Biomedical subjects

M Sugawara

Publications and source records attributed to M Sugawara.

At least 91 records · Page 5Linked to original sources

PubMed1999

A case of cimetidine-induced acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody.

We present a case of acute tubulointerstitial nephritis (ATIN) that developed in a 63-year-old man who had been taking cimetidine for treatment of a gastric ulcer. The constellation of clinical, laboratory, and histopathologic findings suggested drug-induced ATIN. Of interest, the patient had antineutrophil cytoplasmic antibody (ANCA) in his sera, reactive with myeloperoxidase, elastase, and lactoferrin. Prominent renal histological features included marked plasmacyte infiltration into the renal interstitium. Withdrawal of cimetidine resulted in complete resolution of renal findings, and the titers of ANCA concomitantly declined. Thus, cimetidine may have played a causative role in the development of ANCA-associated ATIN.

Anti-Ulcer Agents↗

PubMed1999

A method for evaluating chemical selectivity of agonists for glutamate receptor channels incorporated in liposomes based on an agonist-induced ion flux measured by ion-selective electrodes.

A new method for evaluating chemical selectivity of agonists for the NMDA subtype of glutamate receptor (GluR) channels is described. The method is based on the magnitude of Ca2+ release from GluR-incorporated liposomes, which is measured by a Ca2+ ion-selective electrode with a thin-layer mode. The partially purified GluRs from rat whole brain were reconstituted into Ca2+-loaded liposomes. Small aliquots (each 50 microl) of the proteoliposomes, in the presence of an antagonist DNQX for blocking non-NMDA subtype, were subjected to potentiometric measurements of Ca2+ release under stimulation by three kinds of agonists, i.e. NMDA, L-glutamate and L-CCG-IV. The amount of the Ca2+ ion flux through the GluR channel induced by the agonists was found to increase in the order of NMDA < L-glutamate < L-CCG-IV, which was consistent with that of binding affinity of the agonists toward the NMDA subtype. However, the range of selectivity of the relevant agonists was much smaller compared with results based on binding affinities. The present method provides physiologically more relevant values for the agonist selectivity of GluRs as compared to that of the conventional binding assay in the sense that the selectivity is based on the very magnitude of Ca2+ flux through the NMDA receptor, i.e. the extent of signal transduction by a given agonist. The evaluation of agonist selectivity based on Na+ release was also investigated by using a Na+ ion-selective electrode, but agonist-induced Na+ release was not detected, because of low permeability of Na+ through the NMDA subtype.

Amino Acids, Dicarboxylic↗

PubMed1999

Effects of interactions between drugs on the renal excretion of trientine in rats--acetazolamide and furosemide increase trientine excretion.

PURPOSE: To elucidate the effects of drug interactions on the urinary excretion of trientine in rats. METHOD: Trientine and various other drugs were intravenously administered to rats and the urinary excretion of trientine was investigated. To clarify the mechanisms of drug-drug interactions, we also investigated the effects of various drugs on spermine uptake by rat renal brushborder membrane vesicles. RESULTS: Cimetidine, a substrate of the H+/organic cation antiporter, and aminoglycoside antibiotics did not affect trientine excretion, while acetazolamide and furosemide, which increase the concentration of sodium ions in renal proximal tubules, increased the excretion of trientine. However, trichlormethiazide, which acts in renal distal tubules, did not affect trientine excretion. Acetazolamide and furosemide did not directly affect the Na+/spermine transporter because these diuretics had no effect on the uptake of spermine into the rat renal brush-border membrane vesicles. CONCLUSIONS: There is no interaction between trientine and the substrate of the H+/organic cation antiporter or aminoglycoside antibiotics. However, drugs that change the concentration of sodium ions in renal proximal tubules, such as diuretics, can increase the trientine excretion since the increase in the luminal concentration of sodium ion accelerates the Na+/spermine antiporter.

Acetazolamide↗

PubMed1999

Reliability of childhood mental disorder: diagnoses by Japanese psychologists.

The recent entry of psychologists into psychiatric practices and schools in Japan calls for diagnostic skills, because psychiatrists are less available in such settings. We examined the reliability of the diagnoses of 10 DSM-IV childhood mental disorders by 11 Japanese psychologists, using 20 case vignettes. Most categories had good reliability (kappa), except for attention deficit hyperactivity disorder. Japanese clinical psychologists may be able to use DSM-IV reliably as a tool for diagnosis of childhood psychiatric disorders, if sufficient training is provided.

Adolescent↗

PubMed1999

Blood-brain barrier produces significant efflux of L-aspartic acid but not D-aspartic acid: in vivo evidence using the brain efflux index method.

The brain efflux index method has been used to clarify the mechanism of efflux transport of acidic amino acids such as L-aspartic acid (L-Asp), L-glutamic acid (L-Glu), and D-aspartic acid (D-Asp) across the blood-brain barrier (BBB). About 85% of L-[3H]Asp and 40% of L-[3H]Glu was eliminated from the ipsilateral cerebrum within, respectively, 10 and 20 min of microinjection into the brain. The efflux rate constant of L-[3H]Asp and L-[3H]Glu was 0.207 and 0.0346 min(-1), respectively. However, D-[3H]Asp was not eliminated from brain over a 20-min period. The efflux of L-[3H]Asp and L-[3H]Glu was inhibited in the presence of excess unlabeled L-Asp and L-Glu, whereas D-Asp did not inhibit either form of efflux transport. Aspartic acid efflux across the BBB appears to be stereospecific. Using a combination of TLC and the bioimaging analysis, attempts were made to detect the metabolites of L-[3H]Asp and L-[3H]Glu in the ipsilateral cerebrum and jugular vein plasma following a microinjection into parietal cortex, area 2. Significant amounts of intact L-[3H]Asp and L-[3H]Glu were found in all samples examined, including jugular vein plasma, providing direct evidence that at least a part of the L-Asp and L-Glu in the brain interstitial fluid is transported across the BBB in the intact form. To compare the transport of acidic amino acids using brain parenchymal cells, brain slice uptake studies were performed. Although the slice-to-medium ratio of D-[3H]Asp was the highest, followed by L-[3H]Glu and L-[3H]Asp, the initial uptake rate did not differ for both L-[3H]Asp and D-[3H]Asp, suggesting that the uptake of aspartic acid in brain parenchymal cells is not stereospecific. These results provide evidence that the BBB may act as an efflux pump for L-Asp and L-Glu to reduce the brain interstitial fluid concentration and act as a static wall for D-Asp.

Algorithms↗

PubMed1999

Complete unilateral anomalous connection of the left pulmonary veins to the coronary sinus with unroofed coronary sinus syndrome: a case report.

We report a case of complete unilateral anomalous connection of the left pulmonary veins to the coronary sinus with unroofed coronary sinus syndrome. Magnetic resonance imaging (MRI) was a useful diagnostic method in our case. At operation, a cut was made from the orifice of the coronary sinus to the unroofed portion of the coronary sinus, and part of the lower atrial septum was excised. The resulting defect was closed with a Dacron patch, diverting the left pulmonary venous blood into the left atrium.

Adult↗

PubMed1999

A surgical management of aortic insufficiency concomitant with mediastinal well-differentiated liposarcoma.

We present a rare case of a mediastinal liposarcoma concomitant with aortic insufficiency due to myxoid degeneration of the aortic valve. Because the patient's left ventricle was in moderate dilatation and a posterolateral thoracotomy combined with median sternotomy was required in order to perform a complete resection of a mediastinal liposarcoma, it was decided to carry out aortic valve surgery and tumor excision in one operation.

Aortic Valve Insufficiency↗

PubMed1999

Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: a prospective study.

Agranulocytosis is the most serious side effect of antithyroid drug (ATD) therapy. We conducted prospective and randomized studies to examine whether granulocyte colony-stimulating factor (G-CSF) is actually effective for ATD-induced agranulocytosis. Twenty-four patients with Graves' disease who developed agranulocytosis during ATD therapy were randomly divided into a G-CSF group (n = 14) and an untreated group (n = 10). Subcutaneous injection of G-CSF (100 to 250 microg) was given daily until neutrophil counts rose to greater than 1000/microL. The untreated group received antibiotic therapy only. Recovery time, which is defined as the number of days required for neutrophil counts to exceed 500/microL, was monitored by daily complete blood count (CBC). Recovery time in the G-CSF-treated group did not differ from that of the untreated group in those patients with moderate and severe agranulocytosis; thus, prolonged use of G-CSF treatment is generally ineffective for ATD-induced agranulocytosis.

Adolescent↗

PubMed1999

Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.

Methimazole (MMI) and propylthiouracil (PTU) are common antithyroid drugs for treating hyperthyroidism because the 2 drugs inhibit thyroid peroxidase (TPO)-catalyzed thyroid hormone formation. We studied whether the 2 drugs actually inhibit cellular TPO activity in cultured porcine follicles. Porcine follicles were cultured in the presence of 1 mU/mL thyrotropin (TSH) for 7 days. Then follicles were exposed to MMI or PTU in the presence of 0.1 microM Kl for 2 days. TPO activity was measured in the 100,000 x g-pellet of the thyroid sonicate by the guaiacol oxidation method. Exposure to MMI (1 microM and 10 microM) or PTU (10 microM and 100 microM) for 2 days caused a significant increase in cellular TPO activity; 100 microM MMI inhibited cellular TPO activity. The presence of cyclic adenosine monophosphate (cAMP)-generating system (forskolin) in TSH-free medium increased MMI-mediated TPO activity. Cyclohexamide inhibited MMI-mediated TPO activation, indicating that new protein synthesis is required for increased TPO activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in TPO mRNA by PTU or MMI. In conclusion, MMI and PTU at therapeutic concentrations can increase TPO mRNA and cellular TPO activity, although the 2 drugs inhibit the TPO-H2O2-mediated catalytic reaction.

Animals↗

PubMed1999

Psychiatric disorders among Japanese children.

OBJECTIVE: To generate current data on the prevalence of psychiatric disorders among Japanese children, using DSM-III-R criteria. METHOD: As part of an ongoing longitudinal study in a Japanese community sample, 114 mother-child dyads were interviewed when the children were approximately 8 years old. DSM-III-R disorders of the children were diagnosed through the administration of a structured diagnostic instrument, the parent and child versions of the Child Assessment Schedule, to both the children and their mothers. RESULTS: The prevalence rate for any diagnosis was 49.1%, which is similar to that of U.S. children and adolescents. CONCLUSION: The Child Assessment Schedule is an appropriate scale for assessing the psychopathology of Japanese children, which is as prevalent as in a U.S. sample.

Adolescent↗

PubMed1999

Detection of gyrA mutations among 335 Pseudomonas aeruginosa strains isolated in Japan and their susceptibilities to fluoroquinolones.

gyrA point mutations in 335 clinical Pseudomonas aeruginosa isolates were examined mainly by nonisotopic single-strand conformation polymorphism analysis and direct sequencing. Seven types of missense gyrA mutations were observed in 70 of 335 strains (20.9%), and ciprofloxacin MICs were > or = 3.13 micrograms/ml for 63 of 70 strains (90.0%). These included two double point mutations and three novel mutations (Ala-67-->Ser plus Asp-87-->Gly, Ala-84-->Pro, and Gln-106-->Leu). Thr-83-->Ile mutants were predominantly observed (63 of 70 mutants) and showed high-level fluoroquinolone resistance (ciprofloxacin MIC at which 50% of isolates are inhibited, 25 micrograms/ml).

Anti-Infective Agents↗

PubMed1999

The presence of an Na+/spermine antiporter in the rat renal brush-border membrane.

This study was aimed at determining the driving force for spermine transport in rat renal proximal tubular brush-border membrane. The uptake of spermine and trientine, a spermine-like drug used for treating Wilson's disease, into rat renal brush-border membrane vesicles was significantly stimulated by an outwardly directed Na+ gradient. The Na+-dependent uptake was temperature dependent and saturable. A kinetic analysis of the initial uptake of spermine with an Na+ gradient gave a Km value of 1.44 microM and a Vmax value of 6.31 pmol (mg protein)(-1)/30s. The Na+ dependent uptake of [3H]spermine was inhibited by spermine, trientine and tetraethylene-pentamine. Substrates of the H+/organic cation transporter (cimetidine and tetraethyl-ammonium), physiological polyamines (putrescine and spermidine) with 2 or 3 amino groups and aminoglycosides (amikacin and tobramicin) with 4 or 5 cationic amines did not affect the uptake of spermine in the presence of an outwardly directed Na+ gradient. These results suggest that the renal tubular secretion of spermine is mediated by an Na+/spermine antiport system which is specific for a straight-chain polyamine compound with more than 4 amino groups.

Animals↗

PubMed1999

Synthesis and degradation of 1-aminocyclopropane-1-carboxylic acid by Penicillium citrinum.

1-Aminocyclopropane-1-carboxylic acid (ACC), which is a precursor of ethylene in plants, has never been known to occur in microorganisms. We describe the synthesis of ACC by Penicillium citrinum, purification of ACC synthase [EC 4.4.1.14] and ACC deaminase [EC 4.1.99.4], and their properties. Analyses of P. citrinum culture showed occurrence of ACC in the culture broth and in the cell extract. ACC synthase was purified from cells grown in a medium containing 0.05% L-methionine and ACC deaminase was done from cells incubated in a medium containing 1% 2-aminoisobutyrate. The purified ACC synthase, with a specific activity of 327 milliunit/mg protein, showed a single band of M(r) 48,000 in SDS-polyacrylamide gel electrophoresis. The molecular mass of the native enzyme by gel filtration was 96,000 Da. The ACC synthase had the Km for S-adenosyl-L-methionine of 1.74 mM and kcat of 0.56 s-1 per monomer. The purified ACC deaminase, with a specific activity of 4.7 unit/mg protein, showed one band in SDS-polyacrylamide gel electrophoresis of M(r) 41,000. The molecular mass of the native ACC deaminase was 68,000 Da by gel filtration. The enzyme had a Km for ACC of 4.8 mM and kcat of 3.52 s-1. The presence of 7 mM Cu2+ in alkaline buffer solution was effective for increasing the stability of the ACC deaminase in the process of purification.

Amino Acids↗

PubMed1999

Temporal variation of validity of self-rating questionnaires: improved validity of repeated use of Zung's Self-Rating Depression Scale among women during the perinatal period.

It has been reported that Zung's Self-Rating Depression Scale (SDS) loses its validity in predicting cases of depression when used repeatedly. The validity of SDS was tested against the subject's Research Diagnostic Criteria (RDC) diagnoses of major/minor depressive disorders in 120 pregnant women four times throughout the perinatal period. Different sets of predictive SDS items were found at different time points. We developed an 'RDC-like' algorithm from SDS items. Though varying in sensitivity, we found that this formula yielded low, but stable, positive predictive values and constantly high negative predictive values. We suggest that the RDC-like algorithm is a better alternative for screening depression among perinatal women.

Adult↗

PubMed1999

Multiplicity of the H+-dependent transport mechanism of dipeptide and anionic beta-lactam antibiotic ceftibuten in rat intestinal brush-border membrane.

To elucidate the transport characteristics of the H+/dipeptide carrier that recognizes the orally active beta-lactam antibiotic ceftibuten, the uptake behaviors were compared of ceftibuten and Gly-Sar by rat intestinal brush-border membrane vesicles. The results show that 1) both the uptake of ceftibuten and that of Gly-Sar were dependent on an inwardly directed H+ gradient; 2) anionic compounds such as hippurylphenyllactic acid competitively inhibited ceftibuten uptake in the presence of H+ gradient, whereas this anion did not inhibit Gly-Sar uptake; and 3) the carrier-mediated uptake of ceftibuten did not disappear even in the presence of 20 mM Gly-Sar. The results provide an evidence that several transporters with different features are potentially responsible for the uptake of beta-lactam antibiotics into the intestinal cells. It is suggested that the dianionic beta-lactam antibiotics that carry a net negative charge such as ceftibuten use multiple H+-dependent transport systems for absorption.

Animals↗

PubMed1999

[Effect of preoperative chemotherapy for bulky N2 non-small-cell lung cancer].

The effect of chemotherapy as the adjuvant therapy to bulky N2 disease (stage IIIA) non-small-cell lung cancer was examined. From January 1992 to December 1996, 464 patients with non-small-cell lung cancer underwent surgery. Seven patients (1.5%) with N2 disease (stage IIIA) received two cycles of preresectional cisplatin and vindesin chemotherapy, followed by standardized surgical resection (Group A). 46 patients (9.9%) had pathological N2 disease (T1-3, M0) after surgery (Group B). In Group A a complete resection was accomplished in two patients (28.6%), and five patients had incomplete resection with a deseased margin, followed thoracic irradiation 60 to 75 Gy. In three patients in Group A the N2 disease was pathologically downstaged to N1 or N0 disease. Overall survival at five years in Group A and in Group B was 48% and 39%, and median survival time was 49 months and 38 months. Although complete resection rate was lower in Group A (28.6%) than in Group B (78.2%), there was no significant difference between five year survival and median survival time in Group A and Group B. These data may be thought to suggest that induction chemotherapy in Group A was effective on occult micrometastatic disease.

Aged↗

PubMed1999

[Hereditary ataxias in Akita prefecture].

To provide a genetic survey of hereditary ataxia, we performed PCR screening of SCA1, SCA2, MJD1 (SCA 3), SCA6, DRPLA, with 71 patients in 61 families living in Akita prefecture (1,205,571 population in 1997) in Japan. Of 71 patients in 61 families, 18 MJD1, 14 SCA6, 5 DRPLA, 1 SCA1 and 1 SCA2 patients were detected. Eighty percent of autosomal dominant inherited spinocerebellar degeneration (AD-SCD) including 7 spoladic patients genetically diagnosed as AD-SCD was MJD1 (45.7%) and SCA6 (34.3%). These suggest the prevalence rate of hereditary ataxias in Akita prefecture; 1.5 and 1.2/100,000 of MJD1 and SCA6, respectively. Only one patient of SCA1 was detected, which was frequently reported in Hokkaido and Tohoku area in Japan.

Genetic Testing↗

PubMed1999

[Assessment of induction therapy and resection in stage IIIb non-small cell lung cancer].

Twelve patients with stage IIIb non-small cell lung cancer underwent induction therapy and resection from January 1990 to July 1998. They were divided into two groups; group A (n = 5) received two (to four) preresectional cisplatin and videsine chemotherapy, group B (n = 7) received chemoradiotherapy (radiation with concurrent low-dose-daily cisplatin). All patients in both groups had clinically down-stage and had no major side effects preventing surgery. 3 patients underwent radical pneumonectomy and 9 patients had radical lobectomy with no operative mortality. In 9 patients the disease was pathologically downstaged. Overall five-year survival was 27%, while in group A it was 50%. In group B 2-year survival was 18% and the longest survivor had pulmonary recurrence four years after surgery. Our data show better prognosis in group A than in group B. This results suggest that chemotherapy may be superior pre-resectional therapy to chemoradiotherapy.

Adult↗