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Biomedical subjects

Y Kudo

Publications and source records attributed to Y Kudo.

At least 109 records · Page 6Linked to original sources
PubMed1999

Cytotoxic activity and cytokine gene induction of Asp-hemolysin to murine macrophages.

We examined the effects of Asp-hemolysin from Aspergillus fumigatus Fresenius-Muramatsu strain on the viability and cytokine gene expression of mouse peritoneal macrophages. The cytotoxic activity of Asp-hemolysin to macrophages cultured in FCS-RPMI medium was increased in a dose-dependent manner. Treatment of Asp-hemolysin with N-ethylmaleimide or sulfo-N-hydroxy-sulfosuccinimide-acetate caused a remarkable loss of the cytotoxic activity, however, the cytotoxic activity of Asp-hemolysin to macrophages cultured in serum-free medium was significantly increased as compared with that in FCS-RPMI medium. As other biological activities of Asp-hemolysin, tumor necrosis factor-alfa (TNF-alfa), interleukin-1 beta(IL-l beta) and interleukin-1 alfa (IL-l alfa) mRNA expression were observed in macrophages cultured with 1 micro g/ml of Asp-hemolysin.

Animals↗
PubMed1999

[The clinical features of patients with probable dementia with Lewy bodies--report of 4 cases].

Recently, McKeith et al. proposed criteria for the clinical diagnosis of dementia with Lewy bodies (DLB). In our study the clinical features of four patients with progressive dementia, visual hallucinations, delusions, and parkinsonism were compatible with those of DLB. To evaluate the neurological and psychiatric features, responses to medications, magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) in patients with DLB, we compared the above DLB patients with age- and gender-matched Parkinson's disease patients showing no signs of dementia. Our DLB patients presented with mild tremor, moderate rigidity and akinesia, severe constitutional dysfunction and recurrent visual hallucinations and delusions. These psychiatric symptoms became worse by anticholinergic agents and dopamine agonists and were difficult to control using neuroleptic medications. MRI revealed atrophy of the cerebrum to be more accentuated in the parietal region. SPECT demonstrated hypoperfusion in the parietal and occipital lobes. These findings suggest that parietal lobe dysfunction is a feature of DLB. It may, therefore, be concluded from this study that brain MRI and SPECT are useful in the clinical diagnosis of DLB, and that great caution should be taken when prescribing longacting dopamine agonists and neuroleptics to such patients.

Aged↗
PubMed1999

[Early phase II study of quetiapine fumarate on schizophrenia].

The efficacy and safety of quetiapine fumurate in the treatment of patients with schizophrenia were evaluated in an 8-week, multicenter, open-label study. The results of this study which included a total of 54 patients showed good efficacy and safety profile for quetiapine fumarate as seen by the improvement rate (moderate or above in the final global improvement rating) of 49.1% and safety rate (no problem in overall safety rating) of 66.0%. The mean BPRS total score decreased significantly from 55.5 +/- 10.9 points at baseline to 45.4 +/- 13.0 points at the completion of administration. The PANSS scores also showed significant improvement on all scales; the mean scores decreased from 20.7 +/- 6.3 points at baseline to 17.7 +/- 6.9 points at withdrawal or completion of administration on the positive scale, from 27.8 +/- 5.8 points to 24.0 +/- 7.3 points on the negative scale, and from 51.4 +/- 10.1 points to 44.7 +/- 12.4 points on the general psychopathology scale. Although the most frequent adverse reactions were somnolence (18.9%), insomnia (17.0%), nervousness (13.2%), dizziness (13.2%), malaise (13.2%), postural hypotension (11.3%), tachycardia (9.4%), and constipation (9.4%), the incidence of extrapyramidal symptoms was low (11.3%). From these results, quetiapine fumarate was suggested to be highly effective and safe for the treatment of schizophrenia.

Adult↗
PubMed1999

A newly designed underwater antenna and its application to underwater radio-telemetry for measuring electroencephalographic activity from the rainbow trout freely swimming in natural environments.

A novel underwater antenna (which we named an 'aquaerial') for telemetering the biological signals from freely swimming fish in freshwater natural environments is presented. It is designed for receiving a 90-100 MHz carrier wave and consists of plural unit receiving antennas (UAs). The plural UAs are placed underwater to cover the area where the target fish carrying the transmitter is swimming. The UAs are equally spaced and have a directional coupling amplifier to supply the signals received to the coaxial cable. The optimal length of the UA was found to be 16.5 cm (a half wavelength in water) and optimal spacing was 2 m (one wavelength along coaxial cable) when 95 MHz was used as the carrier frequency. Using this 'aquaerial', long-term monitoring of EEG signals from the olfactory bulb of the rainbow trout (Oncorhynchus mykiss) swimming freely in natural environments was achieved.

Animals↗
PubMed1998

Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is an indicator of malignant behavior in oral squamous cell carcinoma.

BACKGROUND: Reduced expression of the cyclin-dependent kinase inhibitor p27Kip1 has been reported to correlate with poor survival in cohorts of breast and colorectal carcinoma patients. Posttranslational ubiquitin-mediated proteasomal proteolysis is related to p27Kip1 protein levels. However, to the authors' knowledge, no previous study has examined the expression of p27Kip1 in oral squamous cell carcinoma (OSCC). METHODS: To examine the expression of p27Kip1 and its clinicopathologic roles in OSCC, the authors studied the expression of p27Kip1 protein by immunohistochemistry in deparaffinized tissue sections of 20 normal oral mucosa specimens, 22 epithelial dysplasia specimens, and 70 OSCCs, and analyzed its correlation with clinicopathologic parameters. They also studied the expression of p27Kip1 mRNA and protein in six OSCC cell lines by Northern blot and Western blot analysis. To examine the mechanism of reduced expression of p27Kip1, OSCC cell lines were treated with the proteasome inhibitor LLnV. RESULTS: All the normal oral mucosa specimens and 73% (16 of 22) of the oral epithelial dysplasia specimens expressed p27Kip1 at high levels, whereas 87% of the OSCCs (61 of 70) showed reduced expression of p27Kip1. Furthermore, the levels of expression of this protein were significantly lower in carcinomas with metastasis than those without metastasis. Although OSCC cell lines expressed p27Kip1 mRNA at various levels, most of them expressed p27Kip1 protein at lower or undetectable levels. LLnV induced the expression of p27Kip1 protein in HSC2 cells, in which p27Kip1 protein was originally undetectable. CONCLUSIONS: These findings suggest that 1) reduced expression of p27Kip1 may correlate with the development and progression of OSCC and can be an indicator of malignant behavior of this neoplasm, and 2) increased proteasome-mediated degradation may play an important role in the reduction of p27Kip1 protein expression.

Adult↗
PubMed1998

Activation of dihydropyridine sensitive Ca2+ channels in rat hippocampal neurons in culture by parathyroid hormone.

We examined the effects of parathyroid hormone (PTH) on rat hippocampal neurons in culture to determine whether it caused a similar intracellular calcium concentration ([Ca2+]i) increase in these cells to that seen with renal epithelial cells and found that PTH induced the effect in about 30% of the neurons. The effects appeared gradually during continuous administration of full-length PTH(1-84) or its active fragment, PTH(1-34), but not of an inactive fragment, PTH(39-84). However, the active fragment of the PTH-related peptide (PTHrP(1-34)) had little effect on [Ca2+]i during 60 min of administration. The PTH effect was inhibited by nifedipine, an L-type Ca2+ channel antagonist, and facilitated by S-(-)-BAY K 8644, an L-type Ca2+ channel agonist. Our findings suggest that PTH is one of the causal factors for the age-related increase in the density of voltage gated Ca2+ channels in hippocampal neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Direct evidence of NO production in rat hippocampus and cortex using a new fluorescent indicator: DAF-2 DA.

The biological functions of nitric oxide in the neuronal system remain controversial. Using a novel fluorescence indicator, DAF-2 DA, for direct detection of NO, we examined both acute rat brain slices and organotypic culture of brain slices to ascertain NO production sites. The fluorescence intensity in the CA1 region of the hippocampus was augmented, especially after stimulation with NMDA, in acute brain slices. This NO production in the CA1 region was also confirmed in cultured hippocampus. This is the first direct evidence of NO production in the CA1 region. There were also fluorescent cells in the cerebral cortex after stimulation with NMDA. Imaging techniques using DAF-2 DA should be very useful for the clarification of neuronal NO functions.

Animals↗
PubMed1998

Oxidized low density lipoprotein inhibits the hemolytic activity of Asp-hemolysin from Aspergillus fumigatus.

We have examined the effect of chemically modified human low density lipoproteins (LDLs), acetylated LDL and oxidized LDL, on the hemolytic activity of Asp-hemolysin. Oxidized LDL, but not acetylated LDL, inhibited the hemolytic activity of this toxin. The inhibitory effects of oxidized LDL increased with the time of Cu(2+)-induced LDL oxidation. Similar inhibition was observed in the filtrate which was separated from the incubation mixture of Asp-hemolysin with oxidized LDL (for 2 h of oxidation) following ultrafiltration through a membrane with a molecular mass cutoff of 100,000. However, at longer LDL oxidation times, the inhibition by the filtrates was less than the control mixture without ultrafiltration. We suggest that the inhibition by oxidized LDL was due to the binding of oxidized LDL to Asp-hemolysin at shorter LDL oxidation times.

Acetylation↗
PubMed1998

Actions of zinc on rapidly inactivating A-type and non-inactivating M-type potassium currents in bullfrog sympathetic neurons.

The actions of zinc on A-type potassium current (I(A)) were studied in dissociated bullfrog sympathetic neurons. Zinc (1-300 microM) caused a parallel shift in the activation and inactivation curves to a depolarizing direction, thereby enhancing I(A) around physiological resting potential. An EC50 value was 70-100 microM for these actions. The zinc actions were non-selective in a sense that zinc inhibited M-type potassium current (I(M)) with an IC50 value of 300 microM. Zinc was without effect on the maximum conductance for I(A) and the kinetic behavior for I(M). The ability of low concentrations of zinc to modulate separate set of potassium currents such as I(A) and I(M) in conceptually distinct manner may therefore assume pathophysiological importance for autonomic neurons.

Animals↗
PubMed1998

Reduced calcium elevation in hippocampal CA1 neurons of ischemia-tolerant gerbils.

Transient forebrain ischemia causes selective neuronal death in the hippocampal CA1 neurons. A short sublethal ischemic episode preceding ischemia of longer duration is known to increase tolerance against cell death. The mechanisms of this ischemic tolerance are still poorly understood. Here we show, using Ca2+ imaging, that intracellular calcium ([Ca2+]i) elevation in CA1 neurons after an anoxic-aglycemic episode is markedly inhibited in the ischemia-tolerant gerbil. The hippocampus of gerbils which did not acquire tolerance showed a high [Ca2+]i elevation during the anoxic-aglycemic episode, similar to controls. Since hypoxia/ischemia-induced neurodegeneration can be triggered by cytoplasmic Ca2+ overload, the tolerant gerbil may regulate calcium and keep [Ca2+]i below the critical level for initiating neuronal death.

Animals↗
PubMed1998

Differential roles of two types of voltage-gated Ca2+ channels in the dendrites of rat cerebellar Purkinje neurons.

The distribution and function of voltage-gated Ca2+ channels in Purkinje neurons in rat cerebellar slices were studied using simultaneous Ca2+ imaging and whole-cell patch clamp recording techniques. Voltage-gated Ca2+ channels were activated by applying depolarizing voltage steps through the pipette attached at the soma in a voltage-clamp mode in the presence of tetrodotoxin. Poor space clamp due to extensive arborization of the dendrites allowed the dendrites to fire Ca2+ spikes. Ca2+ imaging with Fura-2 injected through the pipette, showed a steady [Ca2+]i increase at the soma and transient, spike-linked [Ca2+]i jumps in the dendrites. omega-Agatoxin-IVA (200 nM) abolished the depolarization-induced Ca2+ spikes, the spike-linked [Ca2+]i increase in the dendrites, and the steady [Ca2+]i increase at the soma. omega-Conotoxin-GVIA (5 microM) and nifedipine (3 microM) had no significant effect on the depolarization-induced responses. In the presence of 4-aminopyridine(2 mM) and omega-Agatoxin-IVA, transient [Ca2+]i increases remained in the dendrites. Low concentrations of Ni2+(100 microM) reversibly suppressed this [Ca2+]i increase. The voltage for half-maximal activation and inactivation of this component were lower than -50 mV and -31 mV, respectively. In normal conditions, low concentration of Ni2+ slowed the onset of the Ca2+ spike without changing the time course of the spikes or the amplitude of the accompanying [Ca2+]i increase. These results show that omega-Agatoxin-IVA-sensitive Ca2+ channels are distributed both in the soma and the dendrites, and are responsible for dendritic Ca2+ spikes, whereas low-voltage activated, Ni2+-sensitive Ca2+ channels are distributed in the whole dendrites including both thick and fine branches, and provide boosting current for spike generation.

Animals↗
PubMed1998

Phosphoisoforms of insulin-like growth factor binding protein-1 in appropriate-for-gestational-age and small-for-gestational-age fetuses.

We analysed phosphoisoforms of insulin-like growth factor binding protein-1 (IGFBP-1) in maternal and cord sera from preterm and term fetus with different growth status. Phosphoisoforms were separated by non-SDS-polyacrylamide gel electrophoresis and detected by immunoblot. Phosphoisoforms were also analysed by anion exchange chromatography on HPLC. The proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was significantly higher in preterm fetus than in their mothers, however, the relative amounts of each IGFBP-1 isoforms were similar between preterm and term fetus. The levels of non-phosphorylated IGFBP-1 were similar between appropriate for gestational age (AGA) and small for gestational age (SGA) fetus at term, however, phosphorylated isoforms of IGFBP-1 were increased in SGA fetus compared to those of AGA fetus and the proportion of non-phosphorylated IGFBP-1 to total IGFBP-1 was lower in SGA fetus than those in AGA fetus. Thus, the profiles of non-phosphorylated and phosphorylated IGFBP-1 in the fetus varies corresponding to fetal growth suggesting that not only total amounts of IGFBP-1 but also the proportion of phosphoisoforms of IGFBP-1 is important for fetal growth.

Biomarkers↗
PubMed1998

Phosphorylated insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) inhibits while non-phosphorylated IGFBP-1 stimulates IGF-I-induced amino acid uptake by cultured trophoblast cells.

The effects of phosphorylated insulin-like growth factor-binding protein (pIGFBP-1) and non-phosphorylated (npIGFBP-1) IGFBP-1 on amino acid uptake induced by IGF-I were studied using cultured trophoblast cells. Trophoblast cells obtained from term pregnancy were incubated with indicated concentrations of pIGFBP-1 or npIGFBP-1 for 24 h and further incubated with 10 nM IGF-I for 3 h. Cells were then incubated with 3H-alpha-amino isobutyric acid (3H-AIB) for 30 min. Both pIGFBP-1 and npIGFBP-1 alone had no effect on 3H-AIB uptake; however, pIGFBP-1 inhibited IGF-I-stimulated 3H-AIB uptake with an ED50 of 0.26 nM while npIGFBP-1 potentiated 3H-AIB uptake with an ED50 of 0.27 nM. Maternal IGF-I promotes fetal growth by stimulating nutrient transport in the placenta. As shown in this study, pIGFBP-1 inhibits while npIGFBP-1 stimulates this IGF-I action in the placenta. Thus, it is suggested that IGFBP-1 phosphoisoforms are also involved in fetal growth by modulating IGF-I action in the placenta.

Amino Acids↗
PubMed1998

Pharmacological detection of AMPA receptor heterogeneity by use of two allosteric potentiators in rat hippocampal cultures.

1. In order to examine whether a recently developed allosteric potentiator for AMPA receptors, 4-[2-(phenylsulphonylamino)ethylthio]-2,6-difluoro-phenoxyaceta mide (PEPA), can be utilized as an indicator of AMPA receptor heterogeneity, the action of PEPA upon the increase of intracellular free calcium ion concentration ([Ca2+]i) elicited by AMPA was investigated in rat hippocampal cultures, and the action was compared with that of cyclothiazide, a well characterized allosteric modulator of AMPA receptors. 2. PEPA dose-dependently potentiated AMPA-induced increase of [Ca2+]i. In 90% (72 out of 80) of the cells in which cyclothiazide acts, PEPA potentiated the increased [Ca2+]i induced by AMPA with pronounced cell-to-cell variation in rat hippocampal cultures. 3. The ratio of the potentiation by PEPA to the potentiation by cyclothiazide (P/C ratio) also varied with cells between 0 and 2.15. It was found that the cultured hippocampal cells consisted of multiple populations with different P/C ratios. Among them two populations exhibited characteristic P/C ratios; low (0 to 0.15; 27 out of 80 cells, 34%) and high (> or = 2.00; 1 out of 80 cells, 1%) P/C ratios. The P/C ratios of the other populations were between 0.25 and 1.20, and these cells constituted 65% (52 out of 80 cells) of the cells tested. 4. Reverse transcriptase-polymerase chain reaction analysis suggested that GluR2-flip, GluR1-flip, GluR2-flop, and GluR1-flop were abundantly expressed (in this rank order) in the cultures used. 5. In Xenopus oocytes expressing GluR1, GluR3, or these subunits plus GluR2, the potentiation of AMPA response by PEPA and by cyclothiazide varied with subunit and splice-variant combinations, and the P/C ratio was between 0.19 and 2.20. Oocytes with low P/C ratios (0.19 to 0.50) and low sensitivity to PEPA potentiation (1.9 fold to 6.41 fold) were those expressing flip variants predominantly, and oocytes with high P/C ratios (1.8 to 2.2) were those expressing flop variants predominantly. Oocytes with intermediate P/C ratios (0.51 to 1.20) were those expressing various combinations of flip and flop variants, and it was impossible to specify the relative abundance of flip and flop variants in these cells. Therefore, the P/C ratio can be used to infer subunit/splice variant expression only when the ratio is low or high. 6. These results suggest that the potentiation by PEPA alone reveals cell-to-cell heterogeneity of AMPA receptors, but a comparison of the actions of PEPA and cyclothiazide further facilitates the detection of the heterogeneity.

Allosteric Regulation↗
PubMed1998

Preoperative nocturnal desaturations as a risk factor for late postoperative nocturnal desaturations.

Severe postoperative hypoxaemia during sleep may increase the risk of postoperative cardiovascular complications. We hypothesized that the severity of hypoxic episodes after surgery are related to the presence of preoperative sleep-disordered breathing (SDB). We tested this hypothesis in a multicentre study designed to elucidate the major risk factors for development of postoperative nocturnal desaturations. We performed overnight oximetry before operation and for one night between the second and fourth day after operation in 80 patients undergoing major surgery. We calculated oximetry variables such as oxygen desaturation index (ODI), defined as the number of oxygen desaturations exceeding 4% below baseline, percentage time spent at SpO2 < 90% (CT90, %) and lowest SpO2 value. After operation, although the change in ODI was not significant (P = 0.34), deterioration in CT90 and lowest SpO2 values were significant (P = 0.036 and P = 0.007, respectively). Multivariate analysis of possible risk factors for postoperative desaturations revealed that preoperative hypoxaemia and apnoea witnessed by others were highly correlated with postoperative hypoxaemia.

Adult↗
PubMed1998

Effect of follicle stimulating hormone and insulin-like growth factors on proteolysis of insulin-like growth factor binding protein-4 in human granulosa cells.

Follicular fluid from dominant follicles, but not atretic follicles, contains insulin-like growth factor binding protein-4 (IGFBP-4) proteolytic activity. The effect of follicle stimulating hormone (FSH) and insulin-like growth factors (IGFs) on IGFBP-4 proteolytic activity was studied using granulosa cell cultures. Proteolytic activity was assessed by the incubation of [1251]-IGFBP-4 with medium and cleaved products which were analysed by autoradiography. The iodinated IGFBP-4 was cleaved into an 18 kDa fragment when cells were incubated with FSH or IGFs while IGFBP-4 remained intact in the control culture. Inhibition of IGFBP-4 degradation by several protease inhibitors suggests that IGFBP-4 degradation was induced by a metalloserine protease. The degradation of IGFBP-4 was not stimulated when cells were incubated with the IGF-I analogue, LR3-IGF-I, and insulin which binds to IGF-I receptor but has little or no affinity for IGFBPs. Addition of IGFs, but not FSH, to medium from untreated granulosa cell cultures stimulated proteolysis of [1251]-IGFBP-4. Similarly, exogenously added covalently cross-linked [125I]-IGF-II-IGFBP-4 complexes were proteolyzed; however, IGFs did not enhance the degradation of these complexes. These results suggest that human granulosa cells produce IGFBP-4 protease and that the increased susceptibility of IGFBP-4 to proteolysis is induced by the binding of IGFs to IGFBP-4. These novel mechanisms may be important in modulating IGF-mediated folliculogenesis in the ovary.

Autoradiography↗
PubMed1998

Distribution of macrophage lineage cells in rat gingival tissue after topical application of lipopolysaccharide: an immunohistochemical study using monoclonal antibodies: OX6, ED1 and ED2.

To discuss the role of macrophage lineage cells on the periodontal tissue destruction, we immunohistochemically examined the phenotype and the dynamics of macrophage lineage cells 1 or 3 h or 1, 2, 3 or 7 d after topical application of LPS (5 mg/ml in physiological saline) from the rat gingival sulcus using 3 monoclonal antibodies: OX6 (antigen-presenting cells), ED1 (monocytes, macrophages and dendritic cells) and ED2 (resident macrophages). We could detect at least 3 different types of macrophage lineage cells, namely OX6+/ED1+/ED2- dendritic cells and exudate macrophages and ED2+ resident macrophages. After LPS application the majority of macrophage lineage cells accumulated in the subjunctional epithelial area were newly extravasated OX6+/ED1+/ED2- dendritic cells or macrophages. The number of these cells increased progressively with time and reached a maximum level at d 2. On the other hand, number and tissue distribution of ED2+ resident macrophages did not change. These results indicate that several types of macrophage lineage cells exist in rat gingival tissue and suggest that dendritic cells and exudate macrophages transiently accumulated after LPS application are responsible for various host immune response and tissue destruction caused by LPS.

Administration, Topical↗