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Biomedical subjects

S Wada

Publications and source records attributed to S Wada.

At least 325 records · Page 18Linked to original sources

Metabolism in vivo of the tropane alkaloid, scopolamine, in several mammalian species.

1. In vivo metabolism of scopolamine was studied in rats, mice, guinea pigs and rabbits. The structures of eight urinary metabolites including unchanged drug were elucidated by mass and nuclear magnetic resonance spectrometry. Determination of these metabolites was achieved by a g.l.c. method using a semi-capillary column. 2. The major metabolites in rats were the three phenolic metabolites, p-hydroxy-, m-hydroxy- and p-hydroxy-m-methoxy-scopolamine. 3. Significant intra-species difference of the metabolism was observed in rabbits. Tropic acid was the major metabolite in two rabbits out of three, while the other rabbit excreted mainly unchanged scopolamine, accompanied by five metabolites. Tropic acid was also the major metabolite in guinea pigs, but was of minor importance in mice. 4. The dehydrated metabolites, aposcopolamine and aponorscopolamine, were abundantly excreted in guinea pigs, moderately in mice, and least in rabbits and rats. 5. Excretion of glucuronide conjugates of scopolamine and norscopolamine were high in mice compared with other species. On the other hand, phenolic metabolites in rat urine; and tropic acid in rabbit and guinea pig urine, were excreted as the free forms. 6. These results indicate that scopolamine metabolism is highly species-specific.

Animals↗

[Hyperthermic treatment in patients with benign prostatic hypertrophy].

Hyperthermic treatment was performed in 31 patients with benign prostatic hypertrophy (BPH). Eight patients of them had a urethral catheter because of urinary retention. The prostate was heated trans-rectally to 43-45 degrees C. The treatment consisted of 10 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before, during and one week after the last hyperthermia session: subjective symptoms score, and residual urine volume, uroflowmetry and transrectal ultrasound of the prostate as objective data. Symptoms score improve in all patients. Of 8 patients with a catheter, the catheter could be removed from 4 patients. There was no significant change in prostate volume, but significant decreases of residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.

Aged↗

[Results of Kock pouch construction fully utilizing an auto-suture instrument].

From March 1987 to the end of February 1991, we performed Koch pouch construction as a urinary diversion on 20 patients who had undergone radical cystectomy due to bladder cancer. The operation was done according to the method of Skinner et al. We fully utilized an auto-suture instrument to ensure safe and stable suturing of the ileum and to shorten the operating time. It was of great concern that the staples placed at several portions might cause stone formation or aggravate infection. However, stone formation was observed only in one patient (5%) at the tip of a nipple valve in which a staple became the nucleus of the stone. Staples are usually not regarded as an obstacle as they are usually covered by the mucous membrane. In all patients, the maximum capacity of the pouch was more than 500 ml, intra-pouch pressure was kept low even when the pouch was inflated up to the maximum capacity, and reflux of urine into the upper urinary tract was not observed. As for complications, there was a slight degree of obstructive uropathy in 4 patients (20%), difficulty in catheter insertion was noted in 3 patients (15%), and stress incontinence-like urinary leakage was present in one patient when the capacity exceeded 500 ml. However, there were no complications which necessitated reoperation. In terms of blood chemistry, although there was a tendency towards a slight increase in BUN or hyperchloremia, no specific treatment was necessary as far as the kidney function was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Transrectal hyperthermia for benign prostatic hyperplasia].

Transrectal hyperthermia was performed on 30 patients with benign prostatic hyperplasia twice a week for a total of ten times with the temperature of the prostatic tissue set at 43.0 degrees C. In our in vitro experiment using an agar phantom, the highest temperature was observed at approx. 1.5 cm from the point where the 915-MHz microwave was generated. Our histopathological study of the prostatic tissue, resected at open surgery after three days of hyperthermia, indicated that the effect of hyperthermia first occurred in the interstitial tissues, and then extended to the epithelial cells. Subjective symptoms and objective findings were evaluated. In almost all cases, improvement was observed in subjective symptoms after completion of the treatment. The residual urine volume improved significantly. Also, significant improvement was observed in our urodynamics study. In 16 out of 30 cases (53%), both subjective symptoms and objective findings were still improved after six months.

Aged↗

[Extracorporeal shock wave lithotripsy for ureteral stones and cystine stones].

We report our experience with extracorporeal shock wave lithotripsy (ESWL) in the treatment of ureteral and cystine stones, which are known to be difficult to treat by this method. First, in order to determine the effectiveness of the ureteral catheter in the destruction of ureteral stones, we compared the clinical results of 121 patients treated without the catheter and 141 patients inserted with the catheter. There was no significant difference in the success rate between the two groups regardless of stone size, which indicates that the use of the ureteral catheter had no effect on the outcome of treatment. We then studied the clinical results of impacted ureteral stones which are especially difficult to destroy. Excretory urography was performed to non-invasively diagnose these stones, and those without visualization in the ureter below the stone were diagnosed as impacted stones and treated by ESWL without the ureteral catheter. Among the stones with a diameter of 1 to 2 cm, the success rate was significantly lower in impacted stones compared to non-impacted stone. These findings suggest that ESWL treatment without the ureteral catheter may be effective for ureteral stones with a diameter of less than 1 cm and non-impacted stones with a diameter of 1 to 2 cm, while combination therapy with other methods such as TUL may be better for other stones. We also performed ESWL on 6 patients with renal stones and 2 patients with ureteral stones which were cystine stones. Renal stones required an average 4.1 treatment with an average of 1,875 shocks per treatment, and ureteral stones required 1.5 treatment with an average of 1,833 shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Evaluation of the results of extracorporeal shock-wave lithotripsy (ESWL) for solitary upper urinary tract stone].

We performed extracorporeal shock-wave lithotripsy (ESWL) on 1,701 patients in a total of 2,438 sessions using the Dornier kidney lithotriptor Model HM III from July 1985 to the end of June 1990. Among the patients with a solitary stone, 1,200 cases were available for the follow-up study in which the results of ESWL were analyzed according to the location and size of the stone. ESWL performed against stones at pelvis and calyces gave the best results. The results obtained on stones less than 20 mm in diameter were especially favorable with a success rate of 84%. ESWL performed against ureter stones showed poor results with a success rate of 62% for the stones smaller than 20 mm in diameter. We further studied the results of ESWL performed against ureter stones by dividing the patients into three groups: the patients treated in situ, the patients with ureteral stents and the patients with D-J stents. The results for stones larger than 10 mm in diameter were significantly better in the patients with D-J stents than in the patients treated in situ or the patients with ureteral stents. Among the patients treated in situ, the results were significantly worse for impacted stones than for non-impacted stones when the stone size was 10-20 mm in diameter.

Evaluation Studies as Topic↗

Cytoplasmic crystalloids in the periodontal tissue of beige mice.

The periodontal tissue of beige mice has been examined by electron microscopy. Specimens of the periodontal tissue from the right mandibular first molars of 10 male beige (bg/bg) and 5 male non-beige (bg/+, controls) mice, were fixed in a mixture of glutaraldehyde and paraformaldehyde, and then decalcified in EDTA. After fixation in osmium tetroxide, the specimens were dehydrated and embedded in epon resin. Ultrathin sections were then stained with uranyl acetate and lead citrate, and observed by electron microscopy. A larger number of cytoplasmic crystalloids were seen in the lysosomes of the histiocytes of the beige mice than in the non-beige mice. These cytoplasmic crystalloids showed striation structures composed of linear densities that were oriented longitudinally, transversely, and obliquely, with about a 4-nm periodicity. The periodontal tissue of the beige mice contained several cells with numerous cytoplasmic crystalloids, whereas there were few cells with fewer crystalloids in the non-beige mice.

Animals↗

[Instillation of a new anticancer preparation for the treatment of superficial bladder cancer: comparison of clinical efficacy between peplomycin emulsion in hydroxypropylcellulosum and peplomycin in saline solution on tumor reduction].

Clinical efficacy of a new preparation of peplomycin emulsion in hydroxypropylcellulosum (HPC-PEP) was studied in 26 patients to compared with that in 14 patients administered with 60 mg of PEP in 20 ml saline (S-PEP). The HPC-PEP was a mixture of 90 mg PEP suspended in 30 ml of 1% HPC. Both of preparations were retained in the bladder cavity over an hour after the instillation. Intravesical instillation was performed once for the patients with HPC-PEP, and 10 times repeatedly for the patients with S-PEP. A clinical evaluation was made on the basis of cytoscopic finding and cytology one week after the final instillation. According to the degree of tumor reduction, the results were classified into "disappearance", "greater than 50% reduction," and "no alteration or further growth" of primary tumor, which were referred respectively to "complete response (CR)", "partial response (PR)" and "not changed (NC)". The rates of CR and response were 27 and 73% respectively for the HPC-PEP administered patients, which were significantly higher than those of 8 and 43% respectively for the patients with S-PEP. In terms of configuration and number of tumor, intravesical HPC-PEP treatment was found to be superior to intravesical S-PEP treatment. In HPC-PEP treatment, a series of untoward symptoms such as bladder irritability and leukopenia was encountered at a frequency of 8%, which is much less than those seen in the S-PEP treatment. These clinical date suggest that HPC-PEP treatment against the superficial bladder tumors is superior to conventional S-PEP instillation in terms of administration frequency and potent doses available to tumor reduction.

Administration, Intravesical↗

Inhibition of renal membrane adenylate cyclase by extract of pancreatic cancer associated with humoral hypercalcemia of malignancy.

The parathyroid hormone (PTH)-like activity, defined by the stimulation of cAMP production in MC3T3E1 cells, in the extract of a pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM) was eluted in two peaks (I and II) by reverse phase HPLC. Both peaks dose-dependently inhibited the binding of human (h) PTH(1-34) to canine renal membrane in an essentially similar fashion to hPTH(1-34) or PTH-related protein (rP). In the renal membrane, neither of these peaks stimulated adenylate cyclase (AC) but rather dose-dependently inhibited AC activity stimulated by hPTH(1-34), PTH-rP(1-34) or forskolin. In rat renal cortical slices, however, both peaks could exhibit their own stimulatory effect and did not inhibit PTH or forskolin-stimulated cAMP production. It has been concluded that a factor which inhibits AC activity, probably reflecting the direct action at catalytic site, can occasionally be produced with PTH-like factor. Although PTH-like and AC-inhibiting activities were very close on reverse phase HPLC, currently the interrelation between these two activities is not clear. It may be important to be aware of the presence of such a factor in the evaluation of the bioassay data employing a broken cell preparation, which is often used to assess the PTH-like activity of tumor products.

Adenylyl Cyclase Inhibitors↗

Modulatory interaction between initial clofibrate treatment and subsequent administration of 2-acetylaminofluorene or sodium phenobarbital on glutathione S-transferase positive lesion development.

The effects of 2-acetylaminofluorene (2-AFF) or sodium phenobarbital (PB) treatment subsequent to clofibrate (CF) administration in terms of preneoplastic lesion development and induction of hepatocellular carcinomas (HCC) were studied using Fischer 344 rats. Animals received CF (0.3% in diet) for the initial 30 weeks, and then either 2-AAF (0.01% in diet), PB (0.05% in diet) or basal diet until week 78. Further groups were initially given basal diet, and then treated with 2-AAF or PB week 30. Two-thirds partial hepatectomy was carried out on all animals at week 3, sacrifice of representative groups being performed at weeks 30, 48 and 78. No glutathione S-transferase placental form positive (GST-P+) or negative focal or nodular lesions were apparent at the cessation of CF administration. The induction of GST-P+ focal lesions by 2-AAF was markedly decreased at week 48 in the group previously given CF (P less than 0.05) and furthermore, the respective incidences of HCC at week 78 were 4/17 (23.5%) in the CF----2-AAF group and 7/17 (41.2%) in the 2-AAF alone case. No significant differences between CF----PB and PB alone groups were evident with regard to either GST-P+ lesions and HCC at weeks 48 and 78. No CF-specific GST-P negative neoplastic nodules or HCC were observed in any of the experimental groups. These results suggest that pretreatment with CF may inhibit the induction of GST-P+ focal lesions and HCC by subsequently administrated 2-AAF and that CF demonstrates no initiating activity for liver carcinogenesis under the present condition.

2-Acetylaminofluorene↗

Promoting action of prolactin released from a grafted transplantable pituitary tumor (MtT/F84) on rat prostate carcinogenesis.

The potential modifying effects of high prolactinemia on rat prostate carcinogenesis was investigated. Male F344 rats were treated at 5 times of 5-week intervals with s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB), each injection following 3 weeks pretreatment with dietary ethinyl estradiol. After completion of the carcinogen administration stage, rats received multiple s.c. transplantations of a prolactin producing transplantable pituitary tumor, MtT/F84 until sacrifice at week 51. The effects of additional or single treatment with bromocriptine, a prolactin suppressing agent, were also investigated. The body, liver and kidney but prostate weights were significantly increased in the groups given MtT/F84. Although the development of prostate carcinomas was not affected by the observed hyperprolactinemia, the incidences of atypical hyperplasia of both ventral and lateral prostate were significantly enhanced. The findings thus indicate that prolactin may have promoting potential for prostate carcinogenesis.

Aminobiphenyl Compounds↗

Para-methoxyphenol strongly stimulates cell proliferation in the rat forestomach but is not a promoter of rat forestomach carcinogenesis.

The modifying effects of para-methoxyphenol (PMP) second stage treatment on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rat forestomach carcinogenesis were investigated. Groups of 15 6 week old male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later were administered powdered diet containing 2.0, 1.0, 0.5, 0.25 or 0% PMP until they were killed at week 52. PMP caused epithelial damage and hyperplasia in a dose-dependent manner in the forestomach epithelium, but nevertheless was not associated with any increase in the incidence of either papillomas or squamous cell carcinomas. The results thus clearly indicated that stimulation of cell proliferation does not necessarily correlate with promotion in the second stage of two-stage forestomach carcinogenesis.

Animals↗

Regression of butylated hydroxyanisole (BHA)-induced hyperplasia but not dysplasia in the forestomach of hamsters.

The reversibility of butylated hydroxyanisole (BHA)-induced hamster forestomach hyperplasia was examined histopathologically. Groups of 10-15 male Syrian golden hamsters were treated with 2% BHA, for 12, 24 or 48 weeks and in each case then placed on basal diet until termination of the experiment at week 72, or treated with 2% BHA continuously for 72 weeks. Although sequential sampling revealed that BHA-induced hyperplasia reverted after cessation of antioxidant treatment, dysplastic lesions such as squamous cell dysplasia and basal cell dysplasia persisted and tended to increase with time on BHA. Basal cell dysplasia was observed in some hamsters later than squamous cell dysplasia, i.e. those treated with BHA for 24 weeks or more and killed up to 48 weeks later. Whereas the increase in labeling index evident in areas of hyperplasia during treatment returned to control level after cessation, this was not the case for the dysplastic lesions which continued to demonstrate elevated proliferation. The results thus suggest that basal cell dysplasia, including regions of squamous cell dysplasia, may be of particular importance as a precursor pre-neoplastic lesion.

Animals↗

Thymus lymphocytes in uraemic rats and the effect of thymosin fraction 5 in vitro.

Cellular immunity of thymus lymphocytes in uraemic rats was studied. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the response of thymus lymphocytes to concanavalin A (Con A) significantly decreased in severely uraemic rats, but did not change in moderately uraemic rats. However, when the thymus lymphocytes were pretreated with thymosin fraction 5, the response to Con A was ameliorated in severely uraemic rats. There was a significant correlation between the effect of thymosin fraction 5 on Con A response and Con A response of thymus lymphocytes. In addition, serum from severe uraemic rats suppressed the response of normal thymus lymphocytes to Con A. These results indicate that severe uraemia may cause an impairment in maturation of thymus lymphocytes, which can be improved by thymosin fraction 5 in vitro.

Animals↗

Clinical studies on cell-mediated immunity in patients with urinary bladder carcinoma: blastogenic response, interleukin-2 production and interferon-gamma production of lymphocytes.

Patients with advanced malignant neoplasms have a variety of abnormal lymphocyte functions. We examined the PHA blastogenic response, interleukin-2 (IL-2) production and interferon-gamma (IFN-gamma) production of lymphocytes in 39 bladder cancer patients and 20 control subjects. Correlation between these parameters was also studied. IL-2 production was measured by 3H-thymidine-labelled CTLL-2 assay, and IFN-gamma production was measured by immunoradiometric assay using 2 mouse monoclonal antibodies. As a result, in high stage bladder cancer patients, the PHA blastogenic response, IL-2 production and IFN-gamma production were impaired. However, these parameters were not significantly different between low stage bladder cancer patients and control subjects. There was a significant correlation between the PHA blastogenic response and IL-2 production but no significant correlation between the PHA blastogenic response and IFN-gamma production.

Aged↗

Comparative sequential changes in serum and biliary levels of bile acid components after a single dose of D-galactosamine or partial hepatectomy in the rat.

In order to characterize changes in bile acid profile during liver cell damage and regeneration, levels of bile acids in serum and bile were determined by high performance liquid chromatography (HPLC) in F344 rats treated with a single dose of D-galactosamine (galactosamine, 300 mg/kg, i.p.) or subjected to two-thirds partial hepatectomy (PH). In the serum, galactosamine caused elevation of conjugated bile acids such as taurocholic acid (TCA) and tauro-beta-muricholic acid (T beta MCA) at the 24 and 48-h time points, whereas unconjugated bile acids including cholic acid (CA) at 24 h and hyodeoxycholic acid (HDCA) at 48 h were increased after PH. In the bile, elevation of TCA showed most remarkable elevation at the 24-h time point in the galactosamine-treated group. All components of biliary bile acids showed rapid decreases from 24 to 48 h. The results demonstrated that while liver tissue damaged by galactosamine is able to conjugate bile acids it allows leakage into the blood stream. In contrast, the results for rats subjected to PH indicated that liver cells during DNA synthesis are not capable of conjugating all free bile acids with taurine although a similar leakage occurs. It is concluded that obvious elevation of serum TCA or CA and biliary T beta MCA could be a useful indicator of hepatocellular proliferation.

Animals↗

Effects of high energy shock wave exposure on renal function during extracorporeal shock wave lithotripsy for kidney stones.

In order to study the effects of high energy shock wave exposure on the kidney in extracorporeal shock wave lithotripsy (ESWL) using Dornier HM3, renal hemodynamics and renal function before and after ESWL were analyzed by 99mTc-DTPA renoscintigraphy. Various urinary enzyme activities (LDH, GOT, GPT, NAG, gamma-GTP) and low molecular protein concentrations (alpha 1-microglobulin, beta 2-microglobulin) before and after ESWL were also compared. In the early phase of the renoscinitgram obtained in the 1st min after injection of 99mTc-DTPA, the time required to reach maximum radioactivity was significantly prolonged after ESWL in both the affected and contralateral kidney. This indicated that renal blood flow decreased in both the affected and contralateral kidney immediately after ESWL. An analysis of the 30-min renoscintigram showed that urinary clearance was delayed in the affected kidney in spite of no overt obstruction due to stone fragments. As for urinary enzyme activities and low molecular protein concentrations, they were standardized by urinary creatinine concentration measured at the same time. Urinary LDH, GOT, GPT and NAG activities remarkably increased on the day of ESWL followed by a decrease close to pretreatment levels on the 4th day, though these levels were still significantly higher than pretreatment levels. Urinary gamma-GPT activity was significantly higher than the pretreatment level only on the day of ESWL. Urinary alpha 1-microglobulin and beta 2-microglobulin concentrations significantly increased on the day of ESWL and were still high on the 4th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗