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Biomedical subjects

T Ohshima

Publications and source records attributed to T Ohshima.

At least 217 records · Page 12Linked to original sources
PubMed1995

[Aspergillus lumbar discitis in a patient with acute lymphoblastic leukemia following induction therapy].

A 47-year-old female was admitted in October 1988 because of anemia and lymphoblastic cells in peripheral blood. A bone marrow aspirate was hypercellular with 93.9% lymphoblasts negative for peroxidase staining. The case was diagnosed as ALL (L2), and treated with JALSG ALL-87 regimen. She developed spiky fever and endotoxin shock due to bacteremia caused by pseudomonas aeruginosa, then was treated with several antibiotics. With the recovery of leukocytes, the chest X-ray showed an infiltrative shadow and a cavity forming lung abscess resembling aspergilloma in her left lung. The cavity improved of transbronchial infusion following amphotericin B (AMPH-B). Although she achieved complete remission, she felt severe lumbago accompanied by a marked erosion of the vertebral body with disc space narrowing on her X-ray. Then she underwent surgery to remove a disc abscess, and 1 colony of the aspergillus species was cultured from the specimen. She was treated with intravenous AMPH-B, and post remission therapies were performed under the injection of anti-fungal agents. No remarkable symptoms of complications were recognized during the chemotherapy. AMPH-B is useful and safe for the management of aspergillus discitis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Natural interferon alpha for chronic myelogenous leukemia in the chronic phase: hematologic, cytogenetic and molecular response].

Twenty one patients with Philadelphia chromosome positive CML were treated with natural interferon alpha. All patients were in the chronic phase, 5 were untreated and 16 had been previously treated with busulfan or hydroxyurea. Eight patients in complete remission (CR) were given IFN subcutaneously at a dose of 5 x 10(6) unit per day as maintenance therapy, whereas 13 non-CR patients were given 2. 5 approximately 10 x 10(6) units for remission induction. Doses and intervals of IFN were adjusted to maintain the WBC count below 5 x 10(9)/l, but additional drugs were given when the WBC count could not be controlled with IFN alone. Six out of 10 evaluable non-CR patients attained CR with IFN only and 4 others achieved with additional drug. Cytogenetic responses were evaluated in 15 patients. CCR, PCR and MCR were attained in 5, 2 and 1 patients respectively. Southern blotting method showed that the BCR gene rearrangement disappeared in 5 out of 13 patients. Cytogenetic response rate was not different between untreated and previously treated patients, however it differed between patients with or without additional drug. The time to first cytogenetic effect was within 12 months in almost all effective cases. Fever and general fatigue were seen in almost all patients. IFN administration was discontinued only patients with severe skin eruption (3 patients) and bone marrow aplasia (1 patient).

Adult↗
PubMed1995

[Rapid detection and identification of mycobacteria by the PCR assay based on the co-amplification of the gene IS6110 and groEL].

In definite diagnosis of mycobacterial infection, prompt and adequate differential diagnosis leads to an appropriate treatment. We developed and evaluated a PCR assay based on co-amplification of the insertion sequence IS6110 and groEL gene that are species-specific for Mycobacterium tuberculosis complex and genus-specific, respectively. The detection limit of the assay system for cultured M. tuberculosis was 2 cells/ml, as compared with 200 cells/ml by culture onto Ogawa's medium. To assess the value of the assay in routine laboratory works, the results obtained by PCR were compared with those by standard microbiological methods for 758 specimens collected for the examinations of mycobacterial infection. The PCR system for detection of mycobacteria gave overall positive rate of 27.6% (209/758), as compared to 6.1% (46/758) by smear and 7.7% (58/758) by culture onto Ogawa's medium. Sensitivity and specificity were 97.8% and 97.3%, respectively, for the IS6110 and groEL gene for detection of M. tuberculosis complex; 91.7% and 80.3%, respectively, for only the groEL gene for detection of atypical mycobacteria. The PCR assay based on co-amplification of the IS6110 and groEL gene would be useful for diagnosis of mycobacterial infections, allowing not only more sensitive detection of mycobacteria but also rapid discrimination between M. tuberculosis complex and atypical mycobacteria. This assay would help to eliminate time-consuming confirmation, and to avoid both unnecessary treatment and hospitalization of the patient.

DNA, Bacterial↗
PubMed1995

Retrospective investigation of medico-legal autopsy cases involving mentally handicapped individuals.

Mentally handicapped individuals were involved in some way in 64 (17.7%) of the total of 362 medico-legal autopsy cases during the past 13 years. Among these 64 cases, 32 were suicides committed by mentally handicapped persons (18 males and 14 females). The most common method of suicide was drowning (65.6%). Five cases were homicides suddenly and unexpectedly committed by mentally handicapped persons. In four of the five cases, the victim was a member of the assailant's family; this was considered to be a characteristic of homicides committed by mentally handicapped persons. On the other hand, there was only one case in which a mentally handicapped person was victimized, that of a 34-year-old female with schizophrenia who was strangled by her mother. In 19 cases, infanticide was committed by mentally handicapped mothers ranging in age from 17 to 40 years old; approximately 80% of the infanticide victims were infants of less than 6 months, and this was the age range most at risk of victims. There were two cases involving either double suicide or murder followed by suicide; in one case, the 45-year-old mother of a mentally handicapped 18-year-old son with congenital hydrocephalus set fire to her own house, and both perished in the fire, and in the other, a 65-year-old schizophrenic female fatally stabbed her neighbor, a 68-year-old female, and then she also cut herself fatally. There were three cases in which mentally handicapped individuals died due to freezing, and one in which an epileptic died suddenly due to status epilepticus. In order to prevent these tragic events, at first, it is necessary to much better understand the circumstances of the mentally handicapped individuals and their families without prejudices against them. The authors propose that a more comprehensive psychiatric medical care including the following systems should be established in Japan: 1) Day care for the mentally handicapped person, especially after the discharge as well as during admission, and support for their relatives, 2) Therapeutic drug monitoring to assess the effective level of psychotropic drugs and to suppress the side effects in the patients receiving the psychotropic drugs for a long time.

Adolescent↗
PubMed1995

Quantitative relationship between structure and peritoneal membrane transport based on physiological pharmacokinetic concepts for acidic drugs.

To describe quantitatively the peritoneal transport of drugs, the kinetic model, which involves changes in the volume and osmolality of the dialysate as well as the diffusion and convection of drugs across the peritoneum, was applied. The apparent peritoneal permeability (Pd) of unbound drugs in rats and the partition coefficient (Papp) in an octanol:water system at pH 7.4 were estimated among acidic drugs. Using the values of unbound fraction (fS), the Pd values of the drugs were estimated from concentration-time profiles in serum and the peritoneal dialysate after intraperitoneal administration of drugs. The intrinsic membrane permeability (Pdm) was calculated based on a physiological pharmacokinetic model. The fS.Pdm values of thiopental and thiamylal (6.5 and 5.4 ml/min) were 2-3 times greater than the effective peritoneal blood flow, indicating that the peritoneal transport of the barbiturates with high lipophilicity was dominantly blood flow-limited. Evidence shows a high degree of correlation between log Pdm and log Papp. By considering the relationships, we estimated the Pdm of quinolonecarboxilic acids. The fS.Pdm values of quinolonecarboxilic acids were < 10% of the peritoneal effective blood flow rate, indicating that the peritoneal transport of quinolonecarboxilic acids was dominantly diffusion-limited because of low lipophilicity. In conclusion, there was a good correlation between log Pdm and log Papp. The prediction of Pdm can be useful to describe the peritoneal pharmacokinetics.

Acids↗
PubMed1994

Epidural herniation of the cerebral tissue in a burned body: a case report.

A case in which herniation of the cerebral tissue was seen in the epidural space of a burned body is reported. The dead, burned body of an 8-year-old female was found in her burnt-out house. Externally, the body (except the back) was burned to the third or fourth degree, although there was no injury, specifically no skull fracture due to a mechanical force. Internally, much soot deposit was observed in the trachea, main bronchi and peripheral bronchioles. A 9.5 cm x 6.0 cm, thermo-coagulated, yellowish-white mass was unexpectedly found lying on the dura mater of the left temporal lobe. Histologically, H&E stain showed that the mass was thermo-coagulated cerebral tissue, although neither intra-cerebral haemorrhage nor cerebral contusion was found. The carboxyhaemoglobin (CO-Hb) concentration in the intracardiac blood was 83%. The cause of her death was diagnosed as death due to fire, based on the autopsy findings described above and the high CO-Hb concentration value. Therefore, the unexpected entry of the cerebral tissue into the epidural space was considered to be one of the morphological changes due to the local action of heat; the authors propose that such a postmortem change should be called 'heat brain herniation'.

Brain Injuries↗
PubMed1994

Altered microtubule organization in small-calibre axons of mice lacking tau protein.

The tau gene encodes a protein (Tau) that is a major neuronal microtubule-associated protein localized mostly in axons. It has microtubule-binding and tubulin-polymerizing activity in vitro and is thought to make short crossbridges between axonal microtubules. Further, tau-transfected non-neuronal cells extend long axon-like processes in which microtubule bundles resembling those in axons are formed. In contrast, tau antisense oligonucleotides selectively suppress axonal elongation in cultured neurons. Thus tau is thought to be essential for neuronal cell morphogenesis, especially axonal elongation and maintenance. To test this hypothesis, we used gene targeting to produce mice lacking the tau gene. We show that the nervous system of tau-deficient mice appears to be normal immunohistologically. Furthermore, axonal elongation is not affected in cultured neurons. But in some small-calibre axons, microtubule stability is decreased and microtubule organization is significantly changed. We observed an increase in microtubule-associated protein 1A which may compensate for the functions of tau in large-calibre axons. Our results argue against the suggested role of tau in axonal elongation but confirm that it is crucial in the stabilization and organization of axonal microtubules in a certain type of axon.

Animals↗
PubMed1994

The purification, characterization, cloning and sequencing of the gene for a halostable and thermostable leucine dehydrogenase from Thermoactinomyces intermedius.

Leucine dehydrogenase has been purified to homogeneity from a moderate thermophilic actinomycete, Thermoactinomyces intermedius IFO 14230. The enzyme can be stored without loss of its activity at a low temperature (e.g., 4 degrees C) for over two years. The enzyme was more thermostable at higher concentrations of salts such as NaCl and KCl. It retained about 90% of activity on incubation at 70 degrees C for at least 40 min in the presence of 3 M NaCl. The Michaelis constants for NAD, L-leucine, NADH, 2-oxoisocaproate and ammonia were determined to be 0.36, 2.0, 0.042, 0.63 and 118 mM, respectively, from initial-velocity analyses. The enzyme showed pro-S stereospecificity for hydrogen transfer of NADH in the reductive amination. The enzyme gene was cloned into Escherichia coli and its complete DNA sequence was determined. The leucine dehydrogenase gene (leudh) consists of a 1098-bp open reading frame and encodes 366 amino acid residues corresponding to a subunit (M(r) 40586) of the octameric enzyme. The amino acid sequence of the enzyme showed 80.7% similarity with that of the Bacillus stearothermophilus enzyme. The enzyme was overproduced in E. coli JM 109 having a recombinant plasmid, pULDH2, which was constructed from pUC18 and the leudh gene. The enzyme was purified from the cell extract to homogeneity in one day, with 78% recovery.

Actinomyces↗
PubMed1994

Defective leukocyte function-related cryoprecipitable protein in cryoglobulinemia.

Cryoprecipitable proteins (CPP), purified from plasmas removed during plasmapheresis treatment of patients with type II and type III cryoglobulinemia (CG), were evaluated in vitro for their effect on normal leukocyte function. CPP reduced normal mononuclear cell blastogenesis and polymorphonuclear cell phagocytosis responses in a dose-dependent fashion. At the maximum concentration studied, 5,000 micrograms/ml, CPP were shown to suppress normal blastogenesis and phagocytosis 30-60% and 50-80% below the albumin control, respectively. A 50% suppression of normal blastogenesis and phagocytosis was observed at 500 micrograms/ml for type III CPP. Leukocyte functions in CG patients were evaluated and compared to those of healthy controls. Blastogenesis and phagocytosis were significantly inhibited in CG patients. These studies suggest that CG patients have defective leukocyte function and that CPP have suppressive effects on normal leukocyte function. Our studies suggest that removal of CPP in CG patients may prove beneficial not only in reducing typical symptoms of CG but also in reducing the potential inhibitory effects of CPP on leukocyte function.

Adult↗
PubMed1994

Toxicological analysis of drugs and poisons in formalin-fixed organ tissues. 2. Volatile substances.

Diethylether, chloroform and toluene were administered by inhalation and ethanol intravenously to rabbits. As soon as possible after death, tissue specimens were collected from the brain, lung, liver, kidney and skeletal muscle and fixed in non-buffered 10% formalin at room temperature (10-20 degrees C) for 4 different periods (1, 2, 5 and 14 days). The volatile substances were analyzed and identified by gas chromatography/mass spectrometry (GC-MS). The measured concentrations of ethanol, diethylether, chloroform and toluene in the brain tissue 1 day after fixation decreased to 8, 23, 73 and 84% respectively compared with those in the non-fixed brain tissue (100%). The rank order of the rate of decrease in the fixed state was: ethanol > diethylether >> chloroform > toluene. These volatile substances could be detected clearly in all the tissue specimens, even after a 14-day fixation period. These results provide useful toxicological information that will help to differentiate whether volatile substances have been administered antemortem or postmortem.

Administration, Inhalation↗
PubMed1994

Construction and characterization of chimeric enzyme consisting of an amino-terminal domain of phenylalanine dehydrogenase and a carboxy-terminal domain of leucine dehydrogenase.

Phenylalanine dehydrogenase of Thermoactinomyces intermedius acts preferentially on L-phenylalanine and L-tyrosine, whereas leucine dehydrogenase of Bacillus stearothermophilus acts almost exclusively on L-leucine and some other branched-chain L-amino acids. The two enzymes share a sequence similarity (47%). Aiming at elucidation of the mechanism of substrate recognition by the two amino acid dehydrogenases, we have genetically constructed a chimeric enzyme consisting of an N-terminal domain of phenylalanine dehydrogenase containing the substrate-binding region and a C-terminal domain of leucine dehydrogenase containing the NAD(+)-binding region. The chimeric enzyme purified to homogeneity acted on phenylalanine with a specific activity of 6% of that of the parental phenylalanine dehydrogenase and showed a broad substrate specificity in the oxidative deamination, like phenylalanine dehydrogenase. However, it acted much more effectively than phenylalanine dehydrogenase on isoleucine and valine. Its Km values for L-phenylalanine and L-leucine were similar to those of phenylalanine dehydrogenase. The substrate specificity of the chimeric enzyme in the reductive amination was an admixture of those of the two parent enzymes. These results suggest that the two domains of phenylalanine dehydrogenase and leucine dehydrogenase probably can fold independently. Accordingly, their chimera forms a new active enzyme which consists of their N- and C-terminal domains containing the substrate- and coenzyme-binding regions, respectively. However, the two domains of chimeric enzyme interact and communicate with each other to form a new active site and consistently show the new substrate specificity.

Amino Acid Oxidoreductases↗
PubMed1994

Rapid detection of common mutation of arylsulfatase A in metachromatic leukodystrophy by polymerase chain reaction with a mismatched primer.

The most common mutation in late-onset metachromatic leukodystrophy is a cytosine-to-thymine substitution in exon VIII. This mutation caused a substitution of leucine for proline at amino acid residue 426. We developed a rapid and simple method for the detection of 426Pro-->Leu mutation by polymerase chain reaction with mismatched primer. Although the 426Pro-->Leu mutation does not alter recognition sequence for restriction enzymes, we created a Pst I restriction site using a 3'-primer mismatched at one nucleotide. As a result, the mutation can be detected as a Pst I restriction fragment length polymorphism.

Age of Onset↗
PubMed1994

Digestion of endothelin-1 on cultured vascular smooth muscle cells.

The degradation of 125I-endothelin-1 (125I-ET-1) was examined on cultured porcine aortic endothelial cell (EC) and rat vascular smooth muscle cell (SMC) by HPLC analysis. The degradation of ET-1 was observed on SMC and was slightly observed on EC. Membrane fractions of SMC had a strong potency for the degradation of ET-1 and retained activity even in plasma. This activity was inhibited with some of the noble inhibitors which were known as enkephalinase inhibitors. These results suggest that endothelin degradation enzyme on SMC is related to enkephalinase and that this enzyme plays a significant role in the degradation of ET-1 in vivo.

Animals↗
PubMed1994

Purification and characterization of endothelin-1 degradation activity from porcine kidney.

In order to identify the membrane-bound peptidase that is responsible for the degradation of endothelin (ET), an endothelin-1 (ET-1) degradation enzyme was solubilized from membrane fractions of porcine kidney with 1% Triton X-100, and subsequently purified by column chromatographies, i.e., diethylamino-Sepharose ion exchange, gel permeation, Con A Sepharose and hydroxyapatite chromatography. On DEAE-Toyopearl ion exchange column chromatography, the ET degradation enzyme and aminopeptidase were separated, but ET degradation enkephalinase activities were not separable. In order to separate ET degradation enzyme and enkephalinase, the active fractions were loaded on each of the column chromatographies: sephacryl S-200, Con A Sepharose or hydroxyapatite. The ET degradation activities were co-migrated with enkephalinase activities on all of the three chromatographies. In addition, the ET degradation activities were inhibited by thiorphan, phosphoramidon and EDTA, which are known to inhibit enkephalinase. These results suggest that ET degradation activity in the membrane fractions of the kidney is related to enkephalinase and may be involved in the degradation of ET-1 in vivo.

Aminopeptidases↗
PubMed1994

Pheophorbide a, a potent endothelin receptor antagonist for both ETA and ETB subtypes.

Many crude drugs were screened for their capacity to inhibit the binding of endothelin-1 (ET-1) to ET receptors; several crude drugs showed significant binding inhibitory activity. Pheophorbide a (1), a potent non-peptide ET receptor antagonist, was isolated from Altemisiae capillaris Flos ("Inchinko" in Japanese), which has been utilized as a remedy for hepatitis in Oriental medicine. In receptor binding experiments, compound 1 inhibited ET-1 binding specifically to both the ETA receptor (ETAR) and ETB receptor (ETBR), with IC50 values of 8.0 x 10(-8) and 2.1 x 10(-7) M, respectively. Thus, compound 1 is an ET-1 binding inhibitor; however, it exhibited no affinity for the other receptors of angiotensin II and atrial natriuretic peptide. We also evaluated the inhibitory activity of porphyrin compounds, and found that some exhibited moderate activity.

Animals↗
PubMed1994

Variability of beta-amyloid protein deposited lesions in Down's syndrome brains.

An immunohistochemical study was carried out on the brains of 7 adult Down's syndrome cases (ages 31 to 62) using antibodies to beta-protein, beta-amyloid protein precursor and tau-protein. Variable forms of beta-protein deposited lesions (including senile plaques and cerebrovascular amyloidosis) were observed in extensive areas of the neocortex of all cases and coexistence of both beta-protein amyloid fibrils and beta-amyloid protein precursors was also seen in some of these lesions. Moreover, 3 cases at an advanced stage showed a few plaque-like lesions with beta-protein immunoreactivity in the white matter. The following temporal morphological change is suggested for the pathogenesis of Alzheimer's disease: senile plaque undergo sequential structural changes and beta-protein amyloid deposits in the form of "early plaque" precede the development of tau-immunoreactive neurofibrillary degeneration.

Adult↗