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Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 667 records · Page 37Linked to original sources

Hemodynamic-force-induced difference of interendothelial junctional complexes.

1. The flow divider of the brachiocephalic branching of the rabbit aorta had both high and low shear stress regions, each of which was covered by endothelial cells with low and high permeability respectively, even in normolipidemic intact rabbits. When rabbits were placed on an atherogenic diet, low shear regions were the most vulnerable for lipid deposition, but the high shear regions were spared from deposition. 2. A freeze fracture study revealed that high shear regions both at the brachiocephalic branching and in the surgically coarctated abdominal aorta of rabbits had a more common appearance of zonular type tight junctions. Mean low shear regions had more macular and less zonular type. 3. Cultured porcine aortic endothelial cells exposed to laminar 30 dyn/cm2 shear stress in a flow chamber developed ridges of membranous protein particles at the cell-cell contact. 4. Increases of magnitude and duration of exposure to shear stress enhanced the structure of the protein ridge of the tight junction and immunohistochemical expression of proteins associated with both tight and adherens junctions.

Animals↗

Effects of shear stress on glycosaminoglycan synthesis in vascular endothelial cells.

Glycocalyx on the surface of endothelium has been suggested to be involved in vascular permeability and anticoagulation. In the present study, we demonstrated that fluid laminar shear stress enhanced a glycosaminoglycan (GAG) synthesis in porcine aortic endothelial cells, in vitro. Shear stress (15, 40 dyn/cm2) for 24 hours significantly increased GAG synthesis, assayed by [35S]sulfate incorporation, in "medium" fraction and "trypsinated" fraction which includes GAGs derived from the cell surface and from the solubilized matrix. Increased GAGs in the trypsinated and medium fractions consisted of mainly heparan sulfate and chondroitin/dermatan sulfate, respectively. Both heparan and chondroitin/dermatan sulfate increases are required to expose the cells to shear stress for more than 24 hours. Shear-stress-induced increase in GAG synthesis was concomitant with a decrease in DNA synthesis and an increase in protein synthesis. These data indicate that relatively high shear stress may suppress atherogenesis by changing endothelial GAG synthesis.

Animals↗

Usefulness of interlocking detachable coil for embolization of the major aorto-pulmonary collateral artery: a case report.

A 5-yr-old male had undergone a right-modified Blalock-Taussig shunt operation at the age of 1 mo for stenotic patient ductus arteriosus and pulmonary atresia with ventricular septal defect. Before a corrective operation, the angiogram revealed one large major aorto-pulmonary collateral artery from the descending aorta to the right upper lung. Embolization of the major aorto-pulmonary collateral artery was successfully performed using interlocking detachable coils. This is the first reported case of embolization of the major aorto-pulmonary collateral artery using this device.

Angiography↗

Ca2+ release from mitochondria induces cytosolic enzyme leakage in anoxic liver.

The mechanisms of elevation of cytosolic Ca2+ concentration during anoxia causing cytosolic enzyme leakage were studied in perfused rat liver. Before anoxia the Ca2+ contents in mitochondria of perfused rat liver were varied by addition of noradrenaline and glucagon, lowering Ca2+ concentration in the perfusion medium, and addition of Ca2+ channel blocker, either singly or in combination. The amount of cytosolic enzyme leakage during anoxic perfusion positively correlated with the mitochondrial Ca2+ content just before anoxia and also with Ca2+ release from mitochondria during anoxia. However, the amount of cytosolic enzyme leakage during anoxic perfusion did not correlate with the Ca2+ concentration in the perfusion medium and microsomal Ca2+ content. These data support the hypothesis that in anoxic liver, the cytosolic Ca2+ concentration is elevated to a pathological level mainly by Ca2+ release from mitochondria, causing the cytosolic enzyme leakage.

Animals↗

Assignment of the developmentally regulated gene NEDD1 to human chromosome 12q22 by fluorescence in situ hybridization.

The developmentally regulated mouse gene Nedd 1 encodes a protein showing similarities with the beta-subunit of heterotrimeric GTP-binding proteins and has growth suppressing activity when overexpressed in various cultured cell types. We have mapped the human homolog (NEDD1) of the mouse gene to chromosome 12q22 by fluorescence in situ hybridization using R-banded human (pro)metaphase chromosomes.

Animals↗

Left atrial plication combined with mitral valve surgery in patients with a giant left atrium.

The benefits of performing left atrial plication during mitral valve surgery for patients with a giant left atrium were evaluated by analyzing the short- and long-term surgical results and changes in the left atrial dimension (LAD) and respiratory function of 30 patients. Of the 30 patients, 2 (7%) died of multiple organ failure on postoperative days 26 and 117, but no other deaths occurred during the mean follow-up of 5.9 +/- 2.1 years. Valve thrombosis was observed in one patient and cerebral complications with no residual deficit were observed in two patients, with a 9-year event-free rate of 87 +/- 7%. The LAD decreased significantly from 69.0 +/- 8.5 mm to 53.7 +/- 9.1 mm (P < 0.01) shortly after surgery, and this decreased was maintained even 5 years after surgery (53.3 +/- 11.4 mm). The cardiothoracic ratio decreased from 74.8 +/- 8.3% to 62.8 +/- 9.0% (P < 0.01) and the vital capacity of the lungs increased from 71.1 +/- 18.0% to 82.9 +/- 22.2% (P < 0.01). Thus, we conclude that performing left atrial plication during mitral valve surgery is safe and effective for patients with giant left atrium.

Adult↗

Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: comparison of adenovirus- and retrovirus-mediated genetic transduction.

Irradiated tumor cells genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine) are potent stimulators of systemic antitumor immunity. For the preparation of a GM-CSF gene-modified tumor vaccine, it is important to achieve efficient genetic transduction of tumor cells, leading to an appropriate expression of the induced gene. In this report, with a view to developing a protocol for an effective cancer vaccination therapy, we examined the vaccination efficacies of tumor cells secreting GM-CSF by either adenovirus- or retrovirus-mediated genetic transduction. By using an adenoviral vector, Adex1CAmGMCSF, a highly efficient gene delivery and a high-level expression of the GM-CSF gene were achieved. Unexpectedly, animal vaccination studies showed that the GM-CSF tumor vaccine transduced with the Adex1CAmGMCSF recombinant adenovirus (adenoviral GM-CSF tumor vaccine) was less efficacious than that transduced with the MFGmGMCSF recombinant retrovirus (retroviral GM-CSF tumor vaccine). The GM-CSF serum concentration attained by the adenoviral GM-CSF tumor vaccine was much higher than that obtained by the retroviral GM-CSF tumor vaccine. Our findings indicate that an optimal level of GM-CSF production is important for the tumor vaccine to elicit an adequate response in the host antitumor immunity.

Adenoviridae↗

Rabbit granulomatous enterocolitis induced by injection of muramyl dipeptide emulsified with Freund's incomplete adjuvant.

We induced granulomatous enterocolitis in rabbits by injecting them with muramyl dipeptide (MDP), a subunit of the peptidoglycan polymers that endow the bacterial cell wall with structural rigidity, emulsified with Freund's incomplete adjuvant (FIA). Injections of 0.1 ml of a water-in-oil emulsion of MDP and FIA were given submucosally at six sites in the rectum and colon, 10 cm proximal to the anus, using a flexible endoscope. Four rabbits each were sacrificed 1, 2, and 4 weeks after a single injection of the emulsion. Another 4 rabbits each were injected six times at 1- and 2-week intervals, and were sacrificed 1 and 2 weeks after the last injection of the emulsion, respectively. In all 20 rabbits, injected with the MDP emulsion, histological findings of the colon consisted of cellular infiltrations of plasma cells and lymphocytes, granulomatous lesions, and granulomas, although the findings differed in degree. Cellular infiltration in hyperplastic villi and denuded epithelia of the small intestine were seen in 2 of 8 rabbits repeated that received MDP emulsion injections. The histological changes in this animal model may be useful for studying the pathogenesis of inflammatory bowel disease in humans.

Acetylmuramyl-Alanyl-Isoglutamine↗

A study of the histological criteria for ulcerative colitis: retrospective evaluation of multiple colonic biopsies.

It is clinically important to distinguish idiopathic inflammatory bowel disease (IBD) from other colitides, and ulcerative colitis (UC) from Crohn's disease (CD); however only a few histological criteria based on colonic biopsies have been established. We investigated 209 consecutive series of biopsies taken from 38 patients with UC, 12 with CD, and 105 with other colitides, to evaluate whether combinations of histological features, selected on the basis of our experience, and listed below, could be useful criteria for the differential diagnosis of IBD, and, more specifically, of UC: (A) chronic inflammation with a predominant increase of plasma cells, (B) crypt distortion, (C) crypt atrophy, (D) diffuse chronic inflammation within a biopsy and between biopsies, and (E) diffuse mucin depletion within a biopsy and between biopsies. Findings that fulfilled all or two of A-C distinguished IBD from the other colitides with high sensitivity (94.3%) and specificity (95.8%). When the findings fulfilled the additional criteria of D and/or E, UC was differentiated from CD or the other colitides with high sensitivity (86.4%) and specificity (99.3%).

Adolescent↗

Systolic and diastolic function after patch reconstruction of left ventricular aneurysms.

Left ventricular function after patch reconstruction for postinfarction left ventricular aneurysms is largely unknown. In this study, 16 patients with an anteroseptal-lateral left ventricular aneurysm were treated by reconstruction of the left ventricle using a Dacron patch. Coronary artery bypass grafting was performed concomitantly in 9 patients. The size of the patch used was 57% +/- 19% of the resected myocardial scar area, including the sewing cuff area to be sutured. In these patients, the ejection fraction increased significantly from 0.28 +/- 0.12 to 0.39 +/- 0.12 (p = 0.007) at rest and from 0.32 +/- 0.14 to 0.41 +/- 0.10 (p = 0.008) during exercise. The left ventricular end-diastolic pressure and left ventricular end-diastolic volume index were reduced significantly from 14 +/- 7.0 to 8 +/- 3.2 mm Hg (p = 0.032), and from 178 +/- 116 to 92 +/- 21 mL/m2 (p = 0.016). The peak filling rate was improved significantly from 1.2 +/- 0.47 to 1.8 +/- 0.6/s (p = 0.048) postoperatively. The ratio of the peak flow velocity during the atrial kick phase to the peak flow velocity in the rapid filling phase, at the level of the mitral valve, improved (p = 0.016) after operation and remained improved up to 16 to 24 months after operation. Patch reconstruction of the left ventricle resulted in the recovery of systolic and diastolic function soon after operation, which has persisted into the late postoperative period.

Blood Pressure↗

Chorda-evoked opening of tight junctions in rat submandibular salivary acini demonstrated by microperoxidase.

The permeability of these junctions from the interstitium to the lumen was examined by using an ultrastructural tracer, microperoxidase, in conjunction with electron microscopy. In the resting gland, the reaction product of microperoxidase was seen in the interstitial and intercellular spaces, but not within acinar lumina; thus the tight junction was impermeable to microperoxidase (junction closed). Intraductal injection of hypertonic sucrose solution (1000 mOsm; 30 microliters) caused a sustained elevation of the luminal pressure, indicating osmotic water flow into the lumen due to the presence of a hypertonic solution. In this gland no opening of the tight junctions was observed. In the chorda-stimulated gland, microperoxidase entered the lumen through the tight junctions, that is, they became permeable to microperoxidase (junction open). These findings suggest that chorda stimulation opens the acinar tight junctions and that the paracellular secretory pathway may be involved in the secretion of small molecules and water from the submandibular acini.

Animals↗

Immunological abnormality in patients with lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare hereditary disorder manifesting hyperammonemia induced by low levels of basic amino acids, these low levels being due to the impaired transport of these acids in the intestinal mucosa and the renal tubules. Low serum arginine levels and probably the consequently low in vivo levels of nitric oxide (NO), which against acts as a physiological and immunological mediator/modulator, are thought to influence the immunological status in patients with LPI. Accordingly, this study was conducted to. We found that patients with LPI had leukocytopenia, high serum IgG levels, a high ratio of CD44B4-positive lymphocytes (helper inducer) to CD42H4-positive lymphocytes (suppressor inducer), low levels of leukocyte phagocytic, cytotoxic, and natural killer cell activity, and increased spontaneous proliferation of lymphocytes. These results were probably the consequence of persistent low NO levels in vivo.

Adult↗

Clinical characteristics of Japanese patients with primary myelodysplastic syndromes: a co-operative study based on 838 cases. Anemia Study Group of the Ministry of Health and Welfare.

The characteristics of Japanese (JPN) patients with myelodysplastic syndromes (MDS) were investigated in 838 retrospectively collected cases. The median age of the JPN patients was 60 years, about 10 years younger than that in most of the reports based on Western patients. Median survivals were 65 months for refractory anemia (RA), 58 months for RA with ring sideroblasts (RARS), 16 months for RA with an excess of blasts (RAEB), 10 months for RAEB in transformation (RAEBT), and 20 months for chronic myelomonocytic leukemia (CMML). Cumulative leukemia-free rates at final observation were 73% for RA, 79% for RARS, 24% for RAEB, 20% for RAEBT, and 53% for CMML. When low-risk (RA and RARS) patients were divided into two groups, those 40 years of age and older, and those under 40, the cumulative leukemia-free rate was 94% for the younger patients (n = 101), compared with 66% for the older patients (n = 318). The prognostic factors for survival were different from those in Western reports, i.e., variables representing quantitative abnormalities (hemoglobin levels, granulocyte, and platelet counts) were not major prognostic factors, while variables representing qualitative abnormalities (morphological abnormalities in granulocytic and megakaryocytic series cells) were highly significant. Two scoring systems for overall survival and for leukemic transformation were developed, based on multivariate prognostic factor analysis. Neither system included variables representing the degree of cytopenia. Whatever the reason for the different prognostic factors in JPN and Western MDS patients, the use of a scoring system based on Western patients for clinical decision-making in a JPN patient could be misleading, and vice versa.

Adolescent↗

Apoptosis in myelodysplasia: a paradox or paradigm.

A growing body of evidence indicates that certain diseases are associated with increased apoptosis or inhibition of apoptosis. Among them, the myelodysplastic syndromes (MDS) are unique in that apoptosis is related, in apparently opposite directions, to the various facets of MDS. Ineffective hematopoiesis may be related to excessive intramedullary cell death via apoptosis and leukemic transformation conceivably results from escape from the apoptotic control. Future studies should be directed to define cellular susceptibility to and circumvention from apoptotic control mechanism(s).

Apoptosis↗

Role of amino acids in salivation and the localization of their receptors in the rat salivary gland.

The distribution of gamma-aminobutyric acid (GABA) receptor subunits such as GABAAR-gamma 1 and GABAAR-gamma 2, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type receptor subunits such as GluR-1, GluR-2/3 and GluR-4, and N-methyl-D-aspartic acid (NMDA) type subunits such as NR1 were investigated by immunocytochemistry. Furthermore, the roles of these amino acids, GABA and glutamate, on salivation were analyzed in the rat submandibular and sublingual glands. Some similarities were observed in the distribution patterns of GABAA type receptors and AMPA receptors. In the submandibular ganglion cells, collecting ducts and striated ducts, these subunits were expressed strongly; however, there were some differences in their expression patterns between the submandibular and sublingual gland acinar cells. Since these receptor subunits were expressed in the acinar cell bodies of the submandibular gland, they were not expressed in the acinar cells but were expressed in the myoepithelial cells in the sublingual gland. On the other hand, no NR1 expression was observed. To examine the roles of GABA and glutamate in salivation, the submandibular and sublingual glands were perfused partially with Ringer's solution via a facial artery to avoid systemic influence, and substrates were infused into the perfusion solution. No salivary secretion was evoked by GABA or glutamate infusion in the absence of electrical stimulation (2-3 V, 5 ms, 20 Hz). Salivary flow evoked by electrical stimulation of the chorda-lingual nerve caused significant inhibition by GABA (10(-6), 10(-5), 10(-4) and 10(-3) M) and the GABAAR agonist muscimol 10(-3) and 10(-6) M) (n = 6, P < 0.05). Such GABA-induced inhibition was antagonized by the GABAAR antagonists bicuculline (BCC; 10(-6) and 10(-3) M) and picrotoxin (PTX; 10(-6) and 10(-3) M). On the other hand, salivary flow evoked by electrical stimulation (8-10 V, 5 ms, 20 Hz) of the superior cervical ganglion (SCG) was not affected by GABA. While high doses of glutamate (10(-1) M) and NMDA (10(-1) M) showed no effects on salivary flow despite application of electrical stimulation, AMPA at a high concentration (10(-1) M) significantly inhibited salivary secretion (n = 6, P < 0.05). These studies revealed that inhibitory and excitatory amino acid receptors such as GABAA and AMPA type receptors are coexpressed in the rat salivary glands, and that GABA inhibits salivary secretion via GABAA receptors which may act with acetylcholine. However, the role of glutamate in salivation remains unclear despite the presence of AMPA type receptors. The present findings suggest that glutamate does not act alone but with other substances such as peptides and/or other amino acids.

Animals↗

Analysis of biological function of poly(ADP-ribosyl)ation in Drosophila melanogaster.

To understand the biological function of poly(ADP-ribosyl)ation of proteins, we have isolated and characterized the gene for poly(ADP-ribose) polymerase from Drosophila melanogaster. Two approaches were taken to analyze the function of the poly(ADP-ribosyl)ation reaction. The first is analysis of the homology of the amino acid sequences of poly(ADP-ribose) polymerase from phylogenetically different eukaryotes, namely human, mouse, bovine, chicken, Xenopus laevis and Drosophila melanogaster and elucidation of the conserved amino acid sequences that appear to be important for the function of poly(ADP-ribose) polymerase. Analysis of the recombinant poly(ADP-ribose) polymerase which had truncated or mutated motifs expressed in E coli would confirm the importance of the conserved amino acid sequence. The interaction of poly(ADP-ribose) polymerase with other proteins involved in DNA repair, replication, recombination and transcription will clarify the function of poly(ADP-ribosyl)ation. The second approach is to get the mutants which have disruption in the poly(ADP-ribose) polymerase gene and to analyse the phenotypes of these mutants. The characterization of these mutants will be discussed.

Amino Acid Sequence↗

Precise localization of VIP-, NPY-, and TH-immunoreactivities of cat laryngeal glands.

The precise distribution of vasoactive intestinal polypeptide (VIP)-, neuropeptide Y (NPY)-, and tyrosine hydroxylase (TH)-immunoreactive (ir) fibers in the cat's laryngeal glands was examined by immunoelectronmicroscopy. A relatively dense population of VIP-ir fibers was recognized close to the basal lamina of the glandular and myoepithelial cells. Some VIP-ir fibers contacted with the basal lamina and some of them pierced it and ran intercellularly in the adjoining glandular cells without making synaptic contacts with them. NPY- and TH-ir fibers were located in the vicinity of the basal lamina, but they were less abundant than VIP-ir fibers at this region. They never terminated or penetrated the basal lamina. Pattern of distribution of TH-ir fibers was similar to that of NPY-ir fibers. The estimated ratio of VIP-, TH-, and NPY-ir fibers was 20:4:1 from the density of fibers in the laryngeal glands. This value was equal between serous and mucous glandular cells, so both types of glandular cells may receive the same pattern of autonomic innervation.

Animals↗