Biomedical subjects
Publications and source records attributed to J Nakamura.
The in-gel endonuclease digestion method was introduced for the molecular epidemiology of molluscum contagiosum virus (MCV). We obtained clear electrophoretic patterns from 90.3% of single lesions. The distribution of MCV types in Western Japan was revealed to be different from that in other countries.
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Sarcoplasmic reticulum with calcium transport activity has been isolated from the cross-striated adductor muscle of the scallop, which lives in cold (< or = 20 degrees C) sea water, by using pH 7.0 buffer solution both to homogenize the tissue and to sediment the membrane fraction. The yield of the preparation was 60-100 mg protein from 100 g of the scallop muscle. Ca(2+)-activated ATPase protein of about 100 kDa accounted for 40-50% of the protein preparation. The maximum activities of ATP-dependent, oxalate-facilitated calcium accumulation and Ca(2+)-ATPase were observed at a pH of about 7.0 and temperature of 20-30 degrees C, and their values were about 2 mumol Ca2+/mg of protein/min and about 3 mumol ATP hydrolysis/mg of protein/min, respectively. At 0 degree C, 10-20% of these activities was maintained, while at 37 degrees C, the activities were irreversibly lost. The Ca(2+)-ATPase activity was half-maximally activated at about 0.3 microM [Ca2+]. The ATPase activity exhibited non-Michaelian behavior with respect to ATP, with two different Km values of approximately 10 microM and 0.1-0.3 mM. GTP, CTP, and ITP were also hydrolyzed by the preparation at a rate of 10-30% of that of ATP. The preparation was stored at -80 degrees C with retention of function for about a year.
We report a 39-year-old Japanese woman with a 30 x 10 mm, skin-colored, soft, hairless, irregularly elevated plaque in the left retroauricular area. Histologically, it consistently showed features of atypical hair follicles; some showed immaturely developed basaloid epithelial islands invaginated with condensed stromal cells, and others were replaced or associated with solid strands, branching cords, or lace-like networks of undifferentiated basaloid cells. Although the clinical appearance of a typical localized basaloid follicular hamartoma is a plaque of alopecia, this case seems to be a variant, because the histological findings are so characteristic of the entity. The relationship of basaloid follicular hamartoma to other hair-follicle derived tumors is also considered.
We have had experience in treating tardive Tourette-like syndrome on a chronic schizophrenic patient. The patient was a 38-year-old woman. A diagnosis of schizophrenia was made in 1971 and she received repeated medications for 17 years. In 1989, she began to show vocal tic with coprolalia and motor tic. The medications were haloperidol 18 mg, zotepine 200 mg, levomepromazine 100 mg, biperiden 3 mg and nitrazepam 10 mg at the beginning of Tourette-like syndrome. We have tried to change the medications but this tardive Tourette-like syndrome continued to hang on. However, the symptoms gradually improved after a change in drugs; cessation of biperiden 3 mg and the administration of clonazepam 3 mg. The present case suggested that tardive Tourette-like syndrome might be a subtype of neuroleptic-associated tardive syndromes which might be treated with clonazepam.
The effects of new thienodiazepine anxiolytics, etizolam and clotiazepam, on the appearance of frontal midline theta activity (Fm theta) were studied by the double-blind crossover method. The results were as follows; 1) Both clotiazepam and placebo tended to increase the Fm theta appearance in all subjects, but etizolam showed no such tendency. 2) Clotiazepam significantly increased the Fm theta appearance as compared with placebo in subjects with a high neurotic tendency (N-scale of MPI above 19). 3) Clotiazepam tended to increase the Fm theta appearance as compared with placebo and etizolam in subjects with a high anxiety level (MAS score above 14). 4) Apparently more subjects complained of drowsiness after the administration of etizolam than after clotiazepam or placebo.
The hydrolysis of salicylic acid-L-alanine conjugate (salicyl-L-alanine) following oral, intravenous, intracaecal and rectal administration (60, 10, 5 and 5 mg kg-1, respectively: salicylic acid equivalent) was examined in rabbits. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-L-alanine and reached a maximum concentration at 10 h, whereas salicyl-L-alanine was rapidly eliminated. In contrast, unchanged salicyl-L-alanine only was found following intravenous administration of salicyl-L-alanine, suggesting that presystemic de-conjugation of salicyl-L-alanine was involved. The intestinal mucosal de-conjugation of salicyl-L-alanine was not recognized in the in-situ intestinal sac preparation with complete mesenteric venous blood collection. Immediate and very extensive salicylic acid formation in the caecum was found following intracaecal administration of salicyl-L-alanine. After oral pretreatment of rabbits with kanamycin sulphate, a significant inhibition of salicylic acid formation following intracaecal administration of salicyl-L-alanine was observed, indicating that the intestinal microorganisms were responsible for the biotransformation of salicyl-L-alanine. In-vitro incubation of salicyl-L-alanine with gut contents showed that the major source of its hydrolysis was the hind gut. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-L-alanine, suggesting the usefulness of salicyl-L-alanine as a prodrug of salicylic acid.
The hydrolysis of salicylic acid-glycylglycine conjugate (salicyl-glycylglycine) following oral, intravenous, intracaecal and rectal administration (434, 72, 36 and 36 mumol kg-1, respectively: equivalent to salicylic acid) was examined in rabbits to develop a novel prodrug of salicylic acid. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glycylglycine and it reached a maximum level (55.6 micrograms mL-1) at 15 h, whereas a small amount of salicyl-glycylglycine was found in the blood. In contrast, unchanged salicyl-glycylglycine was found mainly in the blood following its intravenous administration, suggesting the involvement of presystemic deconjugation in the hydrolysis of salicyl-glycylglycine. Immediate and very extensive salicyclic acid formation in the caecum was observed following intracaecal administration of salicyl-glycylglycine, suggesting that the intestinal microorganisms were responsible for the biotransformation of this compound. In-vitro incubation of salicyl-glycylglycine with caecal content showed that salicyl-glycylglycine was hydrolysed efficiently in the caecum. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicyl-glycylglycine, indicating the usefulness of salicyl-glycylglycine as a prodrug of salicylic acid.
Throat secretions (TS) and bronchial secretions aspirated from tracheostomy (TSTA) were cultured at the same time in 9 subjects with long term tracheostomy every two weeks from January, 1990 to December, 1990. Total number of each examination in TS and TSTA were 200 times. Mean number of bacteria isolated by single culture were 2.9 strains in TS and 1.8 strains in TSTA. Isolated bacteria were mainly alpha-Streptococcus (84.8%) and Neisseria (69%) in TS, and Pseudomonas aeruginosa (53.5%) and Serratia marcescens (30%) in TSTA. Only 20% of P. aeruginosa or S. marcescens in TSTA were isolated from TS. In 8 cases of 9, P. aeruginosa in TSTA were isolated with every time or long term. There were 14 episodes of respiratory infections in 6 cases. P. aeruginosa were causative organisms in 7 episodes. It suggests that P. aeruginosa tended to colonize in lower respiratory tracts of the patients with long term tracheostomy and to become causative organisms in respiratory infections.
We investigated the transpleural penetration of lomefloxacin (LFLX) and ceftriaxone (CTRX). LFLX (200 mg) was administered orally to three patients with transudative fluid and four with exudative fluid, and 2 g of CTRX was administered by drip infusion to four patients with transudative fluid and three with exudative fluid. For both groups that received LFLX and CTRX, blood samples were drawn at time zero and 1, 2, and 6 h after drug administration. Thoracocentesis of each group was performed at 6 h after drug administration. The mean ratios of concentrations in pleural fluid/maximum concentrations in serum (P/S max) of LFLX were 66% in patients with transudative fluid and 69% in patients with exudative fluid. The mean ratios of P/S max of CTRX were 9.1% in patients with transudative fluid and 13.5% in patients with exudative fluid. The P/S max ratios for the penetration of LFLX were five to six times higher than those for CTRX. In addition, there was less differentiation in concentrations of LFLX in pleural fluid between the transudative and exudative effusions than there was in the concentrations of CTRX.
A series of interrelated biochemical and functional defects, induced by hyperglycemia, associated with intracellular depletion of D-myo-inositol, and corrected by aldose reductase inhibitors, have been ascribed to abnormal phosphoinositide metabolism in several tissues prone to diabetic complications. However, reductions in tissue D-myo-inositol content are not universally found in complications-prone diabetic tissues, and direct mass-action effects of cellular D-myo-inositol depletion on the critical CDPdiacylglycerol-inositol 3-phosphatidyltransferase (PI synthase; EC 2.7.8.11) step have never been shown conclusively in relevant cells. The studies reported here simultaneously estimated the chemical mass of CDP diglyceride by equilibrium labeling with 5-[3H]cytidine and phosphoinositide biosynthesis by the incorporation of [32P]orthophosphate into phosphoinositide. This was done to assess the degree of inhibition of PI synthase under various degrees of D-myo-inositol depletion and sorbitol accumulation induced by glucose and other metabolic manipulations in cultured human retinal pigment epithelial cells, a new in vitro model for diabetic complications. The results suggest that sorbitol accumulation limits the PI synthase reaction in these cells by selectively depleting specific intracellular pools of D-myo-inositol and/or by possible independent effects of sorbitol on PI synthase.
An assessment of 5-fluorouracil (5-FU)-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The mucosal damage in the intestine 48 h after oral administration of 5-FU (30 mg/kg) was examined using a scanning electron microscope. By the oral pretreatment with 5-FU, the morphological changes of jejunal and ileal mucosa were recognized compared with the control. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with 5-FU, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with 5-FU orally. However, the blood concentration of SAMG after intravenous administration of SAM was not increased compared with the control. These findings suggest that the change in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage by oral pretreatment with 5-FU. The alteration of intestinal first-pass metabolism of a marker compound may be utilized for the assessment of intestinal mucosal damage in vivo.
Indomethacin-induced mucosal damage was assessed in vivo by measuring salicylamide (SAM) metabolism in rabbit intestine. Intestinal mucosal damage 48 h after oral indomethacin (500 mg/kg) administration was examined using a scanning electron microscope. Duodenal, jejunal and ileal mucosal toxicity was compared with that in controls. Intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with intact mesenteric venous blood collection. The appearance of both SAM and its metabolites in the mesenteric venous blood was measured following cannulation of the mesenteric vein of the exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with indomethacin, the appearance of SAM and SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The concentrations of SAM and SAMG in the blood increased following intraduodenal administration of SAM in vivo in rabbits orally pretreated with indomethacin compared with controls. However, after intravenous administration of SAM, the blood concentration of SAM and SAMG was not increased compared with controls. These findings suggest that the differences in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral indomethacin pretreatment. The results indicate that the alteration of intestinal first-pass metabolism of a marker compound may be utilized to assess intestinal mucosal damage in vivo.
Sulphate conjugation of p-nitrophenol (p-NP) in the liver and platelet cytosol of guinea pigs, rabbits and dogs were studied. The dependency of phenol sulphotransferase (PST) activity on p-NP concentration in the liver of guinea pigs and rabbits and in the platelets of guinea pigs were similar to that reported for the liver (Mizuma et al., J. Pharmacobio-Dyn., 6, 851 (1983)) and platelets (Nakamura et al., J. Pharm. Pharmacol., 42, 207 (1990)) of rats. There was one peak of PST activity on p-NP at the concentration of 1 to 10 microM, and the PST activity was increased again with an increase of p-NP concentration above the original concentration. On the other hand, a peak in PST activity on p-NP at the concentration of 1 to 10 microM was not observed in the platelets of rabbits and dogs. These results indicated species and organ differences in PST activity on p-NP in liver and platelets. The biphasic activities of the PST and p-NP in platelets and liver of rat and guinea pig were similar to that reported in humans (Reiter et al., Naunyn-Schmiedeberg's Arch. Pharmacol., 324, 140 (1983)).
The fate of salicylic acid-glutamic acid conjugate (salicyl-glutamic acid) following oral, intravenous, intracecal and rectal administration (60, 10, 5 and 5 mg/kg, respectively: salicylic acid equivalent) was examined in rabbits. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glutamic acid and it reached the maximum level (69.4 micrograms/ml) at 18 h after the dose. A high blood concentration of salicylic acid (24.8 micrograms/ml) was observed up to 36 h. But only a small amount of salicyl-glutamic acid was detected in the blood (less than 2.5 micrograms/ml, as salicylic acid). In contrast, unchanged salicyl-glutamic acid was found mainly in the blood following intravenous administration of salicyl-glutamic acid, suggesting that presystemic de-conjugation of salicyl-glutamic acid predominantly occurred. The intestinal mucosal de-conjugation of salicyl-glutamic acid was negligible in the in situ intestinal sac preparation with complete mesenteric venous blood collection. Immediate and very extensive salicylic acid formation in the cecum was found following intracecal administration of salicyl-glutamic acid. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg), a significant inhibition of salicylic acid formation following intracecal administration of salicyl-glutamic acid was observed, indicating that the intestinal microorganisms were responsible for the biotransformation of salicyl-glutamic acid. Also, in vitro incubation of salicyl-glutamic acid with gut contents showed that the primary location of hydrolysis was the hind gut.
We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl-tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior following intraduodenal and intracecal administration (72 and 36 mumol/kg, respectively: salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl-methionine, without being metabolized to salicylic acid in the small intestinal mucosa. On the contrary, salicylic acid was detected in the blood following intraduodenal administration of salicyl-tyrosine, suggesting that salicyl-tyrosine was metabolized in the small intestinal mucosa. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg) or tinidazole (6 x 160 mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine following intracecal administration was inhibited significantly, indicating that the intestinal microorganisms were responsible for the biotransformation of these prodrugs. Furthermore, in rabbits orally pretreated with both kanamycin sulfate and tinidazole, a significant inhibition of salicylic acid formation from salicyl-tyrosine and salicyl-methionine following intracecal administration was observed.
The behavior of salicylic acid-D-alanine conjugate (salicyl-D-alanine) following intravenous, oral and intracecal administration was examined in rabbits, then compared with that of salicylic acid-L-alanine conjugate (salicyl-L-alanine) as reported previously. Following intravenous administration, salicyl-D-alanine eliminated rapidly from the blood, and its blood concentration was almost identical with that of salicyl-L-alanine. In both cases, salicylic acid could not be detected in the blood, indicating that systemic de-conjugation of D-alanine might not occur. Unchanged salicyl-D-alanine was found in the blood mainly following oral and intracecal administration of salicyl-D-alanine. On the other hand, salicylic acid formed extensively following oral and intracecal administration of salicyl-L-alanine, suggesting that the presystemic de-conjugation of D-alanine and L-alanine was unequal. Furthermore, in vitro incubation of salicyl-D-alanine with cecal content, in which the major source of salicyl-L-alanine hydrolysis is found, showed that the hydrolysis of salicyl-D-alanine was negligible in rabbit intestinal microorganisms.
An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with salicylic acid, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased compared with the control. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with salicylic acid orally. The blood concentration of SAMG after the intravenous administration of SAM was not increased compared with the control. We suggest that the change in the intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral pretreatment with salicylic acid. The measurement of SAM metabolites may be of value in the assessment of intestinal mucosal damage in vivo.