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Biomedical subjects

S Kohno

Publications and source records attributed to S Kohno.

At least 145 records · Page 8Linked to original sources

Defective electron transfer in complexes I and IV in patients with aceruloplasminemia.

Aceruloplasminemia is a disorder of iron metabolism caused by mutations in the ceruloplasmin gene. It is characterized by progressive neurodegeneration of the retina, basal ganglia, dentate nucleus and cerebral cortex in association with iron accumulation in these tissues. Enzyme activities in the mitochondrial respiratory chain of the cerebral cortices of two patients were reduced to 62% and 71% for complexes I and IV. Malondialdehyde, a marker of lipid peroxidation, was three times higher than the control value and was accompanied by increased expression of superoxide dismutase 2 (Mn SOD). These findings suggest that iron-mediated free radicals contribute to the impairment of mitochondrial energy metabolism in aceruloplasminemia

Aged↗

Head movements and neck muscle activities associated with the jaw movement during mastication in the rabbit authors.

Rhythmical head movements and neck muscle activities associated with the masticatory jaw movement were investigated in rabbits. In natural mastication, head movements and neck muscle activities showed a rhythmical feature synchronized with jaw movement. During cortically induced rhythmical jaw movements, some neck muscle showed rhythmical activity induced by biting a wooden stick. Neck muscles may contribute to the rhythmical head movement after loading the tooth with food.

Animals↗

Effects of androgens on telomerase activity in normal and malignant prostate cells in vitro.

BACKGROUND: Recent studies have shown that sex hormones regulate telomerase activity in endometrium and breast tissues. The present study was designed to clarify the effects of androgen on telomerase activity in normal and malignant prostate cells. METHODS: Androgen-sensitive (LNCaP) and -independent (TSU-Pr1 and DU145) prostate cancer cell lines and normal prostate cells including basal cells were cultured in the presence or absence of 5alpha-dihydrotestosterone (DHT). RESULTS: Prostate cancer cell lines exhibited high telomerase activity, and normal prostate cells showed low activity. Short or prolonged androgen-deprivation reduced telomerase activity in LNCaP cells, and DHT induced telomerase activity at the G(1) phase of the cell cycle. DHT did not modulate telomerase activity in TSU-Pr1, DU145, and normal cells. CONCLUSIONS: LNCaP cells had an androgen-dependent pathway to activate telomerase, whereas TSU-Pr1 and DU145 cells as well as normal prostate cells had an androgen-independent pathway. These findings suggest that the regulatory mechanism of telomerase varies during the progression of prostate cancers.

Androgens↗

Serial changes in enzyme inhibitory antibody to pyruvate dehydrogenase complex during the course of primary biliary cirrhosis.

To assess the usefulness of enzyme inhibition assay for the diagnosis of primary biliary cirrhosis (PBC), we determined the serial changes in enzymatic inhibitory antibody to pyruvate dehydrogenase complex (PDC) in patients with PBC, and compared the results to those of immunofluorescence and immunoblotting. Forty-nine sera from 19 patients with PBC who were followed-up for at least 16 months were tested for antimitochondrial antibodies (AMA) by indirect immunofluorescence, immunoblotting on bovine heart mitochondria, and enzyme inhibition assay using commercially available TRACE Enzymatic Mitochondrial Antibody (M2) Assay (EMA) kit. Of the 49 sera, 39 (80%), 35 (71%), 38 (78%), 31 (63%), and 36 (73%) were positive for AMA by immunofluorescence, for immunoglobulin G (IgG), IgM, and IgA class antibody against E2 subunit of PDC (PDC-E2) by immunoblotting, and for enzymatic inhibitory antibody to PDC by EMA, respectively. AMA titers determined by immunofluorescence did not change in 9 patients (47%), increased in 4 (21%), decreased in 3 (16%), and fluctuated in 3 (16%) during follow-up. The number of anti-M2 bands by immunoblotting did not change in 9 (47%), increased in 6 (32%), decreased in 2 (11%), and fluctuated in 2 (11%). Units of PDC activity by EMA did not change markedly in 16 (84%), increased in 2 (11%), and fluctuated in 1 (5%). Positive EMA results were common in cases with high levels of serum alkaline phosphatase and IgM, and the units of PDC activity by EMA correlated significantly and inversely with AMA titers by immunofluorescence, and serum reactivity to PDC-E2 by immunoblotting, respectively. There was no correlation between serial changes in biochemical data and units of PDC activity by EMA. In three patients who showed a decrease in AMA titers, AMA titers correlated more with EMA results than immunoblotting. Moreover, in a patient with fluctuating AMA titers, the units of PDC activity by EMA paralleled AMA titers. Our results suggest that EMA is useful for the diagnosis of AMA-positive PBC, and also could be used for monitoring the disease course in PBC.

Adult↗

Antifungal activity of a new triazole, voriconazole (UK-109496), against clinical isolates of Aspergillus spp.

Voriconazole is a new triazole antifungal agent with potent activity against yeast and molds. We investigated the in-vitro activity of voriconazole compared with that of other antifungal agents against 50 clinical isolates of Aspergillus spp., measured by the National Committee for Clinical Laboratory Standards (NCCLS) reference method described in the M27-A document, and by an alamar blue colorimetric method. Voriconazole was the most potent agent against Aspergillus fumigatus (minimum inhibitory concentration [MIC]90, 0.5 mg/l) and Aspergillus niger (MIC90, 1.0 mg/l). Voriconazole was less active (MIC90, 1.0 mg/l) against Aspergillus flavus than itraconazole (MIC90, 0.5 mg/l). Voriconazole was more active than itraconazole against Aspergillus fumigatus and Aspergillus flavus by the alamar blue indicator method for the measurement of MIC. Based on these results, voriconazole has promising activity against commonly encountered isolates of Aspergillus spp., and its clinical usefulness should be established by further studies.

Antifungal Agents↗

l-Ephedrine is a major constituent of Mao-Bushi-Saishin-To, one of the formulas of Chinese medicine, which shows immediate inhibition after oral administration of passive cutaneous anaphylaxis in rats.

OBJECTIVE AND DESIGN: Whether Mao-Bushi-Saishin-To (MBST), one of the formulas of classical Chinese medicine, is effective on 48-h passive cutaneous anaphylaxis (PCA) in rats and which substance in the formula is responsible for its inhibitory action were examined. TREATMENT: In the studies on PCA, MBST (hot water extract of the whole herbal formula), extracts of Ephedra herb (Mao), l-ephedrine and other reference drugs were orally administered immediately or at various times before or 5 min after the antigen challenge. In the experiments on anaphylactic histamine release from rat peritoneal mast cells, l-ephedrine and d-pseudoephedrine were added at 10(-4)-10(-7) g/ml at 30, 10, 3 or 0 min before antigen provocation. RESULTS: The time course study indicated that MBST produced a prompt and long lasting inhibition of PCA. Among the constituents of Mao, l-ephedrine exerted this prompt inhibitory activity, but d-pseudoephedrine did not. Neither pseudoephedrine nor l-ephedrine prevented the anaphylactic histamine release from isolated peritoneal mast cells. CONCLUSIONS: It is strongly emphasised that the rapid suppression of PCA by orally administered l-ephedrine must be exerted by a mechanism distinct from that of suppression produced following gastrointestinal absorption of the drug, because the time required for the inhibition was extraordinarily short. However, direct inhibition of anaphylactic histamine release from isolated mast cells was excluded in this inhibition of PCA.

Animals↗

Immediate inhibition by oral l-ephedrine of passive cutaneous anaphylaxis of rats: indirect inhibition of anaphylactic chemical mediator release from the mast cell.

OBJECTIVE AND DESIGN: We previously reported that oral l-ephedrine showed extraordinarily rapid inhibition of 48-h passive cutaneous anaphylaxis (PCA) in rats. In the present study, in vivo and in vitro experiments were performed to elucidate a possible mechanism for the inhibition. MATERIALS: Rat antiserum was prepared with dinitrophenylated Ascaris suum extract + Bordetella pertussis. TREATMENT: Wistar rats were passively skin-sensitised, actively sensitised or non-sensitised. l-Ephedrine immediately before provocations was orally or intravenously administered in in vivo experiments. In in vitro experiments, the drug was added at various time and concentrations before the challenge. METHODS: The intensity of PCA was assessed by dye leakage method. Histamine and serotonin released in vitro or retained in the skin in vivo by anaphylaxis were assayed fluorometrically. RESULTS: Oral l-ephedrine rapidly inhibited the PCA by inhibiting the release of histamine and serotonin from the reaction site, whereas anaphylactic histamine and serotonin releases from skin fragments were not affected by the drug. Furthermore, the orally administered drug influenced neither the histamine- nor serotonin-induced cutaneous vascular permeability. CONCLUSIONS: These results were strongly indicative that the prompt suppression of the PCA by oral l-ephedrine was not exerted following the drug was absorbed from the gastrointestinal tract. Thus, the result may be from an indirect inhibition of chemical mediator release, possibly through an unidentified stimulation of the nervous system, but not from the inhibition of chemical mediator release by the direct interaction of drug to mast cells and not from the decreased vascular permeability.

Administration, Oral↗

Oral beta-stimulants can inhibit passive cutaneous anaphylaxis in rats through an indirect inhibitory mechanism: possible involvement of afferent and efferent nervous system via gastric beta2-adrenoceptor stimulation.

OBJECTIVE AND DESIGN: We previously demonstrated that oral l-ephedrine exerts an extremely rapid (within 20 s) inhibition of 48-h passive cutaneous anaphylaxis reaction (PCA) in rats by a possibly unidentified mode of action. In the present experiments, we elucidated the mechanism of the PCA inhibition by l-ephedrine using adrenoceptor agonists and antagonists. MATERIALS: Rat antiserum was prepared with dinitrophenylated Ascaris suum extract + Bordetella pertussis. TREATMENT: Passively skin-sensitised Wistar rats were mainly used. l-Ephedrine, and adrenoceptor agonists and antagonists were orally administered immediately before PCA provocation. Catecholamine depleting (6-hydroxydopamine, 6-OHDA), amine depleting (reserpine) or ganglion blocking (hexamethonium) agent was intraperitoneally or intravenously administered before the provocation. METHODS: The effects of the drugs on PCA were assessed by inhibition of the dye leakage. RESULTS: beta-(propranolol) and beta2-(butoxamine) blocking agents reduced the inhibition of PCA by l-ephedrine, while the inhibition was not altered by either an a-blocking agent (phentolamine) or a beta1-(atenolol) selective antagonist. On the other hand, beta-(isoproterenol) and beta2-selective (salbutamol) agonists showed extremely rapid inhibition of PCA. However, the beta-selective agonist (dobutamine) had no effect on the reaction. The pretreatment with hexamethonium, reserpine or 6-OH-DA substantially attenuated the inhibitory effect of l-ephedrine on PCA. CONCLUSIONS: The results strongly suggest that beta2-adrenoceptors locate in the stomach and that their receptor excitement finally may lead to the inhibition of PCA via the stimulation of the central and peripheral nervous systems.

Adrenergic beta-2 Receptor Agonists↗

Concerted evolution of a highly repetitive DNA family in eptatretidae (Cyclostomata, agnatha) implies specifically differential homogenization and amplification events in their germ cells.

In eight hagfish species, it is known that chromosome elimination occurs during early embryogenesis, and some highly repetitive DNA families, restricted to germ cells, have been isolated. One of these families, "EEEo2," has been isolated as DNA fragments by restriction enzyme analyses from Eptatretus okinoseanus and E. cirrhatus. In this study, EEEo2 sequences were isolated from germline DNA in E. burgeri, Paramyxine sheni, and P. atami using PCR methods. Sequence analysis revealed that these sequences are intraspecifically homogeneous, except in E. burgeri, and are interspecifically conserved with heterogeneity. The intraspecific sequence variability tends to decrease as the copy number increases. These results indicate that EEEo2 has evolved in a concerted manner. Moreover, an ancestral repeating motif consisting of triplicate subrepeats was deduced. These results suggest that EEEo2 arose as an initial amplification of this subrepeat and has evolved by saltatory replication. Phylogenetic analyses suggested the possibility that EEEo2 in E. okinoseanus and E. cirrhatus has been subjected to strong homogenizing forces for concerted evolution, whereas the force is weak in E. burgeri. In addition, EEEo2 in P. sheni and P. atami appear to have been incompletely subjected to these forces. Chromosomal in situ hybridization experiments revealed that EEEo2 sequences were located along almost their entire length of several heterochromatic chromosomes that are restricted to germ cells. These chromosomes are disposed to form a secondary association during the first meiotic metaphases, except in P. sheni. This chromosomal distribution may promote a concerted mode of sequence evolution in both nonhomologous chromosomes and homologous chromosomes and reflect the differential driving forces between species.

Animals↗

Autoimmune reactivity of sera to hepatocyte plasma membrane in type 1 autoimmune hepatitis.

Type 1 autoimmune hepatitis (AIH-1) is an organ-specific autoimmune liver disease for which no tissue-specific autoantigen has yet been identified. We examined the reactivity by sensitive immunoblotting with enhanced chemiluminescence (IB-ECL) of 43 sera from patients with AIH-1 and 182 sera from patients with other diseases on hepatocyte plasma membrane derived from rat or human liver (RHPM, HHPM) and separated by aqueous two-phase partition. The sera studied were from patients with AIH-1, primary biliary cirrhosis, chronic viral hepatitis, and systemic lupus erythematosus (SLE); and from normal subjects. Specificity of reactivity by IB-ECL was sought: (i) by testing sera on human or rat liver membrane; (ii) by testing sera on liver or kidney membrane; (iii) by serial titration of reactive sera; and (iv) by testing reactive sera from AIH-1 before and after successful treatment with prednisolone. The results were that in AIH-1 there were multiple reactive components which were not species-specific, since they were detected with both RHPM and HHPM, but were mostly tissue-specific for liver. There was no significant correlation between antinuclear antibodies (ANA) titer and the frequencies of sera reactivities against RHPM. Most of these reactive components were demonstrable at a lesser frequency in other liver diseases and in SLE. There was a striking decrease in reactivity by IB-ECL of AIH-1 sera with liver membrane after clinical remission, further suggesting that differences between AIH-1 and other inflammatory liver diseases and SLE are predominantly quantitative rather than qualitative. However, our study did point to candidate liver membrane antigens with molecular sizes of 136, 116, 81, and 49 kDa, additional to components previously described by others. The molecular identification of these prominent reactants with AIH-1 sera could prove informative for ascertaining pathogenesis.

Adult↗

Primary biliary cirrhosis associated with idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (IRF) and primary biliary cirrhosis (PBC) are distinct clinical disorders which rarely occur in the same patient. We report a 79-year-old man with the coexistence of both conditions. The patient had antibodies to both centromere and mitochondria, as indicated by indirect immunofluorescence. Diagnoses of IRF and PBC were confirmed histologically. Although the association between IRF and PBC is obscure, IRF may be involved in many autoimmune diseases associated with PBC.

Aged↗

Effect of intermittent administration of human parathyroid hormone (1-34) on the mandibular condyle of ovariectomized rats.

Intermittent administration of human parathyroid hormone (1-34) (PTH) increases bone mass in lumbar vertebrae and long bones of osteoporotic experimental animals. However, whether PTH has the same effect on jaw bones remains unclear. This study determined the effect of intermittent administration of PTH on rat mandibular condyle affected by estrogen deficiency. Fifty 6-month-old rats were either sham operated or ovariectomized, then divided into five groups depending on surgical procedure and hormone administration: sham + vehicle (SV), OVX + vehicle (OV), OVX + PTH 6 micrograms/kg once per week (OP6-1), OVX + PTH 60 micrograms/kg once per week (OP60-1), and OVX + PTH 20 micrograms/kg three times per week (OP20-3). PTH or vehicle was injected intermittently for 6 months in 5 rats of each group either immediately after surgery in a preventive administration experiment, or injected starting 6 months after surgery in a therapeutic administration experiment. The mandibles were excised, and bone morphometry was performed using confocal laser scanning microscopy and soft X-ray images. In both experiments, the bone volume of the OV groups was significantly lower than that of the SV group (P < 0.01); also, depending on dose and frequency, the bone volume of the OP group was higher than that of the OV group, particularly in the OP20-3 group. The value of mineralized surface of the OP groups was significantly higher than that of the OV group (P < 0.01), whereas the value of eroded surface of the OP groups was not significantly higher than that of the OV group. This study indicates that preventive and therapeutic intermittent administration of PTH in ovariectomized rats increase the bone formation in rat mandibular condyle without accelerating bone resorptive activity. This anabolic effect was best induced by the injection mode of 20 micrograms/kg three times per week.

Animals↗

Synergistic effect of ofloxacin and fluconazole against azole-resistant Candida albicans.

We investigated the combination effects of ofloxacin and fluconazole against azole-resistant Candida albicans strains in vitro and in vivo. Ofloxacin alone showed no efficacy against the azole-resistant C. albicans strain, C26. The in-vitro combination effects were evaluated by the checkerboard method, calculated as the fractional inhibitory concentration (FIC) index, but there was no synergistic effect of the combination. The activity of the drug efflux pump in the azole-resistant C. albicans strains was measured by intracellular rhodamine 6G concentration. When the cells were incubated with ofloxacin or grepafloxacin, the intracellular rhodamine 6G concentration was significantly increased in the azole-resistant C. albicans strain. In-vivo combination effects were evaluated in murine disseminated candidiasis. The survival of the mice was not prolonged, but counts of the yeast cells in the kidney and spleen were reduced following treatment with the combination of ofloxacin (20 mg/kg) and fluconazole (20 mg/kg). The combination of ofloxacin and fluconazole may represent an effective strategy to treat infections caused by azole-resistant C. albicans.

Anti-Infective Agents↗

Effects of insulin-like growth factor-I on nasopremaxillary growth under different masticatory loadings in growing mice.

It is well accepted that reduced masticatory function induced by a diet with soft physical consistency causes alterations in the craniofacial morphology in growing animals. It is assumed that these alterations are associated with reduced proliferative activity of osteoblasts on the bone surface, indicating a significant role for mechanical stimuli mediated by various local growth factors including insulin-like growth factor-I (IGF-I). Here, the effects of IGF-I on the linear growth of nasal and premaxillary bones subjected to different masticatory loadings were examined. The length of the nasal bone and the width of the premaxilla were measured. These dimensions were significantly greater in mice fed a solid diet than in mice fed a granulated diet. In animals treated with IGF-I, the nasal bone length and premaxillary width increased significantly in a subgroup receiving a solid diet, but these changes were not found in a similar group fed a granulated diet. No statistically significant differences in these dimensions were found between solid-diet mice injected with saline and granulated-diet group injected with IGF-I. It is concluded that IGF-I induces nasal and premaxillary growth, and that its effect is enhanced or accelerated by increased mechanical masticatory loading.

Analysis of Variance↗

Regional specificity of localized cortical lesions in West syndrome.

West syndrome, although classified as a generalized epilepsy, is associated with localized cerebral lesions in some cases. However, similar localized cortical abnormalities usually can result in partial epilepsy, instead of West syndrome. We performed this study to determine the additional factors that result in West syndrome instead of partial epilepsy in patients with localized cerebral lesions. We reviewed the pathologic features, topographic localization, and side of unilaterally defined cerebral lesions in relation to the seizure types in 39 epileptic patients, including five patients who presented with West syndrome. The lesions of all five patients with West syndrome involved the temporal or occipital lobes (or both). Among the nine with an occipital lesion, four had West syndrome. In the 19 with a temporal lesion, three had West syndrome. However, in the 16 patients with a frontal lesion, none exhibited epileptic spasms. In four of the five with West syndrome the lesions were on the right side; 23 had lesions on the right, 16 had them on the left. Temporo-occipital lesions and lesions on the right were related to the genesis of West syndrome, which would be in close correlation with normal brain maturation.

Brain Mapping↗

Effects of sodium cromoglycate on cytokine production following antigen stimulation of a passively sensitized human lung model.

BACKGROUND: Interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-alpha) play key roles in bronchial asthma. Sodium cromoglycate (DSCG) and dexamethasone (Dex) are used in the treatment of asthma as anti-inflammatory agents. OBJECTIVE: We investigated whether DSCG inhibited the expression of IL-5 and TNF-alpha mRNA and proteins from isolated human lungs, and compared these findings with those of Dex. METHODS: Human lung specimens were passively sensitized with sera from atopic patients, then preincubated in the presence of DSCG (10(-3), 10(-4), 10(-5) M) or Dex (10(-6) M) for 2 hours. The specimens were stimulated with Dermatophagoides antigen, then cultured for 48 hours. The supernatant was collected 1, 2, 4, 8, 24, and 48 hours to measure IL-5 and TNF-alpha by enzyme-linked immunosorbent assay. mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Tumor necrosis factor-alpha protein reached a peak level at 4 hours (156.57 +/- 18.29 pg/mL). Dex decreased TNF-alpha protein to 31.86 +/- 4.67 pg/mL (P < .001). There was also a decrease of TNF-alpha protein to 107.43 +/- 14.25 pg/mL by 10(-4) MD SCG (P < .001). Antigenic stimulation also increased the release of IL-5 protein at 4 hours and the peak level was observed at 24 hours (150.29 +/- 19.12 pg/mL). Dex decreased IL-5 protein to 28.57 +/- 5.27 pg/mL (P < .0001), 10(-4) M DSCG also decreased to 111.57 +/- 15.28 pg/mL (P < .05). RT-PCR analysis showed persistence of IL-5 and TNF-alpha mRNA expression from 1 to 24 hour after antigen stimulation. Dex but not DSCG inhibited IL-5 and TNF-alpha mRNA levels. CONCLUSION: Our results showed that DSCG significantly inhibited IL-5 and TNF-alpha production by human lung specimens, suggesting that it acts as an anti-inflammatory agent.

Aged↗