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Biomedical subjects

M Okabe

Publications and source records attributed to M Okabe.

At least 55 records · Page 3Linked to original sources
PubMed2001

A case of cardiomyopathy showing progression from the hypertrophic to the dilated form: association of Mt8348A-->G mutation in the mitochondrial tRNA(Lys) gene with severe ultrastructural alterations of mitochondria in cardiomyocytes.

This report describes a case of cardiomyopathy with a novel point mutation of mitochondrial DNA coding lysine tRNA in association with severe ultrastructural alterations of the mitochondria in the cardiomyocytes. Abnormalities of energy production and/or abnormal protein synthesis because of the mutation of mitochondrial DNA may have played an important role in the pathogenesis of this case, which showed severe cardiomyocyte degeneration and deterioration from hypertrophic cardiomyopathy to severe dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed2001

Myocardial inflammatory cell infiltrates in cases of dilated cardiomyopathy as a determinant of outcome following partial left ventriculectomy.

Partial left ventriculectomy (PLV) can be used to treat refractory congestive heart failure caused by dilated cardiomyopathy (DCM). In order to understand the relationship between the underlying myocardial injury and early clinical outcomes after PLV, histopathologic, immunohistochemical and virologic studies of the resected myocardium were performed. The posterolateral left ventricular walls from 27 patients with idiopathic DCM were examined. Cardiomyocyte diameter, degree of myocardial fibrosis, degree of cardiomyocyte degeneration, and degree of inflammatory cell infiltration were compared with mortality rates. Polymerase chain reaction was performed to detect enterovirus genome in the myocardium. Some patients had inflammatory cell infiltrates with focal accumulations of lymphocytes and macrophages, including both cytotoxic/suppressor T-cells and helper/inducer T-cells. The number of inflammatory cells (activated lymphocytes plus macrophages/mm2) was significantly greater in patients who died of cardiac insufficiency after surgery (27.8 +/- 5.7; n = 7) than in the survivors (11.1 +/- 2.5; n = 15). There was no significant difference in the degree of myocardial fibrosis, cardiomyocyte diameter or degree of cardiomyocyte degeneration between the 2 groups. Enterovirus genome was detected in the myocardium of 9 (38%) of 24 patients examined and 5 of these enterovirus-positive hearts had severe inflammatory cell infiltrates (37.9 +/- 2.5/mm2). Early survival in patients undergoing PLV for DCM is significantly affected by the degree of myocardial inflammation, so patients with more severe or ongoing inflammation may have poor clinical outcomes. Chronic myocarditis may play an important role in the etiology and pathophysiology of idiopathic DCM.

Adolescent↗
PubMed2001

Early and long-term mortality of the clinical subtypes of myocarditis.

The frequency of myocarditis and the prognosis for patients remains uncertain and, moreover, the clinical classification of myocarditis is controversial. From 1985 to 2000, 71 adult patients with clinically suspected myocarditis were admitted to 11 cardiovascular centers. Of these, 48 cases had histology proven myocarditis: 41 cases of lymphocytic myocarditis, 6 of giant cell myocarditis and 1 of eosinophilic myocarditis. Myocarditis was classified as acute (30 cases) or chronic (18 cases) according to the onset of the disease, and acute myocarditis was further categorized into common or fulminant type depending on whether or not patients required mechanical circulatory support in the management of heart failure (9 and 21 cases, respectively). Chronic myocarditis was divided into 3 subgroups: a persistent type lasting over 3 months after distinct onset (3 cases), a recurrent type (2 cases) and a latent form (13 cases). The early mortality of these 5 subtypes of myocarditis were acute common 22%, acute fluminant 43%, chronic persistent 33%, chronic recurrent 50%, and chronic latent 38%. The overall early mortality of all patients with myocarditis was 38% in spite of aggressive treatment during hospitalization. On the other hand, the long-term prognosis of patients with myocarditis was favorable; only 4 cases, who survived the active phase, died in the late phase: 1 had fulminant myocarditis and the other 3 had the chronic latent form. Thus, the early mortality of patients with myocarditis was very high regardless of the subtype, but if patients can survive the active phase, they have a favorable prognosis except with the chronic latent form.

Adolescent↗
PubMed2001

Enhancement of epsilon-polylysine production by Streptomyces albulus strain 410 using pH control.

The enhancement of epsilon-poly-l-lysine (epsilon-PL) production by Streptomyces albulus strain no. 410 (S410) by means of a pH control strategy was investigated. S140 cells produce epsilon-PL at a high concentration if the culture pH remains at about 4.0; however, if it shifts to higher than 4.0, the accumulated epsilon-PL is depolymerized. We therefore suggest a pH control strategy for cell growth and epsilon-PL production aimed at increasing the amount of epsilon-PL produced. The cultivation was divided into two control phases. In phase I, cell growth was accelerated by maintaining the pH at higher than 5.0; in phase II, epsilon-PL production was increased by maintaining the pH at about 4.0. To avoid an increase in the pH during phase II as a result of glucose depletion, the glucose concentration was kept at around 10 g/l by glucose feeding. This control strategy enhanced the production of epsilon-PL to 48.3 g/l from 5.7 g/l in the case of batch culture.

Journal Article↗
PubMed2001

Improvement of production of Kojic acid by a mutant strain Aspergillus oryzae, MK107-39.

A strain designated MK107-39, producing kojic acid with a high yield, was obtained by a new screening method using a 96-well microtiter plate after NTG treatment of Aspergillus oryze ATCC 22788. The amount of kojic acid produced by strain MK107-39 in a shaking flask was 28 g/l from 100 g/l of glucose, which was 7.7-times higher than that produced by parent strain. The kojic acid yields per cell and the amount of glucose consumed were 9.8 and 6.0-times higher than those of the parent strain. Based on differences in the use of carbohydrates and organic acids, it seems that strain MK107-39 has some mutation regarding carbohydrate metabolism. By customizing the medium and culture conditions such as glucose concentration, dissolved oxygen concentration and pH of the fermentation broth, more than 110 g/l of kojic acid was produced in a 3-l jar fermentor. Upon scale up to a 600-l pilot fermentor, enhanced production of kojic acid was successfully achieved. The kojic acid yield from glucose consumed, Y(P/S), was 0.43 (g/g) in this pilot plant-scale fermentation.

Journal Article↗
PubMed2001

Optimization of tylosin feeding rate profile in production of acetyl-isovaleryl tylosin (AIV) from tylosin by Streptomyces thermotolerans YN554.

An optimal feed rate profile of a substrate (tylosin) for a novel antibiotic, acetyl-isovaleryl tylosin (AIV) production process was investigated. In the first step of optimization, a kinetic model for production of AIV from tylosin by Streptomyces thermotolerans was established properly using the least square method, followed by the confirmation that the proposed model could be used to predict the production process of AIV from tylosin. An objective function, state equations and an inequality constraint with respect to the tylosin feeding rate profile were applied to maximize the amount of AIV produced from tylosin in a fed-batch culture. The optimized tylosin feeding rate profile was determined using a direct iterative search algorithm based on the modified complex method. The simulation of AIV production at the optimal tylosin feeding profile indicates that the final amount of AIV is expected to be about 30% higher than that at the conventional constant tylosin feeding rate, which was also confirmed experimentally using a 30-l jar fermentor.

Journal Article↗
PubMed2001

Kojic acid production in an airlift bioreactor using partially hydrolyzed raw corn starch.

In a culture of Aspergillus oryzae MK-107-39 in a 3-l airlift bioreactor, kojic acid was not produced when glucose/wheat germ medium (GM1) was used. However, when a jar fermentor was used, the kojic acid yield was high. A suitable medium for culture in an airlift bioreactor consisting of partially hydrolyzed corn starch and a small amount of corn steep liquor (CSL) (SM1) was selected. In the cultivation in the airlift bioreactor using SM1, nearly 40 g/l of kojic acid was produced, which was the same as the amount produced in the jar fermentor containing GM1. The optimum aeration rate for the airlift bioreactor was 2.0 vvm (0.66 cm/s of superficial linear velocity (Vs)). The cost of SM1 using the airlift bioreactor was reduced to 40% that of GM1 using the jar fermentor. Furthermore, the energy cost of kojic acid production using SM1 in the airlift bioreactor was less than one-fourth of that for the jar fermentor using GM1.

Journal Article↗
PubMed2001

Antimicrobial susceptibility of Staphylococcus intermedius isolated from healthy and diseased dogs.

A total of 90 strains of Staphylococcus intermedius isolated from dogs were examined for antimicrobial susceptibility. There were no significant differences in the distribution patterns of MICs between strains from 1982 to 1985 and those from 1999, and between strains from healthy dogs and those from diseased dogs. All of the strains were susceptible to ABPC, DMPPC, CEX, TDM, ERFX, BFLX, and FF at concentrations of 0.05 to 6.25 microg/ml. The MICs of OTC, KM, EM, AIV-TS, and LCM were distributed in a broad range of 0.1 to >100 microg/ml, indicating the existence of resistant as well as susceptible populations of S. intermedius. Thirty-three strains (36.7%) were resistant to one or more anitmicrobial agents such as OTC (n=32), KM (n=9), EM (n=7), AIV-TS (n=7), and LCM (n=7).

Animals↗
PubMed2001

von Recklinghausen disease complicated by pulmonary hypertension.

Two patients with von Recklinghausen disease (neurofibromatosis type 1) were admitted to the hospital because of progressive heart failure. Both patients had prominent pulmonary hypertension revealed on cardiac catheterization. A lung perfusion scan did not show any gross defect. There were no underlying causes of pulmonary hypertension in either patient, such as chronic lung disease, congenital or acquired heart disease, deep vein thrombosis, or systemic hypercoagulable states. There may be an unrecognized association between von Recklinghausen disease and pulmonary hypertension.

Adult↗
PubMed2001

[Refractory idiopathic cold agglutinin disease successfully treated with intermittent high-dose cyclophosphamide].

A 56-year-old woman, who had been suffering from idiopathic cold agglutinin disease and treated unsuccessfully with prednisolone and cyclosporine A for 6 months, was referred to our hospital in November 1998. She was given methylprednisolone pulse therapy followed by low-dose cyclophosphamide, but her anemia did not improve. We then began administration of intermittent high-dose cyclophosphamide (1,200 mg/day, every 4 weeks), and this resulted in a dramatic increase of her hemoglobin level and improvement of her symptoms. She is currently receiving 500 mg of cyclophosphamide every 2 months and showing a good response. Intermittent high-dose cyclophosphamide therapy can be an effective treatment for refractory cold agglutinin disease.

Anemia, Hemolytic, Autoimmune↗
PubMed2001

Rapid and simple fixation-staining technique of fresh frozen cryostat sections for SIMS microscopy.

Before observing freeze-dried cryosections by ion microscopy, it is necessary to perform localization of the analysis site by light microscopy. The present study reports a rapid fixation-staining method for preparing freeze-dried or air-dried cryosections, wherein cryosections are observed after immersion in Carnoy-Lebrun fixative for 30 s and staining in undiluted Giemsa solution for 30 s. Cryostat sections of goldfish intestine and kidney tissue on the silicon wafer substratum were subsequently examined by SIMS. Positive cesium ion images showed a general histology of the intestinal villi with goblet cells. Their granules contained large amounts of sodium, magnesium, potassium and calcium on ion images. By contrast, iron, copper and CsFe ion images showed diffuse distribution throughout the sections.

Acetic Acid↗
PubMed2001

Manual control in space--research on perceptual-motor functions under zero gravity condition.

Microgravity effects on human factor were studied through a series of manual control experiments conducted in the First Material Processing Test. The Japanese Payload Specialist operated a finger stick for 130 seconds to maintain a light spot movement around the center of a vertical LED array display. The stick angle is doubly integrated to make the controlled element motion. The light spot position indicates the difference between the motion and pseudo-random wave patterns which drives the man-machine tracking system. 24 runs were conducted in each of 2 months before launch, immediately pre-flight, and post-flight experiments. During the flight experiments, the PS felt pain in fast eye movement. He was obliged to fix his line of sight at the center of display and to watch the displayed error movement using peripheral view. He also felt difficulty in supporting his body against reaction force of his hand movement. During a few days after landing, disturbance was observed in the PS's posture. The operator describing function analysis revealed the disappearance of the "regression" phenomenon and increment of the effective time delay. As the result, the flight describing function showed better fit to the simplified model of lead with pure time delay.

Adaptation, Physiological↗
PubMed2000

Origins of intestinal intraepithelial lymphocytes: direct evidence for a thymus-derived gamma delta T cell component.

The contribution of T cell precursors from the thymus and the bone marrow to the pool of intestinal intraepithelial lymphocvtes (IELs) has been studied in a system using donor cells from enhanced-green fluorescent protein (EGFP+ ) transgenic mice a doptively transferred into EGFP- recipient mice. Consistent with previous studies, regeneration of gamma delta and alpha beta T cell populations in the intestinal epithelium occurred within 2-3 weeks of bone marrow transfer into irradiatiated EGFP- animals and prior to T cell repopulation of the spleen, of interest, however, although transfer of whole adult EGFP+ thymocytes to non-irradiated EGFP- congenitally-athymic nude mice produced alpha beta T cells in both the spleen and intestine. Gamma delta T cells in significant number were detected only in the intestine of recipient mice. In contrast, transfer of CD3-, CD4-, CD8- immature thymocytes resulted in no detectable T cells in either the intestine or the spleen of nude mice up to twelve weeks post-cell transfer, suggesting that intestinal IELs generated from thymocytes arose from differentiated lineage-committed cells rather than from immature thymocytes. These findings provide direct evidence for both thymus-independent and thymus-dependent sources of intestinal gamma delta T cells, and they suggest that murine IELs consist of diverse groups of T cells with distinct developmental origins.

Animals↗
PubMed2000

Homeobox gene Hex is essential for onset of mouse embryonic liver development and differentiation of the monocyte lineage.

Disruption of the mouse Hex gene resulted in embryonic lethality around embryonic age (E) 10.5, due to no substantial liver formation. Expression of albumin was detectable in heterozygous (Hex(+/-)) but not in homozygous (Hex(-/-)) [corrected] embryos at E8.5. Instead of liver bud formation at E9.5, a liver-like capsule structure was observed in Hex(-/-) [corrected] embryos. In Hex(-/-) [corrected] mutant liver, we found no hepatocytes but no signs of apoptotic cell death in the area. Expression of transcription factors involved in hepatocyte differentiation, hepatocyte nuclear factor (Hnf)3beta, Hnf6, Hnf4alpha and Hnf1alpha, were restricted to the capsule and internal matrix-like structure in the mutant liver and expression of a subset of these factors were reduced. Hematopoiesis of monocytes was impaired in mutant embryos while erythroid lineage was unaffected. These results indicate that Hex plays an essential role in progenitor cells which commit to the hepatic endoderm and in the hematopoietic differentiation of the monocyte lineage.

Albumins↗
PubMed2000

Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate.

We have isolated a rat novel multispecific organic anion transporter, moat1. The isolated clones were originated by alternative splicing of the moat1 mRNA. The nucleotide sequences predict a protein of 682 amino acids with moderate sequence similarity to LST-1, the oatp family, and the prostaglandin transporter. Northern blot analysis of rat moat1 identified a predominant transcript of 4.4 kilonucleotides in all tissues. Northern blot and in situ hybridization analyses of rat brain further indicated that moat1 mRNA is widely distributed in neuronal cells of the central nervous system, especially in the hippocampus and cerebellum. moat1 transports prostaglandin D(2) (K(m); 35.5 nM), leukotriene C(4) (K(m); 3.2 microM) and taurocholate (K(m); 17.6 microM) in a sodium-independent manner. moat1 also transports prostaglandin E(1), E(2), thromboxane B(2), and iloprost but not dehydroepiandrosterone sulfate and digoxin, of which the substrate specificity is similar, but definitively different from those of any other organic anion transporters.

Alternative Splicing↗
PubMed2000

Diverse effect of tributyltin on apoptosis in PC12 cells.

It has not been fully elucidated how endocrine-disrupting chemicals disrupt hormone functions or how strong their effects are compared with natural hormones. There is little information concerning the effects of tributyltin (TBT), one of the endocrine disrupters on living organisms. Although TBT at high concentration induced apoptosis in PC12 cells, TBT at low concentration inhibited the DNA fragmentation in the cells cultured in serum-free medium or in medium containing 6-hydroxydopamine. The cell viability grown in both medium conditions increased after treatment with TBT. These findings suggest that TBT exerted a apoptosis-inducing and -inhibiting effect. These diverse effect of TBT on apoptosis would cause serious damages on cell differentiation.

Animals↗
PubMed2000

Spermatocyte-specific gene excision by targeted expression of Cre recombinase.

Transgenic mice carrying the coding sequence of the Cre recombinase, whose expression was driven by the spermatocyte-specific Pgk-2 promoter, were generated. These mice were crossed with a reporter transgenic line, which produces beta-galactosidase depending on the occurrence of loxP-mediated DNA recombination. When DNA of the offspring was analyzed by PCR and Southern blotting, signals that appear after the recombination were detectable only in the testis. Histochemical analyses revealed that beta-galactosidase was present in spermatocytes and spermatogenic cells at later differentiation stages. However, the distribution of the protein was not uniform in all spermatocytes. Analyses of genomic DNA of the next generation indicated that recombination took place in about 70% of spermatogenic cells. From these results, we concluded that this transgenic line possessing Pgk-2-driven expression of the Cre recombinase should be useful for identifying spermatogenic genes that function at or after the spermatocyte stage.

Animals↗