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Biomedical subjects

T Ohshima

Publications and source records attributed to T Ohshima.

At least 235 records · Page 13Linked to original sources

[Studies on urinary protein components in renal disease in children, II--Comparison between children with orthostatic albuminuria and children with remission of glomerulonephritis].

The urinary protein components of 14 children with orthostatic albuminuria (group OA) and also that of 9 children with remission of IgA nephropathy or Henoch-Schönlein purpura nephritis (group GN) after forced lordosis were analyzed. The results were as follows; (1) Urinary total protein excretions after forced lordosis were greater than 30mg/dl in 50% of 26 children with remission of glomerulonephritis, therefore a high percentage of children with remission of glomerulonephritis were complicated with orthostatic albuminuria. (2) Urinary total protein excretions after forced lordosis were 150 +/- 91mg/dl in the group of OA and 149 +/- 88mg/dl in GN (p > 0.05). (3) In the urinary protein components, the percentage of urinary albumin and alpha 1-antichymotrypsin excretions were significantly higher in the OA group than the GN group (p < 0.01, p < 0.001 respectively), while the percentage of urinary transferrin, IgA and IgG excretions were significantly higher in the GN group than the OA group (p < 0.01, p < 0.001 and p < 0.05 respectively). (4) The ratio of urinary IgG/IgA and serum IgG/IgA was significantly lower in the GN group than the OA group (p < 0.05), suggesting that serum IgA tended to be excreted in urine in the GN group.

Adolescent↗

[Genomic analysis of Japanese patients with adult-type metachromatic leukodystrophy].

We performed the genomic analysis of arylsulfatase A (ASA) gene in five Japanese patients with adult-type metachromatic leukodystrophy (MLD) including two sibling cases. Sequencing of amino acid coding region of ASA gene of proband case of family A disclosed 426Pro (CCG)-->Leu (CTG) mutation, which was reported to be frequently found in Caucasian patients with late-onset MLD. We developed mismatch primer PCR/RFLP method for detection of this mutation. If 426Pro-->Leu mutation exists in genomic DNA, Pst I site is newly created by PCR with a 3'-primer mismatched at one nucleotide. Genomic analysis of family A members using this method revealed that younger patient was homozygote of 426Pro-->Leu mutation and patient's parents and her younger brother were heterozygotes, which were confirmed by sequencing of exon 8 of ASA gene. Screening of this mutation using mismatch primer PCR/RFLP method was performed in one sibling case and one autopsy case. This point mutation was found in the sibling case. These results showed the possibility of world-wide spread of 426Pro-->Leu mutation in late-onset MLD patients and usefulness of our mismatch primer PCR/RFLP method for screening of this mutation.

Adult↗

[Atrial pacing with the A-V paceport pulmonary artery catheter].

Atrial pacing is often necessary during cardiac surgery. A total of 20 patients undergoing cardiac surgery were atrially paced with either a multipurpose pulmonary artery catheter (PAC) or an A-V paceport PAC (n = 10 each). Atrial pacing was successful in all the patients before cardiopulmonary bypass. The output threshold was 4.2 +/- 0.7 mA for a multipurpose PAC and 3.8 +/- 0.7 mA for A-V paceport PAC. Atrial pacing with both PAC's was readily performed and useful during cardiac surgery.

Catheterization↗

[Studies on urinary protein components in renal diseases in children. I--Characteristics of urinary protein components in renal diseases in children, with a focus on the relationship between IgA nephropathy and urinary IgA excretion].

Urinary protein components in children with renal disease were analyzed by the Reversed-Single Radial Immunodiffusion (R-SRID) method. The results were as follows: (1) In idiopathic nephrotic syndrome, the percentage of urinary albumin excretion was very high (79.5%). Urinary IgA excretion was 0.1% and IgG excretion was 1.6%, hence the excretion of these high-molecular-weight proteins amounted to 1.7% of the total urinary protein. (2) In membranous glomerulonephritis, urinary IgA was not detected, whereas the percentage of urinary IgG excretion was high (5.4%). (3) The percentage of urinary IgA excretion was higher in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) (2.4%, 1.6% respectively) than in other diverse renal diseases. (4) The percentage of urinary IgA excretion was correlated significantly with the serum IgA concentration in IgAN and HSPN (P < 0.001), but there was no such correlation in other diverse renal diseases. (5) In IgAN, the percentage of urinary IgA excretion was significantly higher in the subgroup with a duration of less than one year from the onset (3.6%) than in the subgroup with a duration longer than one year (1.5%) (p < 0.01).

Adolescent↗

Toxicological analysis for drugs and poisons using the formalin-fixed organ tissues. 1. Methamphetamine.

Methamphetamine (MA) was analyzed using formalin-fixed organ tissues from experimental animals and an autopsied cadaver. The brain, lung, liver, kidney and skeletal muscles of rabbits that had been administered MA were collected, and then fixed with a non-buffered 10% formalin solution at room temperature (10-20 degrees C) for five different fixation periods (1, 3, 7, 14 and 28 days). After the Extrelut column extraction, MA was derivatized using anhydrous trifluoroacetic acid (TFA) and analyzed by GC-MS using a DB-17 column. MA-TFA in the eluates from the organ tissues after the formalin-fixation could be identified by GC-MS. Even one day after the formalin-fixation, concentrations of MA in the fixed organ tissues already significantly decreased to 1.3-3.1% when compared with those of MA in the non-fixed tissues, and to 0.04-0.4% in all of the fixed organ tissues at 28 days after the fixation. Moreover, MA in the organ eluates from the autopsied male cadaver after one-month formalin-fixation was qualitatively detected. These results obviously show the usefulness of MA detection using formalin-fixed organs in the practice of forensic medicine and police science.

Animals↗

[A case of oligomeganephronia--quantitative measurement of the glomerular surface area and the number of glomeruli with a color image analyzer].

We report here a nine-year-old boy with oligomeganephronia. The patient had proteinuria and morphometric analysis of the renal biopsy specimen confirmed the diagnosis of oligomeganephronia. We employed a color image analyzer (OLYMPUS Corp.) to determine the glomerular surface area and the number of glomeruli per mm2 of the renal cortex of the patient. All the scanned glomeruli showed marked hypertrophy; the mean maximal surface area for the 5 glomeruli was 46 x 10(3) microns 2, which is approximately 4 times larger than that of normal children of the same age. The number of glomeruli per mm2 of the renal cortex of the patient had decreased to 1. 11 per mm2, which is approximately one fourth that of normal controls with IgA glomerulonephritis. The color image analyzer proved to be useful for the diagnosis of oligomeganephronia enabling the quantitative measurement of the glomerular surface area and the number of glomeruli per mm2 of the renal cortex.

Child↗

[Effect of hydralazine on the blood flow of normal and tumor tissues in hyperthermia].

We examined changes in blood flow in normal muscle and SCC-VII tumors of C 3 H/He mice following hyperthermia (HT) combined with the vasodilator hydralazine (Hyd) and compared them with similar changes after Hyd treatment or HT alone. Blood flow was measured by the Laser Doppler method, and oxygen tension was evaluated by polarography. The mean blood flow for the tumors in the Hyd group decreased. After HT treatment, it decreased to a low level. The largest decrease in tumor blood flow was observed after HT combined with Hyd administration. In normal muscle, no decrease in blood flow was induced by HT, Hyd or their combination. The magnitude of action of Hyd on the heat-induced changes in tumor blood flow and on damage to tumor vessels is considered to depend on the initial perfusion level. Therefore, we tried to clarify how this parameter was correlated with Hyd and/or HT-induced changes. In the HT and combined groups, the higher the temperature, the more significant the decrease in blood flow. In conclusion, these results suggest that the decrease in blood flow inside the tumor caused by Hyd plays an important role in enhancement of the hyperthermic anti-tumor effect.

Animals↗

Congenital histidine-rich glycoprotein deficiency.

The proband, a 43-year-old woman, suffered from right transverse sinus thrombosis during oral contraceptive treatment. A month after stopping the drug, her plasma activities of antithrombin III, protein C, protein S, heparin cofactor II, plasminogen and plasminogen activator inhibitor were normal, but her plasma histidine-rich glycoprotein (HRG) level was only 21% of the normal level of 109.5 +/- 51.5% (mean +/- 2 SD). The HRG concentrations in her plasma determined on four different occasions over 6 months were similar. She showed no clinical signs of liver insufficiency or sepsis. Low levels of plasma HRG (20% to 35% of normal) were also found in her aunt, uncle and two daughters. These results suggest that congenital HRG deficiency is inheritary in this family.

Adult↗

Dye-linked L-malate dehydrogenase from thermophilic Bacillus species DSM 465. Purification and characterization.

The distribution of dye-linked L-malate dehydrogenase (L-malate: acceptor oxidoreductase, EC 1.1.99.16) was investigated in many thermophilic bacteria. The enzyme occurred widely in thermophilic spore-forming bacteria like bacilli and thermoactinomycetes. The enzyme was purified to homogeneity from a thermophile, Bacillus sp. DSM 465, with a 2.7% overall recovery by DEAE-Toyopearl column chromatography, Sephacryl S-400 column chromatography and preparative slab PAGE. The enzyme had a molecular mass of about 660 kDa and consisted of about ten subunits all with a molecular mass of 66 kDa. The enzyme retained its full activity upon heating at 55 degrees C for at least 60 min and with incubation at pH 5.0-10.0, 55 degrees C, for 10 min. The enzyme exclusively catalyzed L-malate dehydrogenation in the presence of an electron acceptor such as 2,6-dichloroindophenol. The Michaelis constants for L-malate and 2,6-dichloroindophenol were determined to be 1.67 mM and 0.050 mM, respectively. FAD was identified as a prosthetic group of the enzyme by HPLC.

Bacillus↗

Bronchodilator activity of xanthine derivatives substituted with functional groups at the 1- or 7-position.

Xanthine derivatives with several functional groups at the 1- or 7-position were synthesized, and their pharmacological activities in guinea pigs were studied. In general, the in vitro tracheal relaxant action and positive chronotropic action of 3-propylxanthines were increased by substitutions with nonpolar functional groups at the 1-position, but decreased by any substitution at the 7-position. On the other hand, because positive chronotropic actions of substituents with allyl, aminoalkyl, alkoxyalkyl, and normal alkyl groups were much less than tracheal muscle became very high with substitutions of 3'-butenyl, (dimethylamino)ethyl, 2'-ethoxyethyl, 3'-methoxypropyl, and n-propyl groups at the 1-position and of 2'-ethoxyethyl, 2'-oxopropyl, and n-propyl groups at the 7-position, compared with theophylline and the corresponding unsubstituted xanthines, 3-propylxanthine and 1-methyl-3-propylxanthine. When compounds were intraduodenally administered to the guinea pig, 1-(2'-ethoxyethyl)-, 1-(3'-methoxypropyl)-, 1-(3'-butenyl)-, and 1-[(dimethylamino)-ethyl]-3-propylxanthines, 1-methyl-7-(2'-oxopropyl)-3-propylxanthine, and denbufylline (1,3-di-n-butyl-7-(2'-oxopropyl)xanthine) effectively inhibited the acetylcholine-induced bronchospasm without heart stimulation or central nervous system-stimulation at the effective dosage range. Particularly, the bronchodilatory effect of 1-(2'-ethoxyethyl)-3-propylxanthine was much stronger and more continuous than those of theophylline and pentoxifylline. On the other hand, there were certain relationships among the in vitro tracheal relaxant activities of these compounds, their affinities for adenosine (A1) receptors in the brain membrane, and their inhibition of cyclic AMP-phosphodiesterase (PDE) in the tracheal muscle. The affinity for A2 receptors of these compounds was very low or negligible. This suggests that both the action on A1 receptors or interaction with adenosine and the cyclic AMP-PDE inhibitory activity contribute to the bronchodilator action of 1- and 7-substituted xanthines. This study indicates that the substitutions with none or low polar functional groups at the 1-position could improve the selectivity and duration of the bronchodilator effects of xanthines.

Administration, Oral↗

Valine dehydrogenase from a non-spore-forming bacterium, Alcaligenes faecalis: purification and characterization.

An NAD-dependent valine dehydrogenase (L-valine:NAD oxidoreductase, deaminating, EC 1.4.1.-), was found in a non-spore-forming bacterium, Alcaligenes faecalis, and purified about 80-fold to be characterized. The molecular mass of the enzyme was estimated to be about 72 kDa and the enzyme consists of two identical subunits with a molecular mass of 40 kDa and is thermolabile. It loses its activity fully on incubation at 50 degrees C for 5 min. The enzyme catalyzes the reversible deamination of L-valine, which is the preferred substrate, and other branched-chain and straight-chain L-amino acids in the presence of NAD. The pH optima are about 10.8 and 8.8 for the oxidative deamination and reductive amination, respectively. The pro-S hydrogen at C-4 of the dihydronicotinamide ring of NADH was exclusively transferred to the substrate in the reductive amination. The amino-acid composition markedly differs from those of Bacillus sphaericus and Clostridium thermoaceticum leucine dehydrogenases. The enzyme did not react with the antibody of C. thermoaceticum leucine dehydrogenase. Therefore, the enzyme is clearly different from leucine dehydrogenases from spore-forming bacteria, which act on valine, and the first valine dehydrogenase to be characterized in detail.

Alcaligenes↗

Suspected maternal infanticide in a case of hydranencephaly.

A medico-legal autopsy case of hydranencephaly in a male infant which was first suspected of maternal infanticide is reported. The infant was 48 cm in height, weighed 2.86 kg and the circumference of the head, the chest and the abdomen was 32.2 cm, 31.0 cm and 30.4 cm, respectively, with no deformities of the head or body. Autopsy examination, however, revealed a severe defect in the central nervous system. The cranial cavity was filled with a cloudy dark red fluid (ca. 310 ml) instead of the cerebral hemispheres. The residual central nervous tissues were mostly subtentorial structures from the midbrain to the spinal cord namely, corpus mamillare, corpora quadrigemina, corpus pineale, crus cerebri, pons, cerebellum, medulla oblongata and spinal cord. The basal ganglia, thalamus, hypothalamus and chiasma opticum could not be found, although atrophic hypophysis, eyeballs and optic nerves were present. The usual distribution of cerebral blood vessels, especially the branches of the anterior and middle cerebral arteries and Willis' ring, was absent despite the presence of the internal and external carotid arteries. Other organs were, in general, congestive. The marked cortical atrophy of the adrenal glands (left 0.5 g, right 0.6 g), especially the zona fasciculata, was characteristic. The hydrostatic lung test gave partially positive results, but this was considered to be due to artificial respiration by an ambulance man because amniotic fluid components were microscopically noted and fully expanded alveoli were not found. In conclusion, the cause of the infant's death was diagnosed as stillbirth due to aspiration of amniotic fluid caused by the severe defect of vegetative hypothalamic function through hydranencephaly.

Brain↗

Site-directed mutagenesis of a hexapeptide segment involved in substrate recognition of phenylalanine dehydrogenase from Thermoactinomyces intermedius.

Phenylalanine dehydrogenase from Thermoactinomyces intermedius and leucine dehydrogenase from Bacillus stearothermophilus show a 59% sequence similarity in their substrate-binding domains, although their substrate specificities are different. We prepared a phenylalanine dehydrogenase mutant enzyme whose inherent hexapeptide segment (124F-V-H-A-A-129R) in the substrate-binding domain was replaced by the corresponding part of leucine dehydrogenase (M-D-I-I-Y-Q) in order to investigate the mechanism of substrate recognition by phenylalanine dehydrogenase. The catalytic efficiencies (kcat/Km) of the mutant enzyme with aliphatic amino acids and aliphatic keto acids as substrates were 0.5 to 2% of those of the wild-type enzyme. In contrast, the efficiencies for L-phenylalanine and phenylpyruvate decreased to 0.008 and 0.035% of those of the wild-type enzyme, respectively. These results suggest that the hexapeptide segment plays an important role in the substrate recognition by phenylalanine dehydrogenase.

Amino Acid Oxidoreductases↗

Clinical effect of WEB 1881 (nebracetam fumarate) on patients with dementia of the Alzheimer type and study of its clinical pharmacology.

We administrated WEB 1881, 800 mg/day (400 mg twice a day), nine patients with dementia of the Alzheimer type for 8 weeks, and undertook an open study to investigate the clinical effects of the distribution into the cerebrospinal fluid (CSF) as well as the influence on the neurotransmitter-related substances in the CSF. These were outpatients living at home with caregivers. Significant clinical improvement was shown by means of the Gottfries, Bråne, and Steen Scale and by Hasegawa's dementia scale. Unchanged WEB 1881 was identified in the CSF. The mean concentration of which was 198.7 ng/ml, this corresponded to 19.0% of the plasma concentration. Of several neurotransmitter-related substances measured in the CSF, a marked rise of AChE activity was observed. Adverse effects consisted of a slight skin eruption in one case and alterations in a clinical laboratory test in another case. These were, however, not significant from a clinical viewpoint. It is suggested that the mechanisms of action of WEB 1881 are based on its transit into the CSF as well as the activation of intracerebral acetylcholinergic systems.

Aged↗

Interstitial pneumonitis possibly due to mitoxantrone.

A 41-year-old patient with chronic myelogenous leukemia in the accelerated phase was treated with mitoxantrone. She developed pyrexia 7 days after receiving the third administration of mitoxantrone. After 3 more days, she experienced dry cough and dyspnea. Bilateral fine crackles were audible, but no signs of heart failure were found. A chest X-ray film revealed diffuse reticulogranular infiltrates bilaterally. An increase in the prednisolone dosage led to an improvement. Specimens of the bronchoalveolar lavage revealed an increase in CD4-/CD8- lymphocytes. The peripheral lymphocytes also expressed neither CD4 nor CD8. Specimens of a transbronchial lung biopsy disclosed thickening of the alveolar wall with infiltration of lymphoid cells.

Adult↗

Purification and properties of extremely thermostable glutamate dehydrogenases from two hyperthermophilic archaebacteria, Pyrococcus woesei and Pyrococcus furiosus.

Glutamate dehydrogenase (L-glutamate: NADP oxidoreductase, deaminating, EC 1.4.1.4) from the hyperthermophilic archaebacteria Pyrococcus woesei and P. furiosus were purified to homogeneity from crude extracts. The enzymes had similar enzymological properties: molecular mass, subunit structure, optimum pHs for the oxidative deamination and reductive amination, substrate specificity and coenzyme specificity as well as thermostability; the activity was not lost after incubation at 105 degrees C for 30 min. However, some differences were detected in resistance to urea denaturation and effects of salts on their activity and stability. The N-terminal 20 amino acid sequences of the two enzymes were identical.

Amino Acid Sequence↗