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Biomedical subjects

M Funakoshi

Publications and source records attributed to M Funakoshi.

At least 37 records · Page 2Linked to original sources

An altered nuclear migration into the daughter bud is induced by the cyclin A1-mediated Cdc28 kinase through an aberrant spindle movement in Saccharomyces cerevisiae.

A strain of Saccharomyces cerevisiae that contains an integrated copy of a Xenopus cyclin A1 gene under the control of the GAL1 promoter has been constructed. On inducing expression of cyclin A1, the nuclear migration that occurs prior to division becomes aberrant. Instead of migrating to the neck between the mother cell and daughter bud, the nucleus, the short mitotic spindle and its associated two spindle pole bodies entered the daughter bud. This phenotype was induced by expression of an indestructible cyclin mutant, but not by a mutated cyclin A1 unable to activate Cdc28 kinase. The nuclear abnormality induced by cyclin A1 was overcome by cdc28 mutations that abolish its ability to bind cyclin A1. Both yeast cyclin Clb3 and Xenopus mitotic cyclin B produced the same phenotype, whereas G1 cyclin Cln2 did not. The results suggest that the proper movement of the nucleus through the spindle function during mitosis requires the appropriate activity of Cdc28 kinase mediated by specific cyclins.

Animals↗

The rise time of the monophasic action potential--a new index of local use-dependent conductivity by sodium channel blockers in human myocardium.

The kinetics of global use-dependent conduction slowing produced by sodium channel blockers in the human heart, estimated as a change in the QRS width, are known to be similar to those of use-dependent block of the maximum rate of depolarization in in vitro studies. However, the kinetics of the regional use-dependent decrease in conductivity have not been investigated. We examined whether the rise time of the monophasic action potential would be clinically useful as a marker of the local use-dependent decrease in conductivity by sodium channel blockers. In 12 patients without organic heart disease, monophasic action potentials (MAPs) were recorded at the right ventricular endocardium using a contact electrode before and after the administration of disopyramide (n = 6, 2 mg/kg, i.v.) or pilsicainide (class Ic agents, n = 4, 1 mg/kg, i.v., and n = 2, 150 mg, po) while the stimulus frequency was abruptly increased from 100/min to 150/min. The rise time, defined as the interval from the pacing pulse to the first peak deflection of the monophasic action potential, and the ORS width were measured simultaneously. In the absence of the sodium channel blockers, the abrupt increase in heart rate did not alter the QRS width or the rise time. In the presence of the agents, both variables were lengthened exponentially. The rate constants of onset changes in the QRS width and the rise time were 2.1 +/- 0.5 beats and 2.1 +/- 0.4 beats after the administration of disopyramide, and 7.5 +/- 3.0 beats and 8.2 +/- 4.0 beats after pilsicainide, respectively. The rate constant of the rise time was closely correlated with that of the QRS width. The present results are very closely comparable with the onset rate constants of use-dependent block of the maximum rate of depolarization in in vitro studies. These results suggest that (1) the rise time is a good indicator of local use-dependent decrease in conductivity by sodium channel blockers in human hearts and (2) the local use-dependent decrease in conductivity has kinetics similar to those of use-dependent sodium channel blocks.

Action Potentials↗

Fracture on removal of the ACE tibial nail.

We report four patients who sustained secondary fractures of the posterior wall of the tibial shaft during the removal of one pattern of intramedullary nail after fracture healing. The cause of this complication is discussed.

Adolescent↗

[Facioscapulohumeral muscular dystrophy (FSHD)].

Facioscapulohumeral muscular dystrophy (FSHD; MIM 158900) is one of the major forms of muscular dystrophy, and is inherited in an autosomal dominant fashion. In most patients with FSHD, deletion of 3.3 kb tandemly repeated units within the EcoRI fragment, as detected by p13E-11 (D4F104S1) on chromosome 4q35, is associated with the disease (FSHD1A or 4q35-FSHD). Rare (< 5%) 4q35-unlinked FSHD (FSHD1B) is also known, and therefore genetic heterogeneity exists among FSHD. Recent studies based on the distinction of 4q35 EcoRI fragments from those of 10q26 improved the reliability of molecular diagnosis of the disease (> 95% accuracy). However, gene for FSHD1A has not been identified yet. Identification of the FSHD gene and characterization of the gene product are waited on tiptoe with expectation.

Chromosomes, Human, Pair 4↗

Coronary angioplasty ameliorates hypoperfusion-induced endothelial dysfunction in patients with stable angina pectoris.

OBJECTIVES: This study sought to investigate the effect of coronary angioplasty on chronic hypoperfusion-induced endothelial dysfunction in patients with coronary heart disease. BACKGROUND: The endothelium is an important component for organ flow regulation. Ischemia with or without reperfusion is known to cause endothelial dysfunction. We tested the hypothesis that chronic hypoperfusion impairs endothelial function in the angiographically normal coronary artery segment distal to stenosis and that the impairment by chronic hypoperfusion is reduced by coronary angioplasty. METHODS: In 13 patients with stable angina pectoris, substance P (10, 30 and 100 pmol) and nitroglycerin (200 micrograms) were sequentially infused into the coronary artery in a cumulative manner on the day after coronary angioplasty. In 10 of these patients, vascular responses to these agents were again investigated 3 months after angioplasty. Changes in vascular diameter were evaluated in vessels located proximal and distal to the target lesion, both of which were angiographically normal, by performing computer-assisted quantitative coronary angiography. In five patients, the transstenotic pressure gradient was also measured with a pressure sensor-mounted guide wire before angioplasty. RESULTS: On the day after angioplasty, the magnitude of dilation by substance P in distal segments was significantly less than that in proximal segments and inversely correlated with the transstenotic pressure gradient (p < 0.05) and lesion stenosis (p < 0.05). There was no difference in nitroglycerin-induced vasodilation between the two vessel segment groups. Three months later, the impaired response to substance P in the distal segment was restored to normal. CONCLUSIONS: We conclude that chronic hypoperfusion impairs endothelium-dependent dilation of coronary artery distal to critical stenosis in patients with ischemic heart disease and that coronary angioplasty ameliorates the endothelial dysfunction within 3 months.

Aged↗

Phenotypic variability in male patients carrying the mutant ornithine transcarbamylase (OTC) allele, Arg40His, ranging from a child with an unfavourable prognosis to an asymptomatic older adult.

In five different Japanese families, we identified six male hemizygotes (aged 6, 9, 15, 17, 56, and 65 years) and a putative candidate (aged 48 years), carrying a mutant allele of the ornithine transcarbamylase (OTC) gene, a G to A substitution at nucleotide 119 in exon 2 generating histidine in place of arginine. OTC activity in the necropsied liver tissue was reduced to approximately 12% of the control and that of COS 1 cells transfected with Arg40His OTC cDNA was 10.2 +/- 1.8% of the control transfected with wild type OTC cDNA. Clinical features ranged from death during a hyperammonaemic attack (a 9 year old) to a 65 year old asymptomatic man. We consider that the amount of protein ingested by these subjects may be one predisposing factor leading to the manifestation of this disease.

Adolescent↗

[T cell receptor V beta repertoire of locoregional lymphocytes in malignant effusions].

We analyzed the T cell receptor (TCR) V beta repertoire of lymphocytes obtained from patients with malignant effusion treated by locoregional immunotherapy. Polymerase chain reaction using a panel of V beta subfamily specific oligonucleotide primers(V beta 1-20) was employed after reverse transcription of mRNA isolated from the locoregional cells. No major oligoclonality of TCR repertoire was observed in effusion lymphocytes before the treatment. The expression level of V beta 13.1 repertoire was significantly higher in effusion lymphocytes than in peripheral blood lymphocytes before treatment. V beta 20 gene expression increased significantly after locoregional administration of OK-432. It is suggested that TCR V beta 13.1 may be responsible for effusion lymphocytes and TCR V beta 20 for OK-432-related antigenic stimulus.

Adult↗

Replication of a Mamestra brassicae nuclear polyhedrosis virus in a newly established Mamestra brassicae cell line.

A continuous cell line, designated MbL-3, was newly established from minced neonate larvae of the cabbage armyworm, Mamestra brassicae. This new cell line is heteroploid, containing triploid cells predominantly at the frequency of about 50%. Doubling time of the cell population is 33 hrs. The Akutsu isolate of a Mamestra brassicae nuclear polyhedrosis virus (MbNPV) was examined for replication in 16 continuous cell lines, including the cell line MbL-3, from seven lepidoptera species: Mamestra brassicae, Pseudaletia separata, Spodoptera exigua, Spodoptera frugiperda, Spodoptera littoralis, Spodoptera litura and Plutella xylostella. Of these cell lines, only the MbL-3 cells supported a high replication of the virus. Four other Mamestra cell lines and a P. separata cell line showed a low virus-susceptibility, while the other cell lines were not permissive for the virus infection. Maximum infection rate of MbL-3 cells to the Akutsu isolate was 23.4%. The growth kinetics of this virus isolate in MbL-3 cells showed that the virus was released from infected cells 24 hrs p.i. and reached a maximal titer 96 hrs p.i. The number of polyhedral inclusion bodies (PIBs) reached a maximum of 10(7.5) PIBs/ml 120 hrs p.i.

Animals↗

In vivo and in vitro characterization of several isolates of spodoptera exigua nuclear polyhedrosis virus.

Spodoptera exigua nuclear polyhedrosis viruses (SeNPVs), isolated form five geographically distinct regions of Japan and Thailand, were characterized by their DNA restriction endonuclease pattern, level of virus production in a continuous cell line of S. exigua and biological activity to S. exigua larvae. The EcoRI and PstI fragments exhibited similar overall patterns with minor differences. Digestion of virus DNA from a plaque-purified isolate, SeNPV-I1, with PstI yielded 14 fragments and the estimated genome size was approximately 123 kbp. The SeNPV wild isolate from Kagoshima, SeNPV-KW, showed the highest yield of extracellular virus (ECV) in the Se301 cell line of S. exigua among five wild isolates, but there was no significant difference in the level of polyhedral inclusion body (PIB) formation. In comparative studies of biological activity using 2nd-instar S. exigua larvae, SeNPV-KW had the highest virulence with an LD50 value of 3.0 PIBs per larva. When 16 clones, plaque-purified from the Isahaya isolate, SeNPV-IW, were examined for genetic relatedness, seven distinct EcoRI patterns were observed, indicating that SeNPV-IW wild isolate consisted of a mixture of different genotypes.

Animals↗

A role of periodontal sensation in development of rhythmical chewing in dogs.

The sucking period of puppies was prolonged by 7 days and the start of rhythmical chewing was delayed to more than 50 postnatal days. In puppies having erupted teeth but no periodontal sensation due to nerve degeneration, chewing rhythm formation was delayed by 20 days. The rhythm of chewing was not affected by extraction of all primary teeth after rhythmical chewing had completed. These results suggest that afferent impulses from the periodontal mechanoreceptors play a role in the chewing rhythm formation at transition from sucking to chewing behavior in new born puppies.

Animals↗

Plaque assay for Spodoptera exigua and Autographa californica nuclear polyhedrosis viruses in a newly established cell line of the beet armyworm, Spodoptera exigua.

The nuclear polyhedrosis viruses of Spodoptera exigua (SeNPV) and Autographa californica (AcNPV) produced plaques in a newly established cell line of the beet armyworm, Spodoptera exigua. Plaques were composed of infected cells containing many polyhedra and were visible without any staining procedure. Dose-response assays showed a direct correlation between the number of plaques and the inoculum size. Growth kinetic studies of the two viruses, using the developed plaque assay system, revealed that the release of extracellular viruses began 6 hrs post infection (p.i.) and the titer reached a plateau 48 hrs p.i. The sensitivity of this plaque assay system was 100 times greater for the heterologous AcNPV than for the homologous SeNPV.

Animals↗

[Skin reaction to OK-432 and its dosage for locoregional administration].

Establishment of optimal dosage of OK-432, a streptococcal preparation, was studied based on its skin test was studied. Locoregional immunotherapy using OK-432 was conducted for patients with malignant fluids. More OK-432 was administered to patients having a weaker skin reaction to OK-432 and less to those having a stronger one, corresponding to their redness diameter of skin reaction. There was a marked difference in OK-432-skin test among patients. Some patients with malignant fluids having small redness responded to the treatment after a large amount of OK-432, and others were well controlled by a smaller dosage of OK-432. It is suggested that OK-432-skin test may provide the optimal dosage for local treatment of malignant fluids.

Ascitic Fluid↗

[Intra-arterial infusion chemotherapy of cisplatin (CDDP)-lipiodol suspension using implantable injection port for unresectable liver cancer patients].

Intra-arterial CDDP-Lipiodol infusion chemotherapy using an implantable port was effective in 10 unresectable liver cancer patients, including 7 hepatocellular and 3 metastatic cases. CDDP-Lipiodol suspension (10 mg of CDDP/1 ml of Lipiodol) was administered at the dose of 25 mg/m2 of CDDP biweekly from 2 to 9 times. The clinical responses were defined as 4 PR (40%), 5 NC (50%), including 3 MR, and 1 PD (10%). The efficacy rate was 40%. The level of AFP and CEA was reduced in all PR and NC cases except one. Side effects were nausea (70%), low-grade pyrexia (50%), abdominal pain (30%), and liver dysfunction (20%), but they were tolerable and transient.

Carcinoembryonic Antigen↗

Gustatory neural responses in preweanling mice.

Taste sensitivity of preweanling mice was studied by examining responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to various taste stimuli, and was compared to that of adult mice. In mice of 7-10 days of age, comparing to that of the CT nerve, threshold of the GL nerve for monosodium l-glutamate (MSG) was low, but those for sucrose and NaCl were high. Sensitivities to HCl and quinine-HCl were similar between the CT and GL nerves, although that to quinine-HCl was larger in the GL nerve than in the CT nerve in adult mice. Enhancement of MSG responses by addition of GMP was observed in the CT nerve but not in the GL nerve in this age group. In mice of 8-16 weeks of age, threshold of the GL nerve for MSG became higher but that for NaCl became lower. Enhancement of MSG responses by addition of GMP appeared also in the GL nerve. Inhibition of NaCl responses by amiloride was observed in the CT nerve. These results suggest that, in mice, the GL nerve is important taste input for umami substances especially during the preweanling period, whereas the CT nerve is for sweet and salty substances. Properties of umami and salt receptor systems change during the postweanling period.

Animals↗

Development of masticatory muscles and oral behavior from suckling to chewing in dogs.

1. At the age of 20 postnatal days, more than a half of the dogs (13/20) showed incisor eruption. At the age of 25 postnatal days, half of the dogs (10/20) showed molar eruption. 2. At the age of 24 postnatal days, half of the dogs (10/20) started chewing behavior. 3. EMG amplitudes of temporal muscle were larger than that of masseter muscle until 26.5 days after birth, but they were reversed at 26.5 days after birth. 4. This suggests that in dogs the earlier teeth erupted, the earlier the dominant oral behavior was changed from suckling to mastication, and concomitantly the dominant muscle for the oral behavior was changed from the temporal to the masseter muscle.

Animals↗

[Clinicopathological estimation of intra-arterial infusion chemotherapy of locally advanced breast cancer].

The effect of intra-arterial infusion chemotherapy with adriamycin as a preoperating procedure was analyzed clinicopathologically in 30 cases with locally advanced breast cancer. A clinical response rate of 53.3% was obtained by the treatment and remarkable degenerative changes of tumor cells were noted histologically in the primary lesions. But there was no relationship between histological therapeutic effect and regression rate in tumors. A recurrence rate showed a higher correlation with histological therapeutic effect in comparison with clinical therapeutic effect. Especially, non-necrosis type that tumor cells were still alive mainly in the vessels showed significantly a higher recurrence rate in comparison with a central necrosis type or focal necrosis with fibrosis and hyalinization type. The local regional recurrence rate of patients receiving intra-arterial infusion chemotherapy was lower than that of patients, as the historical controls, receiving no therapy before operation. But prognostically, there was no significant difference in a survival rate between both groups. So, after operation, other alternative or multidisciplinary adjuvant chemo-endocrine therapy seems to be necessary for improving the survival rate.

Breast Neoplasms↗