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Biomedical subjects

Y Shindo

Publications and source records attributed to Y Shindo.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mitochondrial trifunctional protein deficiency associated with recurrent myoglobinuria in adolescence.

A 23-year-old man with recurrent myoglobinuria had low muscle-free carnitine levels and deficient fasting ketogenesis. Urinary organic acid analysis showed large amounts of C6-C14 3-hydroxydicarboxylic acids. Mitochondrial trifunctional protein (TP), harboring long-chain enoyl-coenzyme A (CoA) hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase, and long-chain 3-ketoacyl-CoA thiolase showed markedly decreased activity in fibroblasts. On immunoblot analysis, the TP content of his fibroblasts was less than 2% that of the control cells. TP deficiency can be a life-threatening disorder with early infantile onset, but it can also present in adolescence with recurrent myoglobinuria.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

The role of histamine in ethanol-induced gastric mucosal injury in the rat.

It has been suggested that changes in the micro circulatory system are related to the early production of acute gastric mucosal injury and inflammatory factors such as prostaglandins, histamine, etc., have been considered as contributing to the development of the injury. We assessed the permeability of the gastric mucosa in rats with ethanol-induced acute mucosal injury by measuring the leakage rate of 51chronium-ethylene-diamine-tetraacetic acid (51Cr-EDTA) into the gastric juice. Histamine concentrations in the gastric mucosa was measured by high performance liquid chromatography. The enterochromaffin-like (ECL) cell counts in the gastric mucosa was performed following histamine staining with an enzyme-labeled antibody, and the histamine released due to degranulation was observed. We also investigated the kinetics of endogenous histamine in the gastric mucosa. Five minutes after the administration of ethanol, an increase in permeability, an increase in histamine concentration, and a decrease in ECL cell count were found in the gastric mucosa. These results suggest that endogenous histamine in the gastric mucosa is closely related to the early development of acute gastric mucosal injury.

Animals↗
PubMed1996

Constitutively enhanced nbl expression is associated with the induction of internucleosomal DNA cleavage by actinomycin D.

Previous studies have found nbl expression to transiently rise and fall during glucocorticoid-induced thymic apoptosis. This induction of apoptosis is blocked by the transcriptional inhibitor actinomycin D. However, actinomycin D can trigger apoptosis in other cell types, e.g., HL-60 cells. This study found that internucleosomal DNA cleavage typical of apoptosis is induced by actinomycin D in cell lines such as HL-60 which constitutively express high levels of nbl above a certain "threshold." In contrast, "DNA ladder" formation was not induced by actinomycin D in cell lines with low constitutive nbl expression. Enhanced nbl expression therefore appears to be associated with apoptosis which is either blocked or induced by actinomycin D.

Amnion↗
PubMed1996

Laparoscopically assisted resection of the lower rectum.

We report a new laparoscopic approach to the resection of the lower rectum which has been successfully used in the treatment of a patient with a small rectal carcinoid tumor. Under general anesthesia a pneumo-peritoneum was established with CO2 gas insufflation and the rectum was mobilized from the sacrum including division of the lateral ligaments under the direct view of the laparoscope. The bowel was divided between the sigmoid colon and the rectum using an endoscopic linear stapler, and the rectum was everted through the anal canal. The lower rectum was transected extracorporeally using a linear stapler and the rectal stump was then returned to the anatomical position. An anvil of a circular stapling device into the oral colon stump through a small skin incision on the left lower abdomen was introduced and the shaft of the device through the rectal stump via anus was inserted. The device was then re-approximated under laparoscopic view and fired. Our procedure described here is applicable to the lower rectal lesion as a minimally invasive, safe, and useful therapeutic tool.

Carcinoid Tumor↗
PubMed1996

Synchronous behavior of spontaneous oscillations of sarcomeres in skeletal myofibrils under isotonic conditions.

An isotonic control system for studying dynamic properties of single myofibrils was developed to evaluate the change of sarcomere lengths in glycerinated skeletal myofibrils under conditions of spontaneous oscillatory contraction (SPOC) in the presence of inorganic phosphate and a high ADP-to-ATP ratio. Sarcomere length oscillated spontaneously with a peak-to-peak amplitude of about 0.5 microns under isotonic conditions in which the external loads were maintained constant at values between 1.5 x 10(4) and 3.5 x 10(4) N/m2. The shortening and yielding of sarcomeres occurred in concert, in contrast to the previously reported conditions (isomeric or auxotonic) under which the myofibrillar tension is allowed to oscillate. This synchronous SPOC appears to be at a higher level of synchrony than in the organized state of SPOC previously observed under auxotonic conditions. The period of sarcomere length oscillation did not largely depend on external load. The active tension under SPOC conditions increased as the sarcomere length increased from 2.1 to 3.2 microns, although it was still smaller than the tension under normal Ca2+ contraction (which is on the order of 10(5) N/m2). The synchronous SPOC implies that there is a mechanism for transmitting information between sarcomeres such that the state of activation of sarcomeres is affected by the state of adjacent sarcomeres. We conclude that the change of myofibrillar tension is not responsible for the SPOC of each sarcomere but that it affects the level of synchrony of sarcomere oscillations.

Animals↗
PubMed1996

A new inhibitor of mitochondrial fatty acid oxidation.

The mitochondrial enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein (trifunctional protein) plays a major role in mitochondrial fatty acid oxidation. The enzyme complex consists of four molecules of alpha-subunit containing both hydratase and dehydrogenase domains and four molecules of beta-subunit containing the thiolase domain. The primary structure of a gastrin-binding protein (GBP) was highly homologous to that of the alpha-subunit of the trifunctional protein. Here, we report that gastrin inhibits the hydratase, dehydrogenase, and thiolase activities of the trifunctional protein. The gastrin/cholecystokinin receptor antagonist benzotript, which inhibited binding of gastrin to the GBP, also inhibited all three activities of the trifunctional protein. In addition, benzotript inhibits the activities of multifunctional enzymes having similar structures, such as the peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein and the Pseudomonas fragi fatty acid oxidation enzyme complex. This reagent, however, hardly inhibited various monofunctional enzymes involved in fatty acid oxidation.

Acetyl-CoA C-Acyltransferase↗
PubMed1996

Clinical and immunogenetic investigation of a Laotian patient with Vogt-Koyanagi-Harada's disease.

Vogt-Koyanagi-Harada's (VKH) disease has been known to be associated with HLA class II antigen, HLA-DR4 and -DR53. Recent recombinant DNA technical advances have allowed us to investigate the genetic polymorphism of HLA antigens at the molecular level. By use of the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique we have found that VKH disease is closely associated with HLA-DRB1*04 (DRB1*0405/ DRB1*0410) and DQB1*04 (DQB1*0401/DQB1*0402) in the Japanese. Here, we will describe a typical case of a Laotian patient with VKH disease and the results of HLA typing: the patient showed a conservation of one of the major haplotypes observed in Japanese VKH patients, DRB1*0405-DQB1*0402.

Adult↗
PubMed1996

[A 13-week oral toxicity study of prulifloxacin (NM441) in dogs followed by a 5-week recovery test].

A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in beagle dogs. Male and female dogs were given the test material orally for 13 weeks at doses of 0 (control), 20, 100 and 500 mg/kg. After discontinuation of the treatment, a 5-week recovery test was also conducted. Vomiting, salivation and decreased body weight gain or reduced body weight were seen in the 100 and 500 mg/kg groups. In the 500 mg/kg group, tremor, paresis of posterior limb associated with prone or sitting position and decreased food consumption were also observed. There were no treatment-related effects on survival and water consumption. Ophthalmoscopic, electrocardiographic and hematologic examinations, and urinalysis failed to show any abnormalities attributable to the treatment. Blood chemical examination showed increased GPT and decreased beta- and gamma-globulins in the 100 and 500 mg/kg groups, and increased GOT in the 500 mg/kg group. In pathological examination, cavitations and erosions were seen in the humeral and femoral articular cartilages in the 100 and 500 mg/kg groups. The above-mentioned changes were satisfactorily reversible except for erosions in the humeral and femoral articular cartilages in the 100 and 500 mg/kg groups. No toxicological findings were seen in the 20 mg/kg group. The results show that the NOAEL of prulifloxacin is 20 mg/kg for 13-week repeated dose toxicity in dogs.

Administration, Oral↗
PubMed1996

[A 4-week intravenous toxicity study of the active metabolite (NM394) of prulifloxacin (NM441) in rats followed by a 4-week recovery test].

A repeated dose toxicity study of ( +/- )-6- fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H- [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (NM394), the active metabolite of a new antibacterial agent, prulifloxacin, was conducted in Sprague-Dawley rats. Male and female rats were given the test material intravenously for 4 weeks at doses of 0 (control), 3, 10 and 30 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted. There were no treatment-related effects on survival, clinical signs, body weight and food consumption. Ophthalmoscopic and hematologic examinations failed to show any abnormalities related to the treatment. Increased water consumption was observed in the 10 and 30 mg/kg groups. In these dose groups, increased urine volume and lowered urine specific gravity, and crystalline substance and small epithelial cells in urinary sediments were seen. Cloudy urine was also seen in the 30 mg/kg group. Blood chemical examination showed decreased gamma-globulin in the 10 and 30 mg/kg groups and increased BUN and creatinine in the 30 mg/kg group. Pathological changes caused by the treatment were as follows. In kidney, tubular nephrosis with crystalline substance was observed in the 10 and 30 mg/kg groups and its organ weight was increased in the 30 mg/kg group. Cecal weight was increased in the 30 mg/kg group. The above-mentioned changes were reversible except for decreased gamma-globulin. Plasma levels and urinary concentrations of the test material were increased in all dose groups with dose-related manner, whereby no sex differences were observed. No effects caused by the repeated dosing were seen in the plasma concentrations. Toxicological findings were not observed in the 3 mg/kg group. The results show that the NOAEL of NM394 is 3 mg/kg for 4-week repeated dose toxicity in rats.

Animals↗
PubMed1996

[Single and 4-week oral toxicity studies of prulifloxacin (NM441) in aged dogs].

Single-dose and repeated dose toxicity studies of prulifloxacin, a new antibacterial agent, were conducted in aged beagle dogs. I. A single-dose toxicity study Prulifloxacin was administered orally to aged female dogs at a single dose of 2500 and 5000 mg/kg. No death occurred in any group. Vomiting was observed in one of two animals at 2500 mg/kg and in both animals at 5000 mg/kg 3-4 hr after dosing. At 5000 mg/kg, vomiting was observed in both animals after feeding on the day after dosing. One animal also showed soft stool. Thereafter, no abnormalities were observed in any animal. No test article related changes were noted in food consumption, water consumption, body weight or pathological examination in any group. The results show that the lethal dose of prulifloxacin is judged to be greater than 5000 mg/kg in aged female dogs. II. A repeated dose toxicity study Aged male and female dogs were given the test article orally for 4 weeks at doses of 0 (control), 20, 100 and 500 mg/kg. No death occurred in any group. At 500 mg/kg, vomiting was observed every day or intermittently throughout the dosing period and salivation was observed almost every day from day 6 to the end of the dosing onward. Decreases or lack of food and water consumption, and decrease of body weight were noted at 500 mg/kg. At 100 mg/kg, slight decreases in food consumption and body weight were noted in the females. No abnormalities were noted in ophthalmoscopic or electrocardio-graphic examination. In urinalysis, decreases in Na+, K+ and Cl- concentrations and the total excretion amount were noted mostly at 500 mg/kg. A low specific gravity was noted in males at 500 mg/kg. In hematology and serum biochemistry, high GPT, BUN and creatinine, and decreases in WBC were noted in both sexes at 500 mg/kg. A high GOT was noted in males, and low Cl- in females at 500 mg/kg. At 100 mg/kg, a high GPT was noted. Rough surface in the kidney and chronic interstitial nephritis (basophilic change of tubule, atrophy of tubule, thickening of tubular basement membrane, interstitial mononuclear cell infiltration, interstitial focal fibrosis) were increased at 500 mg/kg. No toxicological findings were seen in the 20 mg/kg group. The results show that the NOAEL of prulifloxacin is 20 mg/kg for 4-week repeated dose toxicity in aged dogs.

Administration, Oral↗
PubMed1996

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(1)--A fertility study in rats by oral administration].

A study of fertility and fetal development of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Male rats were given the drug orally from 63 days before mating to the end of the mating period. Female rats were given from 14 days before mating to day 7 of pregnancy. The dose levels for both males and females were 0 (control), 30, 170 and 1000 mg/kg. The females were sacrificed on day 20 of pregnancy for examination of their fetuses. In the 170 mg/kg group, water consumption increased in the female rats, and food consumption decreased and the cecum increased in weight and was enlarged in the males and the females. In the 1000 mg/kg group, body weight gain was suppressed in the males, and food consumption decreased, water consumption increased and cecum increased in weight and enlarged in the males and the females. Moreover, this dose caused white spots and rough surface of the kidney in the males. Prulifloxacin had no adverse effects on reproductive function of the parent animals, and also on development of the fetuses. These results show that the NOAEL of prulifloxacin are 30 mg/kg for general toxicity in parent animals, 1000 mg/kg for reproductive function of parent animals and for development of fetuses.

Administration, Oral↗
PubMed1996

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(2)--A teratogenicity study in rats by oral administration].

A study of the effect of prulifloxacin, a new antibacterial agent, during the period of organogenesis was conducted in Sprague-Dawley rats. Female rats were given prulifloxacin orally at dose levels of 0 (control), 30, 300, and 3000 mg/kg from day 7 to day 17 of pregnancy. Twenty-four or twenty-five female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and the pregnant rats (12-15 per dose levels) were allowed to deliver naturally for postnatal examination of their offspring. In the 300 or 3000 mg/kg groups, the food consumption decreased and water consumption increased in the dams. In the 3000 mg/kg group, the body weight gain was suppressed in the dams. In the 300 and 3000 mg/kg groups, the weights of cecum increased and the enlargement of cecum was observed. In the 3000 mg/kg group, white spots and rough surface of the kidney and renal tubular nephrosis with crystalline substance were observed and the weight of the kidney increased in the dams, and the body weight decreased and retarded ossifications in the fetuses. Prulifloxacin had no effect on the number of corpora lutea and implantations, or on fetal mortality, sex ratio, or external and visceral development of the fetuses. Prulifloxacin also did not affect delivery and the number of live newborns and birth index, or have any adverse effects on the postnatal development of the first generation offspring (F1) such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. Prulifloxacin also had no adverse effects of the second generation offspring (F2). These results show that the NOAEL of prulifloxacin are 30 mg/kg for general toxicity in mother animals, 3000 mg/kg for pregnancy and delivery of mother animals and 300 mg/kg for development of their offspring.

Abnormalities, Drug-Induced↗
PubMed1996

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(3)--A teratogenicity study in rabbits by oral administration].

A study of the effect of prulifloxacin, a new antibacterial agent, during the period of organogenesis was conducted in New Zealand White rabbits. Female rabbits were given prulifloxacin orally at dose levels of 0 (control), 10, 30 and 100 mg/kg from day 6 to 18 of pregnancy. Female rabbits were sacrificed on day 29 of pregnancy for examination of their fetuses. In the 30 mg/kg group, food and water consumption decreased. In the 100 mg/kg group, soft stool was observed and body weight gain, food consumption and water consumption decreased. Premature delivery (2/16) occurred and enlargement of cecum and increased weight of cecum were observed. The number of fetal death increased in the 100 mg/kg group. However, prulifloxacin had no effects on the number of corpora lutea, implantations and live fetuses, and on body weight, placental weight, sex ratio, and external, visceral and skeletal development of live fetuses. These results show that the NOAEL of prulifloxacin are 10 mg/kg for general toxicity in mother animals, 30 mg/kg for pregnancy of mother animals and for development of fetuses.

Abnormalities, Drug-Induced↗
PubMed1996

[Reproductive and developmental toxicity studies of prulifloxacin (NM441)(4)--A perinatal and postnatal study in rats by oral administration].

A peri- and postnatal study of prulifloxacin, a new antibacterial agent, was conducted in Sprague-Dawley rats. Female rats were given prulifloxacin orally at dose levels of 0 (control), 30, 100 and 300 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. Food consumption in the period of pregnancy decreased in the dams given 100 and 300 mg/kg, and food and water consumption during lactational period increased in the dams given 300 mg/kg. The weight of the cecum of the dams increased in 100 and 300 mg/kg groups, and these doses caused enlargement of the cecum. Prulifloxacin had no effects on general sign, delivery, nursing, body weight gain, and kidney. Prulifloxacin also did not affect the number of live newborns and birth index, and have any adverse effects on the postnatal development of the first generation offspring (F1) such as differentiation, functional development, emotionality, motor ability, learning ability and reproductive performance. Prulifloxacin also had no adverse effects on the second generation offspring (F2). These results show that the NOAEL of prulifloxacin are 30 mg/kg for general toxicity in mother animals, 300 mg/kg for pregnancy and delivery of mother animals and development of their offspring.

Administration, Oral↗
PubMed1996

[Antigenicity studies of prulifloxacin (NM441)].

Antigenicity of prulifloxacin, a new antibacterial agent, and that of its active metabolite (NM394) were investigated using guinea pigs and mice in this study. In the study with guinea pigs, the animals were immunized with prulifloxacin by oral administration, the predetermined clinical route, and with prulifloxacin alone or emulsified with Freund's complete adjuvant (FCA) by s.c. When active systemic anaphylaxis (ASA) test and passive cutaneous anaphylaxis (PCA) test of these animals were conducted by eliciting with NM394 alone or protein conjugate (NM394-GPSA) of NM394 and guinea pig serum albumin (GPSA), no ASA and PCA reactions were observed. When guinea pigs were immunized subcutaneously with protein conjugate (NM394-BSA) of NM394 and bovine serum albumin (BSA) together with FCA, ASA and PCA reactions were positive by eliciting with NM394-GPSA or NM394-BSA, but were negative by eliciting with NM394 alone. In the study with mice, the animals were immunized orally with prulifloxacin and intraperitoneally with prulifloxacin alone or suspended with aluminum hydroxide gel (alum). When rat PCA test of sera from these mice was conducted by eliciting with NM394 or NM394-GPSA, no positive PCA reaction was observed. When mice were immunized intraperiotneally with NM394-BSA together with alum, PCA reactions were positive by eliciting with NM394-GPSA or NM394-BSA, but were negative by eliciting with NM394 alone. These results show that prulifloxacin has no immunogenicity to guinea pigs and mice, and NM394 as its active form has no eliciting potential to anti-NM394-BSA antibody.

Anaphylaxis↗
PubMed1996

[Mutagenicity studies of prulifloxacin (NM441) and the active metabolite (NM394)].

The mutagenicity of prulifloxacin, a new antibacterial agent, was investigated by the reverse mutation test in bacteria, the chromosomal aberration test in cultured cells, and the micronucleus test in mice. In addition, NM394, an active metabolite of prulifloxacin, was examined for mutagenicity in the chromosomal aberration test in cultured cells. The reverse mutation test was performed at dose range of 0.0078-0.25 micrograms/plate using Salmonella typhimurium strains (TA100, TA1535, TA98, and TA1537), and Escherichia coli (WP2uvrA). Prulifloxacin did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S9 mix). The chromosomal aberration tests were carried out in cultured Chinese hamster lung cells (CHL/IU). Prulifloxacin increased aberrant cells without S9 mix, and NM394 also induced chromosomal aberrations. In human lymphocytes, no significant increases of the frequencies of cells with chromosomal aberrations were observed at dose range of 5-320 micrograms/ml with or without S9 mix. The micronucleus test was conducted at doses of 625-5000 mg/kg in the bone marrow cells of Slc : ddY male mice. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes.

Animals↗