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T Kawarabayashi

Publications and source records attributed to T Kawarabayashi.

At least 73 records · Page 4Linked to original sources
PubMed1997

Small-cell carcinoma of the endometrium: an immunohistochemical and ultrastructural analysis.

Small-cell carcinoma of the endometrium is a rare neoplasm, and its aggressive behavior has been reported. We report a case of small-cell carcinoma occurring primarily in the endometrium of a 62-year-old woman with postmenopausal vaginal bleeding and lower abdominal pain. The excised uterus showed a necrotic polypoid mass and histologically displayed an endometrial small-cell carcinoma. Immuno-histochemically, the tumor cells were positive for cytokeratin, the epithelial membrane antigen, neuron-specific enolase, and chromogranin, but were negative for the leukocyte common antigen and Grimelius stain. Ultrastructural analysis revealed the presence of dense core granules in the cytoplasm of tumor cells. The patient died 2 months after surgery because of aggressive behavior of the tumor. We wish to distinguish small-cell carcinoma of the endometrium from conventional epithelial tumors of the endometrium, because of the former's distinctive histopathologic, immunohistochemical, and ultrastructural characteristics.

Carcinoma, Small Cell↗
PubMed1997

Effects of oxytocin, prostaglandin F2 alpha and prostaglandin E2 on intracellular free calcium concentrations of longitudinal muscle cells isolated from term pregnant rat myometrium.

The effects of oxytocin, PGF2 alpha and PGE2 on [Ca2+]i of isolated longitudinal muscle cells of term pregnant rats were investigated using Fura-2. Oxytocin, PGF2 alpha and PGE2 induced an initial rapid increase followed by a secondary gradual increase in [Ca2+]i in the presence of 1.5 mM Ca2+. The initial maximum increases in [Ca2+]i were obtained at 6 s for oxytocin, 20 s for PGF2 alpha and 30 s for PGE2 after addition of the stimulants. The EC50 values obtained from the curves were 2.0 nM for oxytocin, 250 nM for PGF2 alpha and 2,200 nM for PGE2. On the other hand, the increases in [Ca2+]i induced by the stimulants were nearly abolished by removal of the extracellular Ca2+. The stimulants induced biphasic increases in [Ca2+]i which were highly extracellular Ca(2+)-dependent processes, and the order of potencies for the stimulants was oxytocin > > PGF2 alpha > PGE2 in terms of affinity as well as magnitude. These results might indicate differences in the weight of the physiological role of the stimulants for regulating uterine contractility.

Animals↗
PubMed1997

Two molecular species of oxytocinase (L-cystine aminopeptidase) in human placenta: purification and characterization.

Two different forms of oxytocinase (L-cystine aminopeptidase, CAP; EC 3.4.11.3) were purified from the 9000 g and 105000 g precipitate fractions of human placenta homogenate by sequential chromatography on columns of hydroxyapatite, DE-32, nickel ion affinity, and Sephadex G-200. One species (CAP-I) purifed from the mitochondrial/lysosomal fraction migrated on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis with an apparent molecular mass of 61 kDa; the other (CAP-II) from the microsomal fraction was composed of two subunits with molecular masses of 56 and 40 kDa. The molecular masses of CAP-I and CAP-II estimated by gel filtration were 64 and 97 kDa, respectively. The specific activities of the two species for S-benzyl-L-cysteine p-nitroanilide increased by 357- (for CAP-I) and 139-fold (for CAP-II) compared with the starting preparations. The optimal pH values toward the artificial substrate were approx. 7.4-8.0 for CAP-I and 6.8-8.0 for CAP-II. The Km and Vmax values toward oxytocin were 5.6 microM and 23.4 micromol/h/mg protein for CAP-I, and 38 microM and 15.6 micromol/h/mg protein for CAP-II. Both enzymes were inhibited by the metal-chelating agents, EDTA and o-phenanthroline, whereas they were specifically activated by addition of Co2+: CAP-I was more sensitive to these reagents than CAP-II. L-Methionine strongly inhibited CAP-I, while CAP-II activity was only slightly affected. CAP-II was more sensitive to amastatin than CAP-I. Thus, the two enzymes are quite distinct in their molecular nature and biochemical properties. They may play a regulatory role in the metabolism of oxytocin and other biologically active peptides in intact placenta.

Cystinyl Aminopeptidase↗
PubMed1996

Intracellular generation of amyloid beta-protein from amyloid beta-protein precursor fragment by direct cleavage with beta- and gamma-secretase.

Two amyloid beta protein precursor (beta APP) fragments involving Met and 103 amino acids of C-terminus of beta APP (delta NOR-beta) and its KM-NL substitution (delta NL-beta) were expressed in COS-7 cells to clarify the proteolytic cleavages to generate amyloid beta protein (A beta). The 4.5-kD protein, A beta with additional N-terminal amino acids, and 4-kD A beta were directly produced and released from 12.5-kD expression proteins without any production of 11.4-kD C-terminal fragment starting at N-terminus of A beta and 3-kD "p3" A beta derivative. Intracellular 4-kD A beta was also detected. The substitution of KM-NL of beta APP found in Swedish familial Alzheimer's disease (AD) promoted the production of intracellular A beta and its release with no increase in level of 11.4-kD C-terminal fragment. These results suggested the presence of a distinct pathway in which A beta is directly cleaved at both N- and C-termini from beta APP fragment intracellularly to release A beta. Since KM-NL substitution enhanced intracellular A beta generation, this pathway may be associated with amyloidogenesis in AD.

Alzheimer Disease↗
PubMed1996

Clostridium difficile colitis associated with cisplatin-based chemotherapy in ovarian cancer patients.

The purpose of this study was to examine the incidence and cause of Clostridium difficile colitis occurring after cisplatin-based combination chemotherapy in ovarian cancer patients. Thirty-three patients with primary ovarian malignancy were treated with cisplatin-based combination chemotherapy ranging from 1 to 12 (mean 4.6) cycles. All patients who developed diarrhea after undergoing the cancer chemotherapy were examined to determine whether or not they were complicated by C difficile colitis. The diagnosis of C. difficile was confirmed by a stool-cytotoxin test and endoscopic examination. Severe C. difficile colitis occurred in 2 patients (6.1%) after receiving cisplatin-based combination chemotherapy for ovarian malignancies. Although both patients recovered from the colitis after the administration of vancomycin, the first case demonstrated a relapse of the colitis after receiving a subsequent course of the same chemotherapy with cisplatin. Both patients were then treated with a carboplatin alternative to cisplatin in the following courses, which resulted in neither a relapse of the colitis nor a recurrence of the malignancies up to this time. This report suggests the importance of searching for the presence of C. difficile and its toxin in patients with diarrhea after undergoing cancer chemotherapy since C. difficile may cause severe colitis. Based on our findings, it is thus concluded that cisplatin may cause C. difficile colitis.

Adult↗
PubMed1996

Comparison of in vitro and in vivo inhibitory effects of peptide and nonpeptide oxytocin antagonists on radioligand binding and uterine contractility of rats during pregnancy.

OBJECTIVE: Our purpose was to compare the effects of peptidyl and nonpeptidyl oxytocin antagonists on the pregnant rat uterus in relation to the progress of gestation. STUDY DESIGN: Pregnant rats with gestational ages of 17 and 21 days were used. A saturation binding of tritiated oxytocin to myometrial membrane preparation and its displacement by unlabeled oxytocin and the oxytocin antagonists were examined. The inhibitory effects of peptidyl and nonpeptidyl oxytocin on spontaneous, oxytocin-induced, and prostaglandin F2 alpha-induced uterine contractions were also evaluated in vitro in vivo. RESULTS: The number of tritiated oxytocin binding sites in myometrial membranes of pregnant rats increased markedly at day 21 of gestation compared with day 17 of gestation, whereas the dissociation constants for tritiated oxytocin did not differ significantly. As for the binding affinities to oxytocin receptors of myometrial membranes, the inhibition constant values of nonpeptidyl oxytocin were 79 and 351 times larger than those of peptidyl oxytocin at pregnancy days 17 and 21, respectively. Both drugs remarkably inhibited oxytocin-induced uterine contractions in a dose-dependent manner. However, peptidyl oxytocin did not effect spontaneous and prostaglandin F2 alpha-induced contractions except for spontaneous ones of rats of pregnancy day 21 in vivo. On the other hand, nonpeptidyl oxytocin suppressed spontaneous and prostaglandin F2 alpha-induced contractions of the uterus both in vivo (pregnancy day 17) and in vitro (pregnancy day 21). CONCLUSION: These results suggest that peptidyl oxytocin may inhibit uterine contractions by selectively antagonizing the oxytocin action at the receptor site, whereas nonpeptidyl oxytocin at high concentrations may have the additional effect of directly suppressing the contractions. This effect of nonpeptidyl oxytocin may become therapeutically advantageous in clinical application for preterm labor.

Animals↗
PubMed1996

Systemic overexpression of a C-terminal fragment of human amyloid beta-protein precursor causes accumulation of Alzheimer beta-amyloid fibrils in pancreas of transgenic mice.

The deposition of amyloid beta-protein (A beta), derived from amyloid beta-protein precursor (beta APP), is a specific and early event in development of Alzheimer's disease. Transgenic mice carrying the carboxyl-terminus of beta APP gene linked to the cytomegalovirus enhancer/chicken beta-actin promoter sequence were studied. Deposition of amyloid fibrils, composing A beta, was observed in the transgenic pancreas, accompanied with cell degeneration. This result will provide a model to investigate the beta APP processing mechanism in vivo and a clue to generate possible A beta amyloidosis in animal brains.

Actins↗
PubMed1996

Hypertrophy of oxytocinergic magnocellular neurons in the hypothalamic supraoptic nucleus from gestation to lactation.

In the present experiments, we examined the changes in cell size (profile area) of oxytocinergic magnocellular neurons during reproductive states and dehydration with quantitative immunohistochemistry. During lactation, hypertrophy was observed in oxytocinergic magnocellular neurons but not in vasopressinergic ones in the supraoptic nucleus. In virgin rats, chronic dehydration increased the cell size in both oxytocinergic and vasopressinergic neurons. After normal weaning time, the cell size decreased, returning to virgin level within 20 days. However, if the mothers were deprived of their litters immediately after parturition, the cell size rapidly returned to virgin level within 5 days. Furthermore, the increase in the cell size of the mothers was not affected by the size of their nursing litters.

Animals↗
PubMed1995

Amyloid beta-protein ending at Thr43 is a minor component of some diffuse plaques in the Alzheimer's disease brain, but is not found in cerebrovascular amyloid.

The distribution of amyloid beta-protein ending at 40 (A beta 40), 42 (A beta 42), and 43 (A beta 43) were immunocytochemically examined in Alzheimer's brains. A large number of diffuse plaques were stained with A beta 42 antibody (S42), but some were weakly labeled with A beta 43 antibody (S43). Immature and mature plaques were labeled with A beta 40 antibody (S40), S42, and S43. Thus, A beta 42 is the major component of diffuse plaques, the initial phase of plaque formation, and A beta 43 is present as a minor component. Only A beta 40 is present in cerebrovascular amyloid.

Aged↗
PubMed1995

Modified amyloid beta protein ending at 42 or 40 with different solubility accumulates in the brain of Alzheimer's disease.

Serial extraction study of Alzheimer's disease (AD) and control brains revealed 4, 3.7 and 3 kD amyloid beta protein (A beta) species accumulated in AD brains. In the fractions extracted with TBS, 10% SDS and formic acid, considerable amounts of A beta species were recovered in SDS fractions besides TBS and formic acid fractions. Immunoblotting with several site-specific antibodies confirmed not only the presence of 4 kD A beta starting at the first amino acid of A beta but also 2 smaller A beta species with modification of their amino-termini in the highly resolutional Tris/Tricine gel system. A beta solubility using these solvents was associated with both modification of the amino-terminus and length of carboxyl-terminus of A beta. Especially, a large amount of modified A beta was found to be accumulated as forms with different solubility in AD brains.

Aged↗
PubMed1995

Role of the sodium-calcium exchange mechanism and the effect of magnesium on sodium-free and high-potassium contractures in pregnant human myometrium.

OBJECTIVE: Periodic uterine relaxation in labor relieves the fetus from hypoxia related to sustained contractions. A reduction in intracellular calcium is essential for relaxation. Therefore we aimed to clarify the extrusion mechanisms of intracellular calcium ions in pregnant human myometrium. STUDY DESIGN: Isometric contraction of small muscle bundles obtained from human myometrium at term was recorded. High-potassium and sodium-free solutions could induce stable contractures that revealed initial phasic contractions followed by tonic contractions. The effects of external calcium, external magnesium, nifedipine, and calcium adenosine triphosphatase inhibitors on both contractures were then examined. RESULTS: Because maximum tonic contraction was induced by 48 mmol/L potassium, this concentration was used. Both contractures depended on external calcium concentrations. Nifedipine, 10(-7) mol/L inhibited both initial phasic contractions and the tonic phase of the high-potassium contracture; however, it could not suppress the tonic phase of the sodium-free contracture. Calcium adenosine triphosphatase inhibitors, cyclopiazonic acid and lauryl sulfate, potentiated the tensions of tonic phases in both contractures; the effect of lauryl sulfate was stronger than that of cyclopiazonic acid. When external magnesium was gradually increased (from 0 to 9.6 mmol/L), both phasic contractions and the tonic phase of the high-potassium contracture transiently increased, followed by a reduction of tension, whereas the tonic phase of the sodium-free contracture was markedly inhibited by magnesium in a dose-dependent manner. CONCLUSION: The presence of the sodium-calcium exchange mechanism and the specific inhibitory effect of magnesium were indicated in human myometrium during pregnancy. These mechanisms might prevent the long tonic contractions, to protect the fetus from hypoxia during pregnancy and parturition.

Calcium-Transporting ATPases↗
PubMed1995

Fos expression in the hypothalamic magnocellular neurons of rats during pregnancy, parturition and lactation.

Changes in Fos expression of magnocellular neurons in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of the rat hypothalamus were investigated using immunohistochemistry during pregnancy, parturition and lactation. Quantitative morphometrical analysis revealed that Fos-positive cells in the hypothalamic magnocellular neurons were rarely seen in days 10 and 20 pregnant rats, however, significantly numerous Fos-positive cells were found in parturient rats. The number of Fos-positive cells was drastically decreased within a few days after parturition. Moreover, it was found using dual immunohistochemistry that the percentage of Fos-positive cells in vasopressin (AVP) magnocellular neurons of the SON was higher than that of the PVN in parturient rats, although oxytocin (OXT) magnocellular neurons showed the same percentage of Fos-positive cells between the SON and PVN. These results demonstrate that the hypothalamic magnocellular neurons express Fos during a limited period after parturition, and Fos expression in AVP magnocellular neurons is heterogeneous between the SON and PVN.

Animals↗
PubMed1995

Maintenance of ultrastructural plasticity of the hypothalamic supraoptic nucleus in the ovariectomized rat.

In the present experiments, we examined the effect of ovariectomy on the increases in litter weight and structural plasticity of MNCs in the supraoptic nucleus (SON) during lactation. Female rats were ovariectomized 2 days after parturition, and the increases in litter weight were measured as the index of milk let-down from dams during lactation. The lactation period was elongated up to 6 weeks by providing new litter to obtain more apparent effects of the ovariectomy. There was no significant difference in the increases in litter weight between non-operated and ovariectomized females. After lactation for 6 weeks, the ultrastructures such as juxtaposition (surface membrane apposition) and multiple synapses (terminals contacting with two or more postsynaptic elements) of MNCs in the SON in nonoperated and ovariectomized females were examined to compare with those of virgins. The percentage of juxtaposition and the number of multiple synapses significantly increased in nonoperated lactating females as compared with those of virgins. Ovariectomized rats showed similar structural changes to those of nonoperated females during lactation. Therefore, we conclude that ultrastructural plasticity of MNCs in the SON is maintained even in the absence of an ovary, and direct or indirect actions of suckling stimulation may be important in maintaining the plasticity during lactation.

Animals↗
PubMed1995

Effect of prolonged beta-adrenergic blockade induced by atenolol on left ventricular remodeling after acute myocardial infarction in the rat.

Beta-adrenergic receptor blockade reduces the mortality rate after acute myocardial infarction (AMI) in humans. However, the effects of beta blockade on left ventricular remodeling remain unknown. Therefore, in the present study we investigated the effect of prolonged beta-adrenergic receptor blockade with atenolol on left ventricular remodeling following AMI in rats. Myocardial infarction (MI) was produced in Wistar-Kyoto rats by ligating the coronary artery. Four groups of rats were studied: sham-operated (n = 10); atenolol (1 g/l in drinking water) treated sham-operated (n = 8); untreated MI (n = 11); atenolol treated MI (n = 10). Hemodynamic measurements were made about 3 weeks after the operation. Infarct size was similar in treated and untreated MI rats (31.2 +/- 2.5% cf. 33.5 +/- 2.0%). MI rats were characterized by increases in left ventricular end-diastolic pressure (LVEDP), right atrial pressure (RAP), right ventricular systolic pressure (RVSP), and left ventricular end-diastolic volume index (LVEDVI), as compared with sham-operated rats. In sham-operated rats, prolonged beta-adrenergic receptor blockade produced only a reduced HR. Atenolol-treated MI rats had a significantly higher LVEDP, RAP and LVEDVI than did rats with untreated MI. Prolonged beta-adrenergic receptor blockade with atenolol appeared to promote left ventricular remodeling after AMI. Thus, the treatment of AMI with beta-adrenergic receptor blockade in the clinical setting should be evaluated with respect to ventricular remodeling during prolonged therapy.

Animals↗