmol/l, which was significantly higher than that in non-pregnant women (5.9 +/- 0.3 pmol/l). During pregnancy, plasma ir-ET concentrations gradually decreased to a minimum of 11.5 +/- 0.4 pmol/l in weeks 20-23, and then increased again towards term (12.5 +/- 0.4 pmol/l after 36 weeks of pregnancy). In women undergoing vaginal delivery, the mean plasma ir-ET concentration (17.1 +/- 0.7 pmol/l) increased significantly, compared with that in late pregnancy. After delivery, the plasma ir-ET concentration decreased abruptly to 4.0 +/- 0.2 pmol/l on the first day. Plasma ir-ET concentrations in umbilical vessels were significantly higher than those in maternal plasma. In addition, concentrations in the umbilical artery were significantly higher than those in the umbilical vein in cases of vaginal delivery. Concentrations of ir-ET in amniotic fluid were much higher than those in maternal or fetal plasma. ir-ET concentrations in neonatal urine on day 1 after birth were below the detection limit (less than 0.1 pmol/l) by radioimmunoassay in 70% of the cases examined but on day 5 after birth ir-ET was present at measurable concentrations in all cases. It is suggested that endothelin may act as a circulating hormone during pregnancy and labour in both maternal and fetal circulations.
Histological changes in cultured neonatal skeletal muscle tissue at the early stage of cartilage induction by syngeneic insoluble bone matrix gelatin (BMG) containing bone morphogenetic protein were examined by light and electron microscopy. Minced skeletal muscle was cultured on hemicylindrical pieces of BMG for 14 days. Chondroblasts first appeared in the crevices of the BMG on Day 7 of the culture, and cartilage tissue was seen to fill the crevices completely by Day 10. The main findings in this work are as follows: 1) the activation of satellite cells and necrosis of myonuclei; 2) the migration of satellite cells from the basement membrane; 3) fibroblasts with increased numbers of organelles between degenerated muscle fibers closely resembling the migratory satellite cells; 4) the migration of the spindle-shaped cells into the crevices of the BMG; and 5) change of the spindle-shaped cells to chondroblasts. These findings suggest that neonatal skeletal muscles, which appear more mature than embryonic muscles, also have a chondrogenetic potential when grown on BMG, and that chondroblasts originate from the spindle-shaped cells which are thought to result from migratory satellite cells as well as fibroblasts.
The authors present a rare case of malignant fibrous histiocytoma originating in the cranial bone. A 72-year-old male was admitted with a diffuse painless swelling in the left occipital region but no neurological abnormality. Plain skull x-ray films and computed tomographic scans showed a large tumor in the left temporo-occipital bone. The tumor invading subcutaneous tissue was totally excised and histologically diagnosed as malignant fibrous histiocytoma. Postoperatively, 40-Gy irradiation was given to the left temporo-occipital region. Several months later, however, the tumor recurred in the posterior fossa. Neuroradiological examination showed tumor extension into the occipital bone and muscle and the subdural space of the posterior fossa. A second operation extirpated all tumors except in the cerebellum. He died of pneumonia on the 14th postoperative day. Autopsy revealed malignant fibrous histiocytoma invading into the bilateral cerebellar hemispheres. Radiation and chemotherapy should be given as soon as possible following extensive surgery for malignant fibrous histiocytoma of the cranial bone.
A 35-year-old female presented with moyamoya disease coincidentally associated with a persistent primitive trigeminal artery (PPTA). Bilateral encephalo-duro-arterio-synangiosis was performed and the postoperative course was uneventful. Moyamoya disease and PPTA might have a congenital origin, but moyamoya disease may be promoted by a PPTA. The hemodynamics of PPTA during progressive occlusive change in the internal carotid artery in moyamoya disease should be re-evaluated to determine its function in the development of moyamoya vessels.
Heterotopic bone formation in skeletal muscle induced by compacted demineralized bone matrix gelatin (BMG) was studied histologically and biochemically. BMG was obtained by dehydrating diaphyseal shafts of femora and tibiae of 4-week-old male Sprague-Dawley rats, cutting the bone into chips, and demineralizing and extracting the chips with various solutions. The BMG was treated with 4 M guanidine-HCl, and compacted BMG was prepared by centrifugation. The compacted BMG was implanted into the rectus abdominis muscle of 5-week-old male Sprague-Dawley rats. The resulting specimens were examined histologically, and their alkaline phosphatase activity and the calcium content of the tissues were measured 3, 5, 7, 10, and 15 days after implantation. The BMG (separated BMG) with 75- to 500-microns particle sizes were implanted into control rats. The results showed that calcification, alkaline phosphatase activity, and bone formation were suppressed by implantation of the compacted BMG and that scarcely any vascularization occurred. Calcification, vascularization, and alkaline phosphatase activity were related and were indispensable for bone formation. In the control group, bone formation was observed at sites of high activity of alkaline phosphatase and well-developed vascularization. These results suggested that compacting of BMG suppressed vascularization, decreased calcification, and consequently reduced the induction of bone formation.
Periodic infusion chemotherapy from the reservoir implanted by direct arterial puncture (Seldinger method) was performed in 21 cases of hepatocellular carcinoma. The effectiveness of treatment in terms of efficacy and liver function in about 12 patients who survived more than 6 months was investigated. Owing to the progressive liver atrophy and liver dysfunction with ascites, some cases had to delay infusion treatment. Thus, it is necessary to check liver function regularly.
The effects of bunazosin hydrochloride, a new highly selective alpha 1 adrenergic antagonist, on the intraocular pressure (IOP) and aqueous humor dynamics in healthy human volunteers were studied. Unilateral topical administration of 0.1% bunazosin significantly lowered IOP from 1 to 10 hrs in bunazosin-treated eyes, and from 2 to 8 hrs in contralateral placebo-treated eyes, with its maximum reduction at approximately 3 hrs, when the IOP decreased 5.0 mmHg in treated eyes, and 3.5 mmHg in contralateral eyes from the baseline, respectively. Fluorophotometrically measured aqueous humor flow rates did not change significantly either in treated or contralateral eyes. Bunazosin caused significant reduction of systolic and diastolic blood pressure 5 hr after application. The difference in pupil diameter between treated and contralateral eyes was found to be statistically significant from 1 to 5 hrs. A small but significant increase in anterior chamber depth also was observed from 2 to 6 hrs. Pulse rate and refraction were not substantially altered. There was moderate conjunctival vessel dilation, however, no serious complications were encountered. The results suggest that bunazosin hydrochloride appears to have great clinical potential for ocular hypotensive therapy.
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We measured vertebral bone density of 59 male alcoholics (ALC) using quantitative computed tomography (QCT). Bone density of ALC was decreased measured on admission compared with age-matched healthy male controls (ALC: 144 +/- 42, CONTROLS: 173 +/- 34 mg/cm3, p less than 0.05). The bone density was not correlated with serum ALP, Ca, and Pi. Serum parathyroid hormone and calcitonin were also not correlated with the bone density in ALC. Serum 25-(OH)-D showed significant positive correlation with the bone density (p less than 0.01) and 1,25-(OH)2-D showed trend of positive correlation with the bone density (p less than 0.01) in ALC. Severity of liver diseases did not have any relation to the bone density in ALC. Although the decreased bone density was not improved at the second QCT examined about 10 weeks after first QCT without medication, patients administered 1 microgram of 1 alpha-(OH)-D3 daily showed a significant increase in the bone density (on admission: 152 +/- 37, 10 weeks later: 162 +/- 35 mg/cm3, p less than 0.02). Combination therapy of 1 alpha-(OH)-D3 and calcitonin did not increase the bone density. These results indicate that bone density was decreased in ALC and a decrease in serum vitamin D metabolites may cause a decrease in the bone density, although liver dysfunction does not have a role in it. These data also suggest that 1 alpha-(OH)-D3 is effective in an increase in the bone density in ALC with osteoporosis after abstinence.