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Biomedical subjects

H Furuya

Publications and source records attributed to H Furuya.

At least 19 recordsLinked to original sources
PubMed1995

Stretching mesangial cells stimulates tyrosine phosphorylation of focal adhesion kinase pp125FAK.

Mechanical loading of cultured mesangial cells has been shown to induce both increased production of matrix proteins and cell proliferation. This in vitro phenomenon has been implicated in the progression of glomerular sclerosis observed in a variety of glomerular diseases. However, it is not yet known how cells sense mechanical stress and transfer this sense into biochemical and biological events. In this study, we show that mesangial stretching rapidly stimulates tyrosine phosphorylation of non-receptor tyrosine kinase pp125FAK. Since pp125FAK is a major constituent of focal adhesions, our findings suggest that the focal adhesion may be a site where mechanical forces are translated into biochemical events, and that pp125FAK may play an important role in this signaling cascade.

Animals↗
PubMed1995

Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs.

p130Cas (Cas) has been recently identified as a 130-kDa protein that is highly phosphorylated on tyrosine residues and is stably associated with p47v-crk (v-Crk) and p60v-src (v-Src) oncogene products in cells transformed by the respective genes. Cas is a novel signaling molecule having a single Src homology (SH) 3 domain and a cluster of multiple SH2-binding motifs. While the tight association of Cas with v-Crk and v-Src is strongly suggestive of a significant role in regulating cellular transformation, the function of Cas in normal untransformed cells is totally unknown. We report here that cell adhesion to fibronectin rapidly promotes tyrosine phosphorylation of Cas in human and rat fibroblast cell lines. The response was equally induced by cell adhesion to plates coated with vitronectin, laminin, and collagen but not by cell attachment to nonspecific substrate poly-L-lysine. The kinetic profile of Cas phosphorylation was almost identical with that of tyrosine phosphorylation of focal adhesion kinase pp125FAK (Fak), which is well known to be activated subsequent to integrin-mediated cell adhesion. Adhesion-dependent Cas phosphorylation was completely inhibited by treating cells with cytochalasin D, an agent that disrupts polymerization of actin stress fibers. These results suggest that tyrosine phosphorylation of Cas is stimulated by normal cell adhesion in close association with Fak phosphorylation and the formation of actin stress fibers. In v-Src- or v-Crk-transformed cells, however, the tyrosine phosphorylation of Cas is markedly increased in an adhesion-independent manner that is insensitive to treatment with cytochalasin D. Thus, Cas plays a role in signaling pathways mediated by cell adhesion as well as by transformation. We propose that Cas may amplify and propagate integrin-mediated signals by interacting with SH2-containing molecule(s).

Animals↗
PubMed1995

Adrenoleukodystrophy: the restoration of peroxisomal beta-oxidation by transfection of normal cDNA.

In order to elucidate the function of ALDP [a protein encoded by the gene responsible for adrenoleukodystrophy (ALD)], normal ALDP cDNA, inserted in an expression vector driven by chicken beta-actin promotor, was transfected into ALD fibroblasts. In a transient expression system, the fatty acid composition did not change even though the ALDP was newly synthesized based on the findings of a western blot analysis. In a stable expression system, 3 cell lines were strongly positive for ALDP. In these cells the level of very long chain fatty acid (C26:0) turned out to be as low as those of the control, while the activities of C24 beta-oxidation, as checked by two different methods, became normal. From these results, it is concluded that ALDP is indispensable for the function of peroxisomal beta-oxidation, and thus the treatment of ALD may be possible by the supplementation of ALDP.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed1995

Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates growth hormone release from GH3 cells through type II PACAP receptor.

Effect of pituitary adenylate cyclase activating polypeptide (PACAP) on growth hormone (GH) release from GH3 cells was studied in a dynamic superfusion system. PACAP-38 and PACAP-27 stimulated GH release from superfused GH3 cells. The stimulatory effect of PACAP-38 was comparable to those of vasoactive intestinal polypeptide (VIP) and PACAP-27 at a concentration of 1 nM, but the duration of action was more prolonged in PACAP-38 than in the other two peptides. PACAP(6-38), a selective antagonist of PACAP, as well as a VIP antagonist blunted the GH release induced by PACAP-38 and VIP. An antagonist of GH-releasing factor (GRF) at a concentration of 1 microM, however, did not affect the GH release induced by PACAP-38. These findings suggest that PACAP and VIP stimulate GH release from GH3 cells through type II PACAP receptor but not through the GRF receptors.

Animals↗
PubMed1995

Molecular analysis of X-linked adrenoleukodystrophy patients.

A molecular analysis of 4 Japanese adrenoleukodystrophy (ALD) patients was carried out, according to the recently published report on ALD gene cDNA. In a Southern blot analysis, we were not able to detect a large deletion in all patients. In a Northern blot analysis, no mRNA was detected in one patient, while the others had normal mRNA in both size and amount. Three patients had missense mutations including; 534Pro-->Leu (1987C-->T), 660Arg-->Trp (2364C-->T), and 512Gly-->Ser (1920G-->A), respectively. These mutations existed in the C-terminal region conserved in the ATP-binding cassette superfamily of transporters. In a Western blot analysis using polyclonal antibodies against the C-terminal peptide as well as the whole peptide of ALD protein, no 80 kDa protein was found in any of the 4 patients, which was observed in the control cells. The ALD protein in 3 patients with a missense mutation might be degraded immediately after translation because of the unstable higher structure or by the disruption of the hitherto unknown targetting signal to the peroxisome. The molecular analysis of the ALD gene as done in this study is thus considered to be the first step to further elucidate the pathogenic mechanism of ALD.

Adrenoleukodystrophy↗
PubMed1995

Effect of continuous subcutaneous administration of a small dose of granulocyte colony stimulating factor (G-CSF) by the use of a portable infusion pump in patients with non-Hodgkin's lymphoma receiving chemotherapy.

The effects of continuous subcutaneous infusion (CSI) of human granulocyte-colony stimulating factor (G-CSF) on the absolute neutrophil count (ANC) and serum G-CSF level were examined in 11 patients with non-Hodgkin's lymphoma (NHL) during cytotoxic chemotherapy. Recombinant G-CSF (rG-CSF) was subcutaneously infused using a portable infusion pump at a constant flow rate of 1 microgram/20 microliters/h for 14 days starting 2 days after the end of the second course of chemotherapy. The ANC was lowered after the chemotherapy without rG-CSF infusion whereas the duration of neutropenia and the nadir level of the ANC after the chemotherapy were ameliorated by the combined administration of rG-CSF (mean +/- S.E., 0.6 +/- 0.5 days vs. 4.7 +/- 1.9 days, P < 0.05; 455 +/- 135/microliter vs. 1906 +/- 598/microliter, P < 0.05). Serum G-CSF levels increased after the start of rG-CSF infusion, reaching a mean peak value of 418.5 +/- 128.5 pg/ml at the 8th day, and then returned to the basal level (35.6 +/- 13.5 pg/ml) immediately after the end of continuous infusion of rG-CSF. Although a slight increase in serum G-CSF was obtained in the patients after the chemotherapy without rG-CSF administration, the mean serum level was much lower than that in the patients after the chemotherapy with rG-CSF administration (88.2 +/- 24.8 pg/ml vs. 199.6 +/- 20.6 pg/ml, P < 0.01). No notable side effects of the CSI of rG-CSF were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of sevoflurane on the middle latency auditory evoked response and the electroencephalographic power spectrum.

We investigated the effects of sevoflurane on the middle latency auditory evoked response (MLR) and the power spectrum of the electroencephalogram (EEG) in 10 elective surgical patients. The MLR and the EEG power spectrum were recorded with a surface electrode placed at the central (Cz) scalp location. End-tidal sevoflurane concentrations of 0%, 0.25%, 0.5%, 0.75%, 1.0%, and 1.5% in 50% nitrous oxide and oxygen were studied. The Na, Pa, and Nb components of the MLR increased in latency and decreased in amplitude in a dose-dependent manner at increasing concentrations of sevoflurane. The latencies for Na, Pa, and Nb increased in a linear fashion (correlation coefficients: r = 0.81, r = 0.81, and r = 0.89, respectively). The EEG delta power was dominant with increasing sevoflurane concentration, and was significantly increased at sevoflurane concentrations of 1.0%-1.5%. The beta power, median power frequency (MPF), and 95% spectral edge frequency (SEF) decreased significantly according to the increases by 0.5% sevoflurane. Regarding the changes evoked by 0.25% sevoflurane, the Nb latency of the MLR responded significantly under 0.75% of sevoflurane. At these low concentrations of sevoflurane, the MLR seemed to be more sensitive to changes in anesthetic concentration than the various EEG variables.

Anesthetics↗
PubMed1995

Preoperative evaluation for risk of venous air embolism in the sitting position.

We report a patient with meningioma and radiological findings of erosive bony change, who developed venous air embolism via the diploic vein in the eroded inner table of the skull during craniotomy in the sitting position. The findings in our case suggest that preoperative radiological imaging evaluation can increase an awareness of the possibility of venous air embolism.

Aged↗
PubMed1995

Do recently developed techniques for skull base surgery increase the risk of difficult airway management? Assessment of pseudoankylosis of the mandible following surgical manipulation of the temporalis muscle.

We report our experience with anesthetic care for six patients with pseudoankylosis of the mandible following neurosurgical procedures, four of whom required fiberoptically guided intubation for anesthesia. We suggest that the development of operative approaches and reconstruction techniques in skull base surgery may increase the risk of difficult airway due to limitation of mouth opening.

Adult↗
PubMed1995

Potassium secretion is inhibited by metabolic acidosis in rabbit cortical collecting ducts in vitro.

The role of metabolic acidosis in the regulation of transepithelial potassium transport was examined in rabbit cortical collecting ducts (CCD) using in vitro isolated tubular microperfusion and conventional microelectrode techniques. Basolateral metabolic acidosis, created by reduction of bicarbonate concentration from 25 to 5 meq/l, pH 7.40 to 6.80, depolarized the transepithelial voltage significantly (-6.5 +/- 1.0 to -2.7 +/- 1.3 mV). Basolateral acidosis also suppressed net potassium secretion (-14.3 +/- 2.1 to -9.0 +/- 1.7 pmol.min-1.mm-1). Electrophysiological study in CCD cells demonstrated that basolateral metabolic acidosis depolarized transepithelial voltage and apical and basolateral membrane voltage with an increase of transepithelial and fractional apical resistance. Basolateral acidosis did not affect the 22Na efflux nor 86Rb efflux. The inhibitory action of basolateral acidosis on net potassium secretion remained in the presence of luminal barium and in the absence of bicarbonate. Ouabain could not abolish the effect of basolateral acidosis on transepithelial voltage completely. These data lead us to conclude that basolateral acidosis affects multiple transport pathways, and it inhibits mainly apical barium-sensitive potassium transport. Additionally, it inhibits apical sodium conductance, barium-insensitive potassium transport, and stimulates a ouabain-insensitive electrogenic transport pathway to some degree.

Acidosis↗
PubMed1995

[Effects of nitroglycerin, prostaglandin E1, trimetaphan and nicardipine on systemic vascular resistance, pulmonary vascular resistance and pulmonary-systemic vascular resistance ratio in dogs].

Effects of the experimentally induced hypotension with 4 vasodilators; nitroglycerin (TNG), prostaglandin E1 (PGE1), trimetaphan (TMP) and nicardipine (NCP) on systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and pulmonary-systemic vascular resistance ratio (PVR/SVR ratio) were studied in dogs. The SVR values were significantly reduced by TNG, PGE1 and NCP, and not affected by TMP. The PVR values were significantly reduced by TNG and PGE1, and not affected by TMP and NCP. The PVR/SVR ratio values were significantly reduced by TNG, and significantly increased by NCP, and not affected by PGE1 and TMP. We concluded that TNG reduced PVR and SVR but it affected PVR more; PGE1 reduced PVR and SVR equivalently; TMP did not affect PVR and SVR remarkably; NCP reduced SVR but did not affect PVR.

Alprostadil↗
PubMed1995

[Apoptosis and cell growth fraction in normal, dysplastic and neoplastic squamous epithelium of uterine cervix].

To assess the transformation of cellular characteristics during a neoplastic change in uterine cervical epithelium, the populations of cells in apoptosis as well as proliferating cycle were examined in normal cervical epithelium, dysplastic change, carcinoma in situ and invasive carcinoma. The percentage of apoptotic cells (%DNA Fr.) decreased with the neoplastic change and was significantly lower in the carcinoma in situ group than in the dysplasia group. Conversely, the percentage of cells in the proliferating cycle (%GF) increased with the neoplastic change and was significantly higher in the dysplasia group than in the normal group. The ratio of %DNA Fr. to % GF was more than 1.0 in the normal group and dysplasia group, but it was less than 1.0 in the carcinoma in situ group and invasive carcinoma group. No significant correlation between %DNA Fr. and %GF was found. These results suggested to us that the decrease in apoptosis may reflect the atypical change in cervical epithelial cells during their neoplastic change, and the proliferative activity in neoplastic lesion was found when the cervical epithelium with dysplastic change was transformed to the carcinoma in situ.

Apoptosis↗
PubMed1994

cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria.

The pig and human dihydropyrimidine dehydrogenase (DPD) cDNAs were cloned and sequenced. The pig enzyme, expressed in Escherichia coli, catalyzed the reduction of uracil, thymine, and 5-fluorouracil with kinetics approximating those published for the enzyme purified from mammalian liver. DPD could be expressed in significant quantities only when uracil was added to the bacterial growth medium. The pig and human enzymes contained 1025 amino acids and calculated M(r) = 111,416 and 111,398, respectively. Conserved domains corresponding to a possible NADPH binding site and FAD binding site were found in the NH2-terminal half of the proteins and two motifs of putative [4Fe-4S] binding sites were found near to the carboxyl terminus of the enzyme. The latter corresponds to the labile COOH-terminal fragment previously shown to contain the iron sulfur centers. A sequence encompassing a peptide corresponding to the uracil binding site was found between the NADPH/FAD-containing NH2-terminal portion of the protein and the iron-sulfur binding sites near to the COOH terminus. Thus, the DPD appears to be derived from at least three distinct domains. The DPYD gene was localized to the centromeric region of human chromosome 1 between 1p22 and q21.

Amino Acid Sequence↗
PubMed1994

Response of pial vessel diameter and regional cerebral blood flow to CO2 during midazolam administration in cats.

Midazolam has been demonstrated to preserve the response of cerebral blood flow to CO2. However, the responsiveness of cerebral vessels or microcirculation during midazolam administration related to alteration of cerebral blood flow has not been explored. The purpose of this study was to examine the effects of midazolam on cerebral microcirculation. Nine cats were paralyzed and mechanically ventilated under nitrous oxide/oxygen anaesthesia. Using the closed cranial window technique and laser Doppler flowmetry, diameter of pial vessels and regional cerebral blood flow (rCBF) were examined on the surface of the cerebral cortex which was perfused by the middle cerebral artery. Before midazolam administration, haemodynamic variables, blood gases, rCBF, and diameter of pial vessels were determined as a control under normocapnia, hypocapnia, and hypercapnia conditions. After midazolam administration, given initially at 0.8 mg.kg-1.min-1 for 10 min and subsequently at 0.04 mg.kg-1.min-1 (total dose 10 mg.kg-1), the same variables were again analyzed. With regard to CO2 responsiveness, an 8.85% increase in rCBF was demonstrated for a Paco2 elevation of 1 kPa before midazolam administration, compared with a 7.47% increase after midazolam administration. With regard to the correlation between CO2 response and vessel diameter, arterioles less than 50 microns in diameter were more sensitive than those more than 50 microns in diameter, although there were no significant differences before or after midazolam administration. We conclude that CO2 responsiveness is preserved in terms of rCBF and vessel diameter after high doses of midazolam (10 mg.kg-1) in cats.

Animals↗
PubMed1994

An autopsy case of acquired immune deficiency syndrome (AIDS) with preceding aplastic anemia.

A case of acquired immunodeficiency syndrome (AIDS) with preceding aplastic anemia is reported. The patient was a 36 year old female who had been diagnosed as having aplastic anemia 10 years before and thereafter had received multiple transfusions. Human immunodeficiency virus (HIV)-seropositivity was revealed 10 months prior to her death, but no particular clinical signs indicating HIV infection, pre-AIDS or onset of AIDS were recognized before serological diagnosis, although the slow progression of leukopenia was noted along with thrombocytopenia. Her general condition deteriorated during the last 10 months accompanied by an acute decrease in the CD4/CD8 ratio. Autopsy revealed full-blown AIDS: systemic aspergillosis, progressive multifocal leukoencephalopathy, Epstein-Barr virus-related B cell lymphoma arising in the diaphragm and severe lymphocyte depletion in the lymph nodes and spleen. Markedly hypoplastic bone marrow was considered to be primarily attributable to the aplastic anemia but the affection of AIDS was not excluded. The possible transmission route of HIV and the effect of the preceding aplastic anemia on the infection and clinical course of AIDS are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1994

Enhanced volume-sensitive K flux in patients on chronic hemodialysis.

Swelling-activated K flux was investigated in erythrocytes from patients on regular hemodialysis. K influx, measured by 86Rb uptake, was increased in hemodialysis patients from 25.5 +/- 0.6 to 47.3 +/- 3.4 nmol/10(9) cells/h (n = 4, p < 0.01), when the medium osmolarity of Hepes buffer was decreased by 100 mosm/kg H2O. In normal subjects, K influx was also stimulated from 28.1 +/- 1.2 to 37.8 +/- 2.1 nmol/10(9) cells/h (n = 4, p < 0.01). The swelling-activated increment of K influx was comparatively higher in hemodialysis patients (85.5 vs. 34.5% in controls). Reduction of the medium osmolarity by 100 mosm/kg H2O also caused a larger increase of K efflux in hemodialysis patients than in control subjects (171.1 vs. 118.1%). K efflux was increased even in the presence of 10(-4) M ouabain (from 284 +/- 25 to 879 +/- 122 nmol/10(9) cells/h), although the increment of K efflux was completely abolished when Cl was replaced by gluconate (555 +/- 47 nmol/10(9) cells/h with Cl and 467 +/- 44 nmol/10(9) cells/h without Cl). These data suggest that in hemodialysis patients, swelling-activated K transport is enhanced via activation of the Cl-dependent ouabain-insensitive K transport pathway.

Adult↗
PubMed1994

Effect of daily subcutaneous administration of recombinant erythropoietin on chronic anemia in rheumatoid arthritis.

Mean (+/- SD) serum erythropoietin (EPO) levels were 18.6 +/- 5.6 mU/ml in 180 normal Japanese subjects. Serum EPO levels were elevated with a negative correlation on a log scale (r = -0.864, P < 0.005) to hematocrit (Ht) values in anemic patients not associated with rheumatoid arthritis (RA) or chronic renal failure (CRF). Serum EPO levels in patients with RA (31.6 +/- 16.4 mU/ml) were relatively lower than those in normal subjects and anemic patients without RA or CRF when matched for comparative Ht values. Seven anemic patients with RA were treated by daily subcutaneous (sc) injection of recombinant EPO (rEPO, 500-1,000 U/day) for 4 weeks. The patients had initial Ht values of 25.1% or less and maintained stable clinical status. The treatment with rEPO raised serum EPO levels (53.8 +/- 15.2 mU/ml, P < 0.05), which resulted in an increase in Ht values (more than 3%) in 6 out of 7 patients with RA. The mean (+/- SD) Ht values at the end of the treatment with rEPO (500-1,000 U/day) were greater than those before the treatment in the 7 patients with RA (28.5 +/- 4.6 vs. 22.7 +/- 2.5%, P < 0.05). These findings suggest that chronic anemia associated with RA may be corrected by daily sc injection of a small dose of rEPO.

Adult↗