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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 541 records · Page 30Linked to original sources

Functional disturbance of naive T lymphocytes in very high IgE producers: depletion of interleukin-4-induced interleukin-4-producing cells.

We examined the capacity of T cells from normal individuals and allergic patients with very high IgE to differentiate into interleukin-4(IL-4)-producing cells in vitro. T cells incubated with anti-CD3 monoclonal antibody plus IL-4 or plus anti-IL-4 antibody in the presence of antigen-presenting cells for 7 days were restimulated and their capacity to express IL-4 mRNA was examined by RT-PCR. In T cells from normal individuals, there was a marked increase in the expression of IL-4 mRNA following the addition of IL-4. After fractionation of normal T cells into naive T (CD45RA+) and memory T (CD45RO+) cells, induction of the increase of IL-4 mRNA was restricted to the naive T cell population. In contrast, in T cells from allergic patients, the stimulation of whole or naive T cells with anti-CD 3 monoclonal antibody in the presence of IL-4 induced much less IL-4 mRNA. These findings suggest the presence of a functional abnormality in IL-4-dependent development of IL-4-producing T cells in the peripheral-blood naive T cells from allergic patients.

Adjuvants, Immunologic↗

Peripheral blood T lymphocytes and basophils, freshly isolated from house-dust-mite-sensitive patients, produce interleukin-4 in response to allergen-specific stimulation.

We examined the capacity of interleukin-4 (IL) production from lymphocytes and basophils, isolated from the peripheral blood of allergic patients sensitive to house dust mite, after stimulation with mite extract. IL-4 production was measured by a sensitive bioassay based on coculture with CT.h4S (a human IL-4-responsive cell line). Lymphocytes and basophils from patients with elevated serum IgE specific to mite allergen [radioallergosorbent test (RAST) score > 3] could produce detectable levels of IL-4 in response to mite extract, whereas those from patients with a RAST score of less than 2 or normal volunteers could not. The sensitivity of basophils to mite extract was high, so that a lower concentration of mite extract (1-10 ng/ml) could induce maximal IL-4 production. On the other hand, a higher concentration (10 micrograms/ml) was required for maximal IL-4 production from the lymphocytes. These findings demonstrate that allergen-specific IL-4-producing cells, lymphocytes and basophils, are generated in vivo in allergic patients and also that there exist characteristic differences between lymphocytes and basophils related to the in vivo source of IL-4.

Allergens↗

Monkey Clara cell 10 kDa protein (CC10): a characterization of the amino acid sequence with an evolutional comparison with humans, rabbits, rats, and mice.

Monkey Clara cell 10 kDa protein (CC10) was purified from monkey lung lavage. This protein showed an apparent molecular weight of about 10 kDa and 5 kDa under non-reducing and reducing conditions, respectively, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From the amino acid sequence data, monkey CC10 protein consisted of two identical 70-amino-acid polypeptide chains joined by two cystine residues, and possessed sequence identities of 78.6%, 52.9%, 52.9%, and 44.3% with human CC10, rat CC10 (PCB binding protein), rabbit uteroglobin, and mouse CC10, respectively. When monkey CC10 was compared with rabbit uteroglobin (progesterone binding protein), two polar residues of Tyr-21 and Thr-60, important for progesterone binding specificity, were substituted for Phe-21 and Met-60, and thus monkey CC10 may not have a binding capacity with progesterone. Monkey CC10 also possessed a surface homology with lipocortin I (anti-inflammatory peptide), thus suggesting that monkey CC10 plays a role in the anti-inflammatory process at the air-liquid interface over the bronchio-bronchiolar epithelium.

Amino Acids↗

Differential expression of gap junction proteins connexin32 and 43 in rat submandibular and sublingual glands.

We examined the expression and localization of the gap junction proteins connexin32 and 43 in rat submandibular and sublingual glands. Western blot analysis with anti-connexin32 and 43 antibodies showed bands of approximately 27 KD and 43 KD, respectively, in both glands. Immunofluorescence microscopy demonstrated the presence of reactive spots for connexin32 between acinar cells in both glands. The frequency of connexin32-positive spots in the submandibular glands was approximately equal to that in the sublingual glands. In contrast, reactive spots for connexin43 were observed at the periphery of the alveolar structures in both glands. The connexin43-positive spots in the sublingual glands were more frequent and larger than those in the submandibular glands. No positive spots for both connexins were detected between duct cells in either gland. Immunoelectron microscopy revealed that connexin32 was localized to the gap junctional membranes between acinar cells. Immunolabeling for connexin43 was located on the gap junctions between thin processes of myoepithelial cells. These results suggest that connexin32 of the gap junction is associated with regulation of the secretory function of acinar cells and that connexin43 is associated with that of contraction of the myoepithelial cells in rat salivary glands.

Animals↗

Induction therapy with all-trans retinoic acid for acute promyelocytic leukemia: a clinical study of 10 cases, including a fatal [correction of fetal] case with thromboembolism.

Ten patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Eight of 10 patients achieved complete remission (CR), and among the 8 newly diagnosed cases, 7 achieved CR. Five of 8 CR cases remained in CR after 8 to 30 months. Except for hypotension and a large gastric ulcer resulting from hyperhistaminemia, the adverse effects of ATRA were generally mild. Severe thrombotic tendency occurred in a patient treated with ATRA combined with tranexamic acid. Intensive chemotherapy consisting of daunorubicin (DNR) and other agents was scheduled for the patients who achieved CR with ATRA.

Adult↗

Empyema following the percutaneous instillation of antifungal agents in patients with aspergillosis.

We report two cases of empyema as a complication of the percutaneous instillation of antifungal drugs for pulmonary and pleural aspergillosis. Case 1 underwent percutaneous administration of amphotericin B and fluconazole for 2 months. Six months later, the patient was found to have an Aspergillus empyema with a bronchopleural fistula. Case 2 with pulmonary and pleural aspergillosis underwent percutaneous administration of amphotericin B for one month. Four months later, the patient underwent pleural drainage due to empyema. Pleural biopsy revealed pleural aspergillosis. In both cases, it was suggested that the preceding Aspergillus infection and percutaneous instillation of antifungals resulted in the development of empyema.

Aged↗

Restriction fragment length polymorphism analysis in the HLA class III genes of patients with diffuse panbronchiolitis.

Although diffuse panbronchiolitis (DPB) is known to be positively associated with certain major histocompatibility complex (MHC) class I antigens, e.g., HLA-B54 in Japanese patients, it is not clear whether the MHC genes predispose to the disease or are markers for other disease susceptibility gene(s). Because the HLA class III genes such as tumor necrosis factor (TNF) or the fourth component of complement (C4) are localized in the proximity of the HLA-B locus, one or more of these genes might be responsible for susceptibility to DPB. To analyze the role of HLA class III genes in DPB patients, we first evaluated the HLA-B54 association in 32 patients with DPB, and subsequently, studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta (TNF-alpha/beta) genes as well as the C4A and B (C4A/B) genes in DPB patients and normal individuals. The HLA-B54 antigen was significantly more frequent in DPB patients than in normal individuals (40.3% vs 13.0%, p < 0.001), however, we did not detect a significant association between DPB and gene polymorphisms of either TNF-alpha/beta or C4A/B. Furthermore, there was no evidence of C4A gene deletion in patients with DPB. These results suggest that the HLA-B54 antigen itself might be directly involved in the pathogenesis of DPB.

Bronchiolitis↗

[A case of acquired immunodeficiency syndrome associated with cryptococcemia and cryptococcal meningitis].

A case of acquired immunodeficiency syndrome (AIDS) developed cryptococcosis which was successfully treated with amphotericin B (AMPH) and fluconazole (FLCZ) is reported. A 52-year-old man was admitted because of pyrexia and oral candidiasis. He had a history of multiple sexual exposures to persons at risk for AIDS in Thailand. On admission, serologic tests for human immunodeficiency virus (HIV)-1 were positive on both EIA and Western blot analysis for anti-HIV-1 antibody. Furthermore, test for cryptococcal antigen and fungal cultures from blood and cerebrospinal fluid revealed that he was suffering from cryptococcemia and cryptococcal meningitis. In spite of identification of Cryptococcus neoformans in his blood and cerebrospinal fluid, the finding of cerebrospinal fluid had a minimal inflammatory response with mild elevation of protein. He was initially treated with intravenous AMPH, 10 to 30 mg a day, for 7 weeks, and then was given oral FLCZ, 400 mg a day, for the suppressive therapy. His fever subsided three weeks after the start of AMPH therapy. He was eventually discharged 9 weeks after the start of therapy without any symptoms, and continued to receive oral FLCZ as an out-patient. Thus, attention should be paid to diagnosis and treatment for cryptococcal meningitis in AIDS patients.

AIDS-Related Opportunistic Infections↗

[Role of serum E-selectin (ELAM-1) and inflammatory parameters in patients with renal cell carcinoma].

(BACKGROUND). E-selectin is an adhesion molecule expressed on IL-1 activated endothelial cells and it binds to carbohydrate ligands such as sialy Lewis A antigen (SLeA) or Lewis X antigen (SLeX) on cancer cells. This mechanism is supposed to play an important role during hematogenous metastasis. Some of renal cell carcinomas (RCC) are known to produce inflammatory cytokines such as IL-1 beta and IL-6 and clinical evidence shows that the prognosis of this type of tumor is generally poor. We investigated whether this adhesion molecule was involved in hematogenous metastasis. (METHOD). In the present study, soluble E-selectin level was measured in the sera of 89 patients with RCC prior to nephrectomy or IFN treatment using sanwich ELISA method. (RESULTS). The results indicated that high E-selectin concentration in the patients' sera was correlated with low incidence of metastasis and consequently correlated with good prognosis of RCC patients. Inflammatory serum parameters, such as serum C reactive protein (CRP), immunosuppressive acid protein (IAP) and erythrocyte sediment rate (ESR) were also assessed and these parameters were revealed to be negatively correlated with the serum level of E-selectin. In order to investigate this mechanism, we performed in vitro study on RCC cell/endothelial cell adhesion. IL-1 beta enhanced adhesion of 2 RCC cell lines and this adhesion was partially inhibited by adding exogenous E-selectin into the culture medium. Expression of SLeA and SLeX were demonstrated on the cell surface of 2 RCC cell lines by flowcytometric analysis. (CONCLUSION). The results suggested that E-selectin and SLeX/SLeA interaction was involved in the adhesion between RCC and endothelial cells and also inflammatory cytokine production by RCC cells was a risk factor for metastasis through E-selectin induction. Although expression of E-selectin on endothelial cells facilitates metastasis, excessive production of E-selectin into the serum was suggested to have inhibitory effect against metastasis.

Aged↗

The angiotensin receptor antagonist 2-ethoxy-1-[[2'-(1H- tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV11974) attenuates the tubuloglomerular feedback response during NO synthase blockade in rats.

Nitric oxide (NO) produced in the juxtaglomerular apparatus may regulate the tubuloglomerular feedback (TGF) response. The inhibition of intrinsic NO results in significant renal hemodynamic changes, a phenomenon similar to that observed after angiotensin II (A-II) administration. We measured stop-flow pressure (Psf) during loop perfusion with artificial tubular fluid in Sprague-Dawley rats to establish whether alterations in TGF responsiveness during NO inhibition depend on the action of endogenous A-II. The NO synthase blocker N omega-nitro-L-arginine-methyl-ester (L-NAME: 10 mg/kg i.v.) significant increased TGF responsiveness, defined as the change in Psf on increasing loop flow from 0 to 40 nl/min compared with control (delta Psf: -21.3 +/- 2.6 vs. -9.7 +/- 0.6 mm Hg, P < .001). After concomitant treatment with the nonpeptide A-II type 1 receptor antagonist 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxic acid (CV11974: 1 mg/kg i.v.) and L-NAME, the TGF response was attenuated significantly (delta Psf: -7.6 +/- 1.9 mm Hg, P < .001). On the other hand, Psf in the absence of loop perfusion was increased similarly by L-NAME treatment in the presence (53.7 +/- 2.2 mm Hg) or absence of CV11974 (Psf 50.7 +/- 3.2 mm Hg). These results suggest that augmentation of the TGF response by endogenous NO inhibition depends, at least in part, on the intrinsic A-II activity.

Angiotensin II↗

Macrophage colony-stimulating factor induces interleukin-8 production in human monocytes.

We have investigated the stimulatory effect of recombinant human macrophage colony-stimulating factor (rhM-CSF) on interleukin-8 (IL-8) production by human peripheral blood monocytes. When monocytes were prepared from peripheral blood and cultured for 24 hours, the average amount of IL-8 in the culture medium was about 8.9 +/- 3.2 ng/2 x 10(5) cells. In contrast, the production of IL-8 by monocytes increased to a level of 19.2 +/- 4.7 ng/2 x 10(5) cells in response to rhM-CSF. This induction by rhM-CSF was dose-dependent. Northern blot analysis showed that expression of IL-8 at the pretranslational level was enhanced after M-CSF treatment. Kinetic studies showed that secretion of IL-8 from monocytes was enhanced within 2 hours after exposure to rhM-CSF, and a saturation level, which was reached around 48 hours, was two-fold higher than that of cells without M-CSF treatment. In addition, conditioned medium of M-CSF-stimulated monocytes activated the chemotaxis of human neutrophils, and this activity was significantly inhibited by anti-IL-8 antibody. These results, taken together, suggest that M-CSF can affect many cellular functions through regulation of IL-8 expression in monocytes.

Animals↗

Profile of cell cycle in hematopoietic malignancy by DNA/RNA quantitation using 7AAD/PY.

Using 7-amino-actinomycin-D/pyronin Y (7AAD/PY), we analyzed the surface phenotypes and cell cycle of 22 hematopoietic cell lines based on their cellular DNA/RNA content. Populations of G1a, G1b, S, and G2M, the DNA index (DI), and the RNA index of S phase (SRI) were calculated by means of DNA/RNA dot plots. Two new parameters were extracted from the cell-cycle profiles: the nucleic acid index of S phase (NI) and the coefficient of variations in the RNA at S phase (SVC). DNA/RNA dot plots of cell lines revealed four characteristic profiles of the cell cycle, defined with the calculated NI and SCV. These were type 0 (small NI, large SCV), type I (small NI, small SCV), type II (large NI, small SCV), and type III (large NI, large SCV). Type O included four stem cell lines: one t(1;19) leukemia, two Ph1+ acute lymphocytic leukemia (ALL), and one biphenotypic crisis of chronic granulocytic leukemia (CGL). Type I included five ALL cell lines: three T-ALL and two common B-ALL. Type II contained 10 myeloid cell lines: five AML and five myeloid crisis of CGL. Type III contained three relatively immature lymphoma cell lines: two Burkitt's lymphoma and one follicular center lymphoma. Calculated NI/SCV (%) were as follows: type 0, 2.27 +/- 0.19/16.7 +/- 3.7; type I, 2.20 +/- 0.30/11.1 +/- 0.7; type II, 3.64 +/- 0.52/11.8 +/- 1.0; and type III, 3.60 +/- 0.53/17.5 +/- 1.9. Cell-cycle analysis of blasts using 7AAD/PY combined with surface phenotyping may yield important information for classifying hematopoietic malignancy within 2 hours of patient admission.

Antigens, CD↗

[DNA strand breaks in epithelial cells from mice with bleomycin induced pulmonary fibrosis].

Bleomycin-induced cytotoxicity is believed to be caused by single- and double-strand DNA breaks. To examine the effect of bleomycin on DNA strand breaks and the role of these breaks in bleomycin induced pulmonary fibrosis in mice, we analyzed DNA strand breaks in situ by TdT-mediated dUTP-biotin nick end labeling (TUNEL), previously described by Gavrieli et al. The nuclei of bronchiolar epithelial cells were strongly stained 1 hr to 12 hr after bleomycin administration, and after that period DNA damage was repaired. Nuclei of alveolar epithelial cells showed positive signals correlated with progression of fibrosis. Although corticosteroids did not block the early DNA damage in bronchiolar epithelial cells, they did inhibit later damage to alveolar epithelial cells and fibrosis. We speculate that the DNA damage in alveolar epithelial cells and the progression of fibrosis in later stages are associated with inflammatory cytokines. These findings show the location and the time course of the DNA damage in bleomycin-induced pneumonitis in mice, and they indicate that the prolongation of DNA damage in alveolar epithelial cells is closely related to fibrinogenesis.

Animals↗

[Swyer-James syndrome with bronchial asthma and recurrent spontaneous pneumothorax].

An 18-year-old woman was admitted to our hospital for treatment of the fifth episode of spontaneous pneumothorax. She had a history of repeated pneumonia in childhood and mycoplasma pneumonia at 12 years of age. A chest X-ray film revealed a left-sided pneumothorax, atelectasis of the left upper lobe, and hyperlucency of the left lung. A bronchogram showed poor filling of the peripheral bronchi by contrast medium and mild cylindrical bronchiectasis in the proximal bronchi. Pulmonary arteriography showed small left pulmonary arteries. From these findings, Swyer-James syndrome was diagnosed. This case was complicated by bronchial asthma, with eosinophilia, a high level of IgE, and airway hyperresponsiveness. Atelectasis, multiple bullae, and bronchial asthma had been caused by mycoplasma pneumonia in childhood. Recurrent pneumothorax had been caused by emphysematous changes in the bronchioli and by underdeveloped pulmonary arteries. Surgery to treat the recurrent spontaneous pneumothorax was considered, but was not done because of the risk of relapse and the ventilation-perfusion imbalance due to the Swyer-James syndrome.

Adolescent↗

[Detection of apoptosis and expression of Fas antigen in human colorectal cancer].

The occurrence of apoptosis in formalin-fixed, paraffin-embedded human colorectal cancer tissues was investigated at a cellular level by in situ nick translation (ISNT). Then the frequency of ISNT-positive nuclei was compared with the proliferative activity assessed by proliferating cell nuclear antigen (PCNA) labeling index, and with the incidence of Fas positive cells examined immunohistochemically with the incidence of Fas positive cells examined immunohistochemically with rabbit anti-Fas serum. As a result, although no significant correlation between the frequency of apoptosis and the proliferative activity was observed, a balance between them may explain a variety of growth rates of colorectal cancers. As for Fas expression, about 33% of the colorectal cancers were more or less positive for Fas antigen.

Animals↗

[A case of leiomyomatosis in pelvic lymph nodes].

We report a rare case of leiomyomatosis in iliac lymph nodes, which was found in a woman operated with a diagnosis as keratinizing epidermoid carcinoma of the cervix. A 39-year-old Japanese female, married, who had received hormonal therapy in her past history, visited the Department of Obstetrics and Gynecology at Kinki University Hospital, with a chief complaint of bloody discharge. Colposcopy and biopsy suggested a diagnosis of keratinizing epidermoid carcinoma of the cervix. A radical hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph nodes dissection was performed. Histopathological examination showed a keratinizing epidermoid carcinoma of the cervix. An intramural leiomyoma nodule (0.5cm in diameter) was detected in the fundus of the uterus. Histopathologically, this was a typical benign leiomyoma. The lymph nodes were free of neoplasms. But bilateral iliac lymph nodes were enlarged up to soybean size. Microscopically, the iliac lymph nodes contained a large amount of well differentiated smooth muscle tissue (11/30). Immunohistochemical investigation showed a positive reaction for smooth muscle actin and desmins in the spindle cells proliferated in the lymph nodes; no cytokeratin positivity was detected. Leiomyomatosis of lymph node may rise through metaplasia of intranodal decidua or endometriosis by myofibroblasts or smooth muscle cells, reflecting the multipotentiality of the pelvic subcoelomic mesenchyme that can be found in the peripheral sinus of lymph nodes.

Adenocarcinoma, Papillary↗

Superficial siderosis--a cause of audiovestibular failure.

Bilateral vestibular end organ failure in adult life is a rare condition with some specific known causes, such as relapsing polychondritis, autoimmune inner ear disease, Lues venerium, and an acute effect of gentamicin. This case report draws attention to a rare condition that is potentially recognizable early in its development. The patient has superficial siderosis, which is iron deposits over the cerebrum, resulting in progressive neurologic failure involving all of the systems. Early in its course before other symptoms appear, there is development of progressive hearing loss and vestibular failure. This case report and literature review are given, including a potential for attempts at therapy if the disorder is recognized early.

Brain Diseases↗