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Biomedical subjects

A Yoshida

Publications and source records attributed to A Yoshida.

At least 397 records · Page 22Linked to original sources

RANTES and macrophage inflammatory protein 1 alpha selectively enhance immunoglobulin (IgE) and IgG4 production by human B cells.

We studied the effects of various chemokines including neutrophil-activating peptide 2 (NAP-2), beta-thromboglobulin (beta-TG), platelet factor 4 (PF-4), melanoma growth stimulating activity (GRO), gamma interferon-induced protein (IP-10), regulated on activation, normal T expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and monocyte chemotactic protein 1 (MCP-1) on Immunoglobulin (IgE) and IgG4 production by human B cells. None of these chemokines with or without interleukin (IL-4), anti-CD40 or -CD58 monoclonal antibody (mAb), induced IgE and IgG4 production by B cells from nonatopic donors. However, RANTES and MIP-1 alpha selectively enhanced IgE and IgG4 production induced by IL-4 plus anti-CD40 or -CD58 mAb without affecting production of IgM, IgG1, IgG2, IgG3, IgA1, or IgA2, whereas other chemokines failed to do so. Enhancement of IgE and IgG4 production by RANTES and MIP-1 alpha was specifically blocked by anti-RANTES mAb and anti-MIP-1 alpha antibody (Ab), respectively, whereas anti-IL-5 mAb, anti-IL-6 mAb, anti-IL-10 Ab, anti-IL-13 Ab, and anti-tumor necrosis factor-alpha mAb failed to do so. Purified surface IgE positive (slgE4) and slgG4+ B cells generated either in vitro or in vivo spontaneously produced IgE and IgG4, respectively, whereas sIgE- and sIgG4- B cells failed to do so. RANTES and MIP-1 alpha enhanced spontaneous IgE and IgG4 production in slgE+ and slgG4- B cells, respectively, whereas neither RANTES nor MIP-1 alpha did so in sIgE- or sIgG4- B cells. Purified sIgE4+ and sIgG4+, but not sIgE- or sIgG4- B cells, generated in vitro and in vivo expressed receptors for RANTES and MIP-1 alpha, whereas they failed to express receptors for other chemokines. These findings indicate that RANTES and MIP-1 alpha enhance IgE and IgG4 production by directly stimulating sIgE+ and sIgG4+ B cells.

Antibody Formation↗

Binding of botulinum type B neurotoxin to Chinese hamster ovary cells transfected with rat synaptotagmin II cDNA.

We have previously identified synaptotagmin, a synaptic vesicle membrane protein from rat brain, as a binding protein for Clostridium botulinum type B neurotoxin. In this report, rat synaptotagmin II was expressed by transfection in Chinese hamster ovary cells and interaction with the neurotoxin was studied. In stable transfectants, the NH(2)-terminal region of synaptotagmin was exposed to the extracellular medium. Synaptotagmin-expressing cells were shown to possess an extremely low binding activity for the radiodinated toxin. However, toxin-binding was markedly increased to cells which had been treated with gangliosides G T1b or G D1a. In synapses, the intravesicular NH(2)-terminus of synaptotagmin becomes exposed at the cell surface after following exocytosis. These findings suggest that the NH(2)-terminal domain of synaptotagmin II forms the binding site for type B neurotoxin by associating with specific gangliosides in presynaptic plasma membranes.

Animals↗

Retarded and aberrant splicings caused by single exon mutation in a phosphoglycerate kinase variant.

The molecular abnormality of a phosphoglycerate kinase variant which was associated with severe tissue enzyme deficiency and episodes of muscle contractions and myoglobinuria was examined. Analysis of the patient's DNA showed the existence of a nucleotide transversion A/T - C/G in exon 7. No other nucleotide change was detected in the coding region of the variant gene. The mutation should produce a single amino acid substitution Glu - Ala at protein position 251 counting from the NH2-terminal acetyl serine residue. The protein abnormality caused by the amino acid substitution cannot explain the enzyme deficiency. Northern blot hybridization indicated that the PGK mRNA content of the patient's lymphoblastoid cells was only about 10% of that of normal. Nucleotide sequence analysis revealed the existence of two PGK mRNA components in the patient's cells. The major component corresponds to the normal PGK mRNA except for A - C change at nucleotide position 755 counting from adenine of the chain initiation codon. The minor component contains 5' region (52 bases) of intron 7 between exon 7 and exon 8. An inframe chain termination codon exists in the minor mRNA component, and the COOH-terminal half is expected to be deleted in the translation product. These results indicate that the low PGK activity in the patient's tissues is mainly due to retarded and aberrant pre-mRNA splicings caused by the change of the consensus 5' splice sequence AGgt to a nonconsensus sequence CGgt at the junction between exon 7 and intron 7 of the variant gene.

Adolescent↗

NADPH-diaphorase in the developing rat: lower brainstem and cervical spinal cord, with special reference to the trigemino-solitary complex.

A previous study indicated that in adult rat, a distinctive neuronal group in the dorsomedial division of the subnucleus oralis of the spinal trigeminal nucleus (SpVo) and the rostrolateral part of the nucleus of the solitary tract (Sn) is stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), and suggested that the labeled structures are involved with sensorimotor reflexive functions. This study aimed to characterize the developmental expression of NADPH-d in SpVo and Sn, including other areas of the lower brainstem and cervical spinal cord, by means of the enzyme histochemical staining technique, from the prenatal through the postnatal period. On embryonic day 12 (E12), no neurons in the brain were stained for NADPH-d, whereas blood vessels were stained. Labeling in the vessels was consistently present throughout pre- and postnatal periods but decreased with development. On E15, labeled neurons appeared in the dorsomedial part of SpVo and the rostrolateral part of Sn, but not in the other nuclei. The labeled neurons in both nuclei increased in numbers drastically to E17. Postnatally, they tended to increase gradually in Sn, but to decrease slightly in SpVo. The cell size of labeled neurons reached a plateau at E17 in SpVo, but at postnatal day 4 (P4) in Sn. In other nuclei on E17, labeling appeared in the lateral paragigantocellular reticular, intermediate reticular, medullary reticular, pedunculopontine tegmental, and spinal vestibular nuclei, and laminae V, VI, and X of the cervical spinal cord. On E20 and P0, labeling appeared in the dorsal column, laterodorsal tegmental, raphe obscurus, parvocellular reticular, ventral gigantocellular reticular, and parahypoglossal nuclei, and laminae IX of the cervical spinal cord. On P4 labeling appeared in the parabrachial and median raphe nuclei, medial and caudolateral Sn, the magnocellular zone of subnucleus caudalis of the spinal trigeminal nucleus (SpVc), and laminae III/IV of the cervical spinal cord. On P10, labeling appeared in the paratrigeminal and dorsal raphe nuclei, the superficial zone of SpVc, and laminae I/II of the cervical spinal cord. No newly labeled neurons appeared in any nuclei after P14. The very early appearance of NADPH-d staining in SpVo and Sn, which precedes the appearance of NADPH-d elsewhere in the brainstem, suggests that the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system has an important role for primitive orofacial sensorimotor reflexive functions. Furthermore, the pattern of developmental expression of NADPH-d in SpVo and Sn suggests that the NO/cGMP system is organized in a distinct manner in different nuclei.

Afferent Pathways↗

Nested-polymerase chain reaction for the detection of Helicobacter pylori infection with novel primers designed by sequence analysis of urease A gene in clinically isolated bacterial strains.

We have established a highly sensitive semi-nested PCR assay for the detection of H. pylori infection using gastric juice samples, which can be aspirated with disposable nasogastric tubes. The primers targeting H. pylori urease A gene were designed based on the sequence conservation analysis of sixteen H. pylori strains isolated from Japanese patients. The efficacy of the PCR assay, designated as the URA-PCR, was confirmed by in vitro and in vivo assessments. Its sensitivity was 97.5% in the gastric juice samples aspirated from forty patients with proven H. pylori infection, and was significantly higher than that obtained with previously described PCR assays.

Base Sequence↗

The high-affinity binding of Clostridium botulinum type B neurotoxin to synaptotagmin II associated with gangliosides GT1b/GD1a.

125I-labeled botulinum type B neurotoxin was shown to bind specifically to recombinant rat synaptotagmins I and II. Binding required reconstitution of the recombinant proteins with gangliosides GT1b/GD1a. Scatchard plot analyses revealed a single class of binding site with dissociation constants of 0.23 and 2.3 nM for synaptotagmin II and synaptotagmin I, respectively, values very similar to those of the high- (0.4 nM) and low-affinity (4.1 nM) binding sites in synaptosomes. The high-affinity binding of neurotoxin to synaptosomes was specifically inhibited by a monoclonal antibody recognizing with the amino-terminal region of synaptotagmin II. These results suggest that this region of synaptotagmin II participates in the formation of the high-affinity toxin binding site by associating with specific gangliosides.

Amino Acid Sequence↗

Assessment of posterior aortic wall motion using echocardiogram in patients with atrial fibrillation.

BACKGROUND AND HYPOTHESIS: Noninvasive evaluation of left ventricular (LV) diastolic function was performed on 12 patients with atrial fibrillation (AF) using posterior aortic wall echocardiogram and a parameter for determining the optimal heart rate in patients with chronic atrial fibrillation was considered. METHODS: Subjects were divided into two groups; one with no underlying cardiac disease (AF only group; n = 7) and the other with dilated cardiomyopathy (DCM group; n = 5). Left atrial emptying index (LAEI) obtained from the posterior aortic wall echocardiogram was used as the parameter of LV diastolic function, and R-R interval-LAEI relation and minimum R-R interval showing LAEI = 1.0 were investigated and compared between the two groups. RESULTS: There was a good correlation between R-R interval and LAEI until LAEI of 1.0 was obtained in all patients. Slope of the regression line was significantly steeper in the AF only group than in the DCM group, and minimum R-R interval showing LAEI = 1.0 was significantly shorter in the AF only group. CONCLUSION: Assessment of R-R interval-LAEI relation was useful for the noninvasive evaluation of LV diastolic function, and this parameter could be used for clinical application to determine the optimal heart rate in atrial fibrillation.

Aorta↗

Inhibition of spontaneous immunoglobulin production by ganglioside GM2 in human B cells.

The effects of gangliosides on spontaneous immunoglobulin (Ig) production in human B cells were studied. Of the various gangliosides tested, including GM1, GM2, GM3, GD1a, GD1b, GD3, GT1b, and GQ1b, only GM2 inhibited Ig production, but not thymidine uptake, in human B cell lines. Moreover, the GM2-induced inhibition was blocked by anti-GM2 mAb, but not by control IgM. Of various cytokines, IL-10 and TNF-alpha each partially counteracted the GM2-induced inhibition, and addition of both IL-10 and TNF-alpha completely counteracted the inhibition. On the other hand, anti-IL-10 mAb plus anti-TNF-alpha mAb inhibited spontaneous Ig production. GM2 inhibited endogenous production of IL-10 and TNF-alpha without affecting the binding of IL-10 and TNF-alpha in B cell lines. GM2 also specifically inhibited spontaneous production of Ig, IL-10, and TNF-alpha in in vivo activated B cells obtained from normal donors. This inhibition was blocked by anti-GM2 mAb and was counteracted specifically by IL-10 plus TNF-alpha. Collectively, GM2 may inhibit spontaneous Ig production by inhibiting endogenous production of IL-10 and TNF-alpha in B cells.

B-Lymphocytes↗

Evidence of cross-link formation of vitreous collagen during experimental ocular inflammation.

PURPOSE: To determine the mechanisms of vitreous changes during ocular inflammation. METHODS: We investigated vitreous changes, with special emphasis on collagen, in an experimental model of ocular inflammation induced by intravitreal injection of endotoxin (Escherichia coli) in rabbits. RESULTS: Inflammation caused gel contraction and loss of elasticity, accompanied by release of a water-like liquid from the gel, and increases in the amount of insoluble material and high-molecular-weight components of vitreous collagen, presumably due to extensive cross-links of the collagen molecules. Those changes were partially inhibited by intravitreal injection of superoxide dismutase. CONCLUSIONS: The cross-links of vitreous collagen may promote vitreous gel contraction and release of a water-like liquid from the gel. Superoxide anion may play a role in this process.

Animals↗

High serum alpha-fetoprotein concentration associated with pseudoinfarction of a cirrhotic liver: report of a case.

We report herein the case of a 65-year-old man with cirrhosis of the liver in whom a portal vein thrombus was found to be the cause of a marked elevation in serum alpha-fetoprotein (AFP). The patient presented with fever and abdominal pain, and a diagnostic work-up revealed a liver mass and an increased serum AFP concentration of 91,000 ng/ml. The mass gradually regressed, and the AFP concentration simultaneously decreased to 163 ng/ml. However, because hepatocellular carcinoma (HCC) could not be ruled out, a partial hepatectomy was performed. Histological examination of the resected specimen revealed a thrombus of the portal vein surrounded by the fibrosis associated with liver cirrhosis, but no neoplastic lesion was found. Thus, portal thrombus associated with liver cirrhosis might induce an extremely high level of AFP production.

Aged↗

Perianal extramammary Paget's disease associated with primary linitis plastica of the rectum: report of a case.

We report herein a case of perianal extramammary Paget's disease associated with primary linitis plastica of the rectum. An 82-year-old woman was admitted to our hospital for investigation and treatment of a perianal eczematous lesion. A skin biopsy of the lesion revealed perianal extramammary Paget's disease and a barium enema demonstrated diffuse narrowing with an irregular contour at the ampulla recti. Under a suspected diagnosis of linitis plastica of the rectum, an abdominoperineal resection was performed to resect both the rectal and perianal lesions with regional lymphadenectomy. Grossly, marked narrowing and wall thickness were observed at the lower rectum, and a histological diagnosis of signet ring cell carcinoma was confirmed. The perianal eczematous lesion revealed many atypical cells with clear cytoplasm, being Paget cells, throughout the entire epidermis. Sparse distributions of signet ring cells were also observed in the subcutaneous tissue beneath the perianal eczematous lesion. The pathogenesis of perianal extramammary Paget's disease in this patient was therefore considered to be an intraepidermal extension of primary linitis plastica of the rectum.

Aged↗

Inward and outward permeability of the blood-retinal barrier in experimental myopia.

BACKGROUND: To investigate the pathophysiology of the retina in myopia, vitreous fluorophotometry was used to evaluate the permeability of the blood-retinal barrier (BRB) in experimentally induced myopia in cynomolgus monkeys. METHODS: Five animals underwent unilateral eyelid suturing. The suture was removed temporarily at 3, 10, 16, 28 and 36 months, and the dioptric power and axial length were measured in both eyes. Vitreous fluorophotometry was performed before and 60 min after intravenous injection of fluorescein-Na. BRB inward permeability (P(in)) was determined by a computer simulation method. At 36 months, fluorescein-Na was injected into the vitreous cavity, and the intraocular fluorescence was measured. BRB outward permeability (P(out)) was determined by the computer simulation method. RESULTS: Significant myopia developed by 10 months after suturing and progressed thereafter. Starting at 10 months, the P(in) of sutured eyes increased significantly compared with control fellow eyes, and the increase continued throughout the observation period. At 36 months, the BRB P(out) was significantly lower (P < 0.05) in the myopic than in the emmetropic fellow eyes, suggesting decreased active transport mechanisms at the BRB in myopia. CONCLUSION: Our study demonstrated, for the first time, abnormal permeability of the BRB in myopic monkey eyes. Such abnormal permeability may play an important role in the development in human myopes of retinal and vitreous changes such as retinal detachment. Thus, simply correcting refractive errors surgically may not represent a cure for myopia. Patients who have had refractive surgery to correct myopia should also be closely followed up by vitreo-retinal specialists to manage vitreo-retinal disorders in originally myopic eyes.

Animals↗

Molecular mechanism of null expression of aldehyde dehydrogenase-1 in rat liver.

In isozyme systems in general, the pattern of tissue-dependent expression of a given type of isozyme is uniform in various mammalian species. In contrast, a major cytosolic aldehyde dehydrogenase isozyme, termed ALDH1, which is strongly expressed in the livers of humans and other mammals, is hardly detectable in rat liver. Thirteen nucleotides existing in the 5'-promoter region of human, marmoset, and mouse ALDH1 genes are absent in the four rat strains examined. When the 13 nucleotides were deleted from a chloramphenicol acetyltransferase expression construct, which contained the 5'-promoter region of the human ALDH1 gene and a low-background promoterless chloramphenicol acetyltransferase expression vector, the expression activity was severely diminished in human hepatic cells. Thus, deletion of the 13 nucleotides in the promoter region of the gene can account for the lack of ALDH1 expression in rat liver.

Aldehyde Dehydrogenase↗

Imaging of epiretinal membranes in macular holes by scanning laser ophthalmoscopy.

PURPOSE: Because recognition and removal of an epiretinal membrane are important in macular hole surgery, we used the scanning laser ophthalmoscope preoperatively to study epiretinal membranes in patients with idiopathic macular holes. METHODS: We studied 67 eyes (60 consecutive patients) with idiopathic macular holes. We evaluated the thickness and the extent of the epiretinal membrane by using a scanning laser ophthalmoscope. We then compared the fundus images obtained with the scanning laser ophthalmoscope with red-free monochromatic fundus photographs. RESULTS: Confocal imaging of the fundus with either argon blue (488 nm) or argon green (514 nm) laser illumination clearly showed the epiretinal membranes. In all eyes, we observed lesions ranging from a patchy glinting light reflex to a dense epiretinal membrane. A well-demarcated dense epiretinal membrane around the macular hole was observed in seven (44%) of 16 eyes with stage 2 macular holes and in 12 (40%) of 30 eyes with stage 3 holes, but in only two (10%) of 21 eyes with stage 4 holes. The prevalence of the dense epiretinal membrane in stage 2 or 3 holes was significantly higher than in stage 4 holes (P = .025 and .024, respectively). CONCLUSIONS: Fundus imaging using the scanning laser ophthalmoscope with argon laser illumination is useful preoperatively to evaluate epiretinal membranes in eyes with idiopathic macular holes.

Aged↗

Enhancement of in vitro spontaneous IgE production by topical steroids in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease. Although topical steroids are widely used for AD, management of severe AD is not satisfactory because of relapse or occasional aggravation of symptoms. Moreover, glucocorticoids induce in vitro IgE production. On the other hand, topical sodium cromoglycate (SCG) solution is a safe and effective treatment for AD. METHODS: We treated 43 patients with AD with SCG solution (n = 21) or with topical steroids, beclomethasone dipropionate (BD) ointment (n = 22). After 2 weeks, clinical evaluation and spontaneous immunoglobulin production by peripheral blood B cells or surface IgE+ B cells from patients in the SCG and BD groups were assessed. RESULTS: Both SCG and BD treatment remarkably improved eczema. However, although SCG treatment decreased spontaneous IgE production by B cells without affecting production of IgG, IgM, or IgA, BD treatment selectively increased spontaneous IgE production. SCG treatment also decreased IgE production by surface IgE+ B cells, whereas BD treatment increased it. CONCLUSION: Topical steroid treatment increases in vitro spontaneous IgE production by B cells. This indicated that topical steroids may decrease inflammation; however, a large-scale study on the effect of topical steroids on IgE production in vitro and in vivo may be necessary.

Administration, Topical↗

Effects of age on endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea and sodium nitrite in mice.

Aging effects on the susceptibility to chemical endometrial carcinogenesis were investigated in ICR female mice. The animals were divided into 3 groups of different ages: 1 month (young), 6 months (middle), and 12 months (old) at initiation of treatment. They received weekly oral administration of mixture of ETU (100 mg/kg body weight) and sodium nitrite (70 mg/kg body weight) for 6 months followed by a withdrawal period of 3 months. All animals were subjected to histopathology. The incidence of endometrial adenocarcinomas was highest in the middle age group (8/20), secondary in the old age group (4/20), and lowest in the young group (1/20). The incidence of atypical glandular hyperplasia, a precursor lesion of the tumor, was also higher in the middle age group. The endometrial adenocarcinomas showed morphological similarities among all age groups and the nuclei of tumor cells lost almost all staining reactivity to estrogen receptors. The labeling indices with bromodeoxyuridine (BrdU) were notably higher in the old age group than in the young and middle age groups. A further investigation on the aging process of female genital organs in control mice revealed that their senility seemed to be preceded by the formation of ovarian cysts which first appeared at 6 months of age with a concomitant elevation of plasma 17 beta-estradiol level. These results indicate that the susceptibility of the mouse endometrium to the carcinogenic effects of N-nitroso ETU could be closely linked with the stage of aging process of the genital organs and it appears to be most susceptible when initiated at around 6 months of age. However, the mitotic activity of neoplastic endometrial glandular cells seems to be higher in older mice than younger ones.

Administration, Oral↗