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T Koga

Publications and source records attributed to T Koga.

At least 199 records · Page 11Linked to original sources
PubMed1998

Carbonyl reductase purified from rabbit liver is not the product of a carbonyl reductase gene (RCBR5 or RCBR6) cloned from the rabbit liver cDNA library.

Six peptides were obtained by the digestion of carbonyl reductase purified from rabbit liver. The amino acid sequences of the six peptides were virtually identical to the corresponding regions in amino acid sequences deduced from two cloned carbonyl reductase genes (RCBR5 and RCBR6). However, there was a difference of one amino acid residue between the sequences of peptides from the purified enzyme and the corresponding region in the amino acid sequences deduced from the two cDNAs. The purified carbonyl reductase was confirmed to exhibit no reactivity towards menadione, even though the transient expression of the two cDNA for rabbit liver carbonyl reductase has been reported to cause a marked increase of menadione reductase activity in COS7 cells. The enzyme purified from rabbit liver was inactivated by thiol-specific reagents, 5,5'-dithiobis(2-nitrobenzoic acid) and sodium tetrathionate, suggesting that menadione probably interacts with the functional cysteine residue(s), and cannot serve as a substrate of the purified enzyme. Based on these results, it is concluded that the carbonyl reductase purified from rabbit liver is not the product of cloned carbonyl reductase gene (RCBR5 or RCBR6).

Alcohol Oxidoreductases↗
PubMed1998

Antioxidative activities of 4-hydroxy-3(2H)-furanones and their anti-cataract effect on spontaneous cataract rat (ICR/f).

We determined the anti-cataract effects and antioxidative activities of four 4-hydroxy-3(2H)-furanones. These four furanones showed similar antioxidative activities in the ferric ion reduction model. 4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) and 2(or 5)-ethyl-4-hydroxy-5(or 2)-methyl-3(2H)-furanone (EHMF) exhibited a higher suppression effect on lipid peroxidation in human plasma than the other furanones did. The effects of hydroxy furanones on the onset of cataract in spontaneous cataract rat (ICR/f rat) were tested, and it was observed that HDMF and EHMF inhibited cataract formation. These results suggest that the antioxidative activity of HDMF and EHMF against superoxide radicals in lens tissue contributed to inhibiting the onset of spontaneous cataract.

Animals↗
PubMed1998

Synthesis of 4-hydroxy-3(2H)-furanone acyl derivatives and their anti-cataract effect on spontaneous cataract rats (ICR/f).

4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) and 2(or 5)-ethyl-4-hydroxy-5(or 2)-methyl-3(2H)-furanone (EHMF) are known to inhibit cataract development in spontaneous cataract rats (ICR/f). Forty-five acylated hydroxyfuranone derivatives were designed and synthesized for an anti-cataract test, and their hydrophobic constants were also tested. Among these derivatives, 2,5-dimethyl-4-pivaloyloxy-3(2H)-furanone (HDMF pivalate) exerted a marked protective effect against the development of cataract in a galactose-induced model using cultured rat lens (in vitro). When tested on an ICR/f cataract model (in vivo), HDMF pivalate showed more significant inhibition of cataract development than parent compound HDMF. This derivative is more lipophilic than HDMF, so that HDMF pivalate can penetrate the cornea more easily than HDMF. The inhibition of cataract development by HDMF converted from HDMF pivalate is supported by the fact that HDMF was observed in the lens of ICR/f rats treated with HDMF pivalate.

Acylation↗
PubMed1998

Synthesis of a novel phosphate ester of a vitamin E derivative and its antioxidative activity.

A novel phosphate ester containing a chromanol structure was synthesized from 1,2-diacyl-sn-glycero-3-phospho-2'-hydroxyethyl-2',5',7',8'-tetramethyl- 6' -hydroxychroman (PCh) by hydrolysis catalyzed by phospholipase C from Bacillus cereus. The structure of the product was found by spectral analyses to be 2-(2',5',7',8'-tetramethyl-6'-hydroxychromanyl)ethylphosphate++ + (Ch-P). Ch-P was highly soluble in the aqueous phase at neutral pH values and exerted higher antioxidative activity than alpha-tocopherol and PCh in the Fe(III)/ascorbic acid-catalyzed peroxidation of a fish oil emulsion and the autoxidation of a rat brain homogenate.

Animals↗
PubMed1998

28-day repeated oral toxicity study of a hypolipidemic agent, NK-104 in rats.

NK-104, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, was administered orally to Wistar rats at a dose of 2, 10, 50 or 100 mg/kg for 28 days consecutively, and the toxicity of NK-104 and its recovery with 2 weeks cessation of drug treatment were examined. As major clinical signs, loose stool, diarrhea, crouching and emaciation were observed in both sexes at 50 or 100 mg/kg, and all females at 100 mg/kg died or became moribund due to severe emaciation before the completion of treatment. The suppression of body weight gain or decrease in body weight was observed in the female dose group at 50 mg/kg and both sexes at 100 mg/kg. Decreased food intake was observed in both sexes at 100 mg/kg. Moreover, an increase in cholinesterase (Ch.E) in the male dose groups at 50 and 100 mg/kg and an increase in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the female dose group at 50 mg/kg were observed in blood chemistry testing. Macroscopic examination showed thickening of the forestomach mucosa in the groups of 10 mg/kg or more. Microscopic examination revealed hyperkeratosis and hypertrophy of the spinous layer associated with both cell infiltration of the mucosal propria and submucosal edema. In addition, skeletal muscle lesions including atrophy, vacuolation and focal necrosis were observed in the female dose groups at 50 and 100 mg/kg. The above-mentioned microscopic changes were not observed on cessation of drug treatment. The non-toxic dose level of NK-104 in the 28-day repeated oral toxicity study using rats was determined to be 2 mg/kg.

Administration, Oral↗
PubMed1998

Six-month repeated oral toxicity study of NK-104 in rats.

NK-104 is a novel potent inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and has been shown to be a highly effective agent in lowering blood cholesterol. In the present study, NK-104 was orally administered to Wistar rats at a dose of 0.3, 1, 3 or 010 mg/kg for 6 months for examination of toxicity. Additional recovery groups of 8 rats each of both sexes receiving 0 and 10 mg/kg were maintained without treatment for 1 month in order to assess recovery. As a result, no toxicological changes were observed in general signs, body weight, food intake, ophthalmological examination, urinalysis, hematological and blood chemical examinations for organ weights. An autopsy revealed thickening of the forestomach mucosa in both sexes at a dose of 1 mg/kg or more. This change was microscopically recognized as hyperkeratosis and hypertrophy of the spinous layer associated with both cell infiltration of the mucosal propria and edema of sub-mucosa in the forestomach in both sexes at doses of 3 and 10 mg/kg. Forestomach changes were not observed in any cases after 1 month cessation of drug treatment. The non-toxic dose of NK-104 in the 6-month repeated oral toxicity study in rats is estimated to be 1 mg/kg/day.

Administration, Oral↗
PubMed1998

Isolated partial growth hormone deficient short stature with syringomyelia not associated with birth injury.

A 59-year-old female with 20-year history of slowly progressing muscle atrophy and sensory disturbance of upper extremities showed short stature, scoliosis, hunger type of sensory dissociation of the upper extremities and pyramidal tract sign of the lower extremities. Magnetic resonance imaging (MRI) clarified hypoplasia of the anterior pituitary lobe, Arnold-Chiari malformation and cervical syringomyelia. Insulin and arginine stimulating tests revealed partial type of isolated growth hormone (GH) deficiency but GH gene analysis detected no defects of GH genes. It was considered to be a rare case of non-hereditary hypopituitarism with Chiari malformation and syringomyelia not associated with perinatal injury, namely a midline anomaly syndrome.

Arnold-Chiari Malformation↗
PubMed1998

Lipid lowering effects of pravastatin in common marmosets.

In the present study it was examined if the common marmoset was susceptible to pravastatin (CAS 81131-70-6, CS 514, Mevalotin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. It has been reported that serum lipid levels in common marmosets resemble those in humans. First serum total cholesterol and lipoprotein cholesterol levels of common marmosets were examined in comparison with those in seven different experimental animals including cynomolgus monkeys, beagle dogs, Watanabe heritable hyperlipidemic rabbits, Japanese White Rabbits, Sprague Dawley rats, Wistar-Imamichi rats and golden hamsters. The animals were fed normal chow diets, and total- and lipoprotein-cholesterol levels were determined under identical conditions. The quantitative and polyacrylamide electrophoresis studies indicated that among animals examined serum lipid and lipoprotein profiles in common marmosets were similar to those in humans. When pravastatin at 1-30 mg/kg was orally administered to common marmosets for 28 days, total, low density lipoprotein (LDL)- and high density lipoprotein-cholesterol levels were decreased in a dose dependent manner, whereas triglycerides and very low density lipoprotein cholesterol did not change. These findings confirm that common marmosets have serum lipid and lipoprotein profiles similar to those in humans suggesting that they are susceptible to lipid lowering effects of HMG-CoA reductase inhibitors.

Animals↗
PubMed1998

Bullous prurigo pigmentosa and diabetes.

Prurigo pigmentosa (PP) is a type of inflammatory dermatosis characterized by pruritic, reddish, papular lesions that normally resolve while leaving gross reticular pigmentation. In severe cases however, they may form edematous infiltrative plaques, but no formation of vesicles or bullae is generally found. We herein present the case of a 32-year-old Japanese male patient with diabetes mellitus, who developed a severe vesicular formation. Minocycline was found to be very effective. In addition, the eruption subsided when the urine glucose and ketone levels were controlled by glibenclamide. The most characteristic feature in this case was the fact that numerous vesicles and bullae were seen both in the beginning and throughout the clinical course. It therefore seems that a sudden exacerbation of diabetes mellitus was associated with a severe formation of vesicles and bullae. The findings of this case may suggest a correlation between diabetes mellitus and PP.

Adult↗
PubMed1998

Long-term efficacy and adverse event of nifedipine sustained-release tablets for cyclosporin A-induced hypertension in patients with psoriasis.

Thirteen psoriatic patients with hypertension during the course of cyclosporin A therapy were treated for 25 months with a calcium channel blocker, sustained-release nifedipine, to study the clinical antihypertensive effects and adverse events during treatment with both drugs. Seven of the 13 patients had exhibited a subclinical hypertensive state before cyclosporin A therapy. Both systolic and diastolic blood pressures of these 13 patients were decreased significantly after 4 weeks of nifedipine therapy, and blood pressure was maintained within the normal range thereafter for 25 months. The adverse events during combined therapy with cyclosporin A and nifedipine included an increase in blood urea nitrogen levels in 9 of the 13 patients and development of gingival hyperplasia in 2 of the 13 patients. Our findings indicate that sustained-release nifedipine is useful for hypertensive psoriatic patients under long-term treatment with cyclosporin A, but that these patients should be monitored for gingival hyperplasia.

Adult↗
PubMed1998

Dermatophytes and host defence in cutaneous mycoses.

Dermatophytosis is the infection of keratinized tissues such as hair, nails and the stratum corneum of the skin by dermatophyte fungi. These fungi are onygenalean anamorphs and anamorphic species belonging to the genera Trichophyton, Microsporum and Epidermophyton. An important characteristic of the dermatophytes as parasites is their restriction to the dead keratinized tissues, except in rare cases where the patient is immunosuppressed. In contrast to many fungi, including normally non-pathogenic species, which can invade systemically in severely immunocompromised (e.g. neutropenic) patients, dermatophytes appear to be unable to cause systemic infection in this population. Thus, these fungi appear to have an unique interaction with the immune system. A better understanding of this interaction will contribute significantly to our knowledge of mammalian host defences.

Arthrodermataceae↗
PubMed1997

Depression of T-cell epitope generation by stabilizing hen lysozyme.

Conformational stability of proteins is an important factor that determines their resistance/susceptibility to proteolytic digestion. Intracellular proteolysis is the key step in antigen presentation events for protein antigens; hence, it is likely that increasing protein stability reduces the antigenicity of proteins. We prepared three hen egg white lysozyme derivatives possessing different stabilities by chemical modification to clarify the relationship between conformational stability and the antigenicity of the protein. One of the derivatives was conformationally unstabilized by removing one intramolecular disulfide bond, whereas the two others were stabilized by the addition of an intramolecular cross-link. The antigenicity of these derivatives was evaluated using hen egg white lysozyme-specific T-cell hybridoma cells and a B-lymphoma cell line, A20, as antigen-presenting cells. With an increase in conformational stability, the T-cell response decreased. However, the reduction was not derived from the inefficiency of internalization to A20 cells nor the alteration of antigenicity by chemical modifications. Moreover, from analyses of their susceptibility to proteolysis and the kinetics of presentation of the T-cell epitope, it was confirmed that increasing protein stability led to the depression of T-cell epitope generation by increasing resistance to proteolysis. These results have an important implication in devising a new strategy for manipulating T-cell response by the stability of protein antigen.

Animals↗
PubMed1997

Capsaicin in the 4th ventricle abolishes retching and transmission of emetic vagal afferents to solitary nucleus neurons.

Systemic tachykinin NK1 receptor antagonists and resiniferatoxin are known to abolish vomiting mediated by vagal afferents. Emetic vagal afferents have been shown to make synaptic contact with neurons in the medial solitary nucleus. These results suggest that substance P participates in the synapse as a mediator. To examine this possibility, the effects of 4th-ventricular application of capsaicin (0.033-33 mM, 20-30 microl) and resiniferatoxin (1.6-160 microM, 20-30 microl) on the activity of neurons in the medial solitary nucleus and fictive retching induced by vagal stimulation were observed in paralyzed decerebrate dogs. Capsaicin (33 mM) and resiniferatoxin (160 microM) initially increased the neuronal firing and occasionally produced retching, then abolished both neuronal and retching responses. However, stimulation of the medial solitary nucleus continued to provoke retching. Field potential changes in the medial solitary nucleus evoked by pulse-train vagal stimulation decreased in amplitude, but did not disappear. Latencies of neuronal firing and evoked potentials were about 300 ms. These results suggest that emetic vagal afferents are capsaicin-sensitive C fibers which may have substance P as an excitatory transmitter or modulator.

Animals↗
PubMed1997

Descending pathway from the central pattern generator of vomiting.

The central pattern generator (CPG) for vomiting has been postulated to consist of non-respiratory neurons in the reticular area dorsomedial to the retrofacial nucleus. CPG neurons are known to produce vomiting activity patterns similar to respiratory spinal motoneurons and premotoneurons in the caudal part of the ventral respiratory group (cVRG). This study was performed to reveal direct connections between CPG neurons and cVRG neurons in dogs. Twenty-seven non-respiratory neurons were identified as CPG neurons based on their responses to vagal stimulation and their firing patterns of vomiting. Nine of these 27 neurons antidromically responded to cVRG stimulation. These results suggest that the CPG directly drives respiratory premotor neurons in the cVRG to produce vomiting motions.

Abdominal Muscles↗
PubMed1997

Most inspiratory neurons in the pre-Bötzinger complex are suppressed during vomiting in dogs.

Pulmonary ventilation is almost completely suppressed during actual retching. Correspondingly, respiratory activity either disappears or changes to retching activity in peripheral respiratory nerves and respiratory neurons of the Bötzinger complex and the caudal part of the ventral respiratory group. These results suggest the possibility that the respiratory rhythm generator is suppressed during retching. Recently, the pre-Bötzinger complex (pre-BOT) has been postulated to generate respiratory rhythm. To evaluate this possibility, the activities of pre-BOT neurons were observed during fictive retching and expulsion in decerebrate paralyzed dogs. Inspiratory (I) neurons in the pre-BOT consisted of pre-, early-, late-, post- and throughout-subtypes, as in cats and rats. Inspiratory firing almost completely disappeared during fictive retching in about 70% of the 158 pre-BOT I neurons examined, and changed to weak bursts produced either with retches or between retches in most of the remaining 30%. Similarly, all but one of the 21 I neurons examined did not produce any discharge with fictive expulsion. In contrast, all of the pre-BOT expiratory and inspiratory-expiratory neurons examined produced vigorous bursts either with retches or between retches, and with expulsion. These results suggest that inspiratory outputs from the respiratory rhythm generator are almost completely suppressed during retching and expulsion, and that expiratory outputs change to retching and expulsion activities.

Animals↗
PubMed1997

Detergent effects on the light-harvesting chlorophyll A/B-protein complex crystallization revealed by fluorescence depolarization.

Detergent effects on the pre-crystallization of light-harvesting chlorophyll a/b-protein complex (LHCII) were investigated through the fluorescence depolarization method. Stable LHCII crystals were formed in the media containing Triton X-100 (TX) or n-nonyl-beta-D-glucopyranoside (NG) and the crystallization efficients were dependent on their concentrations. The second virial coefficient of crystallizing system, estimated by the fluorescence depolarization analysis of LHCII, showed the most harmonious value under the condition yielding the most efficient crystallization of LHCII to suggest that some specific molecular interaction leading to the crystal growth would be induced according to the concentration of TX or NG.

Chlorophyll↗
PubMed1997

The gnd gene encoding a novel 6-phosphogluconate dehydrogenase and its adjacent region of Actinobacillus actinomycetemcomitans chromosomal DNA.

A 10-kb DNA fragment containing the gnd gene from Actinobacillus actinomy-cetemcomitans Y4 was isolated and sequenced. The structural gnd gene codes for 6-phosphogluconate dehydrogenase that consists of 484 amino acids. In contrast to the gnd gene in Escherichia coli, Salmonella typhimurium, or Klebsiella pneumoniae, the gnd gene of A. actinomycetemcomitans was not located in the rfb or cps operon. The zwf gene encoding glucose 6-phosphate dehydrogenase, which is another enzyme consisting of pentose-phosphate pathway, sided at 3.8-kb upstream from the gnd gene. A phylogenetic tree based on sequence analyses showed higher homology of 6-phospho-gluconate dehydrogenase of A. actinomycetemcomitans with the eucaryotic enzymes rather than with bacterial enzymes.

Actinobacillus↗