Biomedical subjects

S Kanai

Publications and source records attributed to S Kanai.

At least 91 records · Page 5Linked to original sources

PubMed1994

Ursodeoxycholic acid reduces the systemic toxicity of 1,2-dichloro,4-nitrobenzene by stimulating hepatic glutathione S-transferase in mice.

Male C57BL/6 mice were fed with normal diet (ND) or diets containing 0.3 or 0.5% ursodeoxycholic acid (UDCA) for 3 weeks. Glutathione S-transferase (GST) activities in the liver cytosolic fraction of these animals toward 1,2-dichloro,4-nitrobenzene (DCNB) as well as to 1-chloro,2,4-dinitrobenzene (CDNB) were significantly increased in a dose dependent manner in UDCA-treated groups compared with the control (ND-fed) animal group (one-way ANOVA). Reduced glutathione (GSH) levels tended to slightly decrease with UDCA diets but the difference did not attain a statistical significance (P > 0.05, one-way ANOVA). Twenty four hr survival rates after an oral challenge of 3.5 mg/kg of DCNB were significantly higher (P < 0.05, Chi-square test) in the two UDCA fed groups (10/10 for 0.5% group, 8/11 for 0.3% group) compared with the control group (3/11). Thus, UDCA appears to reduce the systemic toxicity of DCNB which is detoxified by the hepatic GST system. Although UDCA has been shown to exert hepatoprotective effects in experimental animals and humans in the past, to the best of our knowledge, the present study is the first report that UDCA reduces the systemic toxicity of a toxicant which is detoxified by the hepatic GST system. Although a direct proof is not available, it is most likely that the reduction of the systemic toxicity of DCNB was achieved by the increase in GST activity caused by UDCA feeding. This finding may open a new research field with regard to the unique biological properties of this bile salt in modulating hepatic detoxifying enzymes.

Alanine Transaminase↗

PubMed1994

Tauro alpha-muricholate is as effective as tauro beta-muricholate and tauroursodeoxycholate in preventing taurochenodeoxycholate-induced liver damage in the rat.

Male Wistar rats were infused intravenously with taurochenodeoxycholate (0.4 mumol/min/100 gm) alone (group A) or with one of the three bile salts (tauroursodeoxycholate [group B], tauro beta-muricholate [group C] or tauro alpha-muricholate [group D]) at a rate of 0.2 mumol/min/100/gm for 1 hr. One-hour bile flow and bile salt excretion rates were significantly lower in group A than in the other three coinfused (B, C, D) groups. Biliary 1-hr outputs of lactate dehydrogenase and albumin in the bile, on the other hand, were significantly higher in group A than in the other groups. Plasma concentrations of lactate dehydrogenase at the time of killing (1 hr) were two to three times higher in group A than in the other groups. Although tauro alpha-muricholate does not possess a 7 beta-hydroxy group, the 6 beta-hydroxy group that tauro alpha-muricholate possesses thus appears to be as effective as a 7 beta-hydroxy group in reducing the liver damage caused by toxic bile salts such as taurochenodeoxycholate. The so-called hepatoprotective effects of tauroursodeoxycholate and tauro beta-muricholate found in previous studies may require explanation(s) other than the presence of a 7 beta-hydroxy group in their molecular structures.

Albumins↗

PubMed1993

Nucleotide sequence of the Mn-stabilizing protein gene of the thermophilic cyanobacterium Synechococcus elongatus.

The nucleotide sequence of the psbO gene encoding the extrinsic 33 kDa protein (the Mn-stabilizing protein) from the thermophilic cyanobacterium Synechococcus elongatus was determined. The deduced amino acid sequence consisted of 272 residues; 26 for the signal peptide and 246 for the mature protein. The amino acid sequences of nine proteolytic peptides from the isolated protein completely agreed with the deduced amino acid sequence. Several unique variations of amino acids were found in the primary structure, of which some may be related to the high thermostability of the protein.

Amino Acid Sequence↗

PubMed1993

Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence.

Seventy male Fischer 344 (F-344) rats were treated with s.c. injection of (-)deprenyl (0.5 mg/kg, n = 35) or physiological saline (n = 35) 3 times a week from the age of 18 months until the time of their natural death. The fifty percent survival time was 28 months in control animals and 30 months in the deprenyl treated group. The mean survival time after the start of treatment (18 months) and after 24 months were 378.3 +/- 97.4 days (mean +/- SD) and 196.3 +/- 97.4 days, respectively, in deprenyl treated rats and 328.7 +/- 108.8 days and 146.7 +/- 108.7 days in control rats. The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant (P < 0.05, two-tailed t-test). The average body weights were comparable for both groups but the variation of body weight was greater in control groups, thus excluding the possibility that the life prolonging effect of deprenyl results from reduced dietary intake. The results confirm those of two previous studies (1,2) which reported a significant life prolonging effect of deprenyl in aged rats and lend added support to the results of a study on male F-344 rats where the effect was only marginally significant (16% increase after 24 months, P = 0.048 by one-tailed t test) (2).

Animals↗

PubMed1993

The optimal dosage of (-)deprenyl for increasing superoxide dismutase activities in several brain regions decreases with age in male Fischer 344 rats.

We previously reported that the optimal dosage of (-)deprenyl to increase superoxide dismutase (SOD) activities in striatum in rats differs 10 fold between young male and female rats (1). Furthermore, in female rats the optimal dosage increased with age (1). In the present study in order to clarify how the optimal dosage of this effect changes with age in male rats, we examined the effects of four different dosages of deprenyl on SOD enzyme activities in striatum and several other tissues in old (28-29-month-old) male Fischer 344 (F-344) rats. Continuous s.c. infusion of deprenyl for 3 wks increased activities of SOD and catalase (CAT) in striatum, substantia nigra and cortical regions but not in hippocampus, cerebellum or the liver. The dose of 0.5 mg/kg/day was found to be most effective, while higher (1.0, 2.0 mg/kg/day) or lower (0.1 mg/kg/day) dosages were less effective. This value of 0.5 mg/kg/day was 4 fold lower than the dosage of 2.0 mg/kg/day which was most effective in increasing SOD and CAT activities in young (5-7 month old) male rats of the same strain (1,2). The decline of the optimal dosage with age found in male rats is best explained by a possible decline with age in the hepatic microsomal monooxygenase enzyme activities that are involved with the metabolism of deprenyl. In view of the large differences in the optimal dosages shown among different sexes and ages of rats, future studies regarding the unique effect of this drug in prolonging the life span of rats must be carefully investigated with the caution in mind that the optimal dosage for the life prolonging effect may well differ depending on sex, age and possibly strain and species of animal model used.

Aging↗

PubMed1993

Taurine conjugate of ursodeoxycholate plays a major role in the hepatoprotective effect against cholestasis induced by taurochenodeoxycholate in rats.

Rats which were taurine-deprived through beta-alanine administration and untreated rats were used to elucidate the mechanism of hepatoprotective effects of ursodeoxycholate (UDC). Animals were infused with taurochenodeoxycholate (TCDC, 0.4 mumol.min-1.100 g-1) alone or in combination with tauroursodeoxycholate (TUDC), or with UDC (both 0.6 mumol.min-1.100 g-1) for 2 h. Ursodeoxycholate as well as TUDC prevented severe cholestasis and liver damage induced by TCDC infusion in both untreated and taurine-deprived rat groups. In untreated rats, however, UDC was less effective in hepatoprotection than TUDC as indicated by sequential changes in biliary LDH output during the period of 30 to 120 min (P < 0.05). In rats receiving UDC and TCDC, total biliary output of LDH for 2 h was significantly higher in taurine-deprived rats than that in the control (73.40 +/- 10.10 vs 41.14 +/- 12.56: P < 0.05), suggesting that the difference became greater upon taurine deprivation. In contrast, in rats receiving TUDC and TCDC, the protective effect was comparable for the taurine-deprived and untreated rats. When the animals were infused with UDC and TCDC, taurine-deprived rats exhibited a biliary excretion rate for TUDC half that of control rats (P < 0.05). Furthermore, a highly significant correlation was observed between the biliary excretion rate of TUDC and biliary output of LDH (r = -0.886, P < 0.0001). These results suggest that UDC conjugates, especially TUDC, and not UDC may play a major role in the prevention of cholestasis and liver cell damage caused by TCDC infusion.

Alkaline Phosphatase↗

PubMed1993

[Antibiotic prophylaxis for transurethral resection of the prostate--comparison of oral administration therapy with intravenous administration therapy].

To compare the prophylactic effect of oral and intravenous antibiotics against postoperative fever and urinary tract infection (UTI) after transurethral resection of the prostate (TUR-P), we conducted a multi-center prospective randomized study. The incidence of pyrexia over 38 degrees C was defined as the primary endpoint. One hundred and fifty patients with sterile urine before TUR-P were entered into this study. The patients were allocated randomly into the two arms; arm A cefotiam 4 g a day for 7 days, arm B tosufloxacin 300 mg a day for 7 days, based on the stratification into the 4 groups determined with/without preoperative indwelling catheters and with/without the history of preoperative UTI. Of these patients, 143 were eligible. We divided 124 patients without preoperative UTI and without indwelling catheters as the "low risk group", and the other 19 patients with preoperative UTI and/or with indwelling catheters as the "high risk group". In the low risk group, 9 patients out of 63 (14.3%) in arm A and 6 out of 61 (9.8%) in arm B had pyrexia during 7 postoperative days. The incidence of fever in arm B was 4.4% less than that in arm A and the 95% confidence limit was from -7% to 16%. In the high risk group, 4 out of 11 (36.4%) patients in arm A and none of 8 in arm B had fever but the difference was not significant. The incidence of post operative UTI in the low risk group on the 4 to 5, 9 to 12, 23 to 26 and 37 to 40 postoperative days was 8.3, 16.4, 25.0 and 23.9% in arm A and 6.7, 16.7, 29.6 and 36.7% in arm B, respectively. The prophylactic effect of oral administration of tosufloxacin is equivalent to that of the intravenous administration of cefotiam. The use of oral antibiotics is beneficial to reducing the cost of medication.

Administration, Oral↗

PubMed1993

[A case of bilateral synchronous renal cell carcinoma treated with partial nephrectomy with temporary occlusion of the segmental renal artery (segmental nephrectomy)].

We present a case of bilateral synchronous renal cell carcinoma. A 57-year-old man visited our hospital with a complaint of fever up. On ultrasonography and computerized tomography scan, a round tumor about 2.5 cm in diameter in the posterior portion of the right kidney and another tumor about 7 cm in diameter arising from the upper pole of the left kidney. Selective renal arteriogram showed that the inferior branch of the posterior segmental artery supplied blood to the right renal tumor. Left partial nephrectomy with temporary occlusion of the main renal artery and posterior segmental nephrectomy of the right kidney were performed at the same time. In patients with cancer confined to the posterior segment of the kidney, segmental nephrectomy can be performed while allowing unimpaired perfusion to the remainder of the kidney from the main renal artery.

Carcinoma, Renal Cell↗

PubMed1992

Sequential changes in activities of superoxide dismutase and catalase in brain regions and liver during (-)deprenyl infusion in male rats.

A continuous s.c. infusion of (-)deprenyl in young male rats at a dose of 2.0 mg/kg/day for 1 week significantly increased total superoxide dismutase (SOD) activities due to increases in both Cu Zn-SOD and Mn-SOD activities in certain brain regions such as the substantia nitra and striatum, but not in the hippocampus or cerebellum, or in the liver. With continuing infusion, enzyme activities of SOD were further increased in the following weeks, reaching a plateau at 3 weeks. In some cerebral cortices the increase became significant at 3 weeks. In contrast to SOD activities, an increase in catalase (CAT) activity became significant only after 2 weeks of infusion, and only in the brain regions where SOD activities were increased earlier. The delay in the increase in CAT activity following deprenyl infusion suggests that this increased CAT activity is an adaptive response to the earlier increase in deprenyl-induced SOD activities rather than a direct effect of deprenyl on CAT activity, although the latter possibility cannot be excluded.

Animals↗

PubMed1992

(-)Deprenyl increases activities of superoxide dismutase and catalase in striatum but not in hippocampus: the sex and age-related differences in the optimal dose in the rat.

The dose of (-)deprenyl (2.0 mg/kg/day, sc, for 3 weeks) which significantly increased activities of superoxide dismutase (SOD) and catalase in the striatum of young male rats significantly reduced these activities in young female rats but did not change the SOD activity in old female rats. In order to clarify these effects, different doses of the drug were continuously infused sc for 3 weeks in three groups of rats (young males and young and old females). When a 10-fold smaller dose (0.2 mg/kg/day) was applied in young female rats, activities of both SOD and catalase were significantly increased, while a higher dose of 0.5 mg/kg/day was ineffective and a lower dose of 0.1 mg/kg/day was substantially less effective. In old female rats, doses of both 0.5 and 1.0 mg/kg/day were equally effective in elevating activities of SOD and catalase, while a lower dose of 0.1 mg/kg/day was less effective. The activity of glutathione peroxidase (GSH Px) remained unchanged in all groups, except for a significant decrease in the activity of non-selenium-dependent GSH Px in both young and old female rats given the highest drug dose (2.0 mg/kg/day). Furthermore, activities of all three enzymes remained unchanged in the hippocampus in most groups. The results indicate that (-)deprenyl significantly increases activities of both SOD and catalase in the striatum, but not in hippocampus of rats, and that the optimal dose is very different depending on the sex and age of the animal.

Age Factors↗

PubMed1992

Intraventricular infusion of leupeptin decreases Bmax of the D2 receptor in the striatum of young rats.

Intraventricular infusion of a thiol protease inhibitor, leupeptin, was previously shown to induce several morphological and immunochemical manifestations of normal and pathological aging in rat brain. The present study attempted to elucidate whether this treatment also perturbs another brain function which declines in aging, dopamine D2 receptor binding in striatum. Intraventricular infusion of leupeptin (0.6 mg per day) for two weeks caused a significant (about 20%) reduction in the binding maximum (Bmax) of dopamine D2 receptors (as examined by [3H] spiperone binding) in the striatum of young male Fischer-344 rats in comparison to (saline-infused) control rats. The apparent Kd values did not differ significantly between the control and leupeptin-treated rat groups. The results suggest that decreased protein turnover may be a factor in the decline in Bmax of D2 receptors during aging.

Animals↗

PubMed1992

The ability of (-)deprenyl to increase superoxide dismutase activities in the rat is tissue and brain region selective.

In a previous study we have shown that chronic administration of (-)deprenyl increases activities of superoxide dismutase (SOD) and catalase (CAT) in rat striatum (1). The present study attempted to clarify how specific the effect of deprenyl is to certain tissues and brain regions in the rat. Two mg/kg/day of deprenyl was continuously infused s.c. in young male Fischer-344 rats. On the 22nd day, rats were sacrificed and enzyme activities of SOD and CAT were determined in several different brain regions and the liver. Activities of both SOD and CAT were significantly increased in striatum and substantia nigra but not in hippocampus, cerebellum or liver. Both types of SOD (i.e. Cu Zn-SOD and Mn-SOD) were significantly increased in striatum, substantia nigra. Interestingly, in cerebral cortices of three different regions, activities also tended to increase (especially those of Mn-SOD), although the increase was not so striking as in substantia nigra and striatum. The results confirm the previous observation that (-)deprenyl can increase free radical scavenger enzyme activities in striatum and provide further evidence that this effect is selective to certain brain regions and tissue types.

Animals↗

PubMed1992

Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat.

Enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the liver as well as several specific brain regions of young and old Fischer-344 rats of both sexes. In the liver of male rats, activities of CAT as well as Mn-SOD were lower, while activities of Cu Zn-SOD were higher in old (30-month-old) rats than in young (7-month-old) ones. Activities of total SOD as well as GSH Px were comparable for young and old male rat livers. In contrast to male rats, in female rat livers, activities of CAT were significantly higher in old (28-months-old) rats, while activities of Mn-SOD were slightly (but significantly) higher in old rat livers. In old male rats, activities of Mn-SOD were significantly higher than in young males in several specific regions of the brain (the substantia nigra (s. nigra), striatum, hippocampus) but lower in the cerebellum. In particular, SOD activities in s. nigra, striatum and hippocampus in old male rats were several fold higher than corresponding values in young male rats. Activities of Cu Zn-SOD were generally unchanged with age. Activities of CAT as well as GSH-Px (both Se-dependent and non-Se-dependent forms) were also relatively unaffected by age. In female rat brains, activities of Mn-SOD as well as those of others all remained mostly unaffected by aging, although there was a general tendency of slightly higher activities in most cerebral regions for Mn-SOD in old female rats. Thus, age-related changes of these antioxidant enzymes in the liver and brain are markedly sex dependent and some enzyme activities (such as CAT in the liver) change in an opposite direction with age. Changes of Mn-SOD in the brain were markedly region-specific in male rats. Results suggest that the significance of the changes of these antioxidant enzyme activities during aging needs to be carefully interpreted, taking into consideration the fact that changes are markedly variable depending on sex as well as the organs and brain regions examined.

Aging↗

PubMed1992

Difference in response of hepatic glutathione S-transferase activities to protein-free diet between young and old C57/BL male mice.

Responses of hepatic glutathione S-transferase (GST) activities to protein-free diet (PFD) and normal diet (ND) refeeding were compared for young (6-month-old) and old (22-month-old) C57/BL male mice. Enzyme activities toward 1-chloro-2,4-dinitrobenzene (CDNB) were not significantly different between young and old rat livers in the basal condition without diet manipulation. When animals were fed PFD for 1 week, GST activities toward CDNB significantly declined in both age groups in comparison to respective basal values, but there was no significant difference in activities between the two age groups after a 7-day PFD. When they were refed with ND for 2 days (on day 2 of ND), the activities in young mice rose to a level significantly higher than the corresponding basal value. In contrast, in old animal livers, the activity slightly but further tended to decline on day 2 of ND. Activities in old rat livers returned to the basal level on day 5 of ND, while activities in young animal livers that increased to levels higher than basal levels due to the overshoot returned to the basal level on day 7 of ND. Enzyme activities toward 1,2-dichloro-4-nitrobenzene (DCNB) were significantly higher in young rat livers than in old ones at the basal period. However, enzyme activities also overshot the basal level on day 2 of ND after 7-day PFD in young mouse livers, while in old mouse livers the activities were lowest on this day. Activities returned to the basal level on day 7 of ND in both age groups. Thus, the greatest difference in enzyme activities between young and old mouse livers for both substrates was observed on day 2 of ND after 7-day PFD, rather than at either the basal period or immediately after 7-day PFD. The results essentially agree with our previous findings on female C57/BL mice as well as female Fischer-344 rats, suggesting that the age-induced changes in the GST system become clearly manifest after diet manipulation of PFD followed by ND refeeding, rather than in values during a basal period without diet manipulation, regardless of sex or species of animal.

Aging↗

PubMed1992

Multi-priming sequencing: a DNA sequencing method involving restriction enzyme-digested DNA fragments as primers.

An improved strategy for fluorescence-labeled dideoxy chain termination sequencing involving restriction enzyme-digested DNA fragments as primers, which are prepared from the DNA to be sequenced, is described. By using modified nucleoside triphosphates for strand protection in chain termination reactions, newly synthesized chains were detached from a primer at the regenerated recognition site by means of suitable restriction enzyme digestion. The digests could be analyzed with commercial automated DNA sequencers. Thus, by using restriction DNA fragments (double-stranded) as primers, sequence information was obtained from both "minus" and "plus" single-stranded DNA templates without subcloning. Nor is the synthesis of oligonucleotide primers needed. This method, named "Multi-Priming Sequencing," was proven to be time-saving, economical, and effective compared to conventional methods.

Base Sequence↗

PubMed1992

[Clinical characteristics and prognosis of renal cell carcinoma. Statistical evaluation of possible determinants for distant metastasis, venous tumor thrombi, and lymph node metastasis].

To clarify the recent clinical characteristics of renal cell carcinomas and to evaluate possible determinants for metastasis and venous tumor thrombi, the authors reviewed data from 99 renal cell carcinoma patients treated at Nagoya University Hospital between 1980 and 1989. According to Robson's classification, stage I tumors were found in 48 patients, stage II in 9, stage III in 16, and stage IV in 26. Incidentally detected tumors appeared to be on the increase in recent years. Grade 1 tumors were significantly associated with low-stage tumors and expansive growth. Univariate and multivariate analyses using a logistic regression model demonstrated that venous tumor thrombi and histological grade were significantly related to distant metastasis. Univariate analysis revealed relative risks of 4.7 for venous tumor thrombus presence (pV1b-pV2 vs. pV0-pV1a, p = 0.005) and 8.5 for histological grade (grades 2 and 3 vs. grade 1, p = 0.04). Local invasion (pT3 vs. pT2a-pTb: a relative risk of 7.5, p = 0.0009) and infiltration pattern (INF beta and INF gamma vs. INF alpha: a relative risk of 11.5, p = 0.002). were associated with venous tumor thrombi. Local invasion (pT3 vs. pT2a-pT2b: a relative risk of 6.6, p = 0.03) was the only significant determinant for lymph node metastasis. The 5-year actuarial survival rate was 60.0% for all 99 patients. The 5-year survival rates for stage I and II tumors were, respectively, 91.8% and 64.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Renal Cell↗

PubMed1992

[Complications of Kock continent reservoir. Report of 103 cases].

We installed a Kock continent reservoir in 103 patients after radical cystectomy or pelvic exenteration between Feb. 1986 and Dec. 1989. They consisted of 81 male and 22 female patients. Patients' age ranged from 30 to 78 years with the average being 63 years. Their original diseases were bladder cancer (96 patients), prostatic cancer (2), sigmoid colon cancer (2) and others (3), The Kock reservoir was made by the procedure described by D. G. Skinner et al. The mean operation time for reservoir creation was 220 minutes. In 99 patients with a Kock reservoir for more than 3 months, the capacity of the reservoir was 200-900 ml with the average being 490 ml and the frequency of self-catheterization was 4 to 6 times a day. Early complications occurred within 3 months in 27 (26%) patients. Complications directly related to the reservoir were urine leakage (5 patients), intestine reservoir fistula formation (3) and necrosis of the reservoir (1). Late complications occurred after 3 months in 25 (25%) patients. They consisted of difficulty of catheterization (9 patients), ureteral reflux from reservoir (2), hydronephrosis (8), abscess (4), metabolic acidosis (2) and others. The results indicated that this procedure is an appropriate urinary diversion since the quality of life in the patients with a Kock reservoir is better. However, after this procedure surgical complications were not infrequent. Therefore, this procedure should be performed in selected patients.

Adult↗

PubMed1992

[A case of CA19-9 producing transitional cell carcinoma of the ureter effectively responsive to combination chemotherapy].

We report a case of CA19-9 producing transitional cell carcinoma of the right ureter effectively responsive to combination chemotherapy (methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) regimen) in a 53-year-old woman. The maximum level of serum CA19-9 showed 3,000 U/ml and clinical staging of the tumor was T4 N3 M0. Marked regression of the tumor was identified by computed tomographic scan and the level of serum CA19-9 returned to the normal range after 3 courses of M-VAC therapy. Right total nephro-ureterectomy and partial cystectomy was done and the surgical specimen revealed no viable tumors. She is alive without evidence of local recurrence or metastasis at 6 months after resection. The serum CA19-9 level was useful for monitoring the clinical course.

Antigens, Tumor-Associated, Carbohydrate↗