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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 919 records · Page 51Linked to original sources
PubMed1985

Dissociation of creatine kinase activity from hydrolytic enzyme activities in muscle of dystrophic mice.

Time course studies were done to reexamine the age-dependency of intramuscular enzymatic changes in dystrophic mice. Most of the activities of hydrolytic enzymes in dystrophic mice were elevated in comparison to the controls throughout the span of 8 weeks which was examined. In contrast, the activity of creatine kinase remained depressed throughout the same period. This tendency was similarly seen in the muscles of forelimb and hindlimb but not in heart muscle. The observations are compatible with the notion that the increased activities of hydrolytic enzymes are causally related to the destruction of muscular tissue, leading to the malfunction of contractile machinery in the dystrophic muscles.

Animals↗
PubMed1984

Hepatic extraction of chenodeoxycholic acid in dogs chronically intoxicated with dimethylnitrosamine.

The pharmacokinetics of chenodeoxycholic acid (CDCA) in hepatic dysfunction were evaluated by analyzing the plasma disappearance curves after simultaneous administration of [3H]- and [14C]-CDCA through the femoral and portal veins, respectively, in dogs chronically intoxicated with dimethylnitrosamine (DMN). The plasma concentration-time curve of intravenously administered [3H]-CDCA was best fitted to a three-exponential equation, while that of intraportally administered [14C]-CDCA was fitted to either a two- or a three-exponential equation. In the DMN-intoxicated dogs, significant decreases were observed in total body plasma clearance (CLp), hepatic extraction ratio (EH) and apparent intrinsic clearance (CLint) compared to those of the untreated (control) dogs. The hepatic blood flow (QH), calculated from CLp, CLint and blood-to-plasma concentration ratio (RB) according to the equation reported by Wilkinson and Shand [Clin. Pharmac. Ther. 18, 377 (1975)], was reduced to approximately 70% in the DMN-intoxicated dogs compared to the control dogs. The bindings of CDCA to plasma and liver cytosol fraction were determined by equilibrium dialysis; no significant difference was observed in the unbound fraction between the DMN-treated and control dogs. By comparing both pharmacokinetic parameters obtained from intravenous and intraportal administration, the usefulness of the oral bile acid tolerance test was examined. From these findings, it was suggested that the decrease in the CLp of the DMN-intoxicated dogs was due to both the decrease in QH and that in CLint, and that the decrease in CLint may be due not to an alteration of plasma or cytosol binding but to that of a carrier-mediated transport system. It is also suggested that the measurement of fasting plasma bile acid concentration or the oral bile acid tolerance test is more sensitive for the detection of hepatic dysfunction than the intravenous bile acid tolerance test.

Animals↗
PubMed1984

Hepatic transport of indocyanine green in dogs chronically intoxicated with dimethylnitrosamine.

Hepatic transport of indocyanine green (ICG) was examined in dogs chronically intoxicated with dimethylnitrosamine (DMN) (2 mg/kg) intraportally once a week for 6 weeks. In pathophysiological consequences, significant increases (p less than 0.05) were shown in both glutamic-pyruvic transaminase (GPT) and total plasma bile acids, but no significant difference was shown in body weight, liver wet weight, glutamic-oxaloacetic transaminase (GOT), plasma alkaline phosphatase activity, total plasma protein, and total plasma bilirubin. By histologic examination of livers from intoxicated dogs, increased fibrosis in periportal, perisinusoidal, and especially pericentral areas, with loss of normal architecture, was observed. Partial fibrous bridging between periportal and pericentral areas was also demonstrated, but extensive pseudolobulation with regenerative nodules was not observed. The portal venous pressure of the intoxicated dogs was increased by approximately 50% of that of control dogs. In intoxicated dogs, delays were shown in both plasma disappearance and biliary excretion of ICG and significant decreases were observed in the pharmacokinetic parameters k12 (plasma to liver transfer rate constant), V2 (distribution volume of liver compartment), and CLtot (total body-plasma clearance), while a significant increase was observed in k23 (intrahepatic diffusion and transport rate constant); the V1 (distribution volume of plasma compartment) was not altered. From these findings, it is suggested that the decrease in the intrinsic clearance of ICG for the hepatic uptake process might explain the decrease in ICG uptake rate into the liver which was observed in the DMN-intoxicated dogs. Dogs chronically intoxicated with DMN might be a good model for studying hepatic dysfunction.

Alanine Transaminase↗
PubMed1984

A trial of adjuvant combination chemoimmunotherapy for stage III carcinoma of stomach.

A chemoimmunotherapy program designed on the basis of experimental results was administered to 27 patients with stage III carcinoma of stomach following curative resection. The treatment regimen consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN)-treated autologous tumor cells admixed with bacillus Calmette-Guérin (BCG) and chemotherapy with drugs such as cyclophosphamide (CY), mitomycin C (MMC), and 5-fluorouracil (FU) which proved to enhance the immune response when administered at optimal dose and timing. Then, it was followed by long-term administration of tegafur (FT) and immunomodulators. This treatment significantly improved survival when compared to that of 41 historical control patients treated with surgery alone (P less than 0.001). As compared to 31 control patients concurrently treated with a bolus dose of MMC followed by long-term FT and immunomodulators, survival had a tendency, but not significantly, to be improved in patients treated with this therapy (P less than 0.1). However, the survival rate at 4.5 years was significantly higher than that of control patients (P less than 0.01). These results appeared to show that this type of adjuvant combination chemoimmunotherapy may be of benefit for this group of patients with gastric carcinoma.

Adult↗
PubMed1984

Immunodepression after surgery: impaired production of interleukin 2.

The capacity of peripheral blood mononuclear cells to produce interleukin 2 (IL 2) was studied serially before and after various surgical procedures in 34 patients. In the group of 6 patients who had minor surgery and were categorized into class 1, IL 2 activity did not differ significantly from the preoperative value, throughout the postoperative course. In the group of 14 class 2 patients who underwent major surgery, however, significant decreases in IL 2 activity were observed 1, 3 and 6 days after operation as compared to findings before surgery. Preoperative levels were reverted to by the 8th postoperative day. The remaining 14 patients underwent major and extensive surgical procedures, and were put into class 3. Here too, were also significant decreases in the activity 1, 3 and 6 days after operation. The activity remained significantly depressed 8 days after surgery, in this group of patients. These results show that depression in the production of IL 2 in postoperative surgical patients correlates relatively well with the extent of the surgical procedures.

Animals↗
PubMed1984

Combination chemoimmunotherapy for advanced gastric carcinoma.

Eighty-nine patients with advanced gastric carcinoma were treated with a combination chemo-immunotherapy regimen that consisted of active immunotherapy with Vibrio cholerae neuraminidase (VCN) treated autologous tumor cells admixed with BCG and drugs including cyclophosphamide, mitomycin C (MMC) and 5-fluorouracil, followed by long term tegafur (FT) and immunomodulators. This treatment significantly improved survival rate of patients in Stages III, IV and unresectable or recurrent carcinoma, compared to that of historical controls. As compared to controls treated with MMC followed by long term FT and immunomodulators concurrently, survival rate of those in Stage III tended to improve (P less than 0.1) and survival rate at 4.5 years in Stage III was significantly higher (p less than 0.01), although it was not improved in Stage IV. In patients with unresectable or recurrent tumor, survival time was not significantly lengthened with this therapy when compared with that in patients given BCG alone in the same treatment schedule (CCI-BCG group). However, none of 19 patients in CCI-BCG group survived more than 15 months, although 4 of 28 patients receiving this therapy survived. These results suggest that this combination chemo-immunotherapy is effective for a selected group of patients with advanced gastric carcinoma.

Adjuvants, Immunologic↗
PubMed1984

Colony growth of cells from primary breast carcinoma in soft agar culture.

An in vitro soft agar culture system was utilized to evaluate the colony growth of cells from primary breast carcinoma. A total of 53 specimens from fifty-three patients were placed in culture. Of these, 29 samples (55 per cent) formed at least 30 colonies per 500,000 cells plated. In relation to histologic type of tumor and clinical status of the disease, 4 of 4 samples from mucous carcinoma grew into colonies and, then, t-categories, i.e. histological extent of primary tumor, and colony growth showed an inverse correlation. Estrogen receptor status did not appear to influence growth of the colonies. The in vitro sensitivity studies to adriamycin showed a dose dependent increase in lethality. However, the in vitro response rate was relatively low. This assay system can be used to study the biology and clinical approaches to treatment of breast carcinoma.

Adult↗
PubMed1984

Role of intramuscular enzymatic changes in the development of muscular weakness in rats with experimental allergic neuritis.

We investigated the role of intramuscular enzymatic changes in the development of muscular weakness in rats suffering from experimental allergic neuritis. At an initial stage without apparent clinical symptoms, enzymatic changes of similar types occurred in the muscles of the forelimbs and hind limbs. At a later stage when the weakness appeared in the hind limb but not in the forelimb, dissociation of the pattern of the enzymatic changes occurred between the two limbs. Comparison of the intramuscular enzymatic changes between the two stages and between the two limbs suggested that the increased activities of aminopeptidases and endopeptidases play some important roles in the development of muscular weakness in this experimental model. Low molecular weight protease inhibitors may thus be worthy of a trial in this disease condition.

Aging↗
PubMed1984

Bilateral facial microsomia associated with separation of the posterior portions of the maxilla. A case report.

A case of bilateral facial microsomia associated with separations of the posterior portion of the maxilla is presented. The X-ray findings revealed hypoplasia of the condyles, absence of the coronoid processes of the mandible, and displacement of the pterygoid processes. Cephalometric analysis revealed a characteristic feature of the facial skeleton a rotation clockwise to the anterior cranial base.

Cephalometry↗
PubMed1984

Difference in enzyme networks between mouse and hamster models of muscular dystrophy.

The present study was undertaken to compare the peculiarity of enzymatic changes in dystrophic hamsters and mice. Various enzymatic activities in muscle, bone, heart, spleen, liver and kidney were measured. The enzymes tested include 7 aminopeptidases, 5 endopeptidases, 3 glycosidases, creatine kinase, phosphatase and esterase. In dystrophic mice, the enzymatic changes were chiefly confined to muscle and bone. In dystrophic hamsters, on the other hand, extensive and pronounced changes in enzymatic activities were seen not only in skeletal muscle but also in bone, heart muscle, spleen, liver and kidney. Furthermore, resemblance of pattern of enzymatic changes was seen among several organs including skeletal muscle, heart muscle, bone and spleen in the hamster model. Comparing the enzymatic changes in these two models, dystrophic mouse may be regarded as more specific a model for musculoskeletal diseases. Dystrophic hamster may be related more to multiorgan diseases possibly associated with immunological or other systemic diseases. These models may represent two different disease categories, respectively.

Aminopeptidases↗
PubMed1984

Similar effects of various low-molecular-weight enzyme inhibitors on enzyme networks in dystrophic mice.

We compared the therapeutic effects of various low-molecular-weight enzyme inhibitors on dystrophic mice. Leupeptin, bestatin, forphenicinol and forphenicine significantly affected the enzymatic activities in the dystrophic muscles. The pattern of enzymatic changes in the muscles of forelimb and hindlimb caused by these inhibitors were similar in spite of the variety of their inhibitory spectra in vitro. However, comparing the pattern of enzymatic changes in spleen, forphenicinol differed from the other inhibitors tested. This may be related to the peculiar effects of this inhibitor on immunologically responsive cells.

Alkaline Phosphatase↗
PubMed1984

Toxicological studies on Amfenac sodium (AHR-5850) (I) Acute toxicities in mice and rats.

Acute toxicities of Amfenac sodium (AHR-5850), new nonsteroidal anti-inflammatory agent, were studied in mice and rats. Each value of LD50 by oral, sc, im, iv and ip administration with this compound was 1190, 580, 540, 550 and 790 mg/kg for male mice and 1450, 625, 610, 630 and 710 mg/kg for female mice, respectively. Rats showed higher lethality than mice. There was no significant difference of sex in the values of LD50 for mice and rats. Movement and respiration rate followed by gastrointestinal ulcer, secondary peritonitis and systemic emaciation. These results suggest that the death is caused by secondary peritonitis and systemic emaciation due to gastrointestinal ulcer.

Animals↗