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Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 505 records · Page 28Linked to original sources

[Effect of the passage and storage of strains, and inoculum size on the change of zone pattern types and sizes produced by protease of methicillin resistant Staphylococcus aureus].

Protease produced by Staphylococcus aureus precipitates digests of casein in standard methods caseinate agar (SMCA) plate, and the various sizes of A to E precipitation types were produced depending on strains of inoculated Staphylococcus aureus, as previously reported. To evaluate these phenomena for epidemiological use, we investigated the effects of bacterial passage, storage and dosage on zonal pattern and the size of precipitation rings. Methicillin resistant Staphylococcus aureus (MRSA) was found to produce variable types and sizes of precipitation rings depending upon the inoculated strains. After 5, 30 and 50 passages in heart infusion broth (HIB), each of the strains randomly selected from MRSA strains showed that the precipitation pattern of A to E produced the same types and sizes of precipitation rings. The storage effects were assessed by comparing those strains in different storage time. The strain stored for 1 and 3 years at room temperature in HIB contained 0.8% agar produced the same pattern of precipitation rings at that of the freshly isolated one. Finally, the dosage of inoculated bacteria was examined. Overnight broth (HIB) cultures of MRSA were directly inoculated in SMCA plates, and were found to produce almost the same size of precipitation rings (reproducible within 3 mm). These findings indicated that protease digestion on SMCA plate provides a rapid, sensitive, and specific assay that can supplement the currently available modalities for typing of MRSA strains.

Agar↗

The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP1 and NFAT.

Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in T cells is activated by the combination of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187), which mimic antigen stimulation through the T-cell receptor. We have previously shown that a fragment containing bp -95 to +27 of the mouse GM-CSF promoter can confer inducibility to reporter genes in the human Jurkat T-cell line. Here we use an in vitro transcription system to demonstrate that a cis-acting element (positions -54 to -40), referred to as CLE0, is a target for the induction signals. We observed induction with templates containing intact CLE0 but not with templates with deleted or mutated CLE0. We also observed that two distinct signals were required for the stimulation through CLE0, since only extracts from cells treated with both phorbol myristate acetate and A23187 supported optimal induction. Stimulation probably was mediated by CLE0-binding proteins because depletion of these proteins specifically reduced GM-CSF transcription. One of the binding factors possessed biochemical and immunological features identical to those of the transcription factor AP1. Another factor resembled the T-cell-specific factor NFAT. The characteristics of these two factors are consistent with their involvement in GM-CSF induction. The presence of CLE0-like elements in the promoters of interleukin-3 (IL-3), IL-4, IL-5, GM-CSF, and NFAT sites in the IL-2 promoter suggests that the factors we detected, or related factors that recognize these sites, may account for the coordinate induction of these genes during T-cell activation.

Animals↗

Reconstituted human granulocyte-macrophage colony-stimulating factor receptor transduces growth-promoting signals in mouse NIH 3T3 cells: comparison with signalling in BA/F3 pro-B cells.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high-affinity human GM-CSF receptor (hGM-CSFR) in a pro-B cell line, BA/F3, by cotransfecting alpha- and beta-chain cDNA clones and showed that the reconstituted receptor could transduce growth-promoting signals. The high-affinity hGM-CSFR was also reconstituted in mouse NIH 3T3 cells, but its ability to transduce signals in fibroblasts remained undetermined. In the present study, we further characterized signal transduction by the reconstituted hGM-CSFR in both NIH 3T3 cells and BA/F3 cells. We found that the reconstituted hGM-CSFR transduces signals in NIH 3T3 fibroblasts and BA/F3 cells in response to hGM-CSF to activate transcription of the c-fos, c-jun, and c-myc proto-oncogenes. hGM-CSF also induces protein tyrosine phosphorylation and DNA synthesis in both cell types. These results indicated that hGM-CSFR is functional in fibroblasts, that signal transduction via hGM-CSFR in fibroblasts involves tyrosine kinase(s), and that association of hGM-CSFR with a factor(s) specific to hematopoietic cell lineage is not essential to transduce growth-promoting signals.

3T3 Cells↗

Small hepatocellular carcinoma: treatment with subsegmental transcatheter arterial embolization.

The effectiveness of subsegmental transcatheter arterial embolization (TAE) therapy for small hepatocellular carcinomas (HCCs) was retrospectively analyzed. TAE was performed in 100 patients with liver cirrhosis. There was a total of 124 nodular-type HCCs less than 4 cm in diameter. TAE was performed by injecting a mixture of iodized oil and anticancer drugs followed by gelatin sponge particles or a mixture of iodized oil and absolute ethanol into the more distal branches of the subsegmental artery. Complete necrosis was seen at histologic examination in seven of 11 resected lesions. Among the remaining 113 lesions in 90 patients followed up without surgery, the 1-and 4-year local recurrence rates after TAE were 18% and 33%, respectively. The 1- and 4-year survival rates for 82 patients with Child class A or B disease were 100% and 67%, respectively. No substantial deterioration of liver function was observed. Subsegmental TAE improved the prognosis of the patients with liver cirrhosis associated with small HCCs.

Carcinoma, Hepatocellular↗

Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene.

Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by progressive primary adrenal insufficiency, without mineralocorticoid deficiency. The cDNA and gene of the human ACTH receptor were recently cloned. The gene encodes a 297-amino acid protein that belongs to the G protein-coupled superfamily of membrane receptors. We hypothesized that the ACTH receptor gene might be defective in IGD. To examine this, we studied its genomic structure by PCR and direct sequencing in a 5-yr-old proband with the disease, his parents, and grandparents. The proband was a compound heterozygote for two different point mutations, one in each allele: (a) a substitution (C-->T), also found in one allele of the mother and maternal grandmother, which introduced a premature stop codon (TGA) at position 201 of the protein; this mutant receptor lacks its entire carboxy-terminal third and, if expressed, should be unable to transduce the signal; and (b) a substitution (C-->G), also found in one of the paternal alleles, which changed neutral serine120 in the apolar third transmembrane domain of the receptor to a positively charged arginine, probably disrupting the ligand-binding site. Standard ovine corticotropin releasing hormone (oCRH) test in the heterozygote parents and maternal grandmother revealed exaggerated and prolonged ACTH responses, suggestive of subclinical resistance to ACTH. We conclude that IGD in this family appears to be due to defects of the ACTH receptor gene. The oCRH test appears to be useful in ascertaining heterozygosity in this syndrome.

Adrenocorticotropic Hormone↗

Pharmacological profiles of aspergillomarasmines as endothelin converting enzyme inhibitors.

Aspergillomarasmine-A and -B (AM-A and -B), which were isolated from the cultured broth of an unidentified fungus N877, showed apparent inhibition against endothelin-converting enzyme (ECE) from bovine endothelial cells as measured by the formation of endothelin-1 (ET-1) converted from big endothelin-1 (bET-1), with IC50 values of 3.4 and 2.5 microM for AM-A and -B, respectively. EDTA also inhibited ECE (IC50 = 1.1 microM), but the inhibitions by AM-A, AM-B and EDTA were each abolished by the addition of 10 microM Zn2+ to the reaction mixture. In mice, AM-A and -B dose-dependently (10-50 mg/kg, i.v.) caused significant prolongation of the latency to sudden death induced by i.v. bET-1 (25 nmol/kg), but not that by ET-1 (5 nmol/kg), accompanied by a decrease in plasma immunoreactive ET-1 formation, while EDTA (24 mg/kg) failed to do so. In mice, the LD50 value of AM-A was calculated to be 159.8 mg/kg, i.v., which was much larger than that of EDTA (28.5 mg/kg, i.v.), indicating the low toxicity of AM-A. AM-A (30 mg/kg, i.v.) also suppressed bET-1-induced hemoconcentration and hypertension in mice and rats, respectively. These findings suggest that although ECE inhibition by AM-A was mainly attributable to its chelating activity, it showed apparent in vivo activities due to ECE inhibition with low toxicity.

Animals↗

Effects of the direction and distance of horizontal arm movements on local muscular strain--a fundamental study on the teller workplace in bank.

This study was conducted to examine the relative differences in the muscular strain of the hand-arm-shoulder system in the repetitive arm movements which would directly depend on the layout of devices at teller counter. The subjects were five young male adults. The manual handling task was standardized and the repetition frequency was in self-pace. The arm movements were characterized by the different direction measured from the frontal plane of the subject between 0 degrees to 150 degrees combined with the distance measured from the acromion to the fixed points of 300, 500 and 700mm. The movements to all of the fourteen points tested were evaluated on both sides of the arms and shoulders by the integration of the EMG signals (IEMG) as to m. deltoid pars media and clavicularis, m. trapezius pars descendens, m. pectoralis major pars clavicularis and m. extensor carpi radialis brevis. It was found that IEMG of the deltoid muscles were sensitive to the direction and distance of the arm movements while the trapezius muscle showed the relative lower dependence on the direction. There were significant combined effects of the direction and distance in all muscles; i.e. effect of reach distance was greater with decreasing the arm angle, which was obvious at distance longer than 500mm in the arm abduction. When IEMG was divided by the task time in self-pace which increased in the arm abduction, the peak value was observed at the angle of 30 degrees. It was suggested that if the repetitive movement was required at the same frequency as at the angle of 30 degrees the position near the arm abduction (the angle of 0 degrees) would become the most expensive working direction.

Adult↗

[Inhibitory effects of Reitakutuukitokasin'i on the antigen-antibody reaction in rats investigated by measuring the increase in blood histamine level and the histamine release from peritoneal mast cells].

The antiallergic effects of Reitakutuukitokasin'i (RKS) on the increase in blood histamine level by antigen challenge were investigated in actively sensitized rats in comparison with those of azelastine and disodium cromoglycate (DSCG). The increase in blood histamine level after a systemic anaphylactic reaction elicited by intravenously injected antigen (egg albumin) was significantly inhibited by oral and intravenous administrations of RKS and azelastine or DSCG. Namely, RKS at 50 and 100 mg/kg (p.o.) caused 17% and 28% inhibition, respectively, and azelastine at 5 and 10 mg/kg (p.o.) caused 28% and 29% inhibition, respectively. RKS at 0.1 and 0.5 mg/kg (i.v.) caused 33% and 29% inhibition, respectively, and DSCG at 10 mg/kg (i.v.) caused 53% inhibition. However, large doses of RKS (500 mg/kg, p.o., 2.5 and 10 mg/kg, i.v.) caused no significant inhibition. The histamine release from rat peritoneal mast cells (RPMC) by antigen-antibody reaction was also investigated, and proved to be inhibited significantly by RKS. Namely, RKS at 5 x 10(-4), 10(-3) and 2 x 10(-3) g/ml caused 42, 71 and 79% inhibition, respectively. These results suggest that RKS is an antiallergic drug similar to azelastine and DSCG with a common inhibitory action on the release of histamine.

Anaphylaxis↗

Elevation of soluble IL-2 receptor and IL-4, and nonelevation of IFN-gamma in sera from patients with allergic asthma.

To determine whether the predominant in vivo activation of Th1 subset or Th2 subset in peripheral blood occurs in patients with allergic asthma, we measured serum levels of Th1 cell-derived interferon-gamma (IFN-gamma) and Th2 cell-derived interleukin-4 (IL-4). In addition, serum levels of soluble interleukin-2 receptor (sIL-2R) released from activated T cells were measured to determine a potential source of these cytokines. The elevation of serum IL-4 levels and nonelevation of serum IFN-gamma levels were observed in patients with allergic asthma compared with normal control subjects. A significant correlation between serum IL-4 levels and serum sIL-2R levels was observed in these patients. These results suggest that there is allergen-induced in vivo activation of Th2-like cells in peripheral blood of patients with allergic asthma.

Adult↗

[A case of quadricuspid aortic valve associated with mitral regurgitation].

A case of a 60-year-old man associated with quadricuspid aortic valve and mitral regurgitation is reported. The aortic valve consisted of three larger cusps and a small accessory cusp situated between the right and the non-coronary cusps. The aortic regurgitation resulted from malcoaptation of the four cusps and the mitral regurgitation resulted from annulus dilatation and thickening of the anterior leaflet. The surgical treatment was performed successfully by the aortic and mitral valve replacements with St. Jude Medical valves. The patient is doing well fifteen months postoperatively. Sixteen Japanese cases of quadricuspid aortic valve which were corrected surgically are reviewed.

Aortic Valve↗

Reconstitution of functional human GM-CSF receptor in mouse NIH3T3 fibroblasts and BA/F3 proB cells.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high affinity human GM-CSF receptor (hGM-CSFR) in a proB cell line BA/F3 by cotransfecting alpha and beta chain cDNA clones and showed that the reconstituted receptor could transduce growth promoting signals. The high affinity hGM-CSFR was also reconstituted in mouse NIH3T3 cells, but its ability to transduce signals in fibroblasts remained unanswered. In the present study, we further characterized signal transduction by the reconstituted hGM-CSFR both in NIH3T3 cells and BA/F3 cells. We found that the reconstituted hGM-CSFR transduces signals in NIH3T3 fibroblasts and BA/F3 cells in response to human GM-CSF to activate transcription of c-fos, c-jun and c-myc protooncogenes. hGM-CSF also induces protein tyrosine phosphorylation and DNA synthesis in both cell types. The ability of hGM-CSFR to transduce signals was affected by inhibitors of tyrosine kinase. These results indicated that the hGM-CSFR is functional in fibroblasts, that signal transduction via the hGM-CSFR in fibroblasts involves tyrosine kinase(s) and that association of hGM-CSFR with factor(s) specific to hematopoietic cell lineage is not essential to transduce growth promoting signals.

3T3 Cells↗

[Intraperitoneal repeated chemotherapy using CDDP combined with MMC for carcinomatous peritonitis].

Based on our experimental study, which indicated that simultaneous combined administration of MMC and CDDP prolonged life more significantly than individual administration, clinical application was performed on three cases of carcinomatous peritonitis from Borrmann type 4 cancer of the stomach. The dosage was 14 mg/m2 (7 mg/m2 at second and following administrations) of MMC and 35 mg/m2 of CDDP and they were repeatedly administered in the abdominal cavity via the drug delivery system. As the result, no severe toxicities were found except for two cases of leukopenia (Grade 2). Effectiveness was indicated in all cases with the negative change of cytology, whereas no improvements in prognosis were obtained. We concluded that some new devices would be necessary to increase the drug delivery to the carcinomatous wall.

Adenocarcinoma↗

[Lymphocyte subpopulations in maintenance hemodialysis patients receiving recombinant human erythropoietin].

The effect of recombinant human erythropoietin (rHuEPO) on the lymphocyte subpopulations of maintenance hemodialysis patients has been studied. Peripheral lymphocyte counts, lymphocyte subpopulations (Two color analysis) and PHA-induced proliferative response were measured before and after rHuEPO administration during 8 months in 22 stable hemodialysis patients (mean age 52 years, mean duration of dialysis 48 months). We could find a significant increase in the proportions of CD4+ Leu8- cells, HLA-DR+ cells, CD8+ HLA-DR+ cells, CD14+ HLA-DR+ cells and CD4+ Leu8-/CD8+ CD11b+ cells ratios after rHuEPO therapy. In addition, a significant decrease in the proportions of CD16+ CD57- cells and CD20+ cells could be found after rHuEPO therapy. These results suggest that rHuEPO administration to stable hemodialysis patients induces increases in lymphocytes categorized into helper subset groups and in activated T lymphocytes.

Adult↗

HTLV-I encoded Tax in association with NF-kappa B precursor p105 enhances nuclear localization of NF-kappa B p50 and p65 in transfected cells.

NF-kappa B is a heterodimeric protein composed of two subunits, p50 and p65, and is sequestered in the cytoplasm as an inactive form through the association with an inhibitory protein, I kappa B. In the present study, the effect of HTLV-I encoded Tax on the exogenously expressed NF-kappa B p105, which encodes a precursor of p50, was investigated using a COS-7 expression system. When p105 was expressed in COS-7 cells, the precursor p105 and the processed p50 were retained in the cytosolic fraction by associating each other, and p50 was not detected in the nuclear fraction. In the cells co-expressing p105 and Tax, the p50/p105 ratio in the cytosolic fraction reduced with an induction of p50 in the nuclear fraction, which gave rise to a significant increase in NF-kappa B binding activity. Enhancement of NF-kappa B binding activity was not observed by adenovirus encoded E1A and bovine papilloma virus encoded E2, and correlated well with the ability of Tax to associate with p105. When p105 delta X which lacks the repeats of the ankyrin motif was expressed in this system, p105 delta X and processed p50 were detected in the nuclear fraction and p50/p105 delta X ratio was not affected by co-expression with Tax. In the same expression system, exogenously expressed NF-kappa B p65 was retained in the cytoplasm by p105 and further expression of Tax allowed entry of p65 in the nucleus. These results suggest that, in this model system, p105 acts as an I kappa B to sequester p50 and p65 in the cytoplasm and that Tax by inhibiting I kappa B activity of p105, enhances nuclear localization of p50 and p65. These findings raise a possibility for a novel mechanism for the induction of NF-kappa B in the nucleus by Tax.

Amino Acid Sequence↗

Primary malignant melanoma of the female urethra: a case report.

A case of primary malignant melanoma of the female urethra is presented. A 65-year-old Japanese woman was referred with dysuria and urethral bleeding. A hemorrhagic blue-black tumor, 3 cm in diameter, was diagnosed as a malignant melanoma by urinary cytology and biopsy. In spite of radical surgery followed by adjuvant immunochemotherapy with beta interferon, dacarbazine, nimustine and vincristine (IFN beta-DAV), the patient died of the disease one year after surgery because of lung metastasis which developed six months after diagnosis. The regional lymph nodes were not involved. In the present paper, we have briefly discussed the diagnostic value of cytological examination for this condition, as well as biopsy, with regard to the risk of hematogeneous tumor spread.

Aged↗

The deep inferior epigastric artery free skin flap: anatomic study and clinical application.

We carried out an anatomic study to create the efficient surgical technique of elevating the inferior epigastric artery free skin flap. The deep inferior epigastric artery bifurcates into the lateral and medial branches. The former usually is larger in diameter and has many skin perforators slightly lateral to the midline of musculature. When a vascular pedicle skin flap is lifted without attaching the rectus abdominis muscle or its anterior sheath, it seems more efficient if the flap uses the skin perforator belonging to the lateral branch. This is so because entry of the inferior epigastric artery is from the lateral side of the rectus abdominis muscle and the lateral branch runs slightly lateral to the midline of the musculature and parallel to the run of the muscular fibers. This would be easier technically and would minimize the damage to the muscle when detaching the lateral branch.

Abdominal Muscles↗

The carboxyl terminus of RAP30 is similar in sequence to region 4 of bacterial sigma factors and is required for function.

Transcription factor beta gamma (RAP30/74) from rat liver was previously shown in biochemical studies to control the binding of RNA polymerase II to promoters by a mechanism analogous to that utilized by bacterial sigma factors, by decreasing the affinity of polymerase for nonpromoter sites on DNA and by increasing the affinity of the enzyme for the preinitiation complex (Conaway, R. C., Garrett, K. P., Hanley, J. P., and Conaway, J. W. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6205-6209). By constructing and analyzing mutants of beta gamma, we have identified a novel functional domain located in the carboxyl terminus of the gamma (RAP30) subunit. This domain shares sequence similarity with region 4 of bacterial sigma factors; in particular, it exhibits striking similarity to the carboxyl-terminal regions 4.1 and 4.2 of SpoIIIC (Bacillus subtilis sigma k). Evidence from biochemical studies argues that a mutant gamma (RAP30), lacking amino acid sequences similar to sigma homology region 4.2, is able to assemble with the beta (RAP74) subunit to form a mutant beta gamma (RAP30/74) with impaired ability to interact with RNA polymerase II.

Amino Acid Sequence↗