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Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 253 records · Page 14Linked to original sources

Pathogenetic role of monoamine metabolism in complex febrile seizures.

To investigate the pathogenetic role of monoamine metabolism for febrile seizures, concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were evaluated in the lumbar cerebrospinal fluid of affected children. This series included children who underwent lumbar puncture within 4 hours after seizures, at which time the lumbar cerebrospinal fluid is presumed to represent a ventricular source of cerebrospinal fluid, without the consequence of a seizure. The subjects were 21 patients with simple febrile seizures, eight with complex febrile seizures, and eight control patients. The complex febrile seizure group had lower homovanillic acid and 5-hydroxyindoleacetic acid levels than the control group, whereas the simple febrile seizure group and control group did not have a significant difference. Although statistically not significant, the complex febrile seizure group was inclined toward lower homovanillic acid and 5-hydroxyindoleacetic acid levels than the simple febrile seizure group. These results implied that abnormal monoamine metabolism contributes to seizure susceptibility in the complex febrile seizure group. The simple febrile seizure group may be heterogeneous, and abnormal monoamine metabolism can play a role in seizure development for some children of this group.

Age Factors↗

Activity-guided isolation of triterpenoid acyl CoA cholesteryl acyl transferase (ACAT) inhibitors from Ilex kudincha.

Activity-guided fractionation of a methanol extract of the leaves of Ilex kudincha led to the isolation of seven acyl CoA cholesteryl acyl transferase (ACAT) inhibitory triterpenes. Four of them were identified by spectroscopic methods as ulmoidol (4), 23-hydroxyursolic acid (5), 27-trans-p-coumaroyloxyursolic acid (6), and 27-cis-p-coumaroyloxyursolic acid (7), and three were new compounds named ilekudinols A-C (1-3). The structures of these new triterpenoids were elucidated as 2alpha, 3beta-dihydroxy-24-nor-urs-4(23),11-dien-28,13beta- olide (1), 2alpha, 3beta-dihydroxy-24-nor-urs-4(23),12-dien-28-oic acid (2), and 3beta, 24,28-trihydroxylupane (3). Compounds 1-7 showed potent inhibitory activity in the ACAT assay.

China↗

Triterpenoid saponins from Ilex kudincha.

Ten new triterpene saponins, ilekudinosides A-J (2, 6-8, 10, 13-17), together with seven known triterpene saponins, ilexoside XLVIII (1); cynarasaponin C (5); latifolosides A (9), C (3), G (12), and H (4); and kudinoside G (11), were isolated from an aqueous extract of the leaves of Ilex kudincha. They possessed oleanane- and ursane-type triterpenoids as the aglycons. The structures were elucidated by 1D and 2D NMR experiments, including ROE difference, HOHAHA difference, 1H-1H COSY, and 1H-13C COSY (HMQC, HMBC) methods and sugar analysis. Compounds 1 and 5 exhibited acyl CoA cholesteryl acyl transferase (ACAT) inhibitory activity.

Carbohydrate Sequence↗

Identification and genetic homogeneity of Trichophyton tonsurans isolated from several regions by random amplified polymorphic DNA.

Trichophyton tonsurans is an anthropophilic dermatophyte mostly causing tinea capitis and tinea corporis. This study was carried out to identify T. tonsurans and to clarify whether it has any genetic differences depending on the phenotype or region of isolation by random amplified polymorphic DNA (RAPD) analysis with three random primers. The assay was performed in 11 Korean, 2 Japanese, 2 Taiwanese, 5 Brazilian and 1 American isolates of T. tonsurans together with the other 10 anamorphic species of dermatophytes and 3 Arthroderma spp. All tested species of dermatophytes showed distinct bands and T. tonsurans was differentiated from other dermatophytes. It was most clearly differentiated from T. mentagrophytes by using primer 5'-GAAGGCTCCC-3' (OPAO-15). No difference was found in RAPD band patterns in all strains of T. tonsurans with these random primers. It was considered that T. tonsurans is a genetically homogeneous species regardless of its isolation regions, morphologic or physiologic characteristics.

DNA, Fungal↗

Mitochondrial DNA analysis of Exophiala jeanselmei var. lecanii-corni and Exophiala castellanii.

A Japanese clinical isolate (KU-A-0094) which was identified by de Hoog et al. as Exophiala jeanselmei var. lecanii-corni with difficulty, was compared with 5 strains including the type cultures of E. jeanselmei var. lecanii-corni, var. jeanselmei and E. castellanii using RFLP (restriction fragment length polymorphism) patterns of mtDNA (mitochondrial DNA). RFLP patterns of KUA-0094 were identical with those of E. jeanselmei var. lecanii-corni and different from those of E. castellanii with restriction enzymes of HaeIII, MspI and hindIII. Therefore, de Hoog et al.'s identification of KU-A-0094 was confirmed. Additionally, mtDNA-RFLP patterns of E. jeanselmei var. lecanii-corni and E. jeanselmei var. jeanselmei were also different from each other. Consequently E. jeanselmei var. lecanii-corni seem to be a species in its own right rather than a variant of E. jeanselmei.

DNA, Fungal↗

Isolation of a new potent cytotoxic pigment along with indigotin from the pathogenic basidiomycetous fungus Schizophyllum commune.

An indole derivative, schizocommunin, was isolated along with indigotin (indigo), indirubin, isatin, and tryptanthrin, from the liquid culture medium in which a culture of Schizophyllum commune, isolated from the bronchus of a human patient with allergic bronchopulmonary mycosis, had been grown. The structure of schizocommunin was established by spectroscopic investigation. Schizocommunin showed the strong cytotoxicity against murine lymphoma cells. The assignments of the 1H- and 13C-NMR signals of indigotin were also listed.

Animals↗

Study on the hyphal responses of Aspergillus fumigatus to the antifungal agent by Bio-Cell Tracer.

The hyphal responses of an A. fumigatus isolate to a trizole derivative-fluconazole (FCZ) were studied with a Bio-Cell Tracer system. The numerical data were recorded as the original growth rate (Pre-GR), the time needed for FCZ reaching to its target in hypha (tau on), the growth rate under the FCZ effect (Exp-GR) and the growth rate after FCZ was removed (Post-GR). Based on above numerical data, the inhibitory rates in the exposure and post exposure periods were calculated as the Exp-I% and Post-I% values. It was found there were variable inhibitory rate values (I%) in individual hyphae corresponding to different FCZ concentrations. It was shown by correlation analysis of the numerical data that the Pre-GR values were negatively correlated with the tau on values and positively correlated with both the Exp-I% and Post-I% values. Additionally, the tau on values are negatively correlated with the Exp-I% and Post-I% values. Those results suggested that the hyphal growth rate and the susceptibility of the FCZ target be the important factors to determine the hyphal responses to the FCZ effect. Serial morphological alternations were captured while the hyphal growth curves were changing under the FCZ effects. Of the morphological data, the interesting alternations were visualized when the hyphae were affected by 16 micrograms/ml FCZ. As shifting of the hyphal growth curves, the hyphae were repeatedly seen as swollen tips and germination from the swollen sites. It is indicated that the hyphal tips are the most sensitive parts of this mycelia fungus to the FCZ affects. Additionally, because the hyphal regrowth was observed as germination from the swollen tips before FCZ was removed, an adaptation phenomenon could be proposed.

Antifungal Agents↗

Tranilast inhibits protein kinase C-dependent signalling pathway linked to angiogenic activities and gene expression of retinal microcapillary endothelial cells.

1. Tranilast, first developed as an anti-allergic drug, has been reported to inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis and vasopermeability. To further clarify the inhibitory mechanism, we investigated the effects of tranilast on VEGF binding and subsequent intracellular signalling pathway linked to angiogenic activities and gene expression of bovine retinal microcapillary endothelial cells. 2. Tranilast significantly (P<0.01) inhibited VEGF, basic fibroblast growth factor (bFGF), and hypoxia conditioned media-induced BREC proliferation in a dose dependent manner with IC50's of 22, 82 and 10 microM, respectively. 3. VEGF-induced migration was also inhibited by tranilast in a dose dependent manner, with IC50 of 18 microM, and complete inhibition was observed at 300 microM (P<0.01). Tranilast suppressed VEGF-induced tube formation in a dose dependent manner with maximum (46%) inhibition observed at 300 microM (P<0.05). 4. Tranilast inhibited phorbol myristate acetate (PMA)-dependent stimulation of [3H]-thymidine incorporation and VEGF- and PMA-induced gene expression of integrin alpha v and c-fos in BREC. 5. Tranilast suppressed VEGF- and PMA-stimulated PKC activity in BREC. 6. Tranilast did not affect VEGF binding or VEGF-induced phosphorylation of tyrosine residues of VEGF receptor- and phospholipase Cgamma and their associated proteins. 7. These data suggest that tranilast might prove an effective inhibitor to prevent retinal neovascularization in ischaemic retinal diseases, and that its inhibitory effect might be through suppression of PKC-dependent signal transduction in BREC.

Animals↗

Retrovirally transduced bone marrow stromal cells isolated from a mouse model of human osteogenesis imperfecta (oim) persist in bone and retain the ability to form cartilage and bone after extended passaging.

Bone marrow stromal cells isolated from a model of osteogenesis imperfecta (oim) mice, were transduced with a retrovirus (BAG) carrying the LacZ and neor genes after passage 21. The transduced cells retained the ability to express alkaline phosphatase activity in vitro when treated with recombinant human bone morphogenetic protein two (rhBMP-2), formed cartilage in vitro in aggregate cultures and formed bone in ceramic cubes after 6 weeks of implantation in nude mice. X-gal staining of ceramic cubes seeded with the transduced cells demonstrated the presence of LacZ-positive cells on the edges of bone and also in the lacunae of the newly formed bone 6 weeks after implantation. After infusion into femurs of oim mice, the transduced cells were detected in the marrow cavity and on the edges of the trabecular bone of the injected and contralateral femurs by X-gal staining and PCR analysis at 4, 10, 20, 30 and 40 days after injection. The LacZ gene was also detected in the lung and liver of the recipient mice at 4 and 10 days after injection but not at later time-periods. The present findings suggest that long-term cultured bone marrow stromal cells from osteogenesis imperfecta (OI) animals have the potential to traffic through the circulatory system, home to bone, form bone and continue to express exogenous genes. These findings open the possibility of using these cells as vehicles to deliver normal genes to bone as an alternative approach for the treatment of some forms of OI and certain other bone acquired and genetic diseases.

Alkaline Phosphatase↗

Modulation of T-lymphocyte proliferation by exogenous natural ceramides and sphingosylphosphorylcholine.

Sphingolipids such as ceramide and sphingosine are abundantly present in the stratum corneum of epidermis. In atopic stratum corneum, sphingosylphosphorylcholine (SPC) is present in association with a reduction in the amount of ceramides. We have previously shown that the cellular kinetics of T cells are affected by exogenous addition of sphingosine and synthetic ceramides, raising the possibility that sphingolipids diffusing from the stratum corneum modulate skin-infiltrating T cells. By using two natural ceramides and murine T cells, this study further clarified the conditions under which exogenous ceramides enhance the proliferation of T cells. KLH-specific T cell clones 28-4 and 24-2 proliferated in response to natural ceramides when cultured for 44-48 h in the presence of concanavalin A at 1 microg per ml. Elongation of culture periods adversely inhibited the T cell proliferation, suggesting the existence of an optimal exposure time. Augmentation of DNA synthesis by natural ceramides was more pronounced in tumor necrosis factor alpha (TNFalpha)-sensitive 28-4 cells than in less sensitive 24-2 cells, and TNFalpha-induced proliferation of 28-4 cells was suppressed by the concomitant addition of natural ceramides. Similar to ceramides, SPC augmented the proliferation of resting spleen cells. Our study suggests that ceramide modulation of T cell proliferation depends on the TNFalpha sensitivity and activation level of T cells and that SPC also has a mitogenic potential for T cells.

Animals↗

Magnetic resonance imaging of experimentally-induced sialadenitis in rat submandibular glands.

OBJECTIVES: To correlate the features of magnetic resonance (MR) images of experimentally induced obstructive sialadenitis in rat submandibular glands with the histopathological changes. METHODS: Changes in MR images of ligated and non-ligated rat submandibular glands were compared with the histopathological changes and wet weight ratios. Spin echo T1 weighted images (SE T1WI), fast spin echo T2 weighted images (FSE T2WI), and gradient echo T2 weighted images (GE T2WI) were obtained at 1, 2, 3, 4, 5, 7 and 21 days after duct ligation with a 0.3 T MR imaging system. RESULTS: There was a significant difference (P<0.05) between the signal intensity ratios of both ligated and non-ligated glands on each day, except at 21 days on GE T2WI. On SE T1WI, small interval changes of signal intensity ratios were observed on both glands, whereas there were large interval changes at 1 - 2 days, 4 - 7 days and 21 days after duct ligation with FSE T2WI. These three periods correlated highly with three phases of histopathological changes, swelling of acinar cells at 1 - 2 days, atrophy of acinar cells and increase of duct-like structures at 3 - 7 days, and proliferation of connective tissue at 21 days, and the changes in wet weight ratios. A similar tendency was observed on GE T2WI to FSE T2WI. CONCLUSIONS: As FSE T2WI showed large changes in signal intensity that correlated highly with histopathological three phases, it is recommended as the MR sequence of choice for diagnosing the degree of damage in obstructive sialadenitis.

Animals↗

A 42-kDa glycoprotein from chicken egg-envelope, an avian homolog of the ZPC family glycoproteins in mammalian Zona pellucida. Its first identification, cDNA cloning and granulosa cell-specific expression.

A glycoprotein with molecular mass of 42 kDa was identified as the major component of the chicken egg-envelope, the filamentous, extracellular matrix known as the perivitelline layer. By using a DNA probe amplified with degenerative primers derived from the protein's partial amino acid sequences, a cDNA clone encoding the egg-envelope 42-kDa glycoprotein (gp42) was isolated from a hen's ovary cDNA library. The gp42 open reading frame encoded 435 amino acid residues, including a putative signal peptide of 20 amino acids. The deduced amino acid sequence of gp42 showed significant similarity to egg-envelope glycoproteins of the ZPC family of several other vertebrate species, including human ZP3, mouse ZP3, Xenopus laevis gp43 and medaka (Oryzias latipes) ZI3 (LS-F), which play important roles for sperm-egg interaction. A single N-glycosylation site present in chicken gp42 is conserved among all five of these proteins: carbohydrate analysis of gp42 revealed the presence of a complex type glycan chain at this site. N-terminal sequence analysis of the mature polypeptide suggests that C-terminal processing of the pro-protein occurs during synthesis and secretion. The 1.4-kb gp42 transcript was detected only in follicles, and was found to be accumulated in granulosa cells in a manner dependent on ovarian follicular development. Furthermore, a metabolically radio-labeled gp42 was immunopreciptated from both cell lysate and culture supernatant of the granulosa cells with specific anti-gp42 antibody, suggesting granulosa cell-specific synthesis and secretion of the glycoprotein.

Amino Acid Sequence↗

Low-grade malignant perineurioma of the paravertebral column, transforming into a high-grade malignancy.

A demarcated 6 x 5 cm right paravertebral tumor at the level of T6 in a 39-year-old male was removed surgically. Histologically, the tumor consisted of monomorphous benign-looking, low-cellular spindle cells embedded in desmoplastic stroma. Ten years later, the tumor recurred locally with metastasis to systemic organs, including the occipital skin. Malignancy was histologically evident by the increased cellularity, cellular atypia and mitotic activity. The patient died of respiratory failure at the age of 49. Retrospectively reviewed, the primary lesion was low-grade fibrosarcoma-like spindle cell tumor, with secondary transformation into a highly malignant form. The differential diagnoses included sclerosing epithelioid fibrosarcoma, low-grade fibromyxoid sarcoma and malignant peripheral nerve sheath tumor. Immunohistochemically, the spindle cells in the primary and recurrent tumors consistently expressed epithelial membrane antigen, vimentin, type 4 collagen and laminin. The tumor cells in the present case showed a differentiation toward perineurial cells, which are normally positive for these immunohistochemical markers. Hence, the appropriate diagnostic term should be 'malignant perineurioma', a subtype of malignant peripheral nerve sheath tumor.

Adult↗

Role of nitric oxide in mediating retinal blood flow regulation in cats.

The role of nitric oxide (NO) was evaluated in mediating control of retinal blood flow in the anesthetized cat. This was done under resting conditions and as a function of decreases in perfusion pressure. The retinal blood flow was calculated by measuring blood velocity with laser Doppler velocimetry (LDV) and retinal blood vessel diameter with image analysis. Graded decreases in perfusion pressure were obtained by increasing intraocular pressure (IOP). Following intravenous administration of 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, the arterial blood pressure increased under resting conditions by 34+/-3% (n = 7), the blood vessel diameter decreased by 18+/-2%, and retinal blood flow significantly declined by 27+/-6% (n = 6). Irrespective of the presence or absence of L-NAME (30 mg/kg), stepwise reductions in perfusion pressure that reached a level that was 35% of the baseline value had no significant effect on retinal blood flow. These results suggest that, under resting conditions, retinal blood flow decreases in response to a putative fall in NO levels. However, NO does not appear to be involved in mediating the autoregulatory response to a decrease in perfusion pressure.

Animals↗

New PCR primer pairs specific for Cryptococcus neoformans serotype A or B prepared on the basis of random amplified polymorphic DNA fingerprint pattern analyses.

Thirty-three strains of Cryptococcus neoformans were isolated from clinical specimens, including specimens from AIDS patients in Brazil, and were classified into two serotypes; we detected 31 and 2 strains of serotypes A and B, respectively. Random amplified polymorphic DNA (RAPD) fingerprint pattern analyses of these strains of serotypes A and B showed that the patterns were similar for strains of each serotype when three 10-mer primers were used as the RAPD primers. Comparative studies of the fingerprint patterns of the study isolates with those of the reference strains also showed that the RAPD patterns for strains of each serotype were related and that most of the fingerprint bands existed commonly for all strains of each serotype tested. The common RAPD bands (an approximately 700-bp band for serotype A and an approximately 450-bp band for serotype B) were extracted and the DNA sequences were determined. Using this information, we prepared two and one PCR primer pairs which were expected to be specific for C. neoformans serotypes A and B, respectively. Use of each PCR primer combination thus prepared for serotype A or B was 100% successful in identifying the respective C. neoformans serotypes, including the 33 clinical isolates tested in the present study. Among these combinations, one for serotype A was found to amplify DNA from C. neoformans serotype B as well as serotype A. Serotype B-specific PCR primer pairs amplified DNA from not only serotype B strains but also from serotype C strains. The usefulness of other serotype-specific PCR primers for clinical C. neoformans isolates is discussed.

AIDS-Related Opportunistic Infections↗

Comparison of low attenuation areas on computed tomographic scans between inner and outer segments of the lung in patients with chronic obstructive pulmonary disease: incidence and contribution to lung function.

BACKGROUND: The low attenuation areas on computed tomographic (CT) scans have been reported to represent emphysematous changes of the lung. However, the regional distribution of emphysema between the inner and outer segments of the lung has not been adequately studied. In this study the regional distribution of low attenuation areas has been compared by quantitative CT analysis and the contribution of the regional distribution to pulmonary function tests evaluated in patients with chronic obstructive pulmonary disease (COPD). METHODS: Chest CT images and the results of pulmonary function tests were obtained from 73 patients with COPD. The lung images were divided into inner and outer segments in the upper (cranial), middle, and lower (caudal) sections. The percentage ratio of low attenuation area to corresponding lung area (LAA%) was then calculated. The LAA% of each segment was also compared with the results of pulmonary function tests. RESULTS: The mean (SD) LAA% of the inner segment was 39.1 (18.5) compared with 28.1 (13.2) for the outer segment (p<0.0001). Linear and multiple regression analyses revealed that airflow limitation is closely correlated with the inner segment LAA% of the lower lung. In contrast, the carbon monoxide transfer factor is closely correlated with the inner segment LAA% of the upper lung. CONCLUSION: Low attenuation areas on CT scans are more often found in the inner segment of the lung than in the outer segment, and the contribution of the inner segment to pulmonary function tests may be greater than the outer segment.

Aged↗

Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease.

The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered.

Administration, Inhalation↗

Clinical study of brain metastasis of renal cell carcinoma.

OBJECTIVES: To evaluate the natural history and the efficacy of treatments for renal cell carcinoma (RCC) with brain metastasis, we reviewed 18 patients with this disease. METHODS: Out of 325 cases with RCC treated at Osaka University Hospital from 1957 to 1993, 18 (5.5%, male:female ratio 16:2) cases developed brain metastases. Median follow-up was 44 months after the initial treatment of the primary lesion. Twelve patients had surgical resection of brain metastases (surgical group), and 7 of them received adjuvant radiotherapy. Six patients with poor performance status were treated with supportive therapy alone (nonsurgical group). RESULTS: Of 18 RCC patients with brain metastasis, 16 were male and 2 female. All brain metastases except for 1 case were symptomatic. Median interval between the initial treatment of the primary lesion and the diagnosis of brain metastasis was 19 months. The most frequent metastatic site prior to brain was the lung, which was detected in 7 cases (38.9%). Median survival of the entire group, measured from the onset of brain metastasis, was 9.5 months. One-year survival rate after the diagnosis of brain metastasis was 43.2% (64.8% in surgical group, 0% in nonsurgical group), 3-year 18.5% and 5-year 0%. Among 109 metastatic RCC, 14 patients were treated by lymphokine-activated killer (LAK) therapy. Out of 14 metastatic RCC patients treated by LAK therapy, 3 (21.4%) developed brain metastases. On the other hand, out of 95 metastatic RCC patients without LAK therapy, 15 (15.8%) had brain metastases. There was no significant difference in the rate of brain metastases between these two groups. CONCLUSION: There was a trend for prognosis of the surgical group to be better compared to that of the nonsurgical group, although it is not statistically significant. The optimum treatment for brain metastasis of RCC remains undefined, but our data suggested surgical resection in selected patients might contribute to prolonged survival of patients with brain metastasis. LAK therapy was not necessarily the risk factor of the brain metastasis.

Adult↗