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Biomedical subjects

K Kurihara

Publications and source records attributed to K Kurihara.

At least 127 records · Page 7Linked to original sources

Cladinose analogues of sixteen-membered macrolide antibiotics. I. Synthesis of 4-O-alkyl-L-cladinose analogues via glycosylation.

The synthesis and biological evaluation of sixteen-membered macrolides possessing a 4-O-alkyl-alpha-L-cladinosyl moiety as the neutral sugar are described. The nine novel derivatives have been synthesized by glycosylation with 1-thio sugars. The most active derivative of them showed prolonged antibacterial activity in rat plasma in vitro and improved pharmacokinetics.

Animals↗

[The accuracy of several brands of portable peak flow meter, and the predicted value of peak expiratory flow rate for children].

The accuracy, reproducibility and interdevice variability of 6 brands of peak flow meter were evaluated by using a flow generator. The accuracy was satisfiable except for Mini-Wright, which overread by up to 29%. It is essential to identify the brands to compare the data of peak expiratory flow rate (PEFR) from different studies. The reproducibility was under 5%, reliable enough for personal monitoring. The low range models were inferior to the normal range models as a whole. There are some studies about the normal value of PEFR for Japanese children. They have drawn different linear equations to obtain the predicted value of PEFR from the body height. However, none of them can be the "gold standard".

Child↗

[Immunologic analysis of milk, hen egg, and soybean proteins in butter and margarine, and clinical assessment for availability of hypoallergenic margarine (HAM)].

To determine the allergenic proteins in commercially available butter and margarine, protein fractions were extracted and immunologically analyzed against milk, hen egg, and soybean antigens. Butter and 10 kinds of margarine were proved to contain these proteins in various concentrations by ELISA and immunoblotting methods by use of the rabbit antisera developed against each food proteins. However, hypoallergenic margarine was found to contain no such proteins at all. Using sera obtained from atopic dermatitis patients, previously detected high levels of IgE antibodies to milk, hen egg, or soybeans, the extracted protein fraction from butter and margarine was analyzed whether these proteins react with IgG antibodies in patients' sera. The sera with high levels of specific IgE recognized protein antigens in these extracts except those from hypoallergenic margarine, suggesting that proteins in butter and margarine may become allergenic for the patients sensitive to the proteins, and that hypoallergenic margarine will be a reasonable alternative for the allergic patients to milk, hen egg, or soybeans.

Adolescent↗

Identification of novel guanylyl cyclases from chemosensory tissues of rat and cattle.

A number of studies have shown that cGMP may play some roles in chemosensory transduction. To identify the structure of guanylyl cyclase in chemosensory tissues, cDNA fragments encoding guanylyl cyclase catalytic domain were amplified from rat and bovine olfactory and tongue epithelium using degenerate oligonucleotide primers and reverse transcription-polymerase chain reaction (RT-PCR). Three novel clones, two membrane type guanylyl cyclases (RAT GC-1, BOV GC-3) and one soluble type guanylyl cyclase (RAT GC-2) were identified. RAT GC-1 was distributed over various rat tissues in addition to these chemosensory organs. BOV GC-3 was similar to but distinct from recent cloned olfactory-specific guanylyl cyclase. RAT GC-2 was identified as rat homologue of alpha 2 subunit of the soluble guanylyl cyclase.

Amino Acid Sequence↗

Involvement of direct phosphorylation in the regulation of the rat parotid Na(+)-K(+)-2Cl- cotransporter.

We identify a 175-kDa membrane phosphoprotein (pp175) in rat parotid acini whose properties correlate well with the Na(+)-K(+)-2Cl- cotransporter previously characterized functionally and biochemically in this tissue. pp175 was the only phosphoprotein immunoprecipitated by an anti-Na(+)-K(+)-2Cl- cotransporter antibody and the only membrane protein whose phosphorylation state was conspicuously altered after a brief (45-s) exposure of acini to the beta-adrenergic agonist isoproterenol. Phosphopeptide mapping provided evidence for three phosphorylation sites on pp175, only one of which was labeled in response to isoproterenol treatment. The half-maximal effect of isoproterenol on phosphorylation of pp175 (approximately 20 nM) was in excellent agreement with its previously demonstrated up-regulatory effect on cotransport activity. Increased phosphorylation of pp175 was also seen following acinar treatment with a permeant cAMP analogue and with forskolin, conditions that have likewise been shown to up-regulate the cotransporter. Combined with earlier results from our laboratory, these data provide strong evidence that the up-regulation of the cotransporter by these agents is due to direct phosphorylation mediated by protein kinase A. AlF(-)4 treatment, which results in an up-regulation of cotransport activity comparable with that observed with isoproterenol (approximately 6-fold), caused a similar increase in phosphorylation of pp175. However, hypertonic shrinkage and treatment with the protein phosphatase inhibitor calyculin A, which also up-regulate the cotransporter (approximately 3-fold and approximately 6-fold, respectively) caused no change in the phosphorylation level. Furthermore, although acinar treatment with the muscarinic agonist carbachol results in a dramatic up-regulation of cotransport activity and a concomitant phosphorylation of pp175, no phosphorylation of pp175 was seen with the Ca(2+)-mobilizing agent thapsigargin, which is able to fully mimic the up-regulatory effect of carbachol on transport activity. Taken together, these results indicate that direct phosphorylation is only one of the mechanisms involved in secretagogue-induced regulation of the rat parotid Na(+)-K(+)-2Cl- cotransporter.

Animals↗

Effects of protein kinase inhibitors and protein phosphatase inhibitors on cyclic AMP-dependent down-regulation of vesicular monoamine transport in pheochromocytoma PC12 cells.

Cyclic AMP down-regulates vesicular monoamine transport in PC12 cells and thereby decreased catecholamine reuptake from the extracellular fluid. We examined the effects of protein kinase inhibitors and protein phosphatase inhibitors on this cAMP action. Treatment of cells with a protein kinase inhibitor, K252a, increased vesicular amine transport and cellular amine uptake, thereby antagonizing the regulatory action of cAMP. In contrast, a protein phosphatase inhibitor, okadaic acid, had the opposite effect on the amine transport, i.e. it enhanced the cAMP action. These results suggest the involvement of a protein phosphorylation process in the cAMP-dependent modulation of vesicular monoamine transport.

Animals↗

Odor responses after complete desensitization of the cAMP-dependent pathway in turtle olfactory cells.

The degree of contribution of the cAMP signal transduction pathway to odor responses was examined by recording current responses from isolated turtle olfactory cells under the whole-cell voltage clamp conditions. The cAMP signal transduction pathway was desensitized by dialyzing 1 mM cAMP and 0.5 mM IBMX from the patch pipette into the cells. Extracellular application of 3 mM cpt-cAMP, a membrane-permeable cAMP analogue elicited no response, indicating that the cAMP pathway was completely desensitized. Application of an odorant cocktail induced a large inward current under these conditions, suggesting that the cAMP-independent signal transduction contributes significantly to generation of odor responses in the turtle.

1-Methyl-3-isobutylxanthine↗

Effects of adenylyl cyclase-linked neuropeptides on the expression of ciliary neurotrophic factor-mRNA in cultured astrocytes.

Ciliary neurotrophic factor (CNTF) is a molecule which has profound effects on various neural cell types. In the central nervous system, expression of CNTF-mRNA is highly concentrated in olfactory bulb. In the present study, we examined the regulatory mechanism of CNTF-mRNA expression in cultured astrocytes from newborn rat brain. Cultured astrocytes from new born rat brain expressed CNTF-mRNA at levels comparable to the level in olfactory bulb in vivo. Treatment of the astrocytes with forskolin, an activator of adenylyl cyclase, led to a decrease of CNTF-mRNA level. The effect of forskolin was mimicked by cAMP-linked agonists, such as VIP, PACAP, isoproterenol and dopamine. Cycloheximide, an inhibitor of protein synthesis, did not abolish the forskolin-induced decrease of CNTF-mRNA. Measurement of the half-life of CNTF-mRNA in the presence of actinomycin D, an inhibitor of transcription, indicated that the degradation of CNTF-mRNA is not destabilized by the forskolin-treatment. These data taken together suggest that the cAMP-induced suppression of CNTF-mRNA is mainly caused by the inhibition of CNTF gene transcription.

Adenylyl Cyclases↗

Intracellular injection of inositol 1,4,5-trisphosphate increases a conductance in membranes of turtle vomeronasal receptor neurons in the slice preparation.

Inositol 1,4,5-trisphosphate (IP3) was injected into turtle vomeronasal receptor neurons in the slice preparation under a whole-cell patch clamp, and the evoked current was measured. Application of 0.1 mM IP3 evoked a prolonged, inward current (52 of 98 neurons) with an average peak amplitude of 89.9 +/- 10.9 pA. The reversal potential of the response induced by IP3 was estimated to be -32.3 +/- 1.5 mV (6 neurons). Bathing the neurons in 10 microM ruthenium red solution greatly reduced the IP3 evoked inward current to 18.0 +/- 4.6 pA (5 neurons). This is the first study to demonstrate that the membranes of the turtle vomeronasal neurons carry IP3-activated conductance.

Animals↗

Selective inhibition of bitter taste of various drugs by lipoprotein.

Previously, we demonstrated that lipoprotein composed of phosphatidic acid (PA) and beta-lactoglobulin (LG) selectively and reversibly suppress the frog taste nerve response to bitter substances. In the present study, we examined the effects of various lipoproteins on the taste sensation to various stimuli in humans by a psychophysical method. Among various lipoproteins composed of different of lipids and proteins, the lipoproteins composed of PA and proteins were most effective in suppressing bitter taste. The lipoproteins composed of PA and LG, bovine serum albumin, ovalbumin, alpha-lactoalbumin or casein similarly suppressed effects on sensation of bitter taste. Using PA-LG, the effects on taste sensation to various stimuli were examined. The bitter taste of all twelve substances examined was inhibited, while saltiness of NaCl and sweetness of sucrose were not inhibited. The inhibition of bitter taste was completely reversible. Masking of the target sites for bitter substances on the taste receptor membranes with PA-LG seems to contribute to the inhibition of bitter taste. Direct binding of the bitter substances to PA-LG in the medium also contributes to the inhibition of bitter taste of certain substances. Among various drugs, basic and hydrophobic substances such as quinine, denatortium and propranolol have low taste thresholds and are said to be the most bitter. PA-LG most effectively suppressed the bitter taste of such substances. PA originates from soybeans and the proteins used except for bovine serum albumin originate from milk or eggs, and hence the lipoproteins can be safely used to mask the bitter taste of drugs.

Caffeine↗

Proliferative vitreoretinopathy in Coats' disease. Clinicohistopathological case report.

We report the clinicohistopathological findings of the proliferative vitreoretinopathy in an eye with Coats' disease using the tissue obtained during surgery. A 28-year-old man, who had experienced poor vision in his right eye for a period of 4 years, was referred to our hospital. Examination revealed an extensive yellow exudate in the subretinal space and a tractional retinal detachment. Prominent teleangiectatic retinal vessels were also temporally present. Evident epiretinal membranes were present in the postequatorial area. We performed a scleral buckling, vitrectomy, membrane peeling, endophotocoagulation and silicone oil tamponade. A histological examination revealed that the epiretinal membrane consisted of collagen fibers, glial proliferation, foam cells and lymphocytes. The foam cell in the epiretinal membrane is a characteristic finding in an eye with Coats' disease.

Adult↗

High sensitivity of the turtle olfactory system to nonvolatile substances: comparison of response properties with those in gustatory systems.

The olfactory responses of the aquatic turtles, Geocylemys reevesii whose nostrils are closed underwater to nonvolatile substances were measured by recording the olfactory bulbar responses. Various salts, acids and bitter substances elicited large responses, while sugars and amino acids did not elicit the responses. The thresholds for the salts were much lower than those of corresponding salts in the rat gustatory system. The responses to the salts were partially suppressed by amiloride. Various acids induced large responses and the magnitudes greatly depended on the anion species. The thresholds for the bitter substances were much lower than those of corresponding substances in the taste systems. Similar to the responses in taste systems, both electrostatic and hydrophobic interactions contribute to the binding of the substances to the receptor membranes. Similar to the taste systems, the response to quinine hydrochloride showed a sharp temperature dependence having a peak around 25 degrees C, while the responses to odorants did not show such peak. The present results suggest that the olfactory system has similar abilities to respond to salts, acids and bitter substances to those in gustatory systems and that the high sensitivity of the olfactory system to chemical stimuli is not only attributable to the second messenger amplification system, but also to the basic property of the receptor membrane independent of the amplification system.

Acids↗

Retinoic acid induces BDNF responsiveness of sympathetic neurons by alteration of Trk neurotrophin receptor expression.

The expression of high affinity neurotrophin receptors (TrkA, TrkB, and TrkC) determines the survival response of different populations of neurons to specific members of the neurotrophin family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). However, the mechanism which controls the expression of neurotrophin receptors during neuronal development is largely unknown. Here we show that the treatment of the cultured sympathetic neurons from newborn rat superior cervical ganglia (SCG) with retinoic acid (RA), a derivative of vitamin A, suppressed the expression of trkA mRNA and induced the expression of trkB mRNA. Expression of the functional TrkB receptor was confirmed by the emergence of trophic dependence of these neurons on BDNF in the absence of NGF. Differential regulation of trk mRNAs by RA provides a possible model for the establishment of neurotrophin dependence of peripheral neurons.

Animals↗

Taste receptor proteins directly extracted by liposome from intact epithelium of bullfrog tongue.

This work first provides that epithelial membrane proteins can be directly transferred from animal intact tissue to liposome. Bullfrog tongue was treated with a specially modified liposome that contains an artificial boundary lipid. Glossopharyngeal nerve responses of the treated tongue were then measured to five taste stimuli (NH4Cl, L-Ala, sucrose, L-Leu, and quinine hydrochloride). The liposomal treatment caused remarkable changes of the taste nerve responses. Gel electrophoretic analysis of the treated liposome revealed that the direct transfer of proteins, likely taste receptor, certainly occurred from the tongue epithelium to the liposome.

Animals↗

Enhancement of the turtle olfactory responses to fatty acids by treatment of olfactory epithelium with phosphatidylserine.

The turtle olfactory epithelium was treated with suspensions of various lipids and their effects on the olfactory responses were examined by measuring the olfactory bulbar responses. The phosphatidylserine (PS)-treatment greatly lowered the threshold for n-valeric acid and enhanced its responses at all concentrations examined. The responses to isovaleric acid and n-butyric acid were also greatly enhanced by the PS-treatment. The responses to ten other odorants examined were a little enhanced or unchanged by the PS-treatment. The enhanced responses to the fatty acids returned to the original level about 10 h after the treatment. It was confirmed that PS was incorporated into olfactory epithelium by incubating the epithelium with PS-suspension containing [14C]PS. The treatment of the epithelium with phosphatidic acid or cardiolipin unchanged or suppressed the responses to odorants including the fatty acids. The present results suggest that lipids as well as proteins in the receptor membranes play an important role in odor reception.

Animals↗

Odor discrimination in single turtle olfactory receptor neuron.

To explore the ability of odor discrimination of olfactory receptor neurons, current responses to odorant cocktails were recorded from an isolated olfactory neuron of the turtle. Twenty-five percent of the neurons tested responded to both cAMP-dependent and the IP3-dependent odorant cocktails. Application of the cAMP-dependent (or the IP3-dependent) odorant cocktail to the neuron after an inward current induced by the IP3-dependent (or the cAMP-dependent) odorant cocktail was adapted induced a large inward current in the neuron. The results suggest that at least two different receptors exist in a single olfactory neuron.

Animals↗