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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 253 records · Page 14Linked to original sources

Suppression of cell-transferred experimental autoimmune encephalomyelitis in defibrinated Lewis rats.

The role of coagulation-fibrinolysis system in experimental autoimmune encephalomyelitis (EAE) was studied by using batroxobin, derived from the venom of the South American pit viper Bothrops atrox moojeni. Batroxobin converts circulating fibrinogen into an insoluble form and causes a profound degree of afibrinogenemia. Batroxobin treatment (30 BU/kg/day) suppressed clinical signs of cell transferred EAE; the mean cumulative clinical score for batroxobin treated rats was 3.97, while saline treated controls scored 6.9 (P < 0.01). Plasma fibrinogen concentration decreased significantly in batroxobin-treated rats. Histologically, the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in batroxobin-treated rats compared to saline-treated control rats, however, deposition of fibrin around the vessels in the spinal cord was markedly suppressed in batroxobin-treated rats. These findings suggest that batroxobin suppresses EAE by preventing fibrin deposition, and provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of blood brain barrier (BBB), are related prerequisites for the clinical manifestation of EAE.

Animals↗

Defective B-1 cell development and impaired immunity against Angiostrongylus cantonensis in IL-5R alpha-deficient mice.

We generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting. The IL-5R alpha-/- mice showed decreased numbers of B-1 cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B cell responses to T-independent antigens. The number of alpha beta T cell receptor-positive thymocytes tended to decrease in 3-week-old IL-5R alpha-/- mice, returning to normal by 6 weeks of age. The IL-5R alpha-/- mice produced basal levels of eosinophils, while their bone marrow cells failed to form eosinophilic colonies in response to IL-5. Impaired eosinophilopoiesis in IL-5R alpha-/-mice enhanced the survival of Angiostrongylus cantonensis. These results indicate that IL-5-induced eosinophils serve as potent effector cells in the killing of Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis↗

Effect of unsaturated fatty acids and antioxidants on immunoglobulin production by mesenteric lymph node lymphocytes of Sprague-Dawley rats.

The effect of UFA on Ig production by rat MLN lymphocytes was examined to clarify their influence on allergic reactions. A 4-h treatment at 1 mM inhibited the production of IgA, IgG, and IgM by the lymphocytes, but stimulated IgE production. The IgE production-stimulating activity became stronger with increasing number of carbon atoms and/or double bonds. However, no saturated fatty acid with carbon numbers from 12 to 18 affected IgE production by the lymphocytes. Hydrogen peroxide exerted Ig production-regulating activity similar to that of UFA, suggesting that the effect of UFA is at least partly due to oxidation products. Thus, the effect of antioxidants on the Ig production-regulating activity of arachidonic acid was examined. alpha-Tocopherol and BHT annulled the stimulation of IgE production by arachidonic acid, but ascorbic acid was not effective. The IgE production-enhancing activity of UFA was closely related to their oxidation rate in culture medium. These results suggest that UFA enhance the allergic reaction through the stimulation of IgE production and the inhibition of IgA production, and that hydrophobic antioxidants are partially effective to annul the adverse effect of UFA.

Animals↗

Effect of E5510 on anastomotic intimal hyperplasia and platelet aggregation in dogs.

We examined the effect of an antiplatelet agent, E5510, which inhibits both platelet aggregation and release of platelet-derived growth factor (PDGF), on anastomotic intimal hyperplasia and platelet aggregation. Twenty Beagle dogs underwent infrarenal aortic reconstruction with an expanded polytetrafluoroethylene (ePTFE) graft 5 mm in diameter and 3 cm long. The dogs were divided into three groups: placebo (control group, 7 dogs), E5510 1 mg/day (1-mg group, 6 dogs), and E5510 4 mg/day (4-mg group, 7 dogs). E5510 was administered orally 2 h before operation and once daily for 3 months after operation. Grafts were harvested 3 months after operation. All 13 grafts in the treated groups remained patent without evidence of intimal hyperplasia, whereas only 4 of 7 grafts (57%) remained patent in the control group, including 1 graft with > 50% stenosis. Three occluded grafts showed severe intimal hyperplasia at the anastomoses. The platelet aggregation ratio (PAR) with collagen (100 micrograms/ml) before drug administration at 3 months in the 4-mg group was significantly lower than that in the control and 1-mg groups. PAR after drug administration at 3 months in the 1- and 4-mg groups was significantly lower than that in the control group. Intimal thickness at the distal anastomosis was 817 +/- 190 microns in the control group, 240 +/- 80 microns in the 1-mg group, and 197 +/- 28 microns in the 4-mg group. Intimal thickness in the control group was significantly greater than that in the 1- and 4-mg groups. Smooth muscle cell (SMC) values in the intima at the distal anastomosis were 65.6 +/- 4.4% extinction (%E) in the control group, 47.6 +/- 3.4%E in the 1-mg group, and 51.3 +/- 3.5%E in the 4-mg group. SMC value in the control group was significantly greater than that in the 1- and 4-mg groups. E5510 inhibited PAR and reduced the degree of anastomotic intimal hyperplasia.

Anastomosis, Surgical↗

Demonstration of antigenic and genotypic variation in Orientia tsutsugamushi which were isolated in Japan, and their classification into type and subtype.

A total of 40 strains of Orientia tsutsugamushi (34 isolates from patients and trombiculid mites in Japan, and 6 prototype strains of antigenic variants) were examined for classification based on the reactivities with type-specific monoclonal antibodies in indirect immunofluorescence tests, and on the restriction fragment length polymorphism of a polymerase chain reaction (PCR)-amplified 56-kilodalton type-specific antigenic protein gene. By these methods, several antigenic and genotypic variants were found among the strains, and these variants were classified into types and further into subtypes. These results suggest that there are many variants in O. tsutsugamushi, and the methods used here seem to be useful for the systematic classification of the numerous variants. A strain which may be a new type distinguishable from those identified previously was also found in this study. Furthermore, variety in the degree of pathogenicity in mice related to type and/or subtype classification were observed.

Animals↗

Relationship of HIV-1 envelope V2 and V3 sequences of the primary isolates to the viral phenotype.

We examined the relationship between the amino acid sequences of the V2 and V3 regions of the envelope protein and the biological properties of ten human immunodeficiency virus type 1 (HIV-1) primary isolates. The infectivity, cytopathic effect (CPE), and syncytium forming activity of these primary isolates were tested against three T cell lines (CEM, MT2, and MOLT4/CL.8 cells), CD8-depleted peripheral blood mononuclear cells (PBMC), and primary monocyte-derived macrophages (MDM) from seronegative donors. In addition to the viral groups which had the syncytium inducing/T-cell line tropic (SI/TT) phenotype or non-syncytium inducing/non-T cell line tropic (NSI/NT) phenotype (including the NSI/macrophage tropic (NSI/MT) phenotype), there was a group of viruses that infected one or two T cell lines and PBMC but could not mediate syncytium formation. We therefore classified this group of viruses as a non-syncytium inducing/partial T-cell line tropic (NSI/pTT) virus. To investigate the relationship between these viral phenotypes and the sequence variability of the V2 and V3 regions of the envelope, we cloned the viral gene segment and sequenced the individual isolates. The sequence data suggested that the SI/TT type changes in the V3 sequence alone mediate a partial T cell line tropism and mild cytopathic effect and that an isolate became more virulent (SI/TT phenotype) if there were additional changes in the V2 or other regions. On the other hand, sequence changes in the V2 region alone could not mediate phenotypic changes but some additional changes in the other variable regions (for example, V3) might be required for the phenotypic changes in combination with changes in V2. These findings also suggested that amino acid changes in both the V2 and V3 region are required for the development of virulent variants of HIV-1 that outgrow during advanced stages of the disease.

Adolescent↗

The effects of omeprazole and famotidine on mucin and PGE2 release in the rat stomach.

BACKGROUND: Gastric antisecretory agents may inhibit the synthesis or secretion of gastric mucin during acid suppression, which would interfere with mucosal protection and limit the efficacy of the agents. METHODS: Rats were dosed with famotidine, omeprazole, or buffer control for 4 weeks. Mucin synthesis, mucin histochemistry, mucin carbohydrate composition and prostaglandin E2 (PGE2) release were measured during and after drug treatment. RESULTS: PGE2 release was maximally inhibited after 2 weeks of omeprazole or 4 weeks of famotidine. Total glycoprotein synthesis was inhibited at all times by omeprazole, but only after the cessation of dosing with famotidine. Sulphated glycoprotein synthesis was inhibited by both drugs at 2 weeks. PGE2 release and sulphated glycoprotein synthesis were restored to control values or more by the 5th day after the end of dosing, at which time total glycoprotein synthesis was significantly suppressed in both groups. Histologically, a reduction of PAS-positive surface mucus was observed after 2 weeks of dosing in both groups. Both famotidine and omeprazole reduced the sialic acid content during and after treatment. CONCLUSIONS: These results suggest that long-term anti-secretory therapy also affects the production of factors involved in primary gastric mucosal defence, which should be considered in the assessment of response to treatment in clinical trials.

Animals↗

Rapid detection of the cisAB allele consisting of a chimera of normal A and B alleles by PCR-RFLPs.

DNA samples were analysed from Japanese individuals with the very rare ABO variant phenotype, cisAB (A2B3), which is characterized by the apparent inheritance of both A and B genes on one chromosome. The nature of the bases present at nucleotide positions (nps) 261, 526, 703, 796 and 803 is important for the specificity of the alleles at the ABO locus and the DNA from the cis AB donors was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine which nucleotides are present at these positions. The results indicated that the cisAB allele had the AAAB-structure, which was a chimera of normal A and B alleles, when the expression 'AAAA' and 'BBBB' indicated the nucleotides of normal A (C, G, C and G) and B (G, A, A and C) genes at nps 526, 703, 796 and 803, respectively. The AAAB allele was found in all 27 individuals (17 families) with the cisAB including three phenotypes A2B3, A1B3 and A2B and no other chimeric gene was found. The causative gene of cisAB was the AAAB allele, and the A and B alleles were not on one chromosome. The cisAB allele appeared to be a product of the normal A allele due to a point mutation at nucleotide position 803, from G to C. The AAAB allele is thought to be normally transcribed and translated to produce an unusual transferase polypeptide, which has weak A- and weaker B-specific activity. PCR-RFLP is a rapid and useful means of detecting the cisAB allele (the AAAB allele) without a family study, even when they have A1B3 and A2B phenotypes, because trans-type A1B3 and A2B samples have obviously different PCR-RFLP profiles.

ABO Blood-Group System↗

Bilateral renal cell carcinoma in a patient with tuberous sclerosis.

A case of pure bilateral renal cell carcinoma (RCC) in a 21-year-old female diagnosed as having tuberous sclerosis is reported. She underwent a left nephrectomy because of her loss of appetite, possibly caused by the tumor compressing her intestines. The preoperative CT scan showed the presence of adipose tissue in bilateral renal tumors, which is highly suggestive of angiomyolipoma (AML). Histological examination, however, revealed no area or component of the tumor with features characteristic of AML.

Adult↗

Locally-confined signet-ring cell carcinoma of the prostate: a case report of a long-term survivor.

It is generally believed that signet-ring cell carcinoma (SRCC) of the prostate is a high-grade neoplasm with a poor prognosis. We report a case of a long-term survivor diagnosed with localized prostatic SRCC (T3N0M0), who has been alive without any clinical evidence of disease for 100 months after combination therapy which consisted of local irradiation and hormone administration. A posttreatment needle biopsy confirmed the pathological complete response.

Administration, Oral↗

Avoidant personality disorder and taijin kyoufu: sociocultural implications of the WHO/ADAMHA International Study of Personality Disorders in Japan.

This paper discusses the characteristics of avoidant personality disorder in a cultural context based on the Japanese concept of taijin kyoufu as well as that of DSM-III-R and DSM-IV social phobia. Sixty-six patients were given the International Personality Disorder Examination and questionnaires including the Beck Anxiety Inventory. Among the 23 DSM-III-R personality disorder patients, 8 patients were diagnosed as having avoidant personality disorder. Six of them were suffering from taijin kyoufu symptoms. Among 27 ICD personality disorder patients, 22 patients were diagnosed as having ICD anxious personality disorder. All DSM avoidant patients were included in the ICD anxious group. These findings suggest that patients with avoidant personality disorder have had a long history of difficulties and share common personality problems with a milder form of taijin kyoufu, which is conceptually different from social phobia.

Adolescent↗

A novel type of mechanoreception by the flagella of Chlamydomonas

A novel type of mechanosensory mechanism is found in Chlamydomonas reinhardtii. When a cell is captured with a suction pipette and a negative pressure is applied, the cell produces repetitive Ca2+ impulses at a frequency of 0.5-1.0 Hz. The impulse frequency increases with the applied pressure. The impulses are produced when the flagella are sucked into the pipette but not when the cell body is sucked in leaving the flagella outside the pipette. Cells with short flagella produce impulses of small amplitude. Thus, the site where the cell senses mechanical stimuli and generates the impulse current must be localized at the flagella. The amplitude, shape and ion selectivity of the pressure-induced impulses are distinct from the all-or-none flagellar current that is evoked by photostimulation. The impulses are possibly produced by a combination of currents passing through mechanosensitive channels and Ca2+ channels. This response probably functions to modulate flagellar beating and thereby to regulate the behaviour of the cell.

Journal Article↗

DNA sequence from a fossil pollen of Abies spp. from Pleistocene peat.

DNA was amplified from individual fossil pollen grains of Abies spp. (Pinaceae), which have been detected from Pleistocene peaty deposits (at least 150,000 years old). To identify the species of the fossil pollen by DNA analysis, the region indicating the species-specific sequence was searched among extant Abies species and the spacer region between rrn5 and trnR in chloroplast DNA was sequenced for four grains of the fossil pollen. Three pollen samples produced the same sequence as extant Abies species. The sequence for the remaining sample differed from that of extant Abies by one substitution. This study showed not only a successful DNA analysis from a single grain of fossil pollen but also a new method to identify the species of fossil pollen for the pollen analysis field.

Base Sequence↗

[Mesonephric adenocarcinoma arising in the female urethral diverticulum].

A forty four-year-old house-wife presented with gross hematuria and difficulty on urination of a year and 3 months duration. Transvaginal examination showed a hen egg-sized soft mass on the anterior vaginal wall. Urine cytology revealed many clusters of malignant cells suggestive of adenocarcinoma. Cystourethrography revealed two urethral diverticula, whose orifices were cystoscopically located at the proximal and distal side of urethral sphincter, respectively. By vaginal digital pressing, a soy-bean sized papillary tumor came out of the proximal diverticulum. Histopathological examination of the biopsied tumor suggested poorly differentiated transitional cell carcinoma with inverted growth. Under the diagnosis of carcinoma arising in the urethral diverticulum, anterior pelvic exenteration with formation of Indiana pouch was carried out. The tumor in the proximal diverticulum was histologically composed of a variety of adenocarcinomatous pattern, such as tubular, papillary and cystic structure with a distinctive pattern of tubules lined by a superficial layer of hobnail cells, leading to the diagnosis of mesonephric adenocarcinoma of urethral diverticulum. Postoperative radiation therapy was given because the diverticulum was adherent to the pubic bone, though lymph node metastasis was negative. She has been well with no evidence of the disease for 1 year and 4 months after the operation. Although the histogenesis of female urethral mesonephric adenocarcinoma was still controversial, this case seems to be the forty fourth case in the world literature.

Adult↗

[Gene therapy for AIDS: current trends].

Genetic manipulation of somatic cells may be of therapeutic value in a variety of infectious diseases, particularly in human immunodeficiency virus (HIV) infection. Stable insertion of "resistance genes" into cells, susceptible to HIV, could reduce the viral burden in infected individuals and potentially retard the characteristic progressive immune dysfunction. Alternatively, ectopic expression of genes that encode viral antigens, might induce potent antiviral immune responses and form the basis for novel prophylactic and therapeutic vaccines. While laboratory studies have proved that the approach works in principle, preclinical and clinical studies will be necessary to evaluate the therapeutic benefits of such gene-based therapies. Currently, more than 400 patients have already been treated by this innovative therapeutic strategy in the US. In Japan, the Expert Committee on Gene therapy was set up in the council on Science and the Public Health and Welfare in 1991. Recently, gene therapy for ADA has been approved. It is thought that the first gene therapy against HIV infection in Japan is not far away.

Acquired Immunodeficiency Syndrome↗

[Coronary artery bypass grafting surgery without cardiopulmonary bypass in a patient with calcified aorta].

Coronary artery bypass surgery in a 67-year-old male with severe calcified ascending aorta was performed without cardiopulmonary bypass under beating heart, utilizing the left internal thoracic artery graft. No neurological complication was observed and postoperative angiogram showed good graft patency. We think coronary revascularization without cardiopulmonary bypass can be one of the safe and reliable methods to avoid complications associated with aortic cross clamping and aortic cannulation with severely calcified aorta.

Aged↗

[A case of renal cell carcinoma with an extremely high serum carcinoembryonic antigen level].

A case of renal cell carcinoma with extremely high serum carcinoembryonic antigen (CEA) levels is presented. A 57-year-old female complained of left flank pain. Computerized tomographic (CT) scan revealed left renal tumor and laboratory examination revealed an extremely high serum level of CEA (815 ng/ml). No abnormal findings were recognized in gastrointestinal or genital systems. Radical nephrectomy was done. The histology was renal cell carcinoma (RCC, intermediate type, mixed type, pleomorphic cell type, G3 > G2, INF gamma, pT2, pV0). Tumor cells were positive for CEA by ABC-peroxidase staining. Levels of tumor markers decreased after operation. However, CEA levels rose again and lymph node metastases appeared. She died 6 months after operation.

Biomarkers, Tumor↗