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Biomedical subjects

T Funakoshi

Publications and source records attributed to T Funakoshi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prognostic factors in supratentorial WHO grade II astrocytoma in adults.

The records of 33 adult patients with supratentorial World Health Organization grade II astrocytoma (A-II) treated between January 1980 and April 1997 at our hospitals were retrospectively reviewed. All tumours were surgically resected or biopsied and their MIB-1 labelling indices (LIs) were less than 1.5%. The median time to tumour progression after the initial surgery was 60 months, and the 5- and 10-year tumour progression-free rates were 53 and 39%, respectively. The median survival time was 107 months, and the 5- and 10-year survival rates were 66 and 43%, respectively. The major cause of death was tumour recurrence with malignant transformation, comprising 93% of all deaths due to unrestrained tumour growth. In a univariate analysis for survival rate by log-rank test, age (< 60 years), Karnofsky Performance Scale score (90-100%), tumour location (except for the basal ganglia), and extent of surgery (more than biopsy) were revealed to be significant positive prognostic factors. A Cox proportional hazard multivariate regression analysis confirmed that the age was the only independent, significant positive prognostic factor in this series. The survival time after the initial surgery in patients without radiotherapy tended to be prolonged compared with those of the patients with radiotherapy. Of the 26 patients who received radiotherapy, however, the survival time after the initial surgery in the nine patients with intraoperative radiotherapy was significantly prolonged compared with the 17 patients who received sole external beam radiotherapy. Gender, symptoms, histology, p53 LI, enhancement on CT/MRI, cyst, calcification and chemotherapy were not shown to be significant prognostic factors. The optimal management strategy for A-II is expected to be established by clarification of the natural history with cytological and molecular biological analyses of the biological features of this disease.

Adult↗
PubMed1998

Prenatal diagnosis of fetal urogenital abnormalities with oligohydramnios by magnetic resonance imaging using turbo spin echo technique.

Turbo spin echo technique is a sequence that enables T2 weighted magnetic resonance (MR) images to be obtained in a few seconds. The purpose of this study is to evaluate the usefulness of this sequence in the prenatal diagnosis of fetal urogenital abnormalities associated with oligohydramnios, which make the ultrasound examination inconclusive. Two fetuses suspected of having prune belly syndrome and polycystic kidney on ultrasound examination were studied by MR imaging using turbo-spin echo method in utero. The images were compared with prenatal ultrasonography or post-mortem findings. In both fetuses, abnormalities were diagnosed correctly. This sequence is useful because it provides images of diagnostic quality in a very short scanning time.

Adult↗
PubMed1997

The mechanisms of nickel uptake by rat primary hepatocyte cultures: role of calcium channels.

The present study was designed to clarify the mechanism of nickel (Ni) uptake in primary cultures of rat hepatocytes. Exposure of the hepatocytes to Ni (2-50 microM; as NiCl2) for up to 6 h was not cytotoxic, as assessed by the tetrazolium-based dye (MTT) assay. Hepatocytes were treated with 10 microM NiCl2 in the absence or presence of calcium (Ca) and magnesium (Mg) (1 mM). Ni uptake was increased by 19% in medium lacking Mg or Ca and was increased by 37% in Ca- and Mg-free medium. The role of Ca channels on Ni uptake by the hepatocytes was investigated. Pretreatment with nicardipine or verapamil (200 microM), potent inhibitors of Ca channels, decreased Ni uptake by 20%. This effect was only observed when the cells were incubated in the absence of Ca. Pretreatment with vasopressin (100 nM), a well-known Ca channel agonist, significantly increased Ni uptake by the hepatocytes (24%). To determine the involvement of carrier-mediated processes on Ni uptake, the effect of temperature was also investigated. At 4 degrees C the Ni uptake was decreased by 20% compared to uptake at 37 degrees C. These results indicate that Ni uptake by the hepatocytes occurs, at least in part, through the Ca channel transport processes. Further study will be required to assess what other mechanisms are involved.

Animals↗
PubMed1997

Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae.

We have isolated 14 apg mutants defective in autophagy in yeast Saccharomyces cerevisiae (Tsukada and Ohsumi, 1993). Among them, APG1 encodes a novel Ser/Thr protein kinase whose kinase activity is essential for autophagy. In the course of searching for genes that genetically interact with APG1, we found that overexpression of APG1 under control of the GAL1 promoter suppressed the autophagy-defective phenotype of apg13-1 mutant. Cloning and sequencing analysis showed that the APG13 gene encodes a novel hydrophilic protein of 738 amino acid residues. APG13 gene is constitutively expressed bot not starvation-inducible. Though dispensable for cell proliferation, APG13 is important for maintenance of cell viability under starvation conditions. apg13 disruptants were defective in autophagy like apg13-1 mutants. Morphological and biochemical investigation showed that a defect in autophagy of delta apg13 was also suppressed by APG1 overexpression. These results imply genetic interaction between APG1 and APG13.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Effects of dithiocarbamates on toxicity of cadmium in rat primary hepatocyte cultures.

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the toxicity of Cd in the rat primary hepatocyte cultures were studied. Cytotoxicity was assessed by measuring cell viability, extra cellular lactic dehydrogenase (LDH) activity, and intracellular lipid peroxidation and active oxygen species. Primary hepatocyte cultures were treated with 109CdCl2 (5, 10 or 50 microM Cd and 1.7 KBq of 109Cd/well) for 30 min or 4 h. BGD or HBGD was added to the culture medium to make the final concentration of 100 microM and incubated for 4.5 h in 30 min Cd exposure or 1 h in 4 h Cd exposure. Decreases in the hepatocyte viability caused by all Cd exposure concentrations were significantly prevented by treatment with BGD or HBGD. The treatment with the chelating agents for 4.5 h after Cd exposure for 30 min significantly prevented increases in extracellular LDH activity. Increases in the lipid peroxidation in hepatocytes exposed to Cd for 30 min or 4 h were prevented significantly by treatment with BGD or HBGD for 4.5 h or 1 h, respectively. Moreover, the increases in the level of active oxygen species caused by Cd exposure for 30 min were significantly prevented by treatment with the chelating agents for 1.5 h. These findings suggest that BGD and HBGD protect against the cytotoxicity of Cd in rat primary hepatocyte cultures and that the protective effects of chelating agents presumably result from a decrease in the Cd level, the effective sequestration of the reactive Cd ion, and the direct preventive effect on the active oxygen species in the hepatocytes.

Animals↗
PubMed1997

Primary pleomorphic adenoma in posterior cranial fossa.

A 35-year-old woman had an intradural tumor in the posterior fossa adjacent to the posterior wall of the left pyramidal bone, which was totally removed and histologically diagnosed as a pleomorphic adenoma. Follow-up examination for 2 years showed no recurrence of the tumor. There was no primary lesion in any other gland of the body, and therefore there is no alternative but to conclude a "migration" of some gland cells. The pathogenesis of this tumor remains unclassified.

Adenoma, Pleomorphic↗
PubMed1997

Effect on prognosis of bone marrow infiltration detected by magnetic resonance imaging in small cell lung cancer.

The staging system of limited disease (LD) and extensive disease (ED) is widely used and has been shown to provide useful prognostic information in cases of small cell lung cancer (SCLC). However, accurate examinations are necessary for correct staging. In this report, we evaluated the clinical usefulness of magnetic resonance imaging (MRI) of bone marrow in SCLC. 37 patients with LD by standard staging and 41 with ED were examined with bone marrow MRI. Results of bone marrow MRI did not influence the choice of treatment in patients with LD. For subsequent analysis, patients with LD were divided into two groups: patients in whom bone marrow infiltration was detected with MRI (MRI-positive LD group) and those in whom it was not (MRI-negative LD group). Focal or diffuse metastases to bone marrow were detected with MRI in 46% (36/78) of all patients and 35% (13/37) of LD patients. The response rates to treatment in patients with MRI-positive LD were lower than those in patients with MRI-negative LD (P = 0.006). The survival of patients with MRI-positive LD was worse than that of MRI-negative LD (generalised Wilcoxon test: P = 0.0157), and closer to that of ED. Multivariate analyses using a Cox model that included the result of bone marrow MRI, performance status, chemotherapy regimen, radiotherapy and serum lactose dehydrogenase (LDH) level showed that the result of bone marrow MRI remained a prognostic factor in SCLC patients with limited disease. Bone marrow examination with MRI is useful for better staging of SCLC. According to our analysis of response rates and survival, MRI-positive LD should be considered a type of ED.

Bone Marrow Neoplasms↗
PubMed1997

Comparative effects of disulfiram and diethyldithiocarbamate against testicular toxicity in rats caused by acute exposure to cadmium.

Disulfiram (DSF) and diethyldithiocarbamate (DED) were compared for their protective effects against the testicular toxicity induced by acute exposure to cadmium (Cd) in rats. Rats were injected subcutaneously with CdCl2 126.7 mumol (3 mg) Cd/kgl, and 30 min later they were injected intraperitoneally with DSF (0.05-0.5 mmol/kg) or DED (0.1-1 mmol/kg). The treatment with DSF at dose levels of 0.1-0.5 mmol/kg prevented the increases in testicular lipid peroxidation and calcium (Ca) concentrations and the decreases in testicular weight that were observed at 7 d after Cd injection. DED at dosage levels of 0.2-1 mmol/kg likewise reduced Cd-induced testicular toxicity. An increase in testicular iron (Fe) concentrations at 7 d and sterility at 59 d after Cd injection were almost completely blocked by treatment with DSF or DED at the highest doses, but lower doses of DSF or DED were ineffective. These results indicated that DSF, which is metabolized to DED, had a protective effect against Cd-induced testicular toxicity nearly equivalent to DED at approximately one-half the dose.

Animals↗
PubMed1997

Preventive effects of saponins from puerariae radix (the root of Pueraria lobata Ohwi) on in vitro immunological injury of rat primary hepatocyte cultures.

The preventive effects of saponins from Puerariae Radix toward in vitro immunological liver injury using an antiserum against the rat liver plasma membranes on primary cultured rat hepatocytes were studied. Crude saponin from Puerariae Radix inhibited the elevation of alanine aminotransferase (ALT) activity at the dose of 90 micrograms/ml. The inhibition was stronger than that of glycyrrhizin, which was a positive control drug. The representative saponins in this drug, soyasaponin I and kudzusaponin SA3, were also more effective than glycyrrhizin, although their effects were weaker than that of crude saponin at the lower doses (90, 200 micrograms/ml). At 500 micrograms/ml, kudzusaponin SA3 showed antihepatotoxic activity equal to that of crude saponin.

Animals↗
PubMed1997

Clinical analysis of recurrent subarachnoid hemorrhage after neck clipping surgery.

The clinical features of recurrent subarachnoid hemorrhage (SAH) after neck clipping surgery were investigated in a series of 1,436 consecutive patients treated between 1980 and 1994, and seven patients treated prior to 1980. Recurrent SAH occurred within 1 month in seven patients and between 1.5 and 20 years in 20 patients (mean interval 9.2 years) from the first surgery. The patients were aged from 31 to 76 years (mean 49.8 years) at the first SAH. There were 19 females and eight males. Recurrent SAH occurred at the same site as the prior aneurysms in 12 cases, at an infundibular dilatation in three cases, de novo aneurysms in nine cases, untreated multiple aneurysms in two cases, and unknown in one case. The main causes for early recurrent SAH were incomplete clipping or untreated multiple aneurysms, whereas late recurrent SAH was due to de novo aneurysms, untreated multiple aneurysms, or regrowth aneurysm at the prior site. The outcomes of late recurrent SAH were good in eight cases, moderate disability in two, severe disability in three, and dead in seven, whereas most cases of early recurrent SAH resulted in poor outcome. Immediate postoperative angiography is desirable in cases with incomplete clipping, because early recurrent SAH resulted in poor outcomes. De novo or regrowth aneurysms caused late recurrent SAH, so follow-up angiography is strongly recommended for young patients, even if complete clipping was achieved.

Adult↗
PubMed1996

Molecular cloning and characterization of murine IL-12 genes.

IL-12 is a heterodimeric cytokine composed of two covalently linked chains, p40 and p35. p40 expression appears to be restricted to monocytes/macrophages and B cells and is highly regulated, while p35 is more ubiquitously and constitutively expressed. To investigate the mechanism involved in the regulation of IL-12 expression, we molecularly cloned and characterized the murine p40 and p35 genes. The p40 gene spans over 14 kb, consists of eight exons and seven introns, and was shown to be localized on chromosome 11A5-B2 by fluorescence in situ hybridization. A single major transcription initiation site was detected by primer extension analysis, and a TATA box was found at approximately 30 bp upstream from the transcription initiation site. The 5' flanking region preceding the transcription initiation site induced the enhanced expression of a promoterless reporter gene after LPS stimulation when transfected into a macrophage-like cell line. In contrast, the p35 gene spans over 8 kb and consists of seven exons and six introns on chromosome 6C, and multiple transcription initiation sites were detected. The 5' flanking region lacks canonical TATA and CAAT boxes at the appropriate position, but, instead, contains GC-rich sequences and constitutively mediated promoter activity when placed upstream of a promoterless reporter gene and transfected into a B cell lymphoma cell line. Thus, the characteristics of promoter regions of p40 and p35 genes are quite different, and this would account for the different regulations of p40 and p35 expression.

Amino Acid Sequence↗
PubMed1996

Preferential localization of annexin V to the axon terminal.

To examine the participation of annexin V, a member of Ca(2+)-dependent phospholipid-binding proteins, in the process of synaptic vesicle exocytosis, rat central nervous tissue was analysed using biochemical and morphological techniques. By both fluorescence and confocal laser scanning microscopy, immunoreactivity for annexin V was predominantly localized around neuronal somata and dendrites, and the reactivity was mostly co-labeled with that for synaptophysin. The annexin V immunoreactivity was also detectable, but less intensely, in neuronal perikarya, glial cells and endothelial cells. Both immunoblot and immunoelectron microscopic analyses with intact tissues, synaptosomes and purified synaptic vesicles showed that annexin V was expressed in neurons, preferentially concentrated in axon terminals and associated with synaptic vesicles. Purified synaptic vesicles were relatively homogeneously distributed in the medium where Ca2+ was removed and thus the amount of annexin V was reduced drastically. The vesicles tended to be clustered in the fraction where endogenous annexin V is maintained, and the clusters were more conspicuous when purified human annexin V was added. Synaptic vesicles forming the clusters were not directly fused with each other but separated by a 10-15 nm gap that corresponded well with the size of single annexin V molecules. In axon terminals, globular structures 12-13 nm in diameter, similar in dimension to annexin V molecules, were distinctly found to be attached to the cytoplasmic surface of both vesicle membranes when the two vesicles were close to each other. These results suggest that annexin V belongs to the group of synaptic vesicle-associated proteins. Although its localization and significance in non-neuronal cells were not analysed here, at least in the axon terminal annexin V may participate in the cluster formation of synaptic vesicles by linking with the cytoplasmic surface of the vesicles in a Ca(2+)-dependent manner.

Animals↗
PubMed1996

Pulmonary toxicity of systemic terbium chloride in mice.

Terbium (Tb) is a rare earth metal that finds use in several emerging technologies. However, little is known about the biological effects of Tb. Thus, in this study the pulmonary toxicity of systemic Tb in mice was investigated. Mice were treated intravenously with a single dose of 20 or 200 mumol Tb/kg, as TbCly and killed at 3, 6, 12, 24, 48, or 72 h later. Administration of Tb at a dose of 200 mumol/kg increased pulmonary weight, lipid peroxidation, and protein content but decreased pulmonary glutathione content. Pulmonary gamma-glutamyl transpeptidase (gamma-GTP) activity was increased after Tb administration at a dose of 200 mumol/kg. Pulmonary alkaline phosphatase (ALP) activity was also increased after Tb administration at a dose of 200 mumol/kg. Investigation of the defense system against oxidative damage in the lung showed that superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all decreased after Tb administration at the higher dose. The concentrations of Tb, Ca, and P in lung was increased by the dose of 200 mumol/kg. These results suggest that pulmonary lipid peroxidation may be an early and sensitive consequence of Tb exposure and that SOD, CAT, and GSH-Px might be considered as potential modulators of Tb-induced lipid peroxidation. The mechanisms involved in Tb-induced pulmonary lipid peroxidation deserve further study.

Alkaline Phosphatase↗
PubMed1996

Selective stabilization of tau in axons and microtubule-associated protein 2C in cell bodies and dendrites contributes to polarized localization of cytoskeletal proteins in mature neurons.

In mature neurons, tau is abundant in axons, whereas microtubule-associated protein 2 (MAP2) and MAP2C are specifically localized in dendrites. Known mechanisms involved in the compartmentalization of these cytoskeletal proteins include the differential localization of mRNA (MAP2 mRNA in dendrites, MAP2C mRNA in cell body, and Tau mRNA in proximal axon revealed by in situ hybridization) (Garner, C.C., R.P. Tucker, and A. Matus. 1988. Nature (Lond.). 336:674-677; Litman, P., J. Barg, L. Rindzooski, and I. Ginzburg. 1993. Neuron. 10:627-638), suppressed transit of MAP2 into axons (revealed by cDNA transfection into neurons) (Kanai, Y., and N. Hirokawa. 1995. Neuron. 14:421-432), and differential turnover of MAP2 in axons vs dendrites (Okabe, S., and N. Hirokawa. 1989. Proc. Natl. Acad. Sci. USA. 86:4127-4131). To investigate whether differential turnover of MAPs contributes to localization of other major MAPs in general, we microinjected biotinylated tau, MAP2C, or MAP2 into mature spinal cord neurons in culture (approximately 3 wk) and then analyzed their fates by antibiotin immunocytochemistry. Initially, each was detected in axons and dendrites, although tau persisted only in axons, whereas MAP2C and MAP2 were restricted to cell bodies and dendrites. Injected MAP2C and MAP2 bound to dendritic microtubules more firmly than to microtubules in axons, while injected tau bound to axonal microtubules more firmly than to microtubules in dendrites. Thus, beyond contributions from mRNA localization and selective axonal transport, compartmentalization of each of the three major MAPs occurs through local differential turnover.

Animals↗
PubMed1996

Active transport of photoactivated tubulin molecules in growing axons revealed by a new electron microscopic analysis.

To determine whether tubulin molecules transported in axons are polymers or oligomers, we carried out electron microscopic analysis of the movement of the tubulin molecules after photoactivation. Although previous optical microscopic analyses after photobleaching or photoactivation had suggested that most of the axonal microtubules were stationary, they were not sufficiently sensitive to allow detection of actively transported tubulin molecules which were expected to be only a small fraction of total tubulin molecules in axons. In addition, some recent studies using indirect approaches suggested active polymer transport as a mechanism for tubulin transport (Baas, P.W., F.J. Ahmad. 1993. J. Cell Biol. 120:1427-1437; Yu, W., V.E. Centonze, F.J. Ahmad, and P.W. Bass, 1993, J. Cell Biol. 122:349-359; Ahmad, F.J., and P.W. Bass. 1995. J. Cell Sci. 108:2761-2769). So, whether transported tubulin molecules are polymers or not remain to be determined. To clear up this issue, we made fluorescent marks on the tubulin molecules in the axons using a photoactivation technique and performed electron microscopic immunocytochemistry using anti-fluorescein antibody. Using this new method we achieved high resolution and high sensitivity for detecting the transported tubulin molecules. In cells fixed after permeabilization, we found no translocated microtubules. In those fixed without permeabilization, in which oligomers and heterodimers in addition to polymers were preserved, we found much more label in the regions distal to the photoactivated regions than in the proximal regions. These data indicated that tubulin molecules are transported not as polymers but as heterodimers or oligomers by an active mechanism rather than by diffusion.

Animals↗
PubMed1996

Deep negative T waves and abnormal cardiac sympathetic image (123I-MIBG) after the Great Hanshin Earthquake of 1995.

The authors report the increased incidence of patients with deep negative T waves without Q wave after the Great Hanshin Earthquake of 1995. Subjects underwent cardiac metaiodobenzyl guanidine (123I-MIBG) imaging, 201Tl scintigraphy, and coronary angiography. Among 2,756 inpatients of the preceding 5-year period, 33 (1.2%) showed the deep negative T waves, whereas 6 of 94 (6.4%; P < 0.001) showed it after the earthquake. Four of six patients had an episode of chest pain. Cardiac metaiodobenzyl guanidine imaging revealed the extent defects in all six patients despite a minimal change of 201Tl image. In addition, cardiac metaiodobenzyl guanidine imaging washout rate was hastened not only in the defect area but also in the nondefect area, which suggested augmented sympathetic activation. Natural disasters can affect the frequency of deep negative T waves, which relate abnormal cardiac sympathetic imaging.

3-Iodobenzylguanidine↗
PubMed1996

Effect of nickel on enzymatic activities in the mouse pancreas.

The effect of nickel (Ni) on the enzymatic activities in the pancreas of mice was studied. Administration of Ni at the dose of 5 mg Ni/kg increased the trypsin activity and decreased carboxypeptidase A activity, but did not affect the activities of chymotrypsin, carboxypeptidase B, amylase, and lipase. Increases in Ca concentrations in the pancreas after Ni administration were observed. In the pancreatic slice experiments, Ni treatment showed a slight decrease in trypsin activity and remarkable decreases in chymotrypsin and carboxypeptidase A activities, and Ca treatment induced increases in the activities of trypsin and carboxypeptidase A. These results suggest that the increase in trypsin activity in the pancreas after Ni administration results from the activation of trypsinogen by the Ca ion and that the decrease in carboxypeptidase A activity is based on the inhibitory effect of Ni on carboxypeptidase A activity.

Animals↗