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Biomedical subjects

I Nagata

Publications and source records attributed to I Nagata.

At least 109 records · Page 6Linked to original sources
PubMed1997

Filopodia and growth cones in the vertically migrating granule cells of the postnatal mouse cerebellum.

The details of the morphology of vertically migrating granule cells were examined semiquantitatively in the postnatal mouse cerebellum by a Golgi method, with special reference to the growth cone-related structures such as filopodia and lamellipodia. The first sign of inward migration was extension of short, vertical filopodium-like processes from the sides of the perikarya of tangentially oriented granule cells, followed by a change of orientation of cell bodies to the vertical axis showing a T-shaped morphology. The T-shaped migratory cells formed sprouted filopodia (side spikes) from their vertical leading processes and perikarya at right angles to the vertical axis. More than three-quarters of the migratory cells extended the side spikes. The presence of such side spikes was confirmed with laser scanning confocal microscopy of granule cells labeled with 1,1', dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate and also with transmission electron microscopy (TEM). In addition, about one-fourth of migratory cells extended lamellipodia of web-like forms along the stem or at the tip of the leading process, some of which showed a typical growth cone. Several morphological variations of vertical granule cells were also observed. Furthermore, TEM observation confirmed that side spikes from migratory cells made direct contact with parallel fibers. The present results suggest that, during vertical migration, growth cone-related structures of the leading processes of granule cells adhere to and probably recognize tangentially oriented parallel fibers. Therefore, the mechanisms of the vertical guidance and migration of granule cells in the cerebellar cortex seem to be multiple, involving not only parallel contact guidance by the Bergmann glia fibers but also perpendicular contact guidance by the parallel fibers. These parallel and perpendicular geometric cues surrounding the granule cells seem to have produced the varying morphology of vertically migrating granule cells.

Animals↗
PubMed1997

Detection of maternofetal transfusion by placental alkaline phosphatase levels.

We investigated the volume of maternofetal transfusion by measuring placental alkaline phosphatase (PLAP) as an indicator of placental passage. PLAP levels were measured in 135 pairs of maternal-neonatal sera. Estimated volumes of maternofetal transfusion were calculated with the following formula: Volume of transfusion (in milliliters) = 85 ml/kg x BW (in kilograms) x (PLAPAB-PLAP1MO)/ PLAPMA, where BW is the birth weight, PLAPAB is the PLAP level in neonatal serum at birth, PLAP1MO is the PLAP level in neonatal serum at 1 month of age, and PLAPMA is the PLAP level in maternal serum at delivery. The mean PLAPMA, PLAPAB, and PLAP1MO levels were 276.95 +/- 159.74 IU/L, 3.83 +/- 2.17 IU/L, and 0.25 +/- 0.22 IU/L, respectively. The mean volume of maternofetal transfusion was estimated to be 3.33 +/- 1.68 ml. The mean estimated volume of maternofetal transfusion per kilogram of birth weight was significantly lower in cases of scheduled cesarean delivery (0.74 +/- 0.35 ml/kg) than in cases of vaginal delivery (1.18 +/- 0.54 ml/kg; p < 0.001) and emergency cesarean delivery (1.73 +/- 1.00 ml/kg; p < 0.01). In scheduled cesarean delivery a significant positive correlation between gestational age and the estimated volumes of transfusion per kilogram of birth weight was observed. In cases of vaginal delivery, the estimated volume of transfusion per kilogram of birth weight was significantly lower in the group with short labor (< 5 hours: 0.92 +/- 0.32 ml/kg) than in the group with prolonged labor (> or = 5 hours: 1.29 +/- 0.61 ml/kg; p < 0.001). PLAP was considered to be useful for estimating the volume of maternofetal transfusion. The transfer volume appeared to relate to uterine contractions and to histologic changes in the placenta with aging.

Adult↗
PubMed1997

Intravenous glucose tolerance test-derived glucose effectiveness in bulimia nervosa.

The aim of the present study was to estimate insulin secretion, insulin sensitivity (SI), and glucose effectiveness at basal insulin (SG) in subjects with bulimia nervosa. Eight bulimic patients and eight age-, body mass index-, and sex-matched healthy control subjects without a family history of diabetes were studied. The subjects all had normal glucose tolerance. They underwent a modified frequently sampled intravenous glucose tolerance test; glucose (300 mg/kg body weight) was administered, and insulin (4 mU/kg body weight/min) was infused from 20 to 25 minutes after administration of glucose. SI and SG were estimated by Bergman's minimal model method. Basal insulin (27 +/- 3 v 45 +/- 3 pmol/L) was significantly lower in bulimic patients than in normal controls (P < .05), but basal glucose was similar between the two groups (4.5 +/- 0.1 v 4.9 +/- 0.1 mmol/L, P > .05). The glucose disappearance rate (KG) and acute insulin response to glucose estimated by the intravenous glucose tolerance test (AIR(glucose)) were similar between the two groups (KG, 1.35 +/- 0.29 v 2.20 +/- 0.21 min(-1), P > .05; AIR(glucose), 2,920 +/- 547 v 2,368 +/- 367 pmol/L x min, P > .05). No significant difference was observed in SI between the two groups (1.34 +/- 0.18 v 1.25 +/- 0.20 x 10(-4) x min(-1) x pmol/L(-1), P > .05). On the other hand, glucose effectiveness at basal (SG) and zero (GEZI) insulin was significantly diminished in comparison to normal controls (SG, 0.011 +/- 0.002 v 0.024 +/- 0.002 min(-1), P < .01; GEZI, 0.008 +/- 0.002 v 0.017 +/- 0.003 min(-1), P < .01). Thus, bulimic patients with normal glucose tolerance without a family history of diabetes were characterized by normal insulin secretion, normal SI, and reduced SG and GEZI.

Adult↗
PubMed1997

Intrasellar meningioma: case report and review of the literature.

BACKGROUND: Intrasellar meningioma is a rare clinical entity, and surgical resection may be difficult when it is hypervascularized. METHODS: A case of subdiaphragmatic hypervascular intrasellar meningioma with attachment to the dura of the anterior wall of the sella turcica is described. Literature review of 18 cases with operatively confirmed intrasellar meningioma discloses unexpected intraoperative bleeding and relatively low resectability of the tumor are also described. RESULTS: We used preoperative endovascular embolization of feeding arteries, and resected a hypervascular intrasellar meningioma by a combined transsphenoidal-transcranial approach safely and without massive bleeding. CONCLUSIONS: Preoperative endovascular embolization of feeding arteries and combined transsphenoidal-transcranial approach are useful for the surgical resection of hypervascular intrasellar meningiomas.

Combined Modality Therapy↗
PubMed1997

Surgical extirpation of the posterior hippocampal arteriovenous malformation.

BACKGROUND: Surgical extirpation of medial temporal (AVMs) arteriovenous malformations has been one of the most challenging issues in neurosurgery. Yaşargil classified mediobasal AVM into four subtypes: amygdala, anterior hippocampal, middle hippocampal, and posterior hippocampal lesions. The lesions around the trigone extending forward to the temporal horn, and medially adjacent to the midbrain, can be referred to as posterior hippocampal AVMs. The therapeutic indications and operative approaches for these lesions remain controversial. METHODS: Nine patients underwent surgical resection for AVMs of the posterior hippocampus using a laterobasal approach. RESULTS: In four patients, AVMs were located chiefly within the lateral ventricle, and the lesions were resected using a laterobasal approach through the occipitotemporal sulcus, or through a hematoma cavity within the fusiform gyrus. Clinical improvement followed the procedure in three of four patients. In the remaining five patients, the nidi were located chiefly within the ambient cistern, extending upward to the basal ganglia. Contralateral hemiparesis occurred in three patients. Two patients showed marked improvement following an initial decline in neurologic status. CONCLUSIONS: A laterobasal transventricular approach is suitable for ventricular AVMs, whereas only limited exposure can be afforded through a transventricular, transchoroidal fissure route for the AVMs within the ambient cistern. For these lesions, a conventional subtemporal approach to the tentorial incisura is preferable.

Adult↗
PubMed1997

Fc portion of intravenous immunoglobulin suppresses the induction of experimental allergic neuritis.

To clarify how intravenous immunoglobulin (IVIg) acts on Guillain-Barré syndrome, we investigated the effects of intact-type IVIg treatment on experimental allergic neuritis (EAN) induced by immunizing with synthetic peptide from bovine P2 protein. Treatment with intact-type IVIg (400 mg/kg/day) on days 0, 7, 14, 15 and 16 after immunization prevented the paralysis, whereas treatment with F(ab')2 failed to alter the clinical course. Intact-type IVIg treatment given on days 0 and 1 showed almost the same efficacy. These results suggest that intact-type IVIg is superior to F(ab')2 in ameliorating the clinical course of EAN and that the Fc portion might affect the immune system.

Animals↗
PubMed1997

Appearance of a fast inactivating voltage-dependent K+ currents in developing cerebellar granule cells in vitro.

To elucidate the molecular mechanisms that regulate the maturation of action potential, we began by examining voltage-dependent K+ currents, known to contribute to the maturation of action potential, of developing granule cells in mouse cerebellar microexplant cultures. The migration of developing granule cells in this culture is reported to mimic the in vivo process, but their specific identification is still incomplete. In this study, we identified and characterized granule cells in this culture. Immunocytochemical analysis found that granule cells migrated radially out from explants and subsequently formed small clusters and also that their morphology changed from a bipolar to a T shape during migration. Moreover, in the electrophysiological study, the GABA response of granule cells in this culture clarified that the electrophysiological properties of granule cells were normally maintained. We therefore have concluded, that this culture system is a powerful tool for investigating the differentiation of cerebellar granule cells. Based on these findings, we recorded voltage-dependent K+ currents of developing granule cells in this culture, while concurrently observing their morphology. Our results show that voltage-dependent K+ currents of developing granule cells change from delayed rectifier to A current in parallel with their morphological changes from bipolar to T-shaped cells.

Animals↗
PubMed1997

Enhancement of antitumour activity of cisplatin by N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine. HCl in human ovarian cancer cells with intrinsic or acquired resistance to cisplatin.

This study was designed to the elucidate sensitising effects of the intracellular histamine antagonist, N,N-diethyl-2[4-(phenylmethyl)phenoxy] ethanamine HCl (DPPE) on the antitumour activity of cis-diamminedichloroplatinum (II) (CDDP) using human ovarian cancer cell lines with different sensitivities to CDDP (KF, sensitive) KFra (acquired CDDP resistant derived from KF), and KK and MH, intrinsically CDDP resistant. The KF cells were most sensitive to CDDP among cell lines used in this study and followed by MH, KK and KFra showing approximately 3.5, 4.0 and 9.1-fold IC50 values to KF, respectively. The acquired CDDP resistant KFra cells were approximately 6.1-fold more sensitive to DPPE than the parent KF cells, while MH and KK cells were more than 10-fold more resistant to DPPE than the KF cells. With regard to the inhibition of human ovarian cancer cell proliferation, phenyltoloxamine and L-histidinol were 5-2500-fold less cytotoxic than DPPE. Analysis of flow cytometry (FCM) revealed that with concentrations based on the IC50 to KF and KFra cells, DPPE resulted in G2-M accumulation in the KF (but not KFra) cells in a time-dependent manner during the course of 48 h incubation time. In addition, from a median effect analysis, DPPE seemed to have additive and somewhat synergistic effects on the antitumour activity of CDDP in KK and MH cells with intrinsic CDDP resistance, while minor antagonism in KFra cells with acquired CDDP resistance was observed. Although DPPE alone did not significantly inhibit the tumour growth of nude mice bearing KF cells, combinations of DPPE with CDDP resulted in improved survival compared with treatment with only CDDP. Adverse side-effects, as confirmed by monitoring haematocrit and the body weight were not observed during the experimental period. These results suggest that DPPE may be of clinical use for the treatment of intrinsically refractory ovarian carcinoma when combined with CDDP.

Adjuvants, Pharmaceutic↗
PubMed1997

Growth-inhibitory effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamine-HCl combined with cisplatin on human ovarian cancer cells inoculated into nude mice.

In 5-day incubation of an estrogen receptor-negative human ovarian cancer cell line (KF) with N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), the concentration of DPPE required for 50% inhibition of KF cell proliferation (IC50) was 1.7 microM. The IC50 of DPPE for inhibition of protein kinase C (PKC) activity was 3.0 microM, a similar value to those of other antiestrogens such as tamoxifen and clomiphene. DPPE also inhibited phosphorylation of mitogen-activated protein kinase in KF cells. When treatment with DPPE was started 7 days after inoculation of KF cells into nude mice, 50 mg/kg DPPE alone resulted in a significant growth retardation in the early stage of tumor growth. Although 25 mg/kg DPPE showed a similar effect to 2 mg/kg cisplatin (CDDP), the combination had the most marked tumor growth-inhibitory effect. Nude mice treated with combinations of CDDP and DPPE survived significantly longer than not only untreated, but also CDDP-alone-treated mice, while 50 mg/kg but not 25 mg/kg DPPE alone had an effect comparable to that of 2 mg/kg CDDP alone. If treatment with DPPE was begun from the day after tumor inoculation, the inhibitory effect of DPPE was further enhanced, especially when combined with CDDP. If treatment with DPPE was started in nude mice with a lower tumor burden, 25 mg/kg as well as 50 mg/kg DPPE had a similar effect to 2 mg/kg CDDP, in terms of survival. When DPPE was combined with CDDP, the effect was significantly enhanced, compared to that of either alone. These treatments could be done without any adverse side effect. Thus, we conclude that DPPE has an antiestrogen action and its tumor growth-inhibiting activity is enhanced on administration in combination with CDDP.

Animals↗
PubMed1997

Altered expression of gamma-glutamylcysteine synthetase, metallothionein and topoisomerase I or II during acquisition of drug resistance to cisplatin in human ovarian cancer cells.

This study was designed to elucidate the mechanisms of cisplatin (CDDP) resistance using two human ovarian cancer cell lines, KF and TYK, and two CDDP-resistant lines, KFr and TYK/R, derived from the former lines. KFr and TYK/R showed about 3-fold higher resistance to the cytotoxic effects of CDDP than their parental lines. They also showed a significant increase in sensitivity to not only etoposide, but also (+)-(4S)-4, 11-diethyl-4-hydroxy-9-[(4-piperidino -piperidino)carbonyloxy]-1H -pyrano[3',4':6,7]inodolizino[1,2-b]quinoline-3,14(4H, 12H)-dione hydrochloride trihydrate (CPT-11). Cellular CDDP accumulation levels in KFr and TYK/R were decreased from those of the parental cells. By contrast, the cellular glutathione (GSH) content in KFr cells was 1.7-fold higher than that in KF, whereas TYK/R cells had a 40% lower content than TYK cells. Cellular mRNA levels of drug-resistance-related genes, such as DNA topoisomerase (topo) I and topo II, glutathione S-transferase-pi (GST-pi), gamma-glutamylcysteine synthetase (gamma-GCS), and metallothionein (hMT) genes, were compared between drug-sensitive KF or TYK and KFr or TYK/R. KFr cells had 8.5- and 24.7-fold higher mRNA levels of gamma-GCS and topo II genes than KF cells while KFr had only a slight increase in GST-pi mRNA level as compared with KF. By contrast, TYK/R cells had 2.9- and 1.7-fold higher hMT and topo I mRNA levels than TYK cells. Acquisition of CDDP resistance in human ovarian cancer cells thus appeared to be related mainly to expression of gamma-GCS, topo II and hMT genes, and partly to that of topo I and GST-pi genes, in addition to a decrease in CDDP accumulation.

Antineoplastic Agents↗
PubMed1997

Hepatitis GB virus-C/hepatitis G virus infection in liver disease.

Hepatitis GB virus-C (HGBV-C)/hepatitis G virus (HGV) infection was investigated in 106 children with liver disease (54 boys and 52 girls, mean age 7.3 years); 12 with chronic hepatitis C virus infection, 29 with positive hepatitis B surface antigen, nine with idiopathic fulminant hepatic failure, seven with graft dysfunction after liver transplantation associated with autoimmune features, 20 with cryptogenic liver disease, and 29 with autoimmune liver disease. HGV RNA detected by reverse transcription polymerase chain reaction was found to be positive in 4/106 patients (3.8%). Risk factors were identified in three patients, including blood transfusion and/or medical treatment in Eastern Europe. The prevalence was higher than that of blood donors but lower than that of 2 adult patients with liver disease. HGV is not associated with any specific disease group and does not seem to be a major aetiological agent of liver disease in childhood in the UK.

Adolescent↗
PubMed1997

Is family history an independent risk factor for stroke?

OBJECTIVE: To estimate the influence of family history on the occurrence of stroke. METHODS: A case-control study was carried out from August 1992 to January 1994. The study population comprised 502 patients with a first stroke, aged between 20 and 70 years, who were treated at 48 affiliated hospitals. The same number of age and sex matched controls were selected from outpatients. Diagnoses were based on CT findings and clinical signs. There were 155 case-control pairs for subarachnoid haemorrhage, 158 for intracerebral haematoma, and 159 for cerebral infarction. Information about the patients and their families was obtained from a questionnaire which included the family histories of each subtype of stroke and other potential risk factors for stroke. The data were analysed focusing on the role of the family histories in the occurrence of stroke. RESULTS: In univariate analysis, the family histories of subarachnoid haemorrhage and intracerebral haematoma were positively associated with each of the subtypes of stroke (odds ratios 11.24 for subarachnoid haemorrhage, 2.39 for intracerebral haematoma), whereas family history of cerebral infarction was not a significant risk factor for its occurrence (odds ratio 1.41). Family history of intracerebral haematoma was correlated with a personal history of hypertension and habitual alcohol consumption. After adjustment for potential risk factors (hypertension, diabetes, hyperlipidaemia, obesity, alcohol consumption, and regular smoking), family history of subarachnoid haemorrhage still remained the most powerful risk factor for subarachnoid haemorrhage, whereas family history of intracerebral haematoma no longer showed a significant association with haematoma. CONCLUSION: Genetic factors play a major part in the pathogenesis of subarachnoid haemorrhage, and family history of subarachnoid haemorrhage is the strongest independent risk factor for the disease. On the other hand, family history of intracerebral haematoma was not an independent risk factor for haematoma, but it might be a good predictor, which indirectly influences the pathogenesis of intracerebral haematoma via certain hereditary components such as hypertension, and even lifestyle factors such as alcohol consumption. In cerebral infarction, genetic factors play a minor part in its pathogenesis.

Adult↗
PubMed1997

Parathyroid-hormone-related protein in human milk and its relation to milk calcium.

Parathyroid-hormone-related protein (PTHrP) is found in high concentrations in human milk. One of the possible physiological roles of PTHrP may be the regulation of calcium transport through the mammary gland. The relationship between milk PTHrP and Ca concentrations was evaluated in lactating women in the present study. Milk PTHrP has been quantified by immunoradiometric assay (IRMA) and radioimmunoassay (RIA). The IRMA detects PTHrP 1-72, and the RIA carboxyterminal region of PTHrP (C-PTHrP). Milk PTHrP 1-72 and C-PTHrP concentrations did not significantly change by breast-feeding. Milk PTHrP 1-72 changed significantly by the time of day, in contrast to C-PTHrP. Thus, PTHrP 1-72 rather than C-PTHrP may reflect an acute change in mammary PTHrP secretion. In lactating women in whom milk PTHrP and calcium concentrations were serially measured at 5-day intervals up to 26-30 days after delivery, milk PTHrP 1-72 progressively increased with duration of lactation. In contrast to PTHrP 1-72, milk C-PTHrP decreased during this period. And milk PTHrP 1-72 levels inversely correlated with C-PTHrP levels. Milk C-PTHrP but not PTHrP 1-72 levels correlated significantly with milk Ca concentrations. Although it is not certain whether the correlation between milk C-PTHrP and Ca levels is causally related, it may be that fragments of PTHrP detected as C-PTHrP are involved in the regulation of Ca transport through the mammary gland in women.

Calcium↗
PubMed1997

Cerebral aneurysms arising at nonbranching sites. An experimental Study.

BACKGROUND AND PURPOSE: The origin and pathogenesis of cerebral aneurysms arising at nonbranching sites are not clear. Using our animal model to induce cerebral aneurysms in rats, we examined induced aneurysms that developed at nonbranching sites. METHODS: In 35 Sprague-Dawley rats, the left common carotid artery was ligated and renal hypertension was produced to induce cerebral aneurysms. Twelve months later, the circle of Willis was carefully examined under a dissecting microscope. RESULTS: Other than cerebral aneurysms at branching sites of the circle of Willis, aneurysmal bulges developing at nonbranching sites were found in the proximal portion of the posteriorice rebral artery (P1) on the side of carotid ligation, which supposedly acted as a major collateral pathway after the ligation, in 19 of 35 treated rats. A total of 30 lesions were found in these 19 rats, and they were classified into fusiform aneurysms (22 lesions) involving the entire vessel wall for a short distance and saccular aneurysms (8 lesions) involving only a part of the wall and expanding laterally from the vessel wall. These P1s became larger in caliber and more tortuous after ligation. Aneurysms developed more frequently in proportion to these changes in these vessels. Moreover, most aneurysms in these vessels developed at or near the curvatures. All of the lateral aneurysms were found on the lateral wall of the curvatures of the vessels. CONCLUSIONS: The present findings indicate that cerebral aneurysms at nonbranching sites and saccular aneurysms at branching sites can occur under the same etiologic conditions. The site of origin is strongly related to hemodynamic stress.

Animals↗
PubMed1997

Anticoagulant therapy during successful pregnancy and delivery in a Kawasaki disease patient with coronary aneurysm--a case report.

Thirty-one-year-old woman with Kawasaki disease wanted a child. She had a large coronary aneurysm on the left main coronary artery and complete obstruction of the right coronary artery, but there was no sign of ischemia. Heparin anticoagulant therapy was begun 8 weeks after the onset of pregnancy. The activated partial thromboplastin time (APTT) was successfully maintained at 1.5 to 2.0 times normal value during pregnancy and puerperium. There were no thromboembolic complications during pregnancy or after an uneventful cesarean delivery. The neonate was healthy.

Adult↗
PubMed1997

Neurotoxicity testing of a new bioactive bone cement.

Bioactive bone cement (BABC) is a novel artificial bone cement. It has some noteworthy characteristics that are applicable to neurological surgery. The toxicity of BABC to the nervous system was tested by implanting BABC and polymethylmethacrylate (PMMA) cement as a control at the parietal and the suboccipital regions of the skull in beagles. The auditory brainstem response (ABR) was tested before and after implantation. Sections of the cerebral cortex and the acoustic nerve were examined at 3 and 6 months after implantation. No abnormal ABR was found in any animals. Histological examination of the cerebral cortex and acoustic nerve demonstrated slight gliosis in both the BABC and PMMA cement groups, but no other abnormalities.

Animals↗
PubMed1997

Potential efficacy of basic fibroblast growth factor incorporated in biodegradable hydrogels for skull bone regeneration.

Biodegradable gelatin hydrogels incorporating basic fibroblast growth factor (bFGF) were evaluated for their efficacy in bone regeneration using a rabbit model. Hydrogels with water contents of 85% and 98% were prepared using chemical crosslinking of gelatin with an isoelectric point of 4.9 in aqueous solution and, after freeze drying, were impregnated with an aqueous solution of bFGF to obtain bFGF-incorporated gelatin hydrogels. When they were implanted into bone defects measuring 6 mm in diameter in rabbit skulls (six animals/group), complete closure of the defect was observed at 12 weeks after implantation, regardless of the water content of the hydrogels. In contrast, bFGF did not enhance bone regeneration when applied to the skull defect in solution with phosphate-buffered saline (PBS). Also, gelatin hydrogels lacking bFGF were not effective in inducing bone formation, with fibrous tissue growing into the defect instead, similar to the skull defect seen in control rabbits treated with PBS. This indicates that the presence of hydrogels did not interfere with bone regeneration at the skull defect, probably because of their disappearance during biodegradation. It is concluded that the gelatin hydrogel is a promising matrix for effective induction of biological activity of bFGF for bone regeneration in skull and sinus defects.

Animals↗