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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 433 records · Page 24Linked to original sources

Th2 suppressor cells are more susceptible to sphingosine than Th1 cells in murine contact photosensitivity.

Murine contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) is a cutaneous delayed-type hypersensitivity reaction in which both positive and negative regulatory pathways exist. The latter pathway is mediated by antigen-specific, CD4+ suppressor T cells (CPS-Ts) that are Th2 cells. We examined the effects of sphingosine and synthetic cell-permeable analogs of ceramide on the cellular kinetics of CPS-Ts and immune lymph node cells from TCSA-photosensitized mice (CPS-LNC), along with other murine T-cell populations. The addition of sphingosine at 10 or 3 microM to in vitro cultures suppressed DNA synthesis of CPS-Ts and Th2 clones, including D10 cells and 24-2 cells, but not that of CPS-LNC or Thl clones, including 23-1-8 and 28-4 cells. This suggested that sphingosine exerts its inhibitory effects preferentially on the proliferation of Th2 cells. Although suppressing DNA synthesis, sphingosine augmented the production and mRNA expression of interleukin-4 (IL-4) and enhanced the expression of the IL-4 receptor in CPS-Ts. In addition, the ability of sphingosine to induce signal transduction of CPS-Ts was confirmed by elevation of the intracellular free Ca++ concentration. Because CPS-Ts exposed to sphingosine exhibited a lower G2M/G1 ratio than control, these seemingly ambivalent phenomena may be caused by retardation of the G1 to S phase progression, a cell-cycle dysregulation known to augment cytokine production. In contrast to sphingosine, cell-permeable ceramide did not affect the proliferation of these cells when stimulated with mitogen/antigen and did not augment IL-4 production by CPS-Ts. Our study suggests that sphingosine modifies the Th1/Th2 balance by preferentially affecting the cellular kinetics of Th2.

Allergens↗

Inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on cultured normal human keratinocytes: possible involvement of ceramide in biologic action of IFN-gamma.

To elucidate the participation of sphingosine and ceramide in the biologic action of cytokines on epidermal keratinocytes, we studied whether inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on cultured normal human keratinocytes. Pretreatment of keratinocytes with L-cycloserine or fumonisin B1, but not 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), significantly suppressed both ICAM-1 and HLA-DR expression induced by IFN-gamma. Because the synthesis of all kinds of sphingolipids is blocked by L-cycloserine and all except that of sphinganine by fumonisin B1, whereas PDMP inhibits the synthesis of glucosylceramide and glycosphingolipids, the result suggests the participation of ceramide and/or sphingosine in IFN-gamma-induced ICAM-1 and HLA-DR expression. Exogenous C2-ceramide reversed the effects of L-cycloserine and fumonisin B1. On the other hand, sphingosine reversed the effect of L-cycloserine, but not of fumonisin B1. These results indicate that ceramide participates in this pathway, as fumonisin B1, but not L-cycloserine, inhibits the synthesis of ceramide from sphingosine. In addition, reverse transcriptase polymerase chain reaction showed that L-cycloserine reduced the mRNA for ICAM-1, HLA-DR alpha, and HLA-DR beta induced by IFN-gamma, and C2-ceramide and sphingosine antagonized the effect of L-cycloserine. Furthermore, the degradation rate of fluorescent sphingomyelin into ceramide in keratinocytes was increased by IFN-gamma, suggesting that IFN-gamma activates sphingomyelin hydrolysis in keratinocytes. These observations suggest the possible role of ceramide in IFN-gamma-induced ICAM-1 and HLA-DR expression on keratinocytes. Ceramide may function as an endogenous modulator mediating the cytokine signals in keratinocytes.

Base Sequence↗

Bladder cancer producing granulocyte colony-stimulating factor: a case report.

A rare case of bladder cancer producing granulocyte colony-stimulating factor (G-CSF) is reported. A 63-year-old man with a progressive, grade 3 transitional cell bladder carcinoma, showed marked leukocytosis (maximum 181,800/mm3) and an elevated serum G-CSF to 131.7 pg/mL. After radical cystectomy and neoadjuvant chemotherapy, the tumor recurred locally. Immunohistochemical examination with monoclonal antibody specific for G-CSF revealed positive staining in the local recurrent tumor. To our knowledge, there have been only seven cases reported of bladder cancer producing G-CSF.

Carcinoma, Transitional Cell↗

A new magnetically suspended centrifugal pump: in vitro and preliminary in vivo assessment.

To overcome problems derived from the shaft within the conventional centrifugal pump, we have been developing a new centrifugal pump, namely a magnetically suspended centrifugal pump (MSCP), which has no shaft and operates as a noncontacting and bearingless pump. The impeller is suspended magnetically between the magnetic bearing and the driving motor. Hemolysis tests were performed in comparison with the Biopump (BP80, BioMedicus). The index of hemolysis (IH) was significantly lower in the MSCP than in the Biopump. In addition, a smaller gap in the MSCP induced lower hemolysis. In preliminary studies using mongrel dogs, the layer of thrombus adherent to the impeller was observed in a few hours, which impaired the pumping efficiency. However, by using an impeller coated with silicone, no aggregations of platelets or fibrin on the impeller were observed in 24 h of continuous pumping. In conclusion, the MSCP had a gentler influence on blood cells than the Biopump, and the impeller coated with silicone may contribute to the long-term pumping of the MSCP.

Animals↗

Ubiquinone systems of the genus Cladosporium and morphologically similar taxa.

The ubiquinone (coenzyme Q) systems of 14 species of Cladosporium were determined. The genus was divided into two groups based on the distribution of the major ubiquinones, Q-10 and Q-10(H2). The group containing Q-10 consisted of six species, four of which were human pathogens, whereas the group containing Q-10(H2) consisted of eight plant pathogenic and/or saprophytic species. The results presented here agree with phylogenetic and physiological studies which have shown that the human-pathogenic species of Cladosporium represent a homogeneous, cohesive group.

Cladosporium↗

Identification of the bud emergence gene BEM4 and its interactions with rho-type GTPases in Saccharomyces cerevisiae.

The Rho-type GTPase Cdc42p is required for cell polarization and bud emergence in Saccharomyces cerevisiae. To identify genes whose functions are linked to CDC42, we screened for (i) multicopy suppressors of a Ts- cdc42 mutant, (ii) mutants that require multiple copies of CDC42 for survival, and (iii) mutations that display synthetic lethality with a partial-loss-of-function allele of CDC24, which encodes a guanine nucleotide exchange factor for Cdc42p. In all three screens, we identified a new gene, BEM4. Cells from which BEM4 was deleted were inviable at 37 degrees C. These cells became unbudded, large, and round, consistent with a model in which Bem4p acts together with Cdc42p in polarity establishment and bud emergence. In some strains, the ability of CDC42 to serve as a multicopy suppressor of the Ts- growth defect of deltabem4 cells required co-overexpression of Rho1p, which is an essential Rho-type GTPase necessary for cell wall integrity. This finding suggests that Bem4p also affects Rho1p function. Bem4p displayed two-hybrid interactions with Cdc42p, Rho1p, and two of the three other known yeast Rho-type GTPases, suggesting that Bem4p can interact with multiple Rho-type GTPases. Models for the role of Bem4p include that it serves as a chaperone or modulates the interaction of these GTPases with one or more of their targets or regulators.

Amino Acid Sequence↗

Dose response study of ipratropium bromide aerosol on maximum exercise performance in stable patients with chronic obstructive pulmonary disease.

BACKGROUND: Although the bronchodilating effect of inhaled anticholinergics has been established in patients with chronic obstructive pulmonary disease (COPD), their effects on exercise capacity are still controversial. Previous studies have suggested that the standard dosage hardly affects exercise tolerance, whereas higher doses might elicit an improvement. The aim of the present study was to determine the dose of ipratropium bromide aerosol that improves exercise performance using progressive cycle ergometry in patients with stable COPD. METHODS: Twenty men with stable COPD of mean (SD) age 69.2 (4.6) years and forced expiratory volume in one second (FEV1) 1.00 (0.37) 1 were studied in a randomised double blind manner. Each patient received ipratropium bromide in doses of 240 micrograms, 160 micrograms, 80 micrograms, 40 micrograms, and placebo from a metered dose inhaler (MDI) with an InspirEase spacer on five separate days. Spirometric parameters were assessed before and at 30, 60, 90, and 120 minutes after each inhalation, and pulse rate and blood pressure were also measured immediately before each spirometric measurement. Symptom limited progressive (20 watts/min) cycle ergometer exercise tests were performed 90 minutes after each inhalation. RESULTS: Ipratropium bromide in doses of 160 micrograms and 240 micrograms produced a greater increase in FEV1 than 40 micrograms or 80 micrograms ipratropium bromide at all time points. Doses of 160 micrograms and 240 micrograms ipratropium bromide also produced greater increases in maximal work load and maximal oxygen consumption than placebo, whereas 40 micrograms and 80 micrograms ipratropium bromide did not. There was a weak correlation between the change in FEV1 and the change in maximal work load (r = 0.45). No differences were found in pulse rate or blood pressure between the treatment and placebo groups, and no side effects were noted throughout the study. CONCLUSIONS: A dose of at least four times the standard dose of ipratropium bromide from an MDI with a spacer device was necessary to improve maximal cycle exercise capacity in patients with stable COPD. Although the data from cycle ergometry cannot be directly applied to exercise performed during day to day activities, it is conceivable that the recommended doses of ipratropium bromide do not elicit the optimal clinical benefits.

Aerosols↗

Erythropoietin-producing adrenocortical carcinoma.

A 62-year-old Japanese male with an erythropoietin-producing adrenocortical carcinoma is presented. The elevated erythropoietin level and erythrocytosis returned to normal after surgical removal of a huge left adrenal tumor weighing 1,580 g. A histopathological diagnosis of adrenocortical carcinoma was made. Despite adjuvant combined chemotherapy, the patient died of lung and liver metastases 3.5 months after operation. Although the possibility that the elevated plasma erythropoietin level and erythrocytosis resulted from local kidney hypoxia, caused by pressure from the huge adrenal tumor, cannot be completely neglected, the positive cytoplasmatic evidence of immunoreactive erythropoietin in the carcinoma cells and the detection of a high erythropoietin level in the tumor extract on radioimmunoassay confirmed that this is a very rare case of erythropoietin-producing adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

Mucinous adenocarcinoma of the male urethra.

We report a case of primary mucinous adenocarcinoma arising in the bulbomembranous urethra. The patient underwent radical cystectomy and total penectomy, followed by systemic chemotherapy. Metastases in lungs, skin, and lymph nodes (inguinal, iliac, para-aortic, and tracheobronchial) were found within 2 months after operation. We reviewed 37 cases of primary adenocarcinomas of the male urethra.

Adenocarcinoma, Mucinous↗

Physiologic factors that determine the health-related quality of life in patients with COPD.

STUDY OBJECTIVE: To determine the physiologic factors that influence the health-related quality of life (HRQL) in patients with stable COPD and to identify the factors that most influence HRQL. METHODS: The Nottingham Health Profile (NHP) was used as a general HRQL measure and the Chronic Respiratory Disease Questionnaire (CRQ) was used as a disease-specific HRQL measure to investigate 132 patients with stable COPD, and measurements of HRQL were compared with physiologic measures. RESULTS: Vital capacity, FEV1, the ratio of the FEV1 to the FVC, diffusion capacity for carbon monoxide, diffusion capacity corrected for alveolar volume, lifetime cigarette consumption expressed as pack-years, and age were weakly correlated with several dimensions of both the NHP and the CRQ. Factor analysis reduced these variables to three factors. Two factors mainly referring to airflow limitation and diffusing capacity were weakly correlated with several dimensions of both the NHP and the CRQ. Logistic regression analysis identified 4 independent predictors of HRQL: airflow limitation (odds ratio [OR] = 0.59 to 0.69), diffusing capacity (OR = 0.75 to 0.82), pack-years (OR = 1.20 to 1.23), and age (OR = 2.13). The CRQ was more sensitive to impairment of HRQL than the NHP. CONCLUSIONS: The HRQL of patients with stable COPD is partly determined by airflow limitation, diffusing capacity, pack-years, and age. However, these factors could not predict the whole spectrum of HRQL, and the contribution of these factors to HRQL was limited. Therefore, HRQL should be measured directly in addition to physiologic measures.

Aged↗

Captopril, an angiotensin-converting enzyme inhibitor, induced pulmonary infiltration with eosinophilia.

In this study, we investigated the association between the drug-induced pulmonary infiltration with eosinophilia (PIE) syndrome in a patient with hypertension and the angiotensin-converting enzyme inhibitor (ACE-I) captopril. Although the patient developed diffuse lung field infiltrates accompanied by productive cough and striking peripheral eosinophilia, these symptoms disappeared after termination of the administration of captopril, pronase and cephalexine. Furthermore, the results of the peripheral lymphocyte stimulation test, skin patch test and provocation test under informed consent showed a positive reaction only for captopril. Therefore, this patient was diagnosed as captopril-induced PIE syndrome.

Angiotensin-Converting Enzyme Inhibitors↗

Histopathology of paracoccidioidomycotic infection in athymic and euthymic mice: a sequential study.

We report the comparative and sequential histologic analysis of lesions developed by Paracoccidioides brasiliensis-infected athymic and euthymic BALB/c mice, using conventional and specific stain to characterize the morphology of fungi and inflammatory cells as well as the extracellular matrix patterns. In both groups, neutrophils and macrophages were the predominant cells; macrophage transition to giant and epithelioid cells was observed. Degenerated fungi and fungal dust were associated with local neutropil infiltration and the presence of pseudoxantomatous macrophages. Paracoccidioides brasiliensis are always found within an extracellular matrix microenvironment. The main differences between lesions developed by nu/+ and nude (nu/nu) mice resided in the more pronounced encapsulating tendency in the former ones. In both groups of animals, lesions in several organs were associated with extensive hemopoiesis. At the first week of infection, there was evidence of fungal destruction and control of its proliferation in both mouse groups. At the fourth and seventh weeks, nu/+ mice maintained the control of the infection, as shown by the scarce numbers of budding yeast cells, while experimental nu/nu mice showed a tumor-like progression of the disease with a striking increase in fungal load in many organs (e.g., omental and mesenteric milky spots, lymph nodes, spleen), some of which present their structure replaced by granulomatous lesions.

Animals↗

Paracoccidioides brasiliensis infection in nude mice: studies with isolates differing in virulence and definition of their T cell-dependent and T cell-independent components.

Athymic and euthymic BALB/c mice infected with highly (Pb18) or slightly (Pb265) virulent Paracoccidioides brasiliensis isolates were compared regarding mortality, presence of viable yeasts, specific immunoglobulin M (IgM) and IgG titers, and the antigen recognition patterns of these antibodies. Isolate Pb18 caused a more severe disease in athymic mice, as supported by higher number of infected organs and shorter survival times. These animals, however, were resistant to Pb265 infection. High titers of antibodies were found only in euthymic mice, seven weeks after Pb18 infection. At this time, euthymic animals presented IgG antibodies to numerous protein bands that were not detected at four weeks postinfection or after Pb265 inoculation. In contrast, antibodies from athymic mice always reacted with few antigen bands. Although the majority of P. brasiliensis antigens are T cell-dependent, the immunodominant gp43 and also the 41.5- and 27.5-kD antigens are here, for the first time, characterized as T cell-independent antigens of P. brasiliensis.

Animals↗

Long-term followup of patients with tumor thrombi from renal cell carcinoma and total replacement of the inferior vena cava using an expanded polytetrafluoroethylene tubular graft.

PURPOSE: Inferior vena caval resection and its reconstruction are sometimes necessary when the inferior vena cava is extensively involved by a large and fixed tumor thrombus from renal cell carcinoma or other malignancies. We successfully replaced the inferior vena cava using tubular expanded polytetrafluoroethylene (Teflon) vascular grafts after en bloc removal of the tumor thrombus and inferior vena cava. We followed the patients long term and observed inferior vena caval patency. MATERIALS AND METHODS: The 3 men and 2 women ranged from 42 to 75 years old. The renal tumors were on the right side in 4 patients and asynchronously bilateral in 1. The suprarenal inferior vena cava was replaced in 3 patients and the infrarenal portion was replaced in 2. The expanded polytetrafluoroethylene tube grafts, 18 to 22 mm. in diameter and 5 to 12 cm. long, were externally stented in 3 patients and not stented in 2. RESULTS: Followup ranged from 6 to 96 months (mean 58). Long-term patency of the graft was maintained in all patients. Of the patients 3 had no evidence of disease at 6 months and 2 died of recurrent tumor at 6 and 84 months. CONCLUSIONS: Total replacement of the inferior vena cava using an expanded polytetrafluoroethylene tubular graft may offer a feasible method with good patency rates in the long term.

Adult↗

A case of Trichuris trichiura infection diagnosed by colonoscopy.

A 65-year-old Japanese female was admitted to our hospital because of right lower abdominal pain. Laboratory and roentgenological tests revealed no abnormalities. Repeated stool examinations revealed no ovum or parasite. However, colonoscopic examination demonstrated the presence of a parasite on the edematous mucosa of cecum. The adult male whipworm (Trichuris trichiura) was then removed endoscopically. Her symptoms disappeared quickly, and no additional parasite was found in the feces during or after the mebendazole treatment. Repeated stool examinations failed to show any ova, because this patient was infected by a single male parasite. Colonoscopic study should be considered a useful tool for the diagnosis of T. trichiura infection, even if no ovum is found in stool examination.

Aged↗

[Temporal modulation transfer function in normal-tension glaucoma patients].

In an attempt to detect patients in an early stage of glaucoma, a new screening test, the Flicker System, by which temporal modulation transfer function is evaluated, was performed in 64 normal-tension glaucoma patients and 65 normal eyes. The early stage of glaucoma, i.e., stage 0-1 of Aulhorn-Greve's classification, showed a significant decrease of the modulation in the range from 20 to 45 Hz in comparison with normal eyes (p value < 0.05). The moderate stage of glaucoma of stages 2-3 also revealed significantly decreased values of the modulation in the range from 14 to 55 Hz. In the range from 25 to 45 Hz, the reduction of modulation in the glaucoma with diffuse visual defect was more profound than in glaucoma with localized or mixed defects. The results seem to be compatible with the presence of diffuse visual function deficit in glaucoma.

Adult↗