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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 325 records · Page 18Linked to original sources

[Clinical study of S 6472 in urinary tract infection].

Clinical studies on S 6472, a longer lasting preparation of cefaclor (CCL), were performed and the following results were obtained. S 6472 was administered orally to 102 patients with urinary tract infections including 16 with acute uncomplicated pyelonephritis, 32 with acute uncomplicated cystitis, 31 with complicated pyelonephritis and 23 with complicated cystitis. 95 patients were treated with 375 mg of S 6472 2 times daily and 7 patients were treated with 750 mg of S 6472 2 times daily. The overall clinical efficacy was evaluated on the basis of the criteria proposed by the Japanese UTI Committee. 1. Clinical efficacies in 11 cases of acute uncomplicated pyelonephritis were excellent in 10 and moderate in 1, with an overall efficacy rate of 100%. Bacteriologically, all 12 strains identified in the acute uncomplicated pyelonephritis cases were eradicated, with an eradication rate of 100%. 2. Clinical efficacies in 21 cases of acute uncomplicated cystitis were excellent in 17, moderate in 3 and poor in 1, with an overall efficacy rate of 95%. As to bacteriological responses, 22 strains identified in the acute uncomplicated cystitis cases (except 1 of Escherichia coli) were eradicated, with an eradication rate of 95%. 3. Clinical responses in 43 cases of complicated urinary tract infections were excellent in 20, moderate in 15 and poor in 8, with an overall efficacy rate of 81%. Bacteriologically, 39 strains, including only one strain of P. aeruginosa, in the complicated urinary tract infection cases (except 4 of E. coli, 1 of Klebsiella pneumoniae, 1 of Enterococcus faecalis and 2 of Enterobacter cloacae) were eradicated, with an eradication rate of 83%. As side effects, slight stomatitis and gastric discomfort were noted in 1 patient each but we were able to continue the medication. Abnormal laboratory test values found were: 1 case of a slight and transient increase of lymphocytes in peripheral blood and 1 case of a slight and transient increase of serum creatinine level.

Administration, Oral↗

[Preventive effect of a novel leukotrienes antagonist ONO-1078 on leukotriene C4- and D4-induced human bronchial smooth muscle contraction].

To study whether a novel leukotrienes antagonist ONO-1078 (4-oxo-8-[4-phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate) prevents leukotrienes C4- and D4-(LTC4, LTD4) induced human bronchial smooth muscle contraction, we examined the bronchial contractile response to LTC4 and LTD4 in the presence or in the absence of ONO-1078 in human bronchial strips. We prepared 4 strips from each of 5 patients undergoing lobectomy of the lung because of lung cancer. We mounted the strips in organ baths and measured the contractile response to LTC4 and LTD4 from 10(-11) M to 10(-7) M after incubation with ONO-1078 (10(-8) M, 10(-7) M and 10(-6) M) and without ONO-1078. ONO-1078 shifted the dose response curve to LTC4 to higher concentration in dose dependent fashion, and it significantly inhibited the contractile response to LTC4 and LTD4. In the presence of L-serine borate complex (45 mM), an inhibitor of gamma-glutamyl transpeptidase, ONO-1078 significantly inhibited the LTC4-induced contraction. On the other hand, ONO-1078 had no effect on the contractile response to acetylcholine. These results suggest that ONO-1078 is a specific antagonist of LTC4 and LTD4 receptors in human bronchial smooth muscle. Because the effect of LTC4 and LTD4 is thought to be an important part of the pathogenesis of bronchial asthma, our results also suggest that ONO-1078 may be a useful prophylactic drug for bronchial asthma.

Bronchi↗

[Postgastrectomy megaloblastic anemia--possible participation of anti-intrinsic factor antibody in its pathogenesis--report of a case].

A case of 78-year old man with megaloblastic anemia occurring 20 years after partial gastrectomy is reported. Since about 2 years earlier he had an episode of convulsion, and he had been on anti-convulsants (diphenylhydantion, phenobarbital) until admission. Physical examination revealed a pale lean man with polyneuropathy and mental impairment. Laboratory findings revealed WBC 3100/microliters, RBC 187 X 10(4)/microliters, HB 7.9 g/dl, MCV 124.4 microns3, MCH 42.7 micrograms, platelet counts 15.7 X 10(4)/microliters, serum vitamin B12 (VB12) 380 pg/ml, and serum folic acid 5.1 ng/ml. Serum autoantibodies to intrinsic factor (IF) and parietal cells were positive. Bone marrow examination revealed erythroid hyperplasia and megaloblastic changes. Schilling test revealed impaired absorption of VB12 with or without IF, but X-ray study of the small bowels was unremarkable. Treatment with intramuscular cyanocobalamin resulted in a rapid clinical improvement. A repeat Schilling test after 4 months of therapy showed a normal VB12 absorption in the presence of IF. These findings suggest that VB12 malabsorption of the 1st Schilling test was due to intestinal dysfunction caused by the VB12 deficiency state itself, and the improvement of VB12 absorption with IF after therapy suggests a pathogenesis similar to pernicious anemia in this patient.

Aged↗

[The ERG recording with high speed scanning of monochromatic stimuli].

Sixteen monochromatic lights with peak wavelengths lying from 400 nm to 700 nm at intervals of 20 nm were adjusted to equal energy. These stimuli were provided in a dark room successively in ascending and descending series from 400 nm to 700 nm were arranged to be continuously sinusoidally flickering. The flickering frequency was changed from 3 Hz to 40 Hz. The spectral responses obtained could be seen and evaluated as a spectral pattern on the oscilloscope rectangular CRT. In both ascending and descending scanning of less than 10 Hz stimulus frequency the spectral response pattern with the low stimulus intensity had maximum amplitude around 500 nm, reflecting the function of the rod system. On the other hand the spectral pattern with the peak response from 540 nm to 580 nm was obtained by the high stimulus intensity, reflecting the function of the cone system. In scanning of more than 20 Hz frequency, the spectral pattern also reflected the characteristics of the cone system. In normal subjects almost the same spectral pattern was obtained at high speed scanning, especially more than 30 Hz for a few seconds, even by averaging. This method can therefore be employed for clinical diagnosis.

Electroretinography↗

Assignment of common allele loss in osteosarcoma to the subregion 17p13.

Human osteosarcomas frequently show loss of alleles on chromosome 17 as well as those on chromosome 13 that harbors the retinoblastoma gene, indicating concerted operation of another tumor-suppressing gene on chromosome 17. To assign the affected gene to a defined region of chromosome 17, we performed mitotic recombination/deletion mapping by the use of 10 polymorphic loci on chromosome 17. Of 37 tumors studied, 28 (75.7%) showed loss of heterozygosity on chromosome 17. The affected regions varied among tumors, ranging in extent from a whole chromosome to a distal segment of the short arm. However, allele loss in one region, notably in 17p13 between D17S1 and D17S30, was common to all 28 tumors, suggesting the presence of a tumor-suppressing gene in this defined region.

Alleles↗

Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production.

Effects of transforming growth factor beta (TGF-beta) on IgA production by LPS-stimulated B cells have been studied. TGF-beta itself could augment polyclonal IgA production in concomitant inhibition of polyclonal IgM and IgG1 production. Furthermore, TGF-beta and IL-5 additively augmented IgA production. TGF-beta exerted its activity early in the culture (by 2 d in a 5-d culture) and IL-5 was required late in the culture. Surface IgA- (sIgA-) B cells responded to TGF-beta for the development of IgA-secreting cells. By contrast, sIgA+ B cells, but not sIgA- B cells, responded to IL-5 for IgA production. These results suggest that TGF-beta has a differential role in the induction of IgA production from IL-5 on murine-activated B cells.

Animals↗

Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities.

In view of the possible effects of the sphingoid base on protein kinases, and the fact that the sphingoid bases used in previous studies were not chemically well-defined, we have studied the effects of chemically well-defined sphingosines and their derivatives on kinase activity. Both (4E)-D- and (4E)-L-erythro-sphingenine showed a weak inhibitory effect, and (4E)-L-threo-sphingenine had a moderate inhibitory effect. In contrast, (4E)-N,N-dimethyl-D-erythro-sphingenine and the sphingosine preparation from a commercial source showed a strong inhibitory effect on PK-C in A431 cells as well as on purified PK-C. Synthetic (4E)-D-erythro-sphingenine and several samples of natural sphingosine inhibited v-src or c-src tyrosine kinase activity measured with polyglutamate-tyrosine (4:1) as substrate. N-Acetylated or N-methylated sphingosines did not inhibit src kinase activity, but rather produced a consistent 1.5-2-fold stimulation of such activity.

Animals↗

First crystallization of a phosphoenolpyruvate carboxylase from Escherichia coli.

Two different forms of crystal for a phosphoenolpyruvate carboxylase from Escherichia coli were obtained by the hanging-drop vapor diffusion technique, using polyethylene glycol 4000 as precipitant. The hexagonal crystal in space group P6(2)22 (or P6(4)22) has cell dimensions of a = 131 A and c = 325 A, whereas the orthorhombic crystal in space group I222 has a = 119 A, b = 252 A and c = 83 A. A tetrameric molecule (396,244 Mr), a subunit of which contains 883 amino residues, has a crystallographic 2 symmetry in the hexagonal crystal or 222 symmetry in the orthorhombic crystal, respectively.

Carboxy-Lyases↗

Development of heat-stable recombinant rinderpest vaccine.

Recombinant vaccinia virus (RVV) containing the full-length cDNA of rinderpest virus (RV)-haemagglutinin (H) gene was constructed. The H gene was inserted into the attenuated vaccine strain of vaccinia virus (VV), Le 16 m0, with two different promoters, namely cowpox virus A-type inclusion body (ATI) promoter or VV 7.5 kilodalton (P7.5) promoter. These RVVs produced the same sized fully glycosylated RV-H protein in RK 13 cells as that of the authentic RV-H. Their heat stability in the lyophylized state was similar to that of the parental VV. All rabbits immunized with these RVVs produced virus neutralizing (VN) antibody to RV as well as anti RV-H antibody. Four weeks after immunization, these animals were challenged with RV intravenously. None of the RVV-immunized rabbits developed any clinical signs of RV infection except one which was immunized with RVV containing the ATI promoter and developed low VN titer. These results indicate the possibility of developing a heat-stable recombinant vaccine for the eradication of rinderpest in tropical countries without cold storage systems.

Animals↗

A simple and efficient method for the oligonucleotide-directed mutagenesis using plasmid DNA template and phosphorothioate-modified nucleotide.

We have developed a simple and efficient method for oligonucleotide-directed mutagenesis with double-stranded (plasmid) DNA as a template. The template was simply and rapidly prepared by cell lysis and the following DNA denaturation with alkali. The chain elongation was performed with phosphorothioate-modified nucleotide at 37 degrees C. After the selective digestion of original DNA with NciI and exonuclease III, the desired mutated gene was obtained at a high frequency (about 70%).

Amino Acid Sequence↗

Improved recombinant LC16m0 or LC16m8 vaccinia virus successfully expressing hepatitis B surface antigen.

An attempt was made to develop a safe, efficacious live recombinant vaccine using low neurovirulent strains of vaccinia virus: LC16m0 (m0) or LC16m8 (m8). Recombinant vaccinia virus (RVV) was constructed by inserting the hepatitis B surface antigen (HBsAg) gene fused to a 7.5 kDa protein promoter (7.5 kDa promoter) within the vaccinia virus thymidine kinase (TK) gene using the m0 or m8 strain as vectors. These RVVs expressed significant amounts of HBsAg (1.1 microgram/2 X 10(5) cells) consisting of 24.5 and 28 kDa (glycosylated) proteins. HBsAg produced by RVV (vaccinia HBsAg) had physical properties very similar to plasma-derived HBsAg. Considering the safety of RVVs from m0 or m8 that have been constructed with HBsAg without the addition of a promoter and the high induction of anti-HBs antibody with RVV from m0 strain in rabbits, the RVVs constructed in the present study are likely to form the basis of a safe live RVV vaccine for hepatitis B virus (HBV).

Animals↗

Surgical treatment for symptomatic spinal adhesive arachnoiditis.

This report concerns the outcome of 36 operations for spinal adhesive arachnoiditis (SAA) performed at Kyoto University Hospital since 1956; the follow-up period ranged from 1 to 25 years (average, 4 years 8 months). The original procedure involved intradural neurolysis after extradural decompression, but more recently microlysis was performed. The percentage of cases in which good results were obtained by nonmicroscopic lysis and microlysis was only 54.8%, however, when microlysis was followed by spondylodesis, the ratio increased to 80%, clearly showing the benefits of this new procedure. The authors therefore emphasize the value of spondylodesis following microlysis for symptomatic SAA.

Adult↗

Factor IX Kawachinagano: impaired function of the Gla-domain caused by attached propeptide region due to substitution of arginine by glutamine at position -4.

Factor IX Kawachinagano (KWC) is a mutant factor IX protein initially recognized in a patient with severe haemophilia B, who had 46% of normal factor IX antigen and no detectable clotting activity. Previous studies indicated that factor IX KWC was not activated by factor XIa in the presence of Ca ions. In the present study, we purified and analysed factor IX KWC at a structural level in an attempt to clarify the nature of the impaired reaction with factor XIa. Kinetic studies showed that activation of factor IX KWC by factor X activator from Russell's viper venom (RVV-X) was normal, whereas activation by factor XIa was defective. Amino acid sequence analysis of tryptic peptides and direct analysis of the NH2-terminal sequence of factor IX KWC demonstrated that this mutant factor IX retained the propeptide region of 18 amino acids due to a substitution of arginine-(-4) by glutamine. These data suggested that the Gla-domain of factor IX KWC was dysfunctional, although the total gamma-Gla content, measured by alkaline-hydrolysis, was normal. We assumed that this attached propeptide region of the molecule directly interferes with the adjacent NH2-terminus and prevents the metal-induced conformational changes which are essential for biological activity of normal factor IX.

1-Carboxyglutamic Acid↗

T-cell colony formation in healthy homosexual men without anti-human immunodeficiency virus antibody.

In order to study the abnormal differentiation and proliferation of precursor T cells in homosexual men, a study was made of T-cell colony formation in 15 healthy homosexual men without anti-human immunodeficiency virus (HIV) antibody. The colony forming method used was the one-step monolayer technique using phytohemagglutinin as an inducer. Our results revealed that colony formation was extremely reduced and 3 cases showed no colony growth. However, with the addition of recombinant interleukin 2 to the culture system, the number of colonies increased up to the same level as in heterosexual controls. In addition, the analysis of CD3+, 4+, and 8+ cells of colony component cells revealed a decrease in CD3+ and 4+ cells. However, with the addition of recombinant interleukin 2, the numbers of CD3+ cells distinctly increased. The above results suggest that a disorder in the differentiation and proliferation of precursor T cells in homosexual men might be one of the causes of immunodeficiency.

Adult↗

Pulmonary involvement in patients with HTLV-I-associated myelopathy: increased soluble IL-2 receptors in bronchoalveolar lavage fluid.

A chronic spastic myelopathy associated with HTLV-I infection (HTLV-I-associated myelopathy: HAM) shows subclinical pulmonary involvement with bronchoalveolar T lymphocytosis. In the present study, we investigated 18 patients with HAM: five HTLV-I carriers without myelopathy and 13 normal control subjects seronegative for HTLV-I to determine if soluble IL-2 receptors (IL-2R), a marker of lymphocyte activation, were increased in serum and bronchoalveolar lavage (BAL) fluid from HAM patients. Serum IL-2R levels were significantly increased in patients with HAM as compared to normal control subjects (HAM versus control subjects: 633 +/- 395 versus 278 +/- 53 U/ml, p less than 0.01). There was also an increase of serum IL-2R levels in one of five HTLV-I carriers. BAL levels of soluble IL-2R were low but detectable in four normal control subjects and in one HTLV-I carrier. In HAM patients, however, soluble IL-2R levels in BAL fluid were remarkably elevated (173 +/- 110 U/mg of albumin) and were nearly 13 times higher on average than in serum (BAL fluid/serum ratio: 13 +/- 10). In patients with HAM, lavage IL-2R levels correlated well with the number of T lymphocytes (CD3+ cells) and CD4+ cells in BAL fluid (p less than 0.01). Furthermore, BAL lymphocytes obtained from HAM patients synthesized DNA spontaneously when cultured in vitro. These results suggest that, in HAM, T lymphocytes increased in the lung are activated locally to produce soluble IL-2R. Based on the results of this study, we conclude that immunologic mechanism(s) may play an important role in the development of pulmonary lesions in HAM patients.

Adult↗

[Intravesical BCG therapy in patients with recurrent superficial bladder tumors].

Intravesical instillation of BCG has recently become a treatment for superficial bladder tumor, and favorable results are reported. We have also obtained favorable results by performing intravesical BCG therapy to totally 32 cases of superficial recurrent bladder tumor and carcinoma in situ (CIS) one indicated for total cystectomy. The subjects were 29 cases of Ta and T1 and 4 cases of Tis, which are classified into 27 cases for treatment and 5 cases for prevention of recurrence after TUR. As the method for administration, 120 or 80 mg of BCG was dissolved in physiological saline and infused intravesically every week a total of 8 times. As a result of designating the patients who received the treatment more than 4 times as the subject, CR and PR were 19 cases (73%) and 5 cases (19%), or respectively, out of 26 assessable cases, and effective rate including PR was 93%. No recurrence has been observed so far in any of 5 cases treated for prevention of recurrence. Side effects which required treatment were observed in 13 cases (41%), but treatment could be continued by symptomatic therapy in most of the cases. Treatment was discontinued in 4 cases, 3 of which were hepatic disorders. It is considered that intravesical instillation of BCG is a therapeutic procedure which is good for trial in future in the light of the great efficacy obtained in the present study.

Administration, Intravesical↗