Biomedical subjects

M Furuta

Publications and source records attributed to M Furuta.

At least 55 records · Page 3Linked to original sources

PubMed1999

Uniformity of biological effect in high-dose rate stepping source brachytherapy: an in vitro study.

In brachytherapy with a high dose rate of iridium-192, to make a flat isodose surface that covers a target volume, the dwell times of the single stepping source are computer adjusted. However, the dose rates of the irradiation vary with the positions in the volume. To examine this effect, we developed an in vitro model of stepping source brachytherapy with a 20 cm long target volume, and determined the uniformity of the biological effect in the volume on two human cancer cell lines (WiDr and A549) plated on a multi-well plate. When the source-cell distance was 10 mm, D1 (radiation dose for 1% survival) was similar in seven positions among the target volume for both cell lines. In contrast, at the 3 mm source-cell distance for one of the two cell lines (A549), D1 in the centre of the volume was significantly higher than at the periphery, suggesting a milder antitumour effect in the centre. Considering the possible decreased effect in the centre of the target volume, where most cancers clinically exhibit their maximum tumour volume, a minimum increase in radiation dose in the centre may be clinically reasonable, especially when dose reference points are set close to the source.

Adenocarcinoma↗

PubMed1999

Isolation and characterization of a novel HS1 SH3 domain binding protein, HS1BP3.

We have isolated a novel gene, HS1BP3, which encodes an HS1 binding protein. Analysis of HS1BP3 cDNA indicates several potentially important segments, including a PX domain, a leucine zipper, immunoreceptor tyrosine-based inhibitory motif-like motifs and proline-rich regions. HS1BP3 associates with HS1 proteins in vivo as confirmed by immunoprecipitation in B and T cell lines. HS1BP3 preferentially associates with the HS1 SH3 domains rather than with other SH3 molecules, suggesting a role of HS1BP3 as an HS1 signaling mediator. Overexpression of mutant HS1BP3 protein in T cell lines results in decreased IL-2 production. Our data suggest a novel role for HS1BP3 in lymphocyte activation.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Endobronchial brachytherapy for recurrent thymoma showing endobronchial polypoid growth.

The authors report a case of recurrent thymoma displaying endobronchial polypoid growth. Initially, the patient had invasive thymoma with intracaval growth into the right atrium. He was treated with multimodality therapy consisting of chemotherapy, surgical resection, and radiotherapy (50.4 Gy). Both 3 years and 6 years after the initial treatment, the tumor recurred outside the reconstructed superior vena cava. The patient was treated with repeated radiotherapy (50.4 Gy and 40 Gy), and remission was achieved. Eight years after the first therapy, an endobronchial polypoid lesion was detected in the right upper lobe bronchus and was histologically found to be thymoma. Endobronchial high-dose rate brachytherapy (20 Gy at 3 mm/5 fractions) was carried out for palliation because the recurrent tumor occurred outside of the superior vena cava area, which had been reirradiated. After the treatment, the endobronchial tumor shrunk remarkably in size without adverse effects. No tumor regrowth has been noted after a follow-up of 10 months.

Aged↗

PubMed1999

Insulin sensitivity is not affected by mutation of codon 972 of the human IRS-1 gene.

We investigated the relationship of codon 972 polymorphism of the insulin receptor substrate-1 (IRS-1) gene with insulin resistance in the Japanese population. Among 130 patients with type-2 diabetes mellitus (DM), we identified 6 who were heterozygous for the Gly972Arg mutation. Among 144 healthy subjects, 6 were heterozygous and 1 was homozygous for the mutation. A hyperinsulinemic euglycemic clamp study was performed in 3 of 6 diabetic patients with the heterozygous Gly972Arg mutation and in 60 without it. Both groups showed almost the same levels of insulin sensitivity (glucose infusion rate, GIR = 50.2 +/- 3.0 vs. 51.3 +/- 12.1 micromol/kg/min). Similarly, there was no difference in insulin sensitivity between healthy subjects with and without the mutation using the homeostasis model assessment (HOMA index = 1.14 +/- 0.50 vs. 1.02 +/- 0.63). The frequency of the Gly972Arg allele was not increased in diabetic patients compared with control subjects even in aged (>50 years old) or obese (BMI >/=25) subjects. Among healthy subjects, we identified a 25-year-old male with the homozygous Gly972Arg allele. He was slightly obese (BMI = 25.5) but showed relatively high insulin sensitivity, almost equal to that of healthy subjects without the mutation (GIR = 67.2 vs. 71.8 +/- 22.0 micromol/kg/min). Because the GIR in healthy subjects was significantly higher compared with that in type-2 DM patients, we speculate that another genetic or environmental factor producing a more deleterious effect on insulin sensitivity may exist in diabetic patients. We conclude that this gene abnormality does not play a role in the pathogenesis of insulin resistance and type-2 DM.

Adult↗

PubMed1999

Clinical evaluation of repeat apheresis donors in Japan.

BACKGROUND AND OBJECTIVES: To ascertain the safety of repeat apheresis donation, hematological and biochemical tests were performed on 511 donors with a donation rate of over 6 times per year for a period of 12-19 months. MATERIALS AND METHODS: Repeat donors who had apheresis more than 6 times in the previous year were chosen. Data for the repeat donors at the start of the experiments were compared with those at the end of the study. Blood samples were taken prior to donation. Serum protein, albumin, immunoglobulin G, A, and M, serum ferritin levels were determined by biochemical tests. RESULTS: When compared to prospective donors of 400 ml, WBC, lymphocytes, and serum ferritin levels were lower in a roughly frequency-dependent manner in female and male donor groups at the beginning of the study. All the data for the male group remained almost constant with increasing frequency of apheresis donation. However, in the female group, ferritin levels significantly decreased with over 21 donations. CONCLUSIONS: The present data showed that the serum ferritin level of the female donors decreased the most with increasing frequency of apheresis donation. The cumulative RBC left in the collecting chamber and for the laboratory test is discussed in relation to a possible cause of iron deficiency in frequent apheresis donors.

Adult↗

PubMed1999

Plasma brain natriuretic peptide levels in normotensive noninsulin-dependent diabetic patients with microalbuminuria.

Brain natriuretic peptide (BNP), a member of the natriuretic peptide family, is produced and released from cardiac ventricles. BNP regulates the body fluid volume, blood pressure, and vascular tones through the A-type guanylate cyclase-coupled receptor. The presence of renal dysfunction in patients with diabetes affects the plasma levels of atrial natriuretic peptide (ANP). In the present study, we investigated the plasma levels of BNP and ANP and their relationship in normotensive diabetic patients with normoalbuminuria and microalbuminuria. Forty-seven normotensive lean noninsulin-dependent diabetic patients (31 with normoalbuminuria, 16 with microalbuminuria), with normal cardiac function, and 30 age-matched control subjects were enrolled in this study. The plasma levels of BNP in diabetic patients with microalbuminuria were significantly higher than those in diabetic patients with normoalbuminuria (16.7+/-2.4 vs. 9.6+/-1.3 pg/mL, P<0.01) or normal subjects (16.7+/-2.4 vs. 7.0+/-0.6 pg/mL, P<0.01). There was a significant positive correlation between plasma BNP levels and urinary albumin excretion rate in all diabetic patients (r = 0.58, P<0.0001). There was also a significantly positive correlation between plasma BNP and ANP levels in diabetic patients (r = 0.62, P<0.0001). The increased plasma level of BNP in patients with microalbuminuria and its significant correlation with urinary albumin excretion rate suggest that the elevated circulating levels of BNP are caused by the presence of diabetic nephropathy. Down-regulation of A-type guanylate cyclase-coupled receptor of renal tubules may explain the increased plasma levels of both BNP and ANP in normotensive diabetic patients with microalbuminuria.

Albuminuria↗

PubMed1999

[Warfarin potassium for impending central retinal vein occlusion].

PURPOSE: We reviewed the records of 10 patients who had impending central retinal vein occlusion in order judge whether anticoagulant treatment with warfarin potassium (Warfarin) was indicated. PATIENTS: 6 men and 4 women, ranging in age from 25 to 83 (average 55) years were studied. RESULTS: Of 6 eyes, retinal hemorrhage disappeared completely within 6 months. Four patients whose visual acuity was 0.1 or less at one month needed photocoagulation. Four other patients whose late venous circulation time at fluorescein angiography improved within 30 seconds had good visual prognosis, 3 eyes of 4 patients aged 65 or older were not successful in regaining their visual acuity. CONCLUSION: Warfarin was not effective for patients who had clearly lost their visual acuity and the elderly in this series. Late venous circulation time at fluorescein angiography was a useful index for this treatment.

Adult↗

PubMed1998

Relationship between SCL-90, Maudsley Personality Inventory and CCK4-induced intracellular calcium response in T cells.

This study examined the relationship between the Symptom Checklist 90 (SCL-90), Maudsley Personality Inventory (MPI) and cholecystokinin 4 (CCK4)-induced intracellular calcium response in T cells. Fifty-two normal volunteers were 37 males and 15 females; they ranged in age from 23 to 44 years. Measures included CCK4-induced intracellular calcium response in T cells, SCL-90 scores, and MPI. Paranoid ideation and interpersonal sensitivity in SCL-90 showed a significant negative association with CCK4-induced intracellular calcium response. Absent were sex differences and extroversion and neuroticism correlations. There were no significant differences between men and women in SCL-90 or MPI scores. There was no correlation among extroversion and neuroticism and CCK4-induced intracellular calcium response. CCKB receptor function might play a role in paranoid ideation and interpersonal sensitivity.

Adult↗

PubMed1998

Effects of moguisteine on the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve in guinea pigs.

The study aimed to further demonstrate the peripheral antitussive properties of moguisteine. Firstly, the antitussive effect of moguisteine on the cough reflex induced by inhalation of citric acid aerosol was evaluated in conscious guinea pigs. Secondly, the effects of both moguisteine and codeine on the centrally mediated cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve were investigated in anesthetized guinea pigs. Moguisteine (2.5-10 mg/kg, intravenously, i.v.) reduced the cough reflex induced by 7.5% citric acid aerosol in a dose-dependent manner, with an ED50 value of 0.55 mg/kg. Both i.v. (0.5-4 mg/kg) and intracerebroventricular (i.c.v., 5-20 microg) injection of codeine dose dependently inhibited the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve; the ED50 values were 0.91 mg/kg and 7.90 microg, respectively. The inhibitory effect of codeine (4 mg/kg i.v.) was abolished by pretreatment with naloxone (2 mg/kg intraperitoneally). In contrast to codeine, neither i.v. (4 and 20 mg/kg) nor i.c.v. (20 microg) injection of moguisteine affected the cough reflex. These results suggest that the antitussive effect of codeine is mediated by central opioid mechanisms, whereas the antitussive effect of moguisteine is mediated by peripheral mechanisms.

Aerosols↗

PubMed1998

Molecular cloning and functional characterization of SecE of a marine bacterium, Vibrio alginolyticus.

SecE is an essential membrane component of the Escherichia coli protein translocation machinery, which utilizes ATP and the proton motive force as energy sources. The secE homologue of marine Vibrio alginolyticus, in which protein translocation requires ATP and the sodium motive force, was cloned, sequenced, and characterized. Unlike most SecE homologues found in various organisms, SecE of V. alginolyticus (Va-SecE) possesses three transmembrane sequences like E. coli SecE (Ec-SecE) and complements the DeltasecE mutation of E. coli. Alignment of the Ec-SecE and Va-SecE sequences revealed that the non-essential N-terminal half was less homologous than the essential C-terminal half between the two SecEs. The E. coli strain was able to grow and translocate the secretory protein in the complete absence of Ec-SecE when Va-SecE was expressed. The stabilization of SecY overproduction by Va-SecE was as effective as that by Ec-SecE, indicating that Va-SecE interacts with E. coli SecY despite the difference in energy requirement.

Amino Acid Sequence↗

PubMed1998

Growth factor receptor-bound protein 2 (Grb2) association with hemopoietic specific protein 1: linkage between Lck and Grb2.

To analyze the growth factor receptor-bound protein 2 (Grb2) signaling pathway in lymphoid cells, we used expression cloning to isolate the genes encoding proteins that associate with Grb2. We find that the Src homology 3 domains of Grb2 directly associate, in vitro and in vivo, with murine hemopoietic specific protein 1 (HS1), a protein identical to Lck-binding protein 1. Because HS1 associates with the p56(lck) and p59(lyn) tyrosine kinases in vitro and in vivo, and becomes tyrosine phosphorylated upon various receptor stimulations, our present data suggest that HS1 mediates linkage between Lck or Lyn and Grb2 in lymphoid lineage cells.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Incomplete processing of proinsulin to insulin accompanied by elevation of Des-31,32 proinsulin intermediates in islets of mice lacking active PC2.

The prohormone convertases PC2 (SPC2) and PC3/PC1 (SPC3) are the major precursor processing endoproteases in a wide variety of neural and endocrine tissues. Both enzymes are normally expressed in the islet beta cells and participate in proinsulin processing. Recently we generated mice lacking active PC2 due to a disruption of the PC2 gene (Furuta, M., Yano, H., Zhou, A., Rouillé, Y., Holst, J. J., Carroll, R. J., Ravazzola, M., Orci, L., Furuta, H., and Steiner, D. F. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 6646-6651). Here we report that these PC2 mutant mice have elevated circulating proinsulin, comprising 60% of immunoreactive insulin-like components. Acid ethanol extractable proinsulin from pancreas is also significantly elevated, representing about 35% of total immunoreactive insulin-like components. These increased amounts of proinsulin are mainly stored in secretory granules, giving rise to an altered appearance on electron microscopy. In pulse-chase experiments, the mutant islets incorporate lesser amounts of isotopic amino acids into insulin-related components than normal islets. In both wild-type and mutant islets, proinsulin I was processed more rapidly to insulin, reflecting the preference of both PC2 and PC3 for substrates having a basic amino acid positioned four residues upstream of the cleavage site. The overall half-time for the conversion of proinsulin to insulin is increased approximately 3-fold in the mutant islets and is associated with a 4-5-fold greater elevation of des-31,32 proinsulin, an intermediate that is formed by the preferential cleavage of proinsulin at the B chain-C-peptide junction by PC3 and is C-terminally processed to remove Arg31 and Arg32 by carboxypeptidase E. The constitutive release of newly synthesized proinsulin from both mutant and wild-type islets during the first 1-2 h of chase was normal (<2% of total). These results demonstrate that PC2 plays an essential role in proinsulin processing in vivo, but is quantitatively less important in this regard than PC3, and that its absence does not influence the efficient sorting of proinsulin into the regulated secretory pathway.

Amino Acid Sequence↗

PubMed1998

Multigeneration exposure test of Drosophila melanogaster to ELF magnetic fields.

Mutations, other than dominant lethals, were accumulated on wild type second chromosomes (+) of Drosophila melanogaster during exposure to 50 Hz sinusoidal alternating magnetic fields of 0.5 or 5 mT (rms) for 40 generations by the Curly/Plum(Cy/Pm) accumulation method. We maintained, for 40 generations under continuous exposure, each (+) chromosome as a heterozygote with (Cy) chromosome. Viability of the (+) chromosome was tested by sib-mating of (Cy/+) male and (Cy/+) female in a culture every 10th generation to obtain the homozygote. Viability indices, defined as twice the ratio of number of (+/+) flies to that of (Cy/+) flies plus 1 in the progeny of the test mating, also were calculated, which equaled 1.00 at the starting point. For the control and 0.5 and 5 mT exposed groups, percent frequencies of recessive lethal lines, defined as a line with (+/+) flies less than 0.3% in the test mating, were, respectively, 1.9, 0.9, and 2.9% (10th), 9.0, 4.9, and 9.5% (20th), 30.3, 22.9, and 30.4% (30th), and 39.9, 32.4, and 43.3% (40th generation). For the control and 0.5 and 5 mT groups, average viability indices, excluding lethals and markedly deleterious, were, respectively, 0.778, 0.796, and 0.752 (20th), 0.704, 0.698, and 0.694 (30th), and 0.669, 0.678, and 0.595 (40th generation). Their decreasing rates were 0.0054, 0.0059, and 0.0078 per generation. No significant difference was detected among the exposure levels in either the recessive lethal mutation frequency or the viability index.

Animals↗

PubMed1998

Hepatic cirrhosis: magnetisation transfer contrast in the globus pallidus.

The magnetisation transfer ratio (MTR), a quantitative tissue characteristic, and the pallidal index were measured in the globus pallidus of 37 patients with hepatic cirrhosis and 37 control subjects. The MTR decreased with severity of the disease, as indicated by the serum total bililubin, indocyanine green 15-min retention rate, and plasma ammonia. The pallidal index correlated significantly with haematological parameters, although the correlation coefficients tended to be lower than those between MTR and haematological parameters. This change in MTR corresponded to the results of the manganese chloride experiments. T1 shortening in the pallidum of patients with cirrhosis is presumably caused by paramagnetic effects, and possibly attributed to manganese deposition.

Case-Control Studies↗

PubMed1998

Malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy.

A case of malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapy is reported. A thoracotomy was performed on a 57-year-old male and a mass was found to invade the trachea, main bronchus, and left atrium. The tumor was unresectable. Subsequently, cisplatin was administered, but the tumor grew in size and radiation therapy was recommended. The tumor responded well to thoracic irradiation (56 Gy) and disappeared. Three months later, lymph nodes metastases were noted in the retrocrural and upper abdominal paraaortic regions, but these were controlled again with palliative irradiation. Without further treatment, he survived free of disease for over 5 years. Specimens obtained during the thoracotomy showed that the tumor consisted mainly of small round cells with a rosette formation. Immunohistochemically the tumor was positive to NSE and slightly positive to keratin, but negative to LCA, L26, UCLH-1, EMA, Leu7, and chromogranin, suggesting a malignant tumor derived from neuroendocrine tissue.

Diagnosis, Differential↗

PubMed1998

An ecologic study of the relationship between mean birth weight, temperature and calorie consumption level in Japan.

This study reports an ecologic analysis of the relationship between mean birth weight (MBW) and nutritional, medical, and social variables, using 1982 data for 47 prefectures in Japan. Correlation analysis showed that variables that correlated significantly with MBW were mean temperature (r = 0.63), total calorie intake (r = 0.56), and body mass index of women (r = 0.60). It is concluded that the MBW level in a given community represents the long and short term nutritional condition of mothers, and that the level may follow Bergman's law: 'In the same species, the body size of an animal increases along with latitude; that is, the lower the temperature, the larger the body size.'

Birth Weight↗

PubMed1998

Construction of mono- and bivalent human single-chain Fv fragments against the D antigen in the Rh blood group: multimerization effect on cell agglutination and application to blood typing.

An expression system for mono- and bivalent single-chain Fv fragments (scFv) of a human antibody against D antigen in the Rh blood group system was established in Escherichia coli. The cDNA encoding the Fv fragment of the anti-D monoclonal antibody D10 was cloned using the polymerase chain reaction and expressed in E.coli by fusing with a peptide tag link in the C-terminus of the light chain variable region. The scFv fragment expressed by the bacteria produced specific agglutination of human D positive red cells in the presence of an anti-peptide tag antibody. Flow cytometric analysis clearly indicated that the bacterially prepared scFv showed high specificity and affinity for D antigen, which was identical with that of the parental IgG. In order to construct bivalent D10 scFv for use in direct cell agglutination, the scFv was fused with a dimeric protein, bacterial alkaline phosphatase (BAP). The fusion protein produced significant agglutination of human red blood cells with D antigen, confirming that the bacterially expressed fusion protein is a functional bivalent antibody fragment. Specific agglutination of D positive red cells by D10 scFv-BAP was enhanced in the presence of anti-BAP antibody, suggesting that further multimerization of scFv led to highly efficient cell agglutination. By grafting BAP enzymatic activity into the scFv fragment (enzyme-linked scFv), blood typing could conveniently be performed. These results indicate that bacterially expressed scFv and scFv-BAP would be of practical use in blood typing. The system reported here could also be applied to the examination of other cell surface antigens and cell agglutination.

Alkaline Phosphatase↗

PubMed1998

Characterization of the promoter of the mouse prohormone convertase PC2 gene.

Prohormone convertase 2 (PC2) is a member of a family of mammalian subtilisin-like endoproteases that are involved in the processing of prohormones, neuropeptides and many other precursor derived proteins. The expression of PC2 is restricted to neuroendocrine tissues such as pancreatic islets, the pituitary and the brain. To understand the regulation of the PC2 gene, we cloned and characterized the promoter region of the mouse PC2 gene. The transcriptional start site of the mouse PC2 gene is identical to that of the human. There is 79% identity in the sequences of the promoter regions between the mouse and human PC2 genes. The mouse PC2 gene, like the human, does not have a TATA-like motif in the region just upstream of the start of the transcription. Studies with promoter-reporter gene, chloramphenicol acetyltransferase (CAT), constructs showed that the region from -400 to -170 bp was necessary for high level expression of the mouse PC2 gene in the betaTC-3 insulinoma cells.

Animals↗