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Biomedical subjects

T Naito

Publications and source records attributed to T Naito.

At least 19 recordsLinked to original sources
PubMed2001

Purification and characterization of an autoregulatory substance capable of regulating the morphological transition in Candida albicans.

The yeast Candida albicans has a distinguishing feature, dimorphism, which is the ability to switch between two morphological forms: a budding yeast form and a multicellular invasive filamentous form. This ability has been postulated to contribute to the virulence of this organism. Studies on the morphological transition from a filamentous to a budding yeast form in C. albicans have shown that this organism excretes an autoregulatory substance into the culture medium. This substance was extracted and purified by normal-phase and reversed-phase HPLC. The autoregulatory substance was structurally identified as 3,7,11-trimethyl-2,6,10-dodecatrienoate (farnesoic acid) by NMR and mass spectrometry. Growth experiments suggest that this substance does not inhibit yeast cell growth but inhibits filamentous growth. These findings have implications for developmental signaling by the fungus and might have medicinal value in the development of antifungal therapies.

Candida albicans↗
PubMed2001

Effects of Ninjin-to on levels of brain-gut peptides (motilin, vasoactive intestinal peptide, gastrin, and somatostatin) in human plasma.

We examined the effects of Ninjin-to, a traditional Chinese (Kampo) medicine, on the levels of brain-gut peptides (motilin, vasoactive intestinal peptide (VIP), gastrin, and somatostatin) in plasma from healthy subjects. A single oral administration of Ninjin-to, at a dose of 6.0 g, caused significant increases in plasma motilin levels at 40 to 90 min and somatostatin levels at 20 to 90 min, compared with a placebo treated group. Transient elevations of gastrin levels in the placebo group were inhibited by administration of Ninjin-to, but the medicine did not alter the levels of VIP. In conclusion, these results suggest that pharmacological effects of Ninjin-to on gastrointestinal functions closely relate to changes of motilin, gastrin, and somatostatin-immunoreactive substance levels in human plasma.

Drugs, Chinese Herbal↗
PubMed2001

Radical cyclization in heterocycle synthesis. 12. Sulfanyl radical addition-addition-cyclization (SRAAC) of unbranched diynes and its application to the synthesis of A-ring fragment of 1alpha,25-dihydroxyvitamin D3.

Sulfanyl radical addition-addition-cyclization (SRAAC) of unbranched diynes proceeded smoothly to give cyclized exo-olefins, while the sulfanyl radical addition-cyclization-addition (SRACA) of diynes having a quaternary carbon gave cyclized endo-olefins. This method was successfully applied to the synthesis of A-ring fragment of 1alpha,25-dihydroxyvitamin D3.

Calcitriol↗
PubMed2000

A new alternative to the mannich reaction: tandem radical addition-cyclization reaction for asymmetric synthesis of gamma-butyrolactones and beta-amino acids

The radical addition-cyclization reaction of substrates having two different radical acceptors such as acrylate and aldoxime ether moieties was studied. This new free radical-mediated Mannich-type reaction proceeded smoothly via a tandem C-C bond-forming process. Furthermore, the diastereoselective tandem reaction provides the novel method for asymmetric synthesis of gamma-butyrolactones and beta-amino acid derivatives.

Journal Article↗
PubMed2000

Radical cyclization in heterocycle synthesis. 11.(1) A novel synthesis of alpha,beta-disubstituted gamma-lactones via sulfanyl radical addition-cyclization using hydroximates as a tether

A combination of sulfanyl radical addition-cyclization of dienes connected with hydroximates and subsequent conversion of the resulting cyclic hydroximate to the lactones provides a novel method for the construction of alpha,beta-disubstituted gamma-lactones. Upon treatment with thiophenol in the presence of AIBN, dienes connected with hydroximates smoothly underwent sulfanyl radical addition-cyclization to give cyclic cis- and trans-hydroximates. Hydrolysis of cyclic hydroximates gave the desired cis- and trans-lactones in high yield. This method was successfully applied to the practical synthesis of (+/-)-oxo-parabenzlactone.

Journal Article↗
PubMed2000

Asymmetry of the human visual field in magnetic response to apparent motion.

Predominance of the lower visual field has been shown in various visual tasks, but whether the upper visual field is involved in a specific neural process is unknown. We used magnetoencephalography to study the effect of orientation and direction on the responses of five subjects to apparent motion from the human extrastriate cortex. The first magnetic response always was the largest, and the peak latency of about 200 ms did not change with the stimulus conditions. Amplitudes of the first responses were highest when motions were oriented at the horizontal meridian, decreasing with the degree of the angle between motion orientation and the horizontal meridian. There was no difference in amplitude between the two directions in the lower visual field, whereas the value of the response to downward motion in the upper visual field was significantly larger than that to upward motion. These amplitude changes are not due to differences in the anatomical distribution of neural activities because the estimated origins for the first responses always were in the same cortical area (around the occipito-parieto-temporal region) and the directions of the current vectors did not change with the stimulus conditions, and the estimated current strength changed with the stimulus conditions as did the response amplitude. These findings suggest that the human extrastriate cortex has a directional preference for downward versus upward motion in the upper visual field.

Adult↗
PubMed2000

Stereocontrol in solid-phase radical reactions: radical addition to oxime ether anchored to polymer support

A high degree of stereocontrol in solid-phase radical reactions was achieved by using triethylborane and diethylzinc as a radical initiator at low reaction temperature. Alkyl radical addition to Oppolzer's camphorsultam derivatives of oxime ether anchored to polymer support proceeded smoothly to give the alpha-amino acid derivatives with excellent diastereoselectivities.

Journal Article↗
PubMed2000

Doxapram accentuates white matter injury in neonatal rats following bilateral carotid artery occlusion.

The effect of the respiratory stimulant, doxapram, on white matter damage was investigated in neonatal rats under cerebral ischemia. Five-day-old rats underwent bilateral carotid artery occlusion with or without 50 mg/kg i.p. of doxapram. Their brains were neuropathologically examined 48 h later. Doxapram induced about a 20% decrease of PCO(2) for 90 min, but did not cause any neuropathological abnormalities. Bilateral carotid artery occlusion resulted in mild cerebrocortical lesions in 67% of pups, and white matter lesions in the internal capsule in 44%. Doxapram, in addition to bilateral carotid artery occlusion, produced more severe white matter injury in the internal capsule (injury score; 0.67+/-0.87 vs. 1.70+/-0.48, P<0.05) and in the subcortical white matter (0.33+/-0. 67 vs. 1.10+/-0.54, P<0.05). These results demonstrated that the use of doxapram under an ischemic condition accentuates white matter damage in neonatal rats.

Animals↗
PubMed2000

Increase in receptor binding affinity for nimodipine in the rat brain with permanent occlusion of bilateral carotid arteries.

The permanent occlusion of bilateral common carotid arteries (2VO) in rats has been shown to cause progressive and long-lasting cognitive deficits which may be due to impairment of memory retention and/or memory recall process. To clarify the function of voltage dependent calcium channels and the receptor binding of nimodipine by chronic cerebral ischemia, we examined specific (+)-[3H]PN 200-110 binding and the effect of oral administration of nimodipine in brain regions and hearts of rats, at 2 weeks to 4 months after permanent 2VO. There was no significant difference in either dissociation constant (Kd) or maximal number of binding sites (Bmax) for (+)-[3H]PN 200-110 in the cerebral cortex, hippocampus, corpus striatum and thalamus between 2VO and sham rats. In addition, in vitro inhibitory effect of nimodipine on cerebral cortical (+)-[3H]PN 200-110 binding in 2VO rats was similar to that in sham rats. Compared to control rats, oral administration of nimodipine to both 2VO and sham rats at 2 months after permanent 2VO brought about a significant increase in Kd values of specific (+)-[3H]PN 200-110 binding in the cerebral cortex, hippocampus, thalamus and myocardium, and the increase in Kd values was much larger in brain regions of 2VO rats than sham rats. However, the increase in Kd values in the myocardium did not differ between 2VO and sham rats. This observation suggests an increased in vivo binding affinity for nimodipine in chronic ischemic brain. In conclusion, the present study has shown that oral administration of nimodipine may cause a greater occupation in vivo of 1,4-dihydropyridine (DHP) calcium channel antagonist receptors in brains of permanent 2VO rats than in sham rats. Thus, nimodipine may be pharmacologically effective in preventing brain dysfunction due to cerebral ischemia in vivo.

Animals↗
PubMed2000

Asymmetric synthesis of alpha-amino acids based on carbon radical addition to glyoxylic oxime ether

The first asymmetric synthesis of alpha-amino acids based on diastereoselective carbon radical addition to glyoxylic imine derivatives is reported. The addition of an isopropyl radical, generated from i-PrI, Bu(3)SnH, and Et(3)B in CH(2)Cl(2) at 25 degrees C, to achiral glyoxylic oxime ether 1 proceeded regioselectively at the imino carbon atom of the oxime ether group to give an excellent yield of the C-isopropylated product 2. The competitive reaction using glyoxylic oxime ether 1 and aldoxime ether 4 showed that the reactivity of the glyoxylic oxime ether toward nucleophilic carbon radicals was enhanced by the presence of a neighboring electron-withdrawing substituent. Thus, the alkyl radical addition to glyoxylic oxime ether 1 proceeded smoothly even at -78 degrees C, in contrast to the unactivated aldoxime ether 4. A high degree of stereocontrol in the carbon radical addition to the glyoxylic oxime ether was achieved by using Oppolzer's camphorsultam as a chiral auxiliary. The stannyl radical-mediated reaction of the camphorsultam derivative 6 with an isopropyl radical at -78 degrees C afforded a 96:4 diastereomeric mixture, 7a, of the C-isopropylated product. The reductive removal of the benzyloxy group of the major diastereomer (R)-7a, by treatment with Mo(CO)(6) and the subsequent removal of the sultam auxiliary by standard hydrolysis, afforded the enantiomerically pure D-valine (R)-12 without any loss of stereochemical purity. To evaluate the new methodology, a variety of alkyl radicals were employed in the addition reaction which gave the alkylated products 7 with excellent diastereoselectivity, allowing access to a wide range of enantiomerically pure natural and unnatural alpha-amino acids. Even in the absence of Bu(3)SnH, treatment of 6 with alkyl iodide and Et(3)B at 20 degrees C gave the C-alkylated products 7 with moderate diastereoselectivities. The use of Et(2)Zn as a radical initiator, instead of Et(3)B, was also effective for the radical reaction. The enantioselective isopropyl radical addition to 1 using (R)-(+)-2, 2'-isopropylidenebis(4-phenyl-2-oxazoline) and MgBr(2) gave excellent chemical yield of the valine derivative 2 in 52% ee.

Journal Article↗
PubMed2000

Activation of hepatic NKT cells and subsequent liver injury following administration of alpha-galactosylceramide.

It has been established that alpha-galactosylceramide (alpha-GalCer), a glycolipid, is recognized by natural killer T (NKT) cells together with the monomorphic MHC-like antigen, CD1d, in mice and humans. In this study, we examined how NKT cells are modulated by in vivo administration of alpha-GalCer in mice. When 2 microg (or more)/mouse of alpha(-GalCer was injected i.p., the majority of NKT cells disappeared in the liver and spleen, possibly undergoing apoptosis, on day 1. At this time, NKT cytotoxicity seen in liver lymphocytes also disappeared. In parallel with this numerical and functional change of NKT cells, there was always concomitant hepatocyte damage, as shown by histology and elevated levels of transaminases. Subsequently, the number and function of NKT cells continued to increase from day 3 to day 7. The response seen in hepatic (and splenic) NKT cells did not occur in thymic NKT cells. All these phenomena induced in the liver did not appear in NKT-deficient mice such as beta2-microglobulin(-/-) and CD1d(-/-) mice. These results shed further light on the in vivo interaction between NKT cells and alpha-GalCer in mice.

Aging↗
PubMed2000

Heterologous enzyme immunoassay for serum androstenediol.

A heterologous enzyme immunoassay for serum androstenediol (Adiol: 3beta, 17beta-dihydroxy-androst-5-ene) was established. The combination of anti-Adiol antiserum raised in rabbit against Adiol 7-O-(carboxymethyl)oxime (Adiol 7-CMO) conjugated bovine serum albumin (Adiol 7-CMO-BSA) and Adiol 7-iminomethylcarboxylic acid conjugated alkaline phosphatase was used for the assay. The sensitivity of the heterologous assay system was superior to that of a homologous assay system in which an antibody raised in rabbit against Adiol 7-CMO-BSA and enzyme labeled antigen, Adiol 7-CMO conjugated alkaline phosphatase, were used. The minimal amount of Adiol detected was 0.4 ngml(-1) and the measurable range was from 0. 4 to 150 ngml(-1). Intra-assay coefficients of variation (C.V.) were 8.6% (1.52+/-0.13 ngml(-1), mean+/-S.D., n=10) and 6.7% (13.4+/-0.9 ngml(-1), n=10). Inter-assay C.V. were 12.9% (1.63+/-0.21 ngml(-1), n=8) and 11.5% (12.2+/-1.4 ngml(-1), n=8). A linear relation was observed between the serum sample dilution and the Adiol concentration. For recovery study, authentic Adiol was added to serum sample (original concentration: 1.43 ngml(-1)). The calculated final Adiol concentration was 2.99 ngml(-1). The recovery was 98.6% (n=5). The Adiol concentrations in healthy subjects measured by the proposed assay (male: 1.1+/-0.3 ngml(-1) (mean+/-S.D.), range: 0.7-1. 7 ngml(-1), age: 22-50, n=10; female: 0.6+/-0.4 ngml(-1), range: 0. 2-1.6 ngml(-1), age: 23-48, n=20) were consistent with reported values.

Adult↗
PubMed2000

Brain distribution of 6-mercaptopurine is regulated by the efflux transport system in the blood-brain barrier.

6-mercaptopurine (6-MP) has been used clinically for 40 years to maintain remission in patients with acute lymphoblastic leukemia (ALL). However, central nervous system (CNS) relapses frequently occur in patients with ALL who continuously receive anticancer drugs, including 6-MP, during remission maintenance therapy. The cause of such CNS relapse is not well understood. One possible reason may involve the restricted distribution of 6-MP in the brain. This study, therefore, investigates the blood-brain barrier (BBB) transport which largely regulates 6-MP distribution in the brain using a quantitative microdialysis technique and centers on the efflux transport of 6-MP across the BBB. The brain tissue, cerebrospinal fluid (CSF), or hippocampal interstitial fluid (ISF) concentration of 6-MP was very low compared with the unbound plasma concentration, suggesting that 6-MP distribution in the brain is highly restricted. Kinetic analyses of this BBB transport showed that the efflux clearance from brain ISF to plasma across the BBB (CLout) is approximately 20-times greater than the influx clearance from plasma to brain (CLin). The CLout was significantly reduced by 1mM N-ethylmaleimide (NEM), a sulfhydryl-modifying agent, suggesting the participation of transport protein in the efflux of 6-MP across the BBB. In addition, efflux transport was inhibited by an intracerebral infusion of probenecid (1.5 mM), p-aminohippuric acid (PAH, 3.0 mM), benzoate (3.6 mM), or salicylate (3.7 mM) administered through a microdialysis probe, but neither choline (0.8 mM) nor tetraethylammonium (TEA, 0.7 mM) had any effect. These data suggest that the restricted 6-MP brain distribution may be ascribed to efficient efflux from the brain, possibly via both the organic anion transport system, shared with probenecid and PAH, and the monocarboxylic acid transport system, shared with benzoate and salicylate.

Animals↗
PubMed2000

Magnetic response of human extrastriate cortex in the detection of coherent and incoherent motion.

Although direction selectivity is a cardinal property of neurons in the visual motion detection system, movement of numerous elements without global direction (incoherent motion) has been shown to activate human and monkey visual systems, as does coherent motion which has global direction. We used magnetoencephalography to investigate the neural process underlying responses to these types of motions in the human extrastriate cortex. Both motions were created using a random dot kinematogram and four speeds (0, 0.6, 9.6 and 25 degrees /s). The visual stimuli were composed of two successive motions at different speeds; a coherent motion at a certain speed that changed to incoherent motion at another speed or vice versa. Magnetic responses to the change in motion consisted of a few components, the first of which was always largest. The peak latency of the first component was inversely related to the speed of the preceding motion, but for both motions it was not affected by the speed of the subsequent motion. For each subject, the estimated origin of the first component was always in the extrastriate cortex, and this changed with the speed of the preceding motion. For both motions, the location for the slower preceding motion was lateral to that for the faster preceding motion. Although the latency changes of the two motions differed, their overall response properties were markedly similar. These findings show that the speed of incoherent motion is represented in the human extrastriate cortex neurons to the same degree as coherent motion. We consider that the human visual system has a distinct neural mechanism to perceive random dots' motion even though they do not move in a specific direction as a whole.

Adult↗
PubMed2000

Blood-brain barrier transport of 125I-labeled basic fibroblast growth factor.

PURPOSE: This study was carried out to examine the blood-brain barrier (BBB) transport of human basic fibroblast growth factor (bFGF) and investigate its mechanism. METHODS: The BBB transport of 125I-bFGF was measured by several in vivo methods including intravenous administration, in situ internal carotid artery perfusion, and intracerebral microinjection. The in vitro binding of 125I-bFGF was characterized using freshly prepared bovine brain capillaries. RESULTS: The distribution volume of 125I-bFGF in the postvascular supernatant increased with the perfusion time, and exceeded the space occupied by the brain microvasculature and its trichloroacetic acid (TCA) precipitability was more than 90%. 125I-bFGF avidly bound to isolated bovine brain capillaries with a Bmax of 206 +/- 48 pmol/mg protein, and a Kd of 36.5 +/- 15.7 nM. This binding was significantly inhibited by unlabeled bFGF and heparin in a concentration-dependent manner. The cationic peptides, protamine and poly-L-lysine (each 300 microM), produced over 85% inhibition of 125I-bFGF binding to brain capillaries. Furthermore, glycosaminoglycans with a sulfate residue, chondroitin sulfate B and C (each 10 microg/mL) also inhibited the binding of 125I-bFGF The in vivo transcytosis of 125I-bFGF from the luminal side to the brain was also inhibited by the presence of heparin (10 microg/mL) and poly-L-lysine (300 microM), whereas neither hyaruronic acid (10 microg/mL) nor insulin (10 microM) had any effect. In addition to these results, the brain efflux index method was used to confirm that the transcytosis of 125I-bFGF from brain to blood across the BBB was negligible. CONCLUSIONS: These results suggest that 125I-bFGF is transported across the BBB, possibly by an adsorptive-mediated transcytosis mechanism that is triggered by binding to negatively charged species on the luminal membrane surface of the brain microvasculature, such as heparan sulfate proteoglycans.

Animals↗
PubMed2000

Disparate effect of beige mutation on cytotoxic function between natural killer and natural killer T cells.

Beige mice lack natural killer (NK) cytotoxicity, although NK cells are normally present. In recent studies, NK T cells have been newly identified. We therefore examined the number and function of NK T cells in beige mice. The number of NK T cells was at a normal level in the liver of beige mice. NK cytotoxicity was decreased in the liver of these mice, whereas NK T cytotoxicity was intact. When immunochemical staining for perforin was conducted, the majority of NK cells and the minority of NK T cells in beige mice carried a giant granule, containing perforin, in the cytoplasm. In the case of control B6 mice, the majority of NK cells and the minority of NK T cells had multiple, dispersed granules containing perforin. These results suggest that NK T cytotoxicity is unaffected by the beige mutation, owing to their cytotoxicity being mediated without the secretion system of perforin.

Animals↗
PubMed2000

Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.

BACKGROUND: We previously described that monocyte chemoattractant protein-1 (MCP-1) plays an important role in progressive glomerular and interstitial damage in inflammatory renal diseases. However, the expression of MCP-1 in diabetic nephropathy remains to be investigated. METHODS: We examined whether locally expressed MCP-1 participates in human diabetic nephropathy via recruiting and activating monocytes/macrophages (Mphi). Urinary and serum MCP-1 levels were measured by enzyme-linked immunosorbent assay in 45 patients with diabetic nephropathy. The presence of MCP-1 in diseased kidneys was determined by immunohistochemical and in situ hybridization analyses. RESULTS: Urinary MCP-1 levels were significantly elevated in patients with diabetic nephrotic syndrome and advanced tubulointerstitial lesions. Moreover, urinary levels of MCP-1 were well correlated with the number of CD68-positive infiltrating cells in the interstitium. In contrast, serum MCP-1 levels remained similar to those of healthy volunteers. Furthermore, we detected the MCP-1-positive cells in the interstitium of diabetic nephropathy via both immunohistochemical and in situ hybridization analyses. CONCLUSION: These observations suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy as well as inflammatory renal diseases.

Adolescent↗