Search PubMed⌕ Search

Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 937 records · Page 52Linked to original sources
PubMed1992

[A successful allogeneic bone marrow transplantation for acute promyelocytic leukemia with anthracycline-induced cardiomyopathy at relapse].

A 14-year-old girl with acute promyelocytic leukemia (APL) developed cardiomyopathy following chemotherapy for remission induction and subsequent consolidation consisting of cumulative doses of 644 mg/m2 of daunorubicin and 31 mg/m2 of mitoxantrone. Six months after the first complete remission, when relapse of APL was recognized an allogeneic bone marrow transplantation (BMT) from her HLA-identical brother was performed. A preconditioning regimen, consisting of cytarabine (Ara-C, 2 g/m2/day x 3 days and 4 g/m2/day x 3 days), total body irradiation (TBI, 1200 cGy) and etoposide (VP-16, 50 mg/kg) caused moderate gastrointestinal symptoms and transient hemorrhagic cystitis, but did not worsen her cardiac function. Both continuous intravenous administration of heparin to control DIC and continuous low dose dopamine infusion to prevent cardiac failure achieved their purpose. The patient is leukemia-free and has no symptoms related to cardiomyopathy at the eight month after BMT. A preconditioning regimen (Ara-C, TBI and VP-16) appeared to be suitable for BMT to a patient with anthracycline-induced cardiomyopathy.

Adolescent↗
PubMed1992

[Effect of aging on control of breathing].

In an attempt of elucidate the effect of aging on control of breathing, we measured hypercapnic ventilatory responses (HCVR) under three different conditions in 14 elderly volunteers (mean age: 69 yrs) and in young control subjects (29 yrs). There was no significant difference in the slope value (S) of HCVR between the two groups when the test was conducted under hyperoxic conditions. However, under hypoxic conditions, the "S" was significantly increased only in the young subjects, but not so in the elderly. When an resistive load (17 cmH2O/L-sec) was added to an inspiratory line, the "S" was not changed as a result of augmented P0.1 response in the young subjects, while the "S" was significantly decreased without any increase in P0.1 response in the elderly. The dyspnea score at the end-tidal PCO2 of 50 Torr, which was evaluated by visual analogue scale, was consistently higher in the elderly than in the young under any conditions. These results suggest that hypoxic-hypercapnic interaction on ventilation and load compensation reflex to inspiratory resistive loading are impired in the elderly subjects and that these are not associated with bluntness of respiratory sensation.

Adult↗
PubMed1992

Specificity of heme for hemopoietic recovery from AZT toxicity.

The toxicity of azidothymidine (AZT) was studied on normal human bone marrow hemopoietic colony growth as determined by assays of CFU-E, BFU-E, and CFU-GM. The potential sparing effect of hemin and heme analogues on AZT-suppressed bone marrow was also investigated. AZT at a lower concentration (0.1 mumol/L) inhibited CFU-E by 68%, BFU-E by 84%, and CFU-GM by 59%. AZT at a higher concentration (1.0 mumol/L) inhibited CFU-E by 88%, BFU-E by 90%, and CFU-GM by 69%. Addition of hemin (10 mumol/L) to cultures containing AZT (0.1 mumol/L) increased CFU-E growth by 279%, BFU-E by 282%, and CFU-GM by 72%. A similar concentration of heme analogues did not have an enhancing effect; in contrast, zinc protoporphyrin (ZnPP) was inhibitory to bone marrow progenitors CFU-E, BFU-E, and CFU-GM. In addition, no enhancement of colony growth was obtained when progenitor cells were cultured in the presence of 10(-2)-10(-5) M iron. These results demonstrate that exogenous hemin has a specific beneficial effect on human bone marrow hematopoietic progenitor cells which is not seen with iron or other metalloporphyrins. Furthermore, this beneficial effect includes a reversal of the cytotoxic effect of AZT on bone marrow progenitors.

Cell Division↗
PubMed1991

Effect of erythroid differentiation factor on megakaryocytic differentiation of L8057, a murine megakaryoblastic leukemia cell line.

To assess the potent effect of erythroid differentiation factor (EDF) on megakaryocytopoiesis, effect of EDF on megakaryocytic differentiation of L8057, a murine megakaryoblastic cell line, was examined. EDF potentiated AchE induction of L8057 in a dose dependent manner. The potency of EDF on megakaryocytic differentiation is comparable to that on erythroid differentiation reported previously. The present results suggest that EDF may play a regulatory role in megakaryocytopoiesis as well as in erythropoiesis.

Acetylcholinesterase↗
PubMed1991

A unique vacuolar processing enzyme responsible for conversion of several proprotein precursors into the mature forms.

Proprotein precursors of vacuolar components are transported from the endoplasmic reticulum into vacuoles, where they are proteolytically processed into their mature forms. However, the processing mechanism in plant vacuoles is very obscure. Characterization of a purified processing enzyme is required to determine whether a single enzyme is responsible for processing many vacuolar proteins with a large variability of molecular structure. If this is true, how can it recognize the numerous varieties of processing sites? We have now purified a processing enzyme (Mr = 37,000) from castor bean seeds. Our results show that the purified enzyme can process 3 different proproteins isolated from either the endoplasmic reticulum or transport vesicles in cotyledon cells to produce the mature forms of these proteins which are found at different suborganellar locations in the vacuole: the 2S protein found in the soluble matrix, the 11S globulin found in the insoluble crystalloid and the 51 kDa protein associated with the membrane. Thus a single vacuolar processing enzyme is capable of converting several proprotein precursors into their respective mature forms.

Amino Acid Sequence↗
PubMed1991

Metabolism of 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE) in corneal tissues: formation of novel metabolites.

12(R)-Hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], a cytochrome P450 arachidonate metabolite, is metabolized by corneal tissues via three distinct metabolic pathways: beta-oxidation, omega-hydroxylation, and keto-reduction. The major metabolite released from the intact rabbit corneal epithelium or cultured cells was identified by mass spectrometric analysis as 8-hydroxy-4,6,10-hexadecatrienoic acid, the tetranor metabolite derived following two steps of beta-oxidation from the carboxy terminus. The beta-oxidation pathway was expressed in both microsomes and mitochondria isolated from bovine corneal epithelium and was dependent on the addition of oxidizing equivalents. The major metabolite of 12(R)-HETE in subcellular fractions of bovine corneal epithelial cells was a dihydro compound, 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE). This derivative is presumably formed by an oxidation of the hydroxyl group followed by two keto-reduction steps, since its formation was accompanied by the appearance of a keto metabolite identified as 12-oxo-5,8,14-eicosatrienoic acid. The omega-hydroxylation, in contrast to other cell types, was a minor route for 12(R)-HETE metabolism in these tissues. Since 12(R)-HETE has been implicated as a modulator of Na(+)-K(+)-ATPase activity and its related functions in ocular tissues, these findings raise the possibility that the newly described metabolites may be involved in regulating corneal functions. In addition, the presence of a keto reductase in the cornea may be of great importance following injury since 12(R)-HETrE resulting from 12(R)-HETE by this activity is a potent ocular proinflammatory compound.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

The Q7 alpha 3 domain alters T cell recognition of class I antigens.

In this study we have analyzed the role of the alpha 3 domain of class I molecules in T cell recognition. Using the laboratory engineered molecules LLQQ (alpha 1/alpha 2 from Ld, alpha 3, and phosphatidyl inositol (PI) linked C terminus from Q7) and LLQL (alpha 1/alpha 2 from Ld, alpha 3 from Q7, transmembrane (TM) and cytoplasmic domains from Ld) we show that these molecules are not recognized by primary Ld-specific CTL. The cell membrane expression of both Ld and LLQL are upregulated by co-culture with an exogenously supplied murine cytomegalovirus-derived peptide indicating that the Q7 alpha 3 domain does not interfere with binding of Ag to alpha 1/alpha 2. However, only peptide pulsed Ld but not LLQL target cells are recognized by Ld-restricted-peptide specific CTL. In contrast to the above results, LLQL and LLQQ molecules can be recognized by bulk alloreactive anti-Ld CTL and 2/3 of CTL clones derived from in vivo primed mice. The fact that these secondary CTL recognize LLQQ indicates that a PI linkage is permissive for presentation of class I epitopes to alloreactive CTL. These secondary CTL are resistant to blocking at the effector stage by mAb against CD8 and express relatively low levels of membrane CD8 molecules compared to CTL from unprimed mice. Further, culture of unprimed CTL precursors in the presence of CD8 mAb also allows for the generation of CD8-independent CTL that recognize LLQL. Taken together, these data indicate that the alpha 3 domain of Q7 (Qa-2) prevents CD8-dependent CTL from recognizing Ld, regardless of whether the class I molecule is attached to the cell surface by a PI moiety or as a membrane spanning protein domain. We hypothesize that this defect in recognition is most likely due to an inability of CD8 to interact efficiently with the Q7 alpha 3 domain and could account for why Q7 molecules do not serve as restricting elements for virus and minor H-Ag-specific CTL.

Animals↗
PubMed1991

Pumpkin malate synthase. Cloning and sequencing of the cDNA and northern blot analysis.

A cDNA clone encoding the glyoxysomal malate synthase (EC 4.1.3.2) was identified by immunoscreening of a cDNA expression library constructed from poly(A)-rich RNA of etiolated pumpkin cotyledons. Determination of the DNA sequence of the 1979-nucleotide cDNA revealed a 1698-nucleotide open reading frame that encodes a polypeptide of 64632 Da. The identification of the cDNA for malate synthase was confirmed by matching three sequences obtained by peptide-sequence analyses of fragments generated by acid treatment of the purified enzyme. Northern blot analysis revealed that the probe hybridized to a single 2.3-kb species of mRNA species from etiolated pumpkin cotyledons which was not present in green pumpkin cotyledons. In a comparison of deduced amino acid sequences, pumpkin malate synthase was found to exhibit 83% and 48% similarity to the malate synthases from rape and Escherichia coli, respectively. Based on the amino acid sequence similarity and the hydropathy profiles of these three malate synthases, the signal for targeting the enzyme to microbodies is discussed.

Amino Acid Sequence↗
PubMed1991

Stopped-flow investigation of the reaction of vitamin C with tocopheroxyl radical in aqueous triton X-100 micellar solutions. The structure-activity relationship of the regeneration reaction of tocopherol by vitamin C.

A kinetic study of the reaction between vitamin C (L-ascorbic acid, AsH2) and a tocopheroxyl radical (7-tert-butyl-5-isopropyltocopheroxyl) in Triton X-100 micellar solution has been performed using stopped-flow spectrophotometry. The second-order rate constants (k2) obtained showed notable pH dependence with a broad maximum around pH 8. For instance, the k2 values obtained were 26 M-1 S-1 at pH 3, 322 M-1 S-1 at pH 7, and 273 M-1 S-1 at pH 10. A good correlation between the rate constants and the mole fraction of ascorbate monoanion (AsH-) was observed, showing that ascorbate (AsH-) can regenerate the tocopherol from tocopheroxyl in biological systems. Furthermore, the results indicate that reduced ascorbic acid (AsH2) does not have the ability to regenerate the tocopherol in aqueous solution. On the other hand, it was found that AsH2 can reduce the tocopheroxyl to tocopherol in benzene/ethanol (2:1) mixtures, although the rate of reaction is only approximately 15% of that observed in micellar solution at pH 7.

Ascorbic Acid↗
PubMed1991

Genetic expression of Menkes disease in cultured astrocytes of the macular mouse.

The copper concentration was investigated in the cultured astrocytes from macular mice, an animal model of Menkes disease. An excessive amount of copper was accumulated in the astrocytes as copper-metallothionein. These results show that the underlying genetic defect of the macular mouse is expressed in the astrocytes. A similar situation may exist in Menkes disease and cause a failure of copper transport to neurones.

Animals↗
PubMed1991

Multicentric reticulohistiocytosis associated with subclinical Sjögren's syndrome.

A case of multicentric reticulohistiocytosis in a 60-year-old Japanese woman associated with subclinical Sjögren's syndrome is presented. The clinical features along with the light microscopic studies are commented. Partial improvement of the skin lesions and tendon sheath swelling was achieved after treatment with cyclophosphamide but the patient's general condition remained unchanged. Taking the rarity of multicentric reticulohistiocytosis into account, coexistence of these two conditions in the present and previously reported cases suggests that an autoimmune mechanism may play a part in the pathogenesis of multicentric reticulohistiocytosis.

Cyclophosphamide↗
PubMed1991

Respiratory outcome in extremely premature infants following ketamine anaesthesia.

Premature infants are prone to develop postoperative apnoea. The purpose of the present study was to determine if risk factors could be identified to predict which patients would require postoperative tracheal intubation and lung ventilation. Twenty-five extremely premature infants (birth weight: 811 +/- 242 g (mean +/- SD) and operation weight: 1585 +/- 394 g) needing cryotherapy for retinopathy were studied. After surgery the tracheas were extubated if there was no prolonged apnoea, SaO2 greater than 85%, and heart rate greater than 120 bpm. In eight, tracheal extubation in the operating room was unsuccessful. Using multivariate discriminant analysis, four risk factors correlated with the need for pulmonary ventilation-gestational duration, birth weight, postconceptional age, and preoperative aminophylline treatment for seven days. A scoring system using these factors successfully predicted the need for a tracheal tube after surgery in 92% of patients. It is concluded that the system may be clinically useful in the perioperative care of low-birth-weight infants as it identifies important variables for evaluating postoperative prolonged apnoea.

Age Factors↗
PubMed1991

Effect of a cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, on myocardial reperfusion injury.

A new cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, was examined to see whether myocardial reperfusion injury could be reduced in a setting of cardioplegic arrest through its antiaggregation effect on leukocytes. Isolated rabbit heart models with whole blood perfusion were used, and 18 hearts were divided into three groups according to the reperfusion method: control (G-1, n = 5), DN-9693 (G-2, n = 7), and leukocyte depletion (G-3, n = 6). The hearts were subjected to 120 minutes of cold global ischemia under crystalloid cardioplegia followed by 30 minutes of reperfusion. A dose of 20 micrograms.kg-1.min-1 of DN-9693 was administered in G-2, and a leukocyte removal filter was used in G-3 during reperfusion. Ultrastructural changes in mitochondrial injuries, intracellular edema, and capillary injuries of the myocardium showed worse changes in G-1 than in G-2 and G-3. Under microscopic study, the intracapillary leukocyte count was significantly higher in G-1 than in G-2 and G-3. Recovery of rate-pressure product, left ventricular developed pressure, and coronary flow were significantly better in G-2 and G-3 than in G-1. There were no significant differences between G-2 and G-3 for all these indices. These results indicate that reperfusion with leukocyte-depleted blood attenuates reperfusion myocardial injury and DN-9693 has a comparable myocardial protective effect with possible inhibition of leukocyte aggregation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Cerebral angio- and neuro-Behçet's syndrome: neuroradiological and pathological study of one case.

Cerebral angio-Behçet's syndrome is extremely rare and pathological studies are scarce. We describe a 63-year-old man who developed left homonymous hemianopsia and hemiparesis 16 years after the onset of cardinal symptoms of Behçet's syndrome. CT, MRI and PET studies disclosed cerebral lesion with reduced neuronal metabolism in the right hemisphere, which was resolved by glucocorticoid therapy. Cerebral angiography showed no filling of the right Rolandic, anterior and posterior parietal and angular arteries. The postmortem study revealed: (a) occlusive panarteritis of some medium-sized pial branches of the right middle cerebral artery, considered as angio-Behçet's pathology, and small infarctions due to the vascular occlusion; (b) patchy or confluent demyelinated foci with perivascular lymphocytic infiltration in the bilateral brain basis, predominantly in the right retro- and sublenticular structures, being equivalent to neuro-Behçet's pathology. Cerebral angio- and neuro-Behçet's syndromes could have occurred and progressed concomitantly, which suggests a close relationship between the two subclassified processes.

Arterial Occlusive Diseases↗