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Biomedical subjects

S Wada

Publications and source records attributed to S Wada.

At least 307 records · Page 17Linked to original sources

[Giant epidermoid cyst of the scrotum: a case report].

A 74-year-old male with the chief complaint of painless enlargement of a mass in the scrotum was diagnosed as having a giant epidermoid cyst on July 8, 1991. He had no past history of injury or pain of the scrotum. Magnetic resonance imaging (MRI) of the scrotum demonstrated a well-circumscribed homogeneous mass, and was distinguished from both normal testes. Under the diagnosis of intrascrotal epidermoid cyst, the mass was resected surgically. The mass measured 23 x 15 x 15 cm, and it contained liquids. The pathological diagnosis was epidermoid cyst of the scrotum.

Aged↗

[Clinical study of prophylactic therapy of interferon on postoperative renal cell carcinoma].

A clinical trial using interferon alpha 2b (IFN alpha-2b) for prophylactic therapy was done on 44 patients who had received nephrectomy for renal cell carcinoma. Principally, the daily intramuscular injection of 3 of 6 million units of IFN alpha-2b was done for 4 consecutive weeks after 2 weeks postoperatively and thereafter followed by injection once every 2 weeks. The clinical evaluation was done for the recurrence rate, the survival rate, the IFN alpha and IFN gamma producing ability, the activity of 2',5' oligoadenylate synthetase (2-5AS) and the side effect. Out of 44 cases entered, 42 were completely evaluable and recurrence was observed in 5 (11.9%) of the 42 cases. The recurrence rate was 5.5% and 16.4%, at the first and second year, respectively. Three (7.1%) of the 42 patients died. The survival rate was 97.6% at the first year, 89.7% at the second year for the followup study. The IFN alpha producing capacity was low in all of the 4 evaluable cases. The IFN gamma producing capacity was high in 3 cases and normal in 1 case. 2-5AS, the enzyme produced by IFN, was activated by IFN alpha-2b administration in all of the 4 evaluable cases. Side effects were observed in 24 (54.5%) of the 44 cases. The main side effect was fever. Leucopenia, general fatigue, appetite loss, temporary elevation of liver transaminase were also observed. However, there were only 5 cases (11.4%) in which administration of IFN alpha-2b had to be discontinued.

Adult↗

[Combined effect of TNF and anticancer chemotherapeutic agents on murine bladder tumor (MBT-2)].

The antitumor activity of combination therapy of recombinant human tumor necrosis factor alpha (rHu-TNF alpha) and chemotherapeutic agents against murine bladder tumor (MBT-2) was studied. Tumors were intradermally transplanted into the hind leg of C3H-HeN mice and allowed to grow until they reached a diameter of 8 to 10 mm 10 days after transplantation. TNF (3,000 units) was given intraperitoneally from day 10 to day 19, and the chemotherapeutic agents, 5-FU (60 mg/kg), CPM (100 mg/kg), CDDP (10 mg/kg) and ADM (5 mg/kg), were applied once intraperitoneally on day 10. The antitumor effects were evaluated based on tumor volume on day 20. 5-FU, CPM and ADM enhanced the antitumor effect when combined with TNF, but CDDP did not. These findings suggest that combination therapy of TNF and certain antitumor chemotherapeutic agents is effective cancer treatment.

Animals↗

[Study of preventive effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU) or combination of HCFU and 2.5-di-O-acetyl-D-glucaro (1-4) (6-3) dilactone (SLA) after preservative operation against bladder cancer].

To treat superficial bladder cancer or invasive bladder cancer presenting as a solitary tumor, conservative therapy such as transurethral resection of bladder tumor or partial cystectomy has long been carried out. We studied the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU), and the effects of the combination of HCFU and 2.5-di-O-acetyl-D-glucaro-(1-4)(6-3) dilactone (SLA) which is an anti-beta-glucuronidase agent, for preventive therapy. In the patients treated with HCFU, the recurrence rate was 3.6% and 26.6% one year and two years, respectively, after conservative operation. In the patients treated with both SLA and HCFU, the recurrence rate was lower than in those treated with HCFU one year or more after conservative operation, and a long-term preventive effect was expected for nondrinkers.

Adult↗

Effects of hyperbaric environment on the P300 component of event-related potentials.

Hyperbaric chamber dives at 19 ATA with helium-oxygen were performed at the Japan Marine Science Technology Center, Yokosuka, from January 31 to February 2 in 1990. During simulated underwater experiments, event-related potentials were recorded in 2 divers for assessment of the cognitive function. Although the P300 amplitude of the potentials did not show any significant change, its latency was clearly prolongated and this prolongation continued to when the decompression reached to 70 m below sea level. These findings indicated that the hyperbaric environment corresponding to 180 m below sea level or less must cause some cognitive dysfunctions and that P300 is useful for early detection of those dysfunctions or HPNS.

Cognition↗

The effect of PGF2 alpha on parathyroid hormone-stimulated cyclic AMP production in mouse osteoblastic cell, MC3T3E1.

The effect of prostaglandin F2 alpha (PGF2 alpha) was investigated in MC3T3E1 cells on the succeeding cAMP response to parathyroid hormone (PTH). PGF2 alpha increased the membrane-associated protein kinase C (PKC) activity, indicating the activation of this enzyme. The effect of PTH to increase cAMP production was enhanced by pretreatment with PGF2 alpha. Phorbol 12-myristate 13-acetate also enhanced cAMP production stimulated by PTH, and PKC inhibitor H7 attenuated the enhancement of PGF2 alpha. A23187 did not reproduce the PGF2 alpha effect, and this effect was not antagonized by the calmodulin antagonist W7. PGF2 alpha did not change the ED50 nor the maximally responsive dose of PTH in stimulating cAMP production. The effect of PGF2 alpha was not affected by pertussis toxin, and PGF2 alpha also enhanced cholera toxin- or forskolin-stimulated cAMP production. In accordance with the response of cAMP to PTH, the resorption of mouse limb bones stimulated submaximally by PTH was enhanced by the concomitant presence of PGF2 alpha. These results indicate that PGF2 alpha modulates cAMP response through the activation of PKC, the target of which might be the catalytic unit of adenylate cyclase. Such interaction between signal transduction systems may have significance in modulating the effect of PTH on bone, i.e., bone resorption.

Animals↗

Purification and partial sequencing of inhibitory factor on renal membrane adenylate cyclase in pancreatic cancer extract: identity with histones H1b or H1d.

Inhibitory activity on renal membrane adenylate cyclase (AC) has previously been found in the extract of a pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM). AC inhibitor was purified employing inhibition of AC activity of renal membrane stimulated by forskolin as its index. N-terminal 9 residues and a digested fragment of purified protein (14 residues) were completely consistent with that of histones H1b and H1d. Not only histone H1 but also histones H2A, H2B and H3 from calf thymus inhibited AC activity. These results indicate that the AC inhibitor in the pancreatic cancer extract is histone H1b or H1d and histones H2A, H2B and H3 also have an AC inhibitory activity.

Adenylyl Cyclases↗

Inner arm dynein ATPase fraction of sea urchin sperm flagella causes active sliding of axonemal outer doublet microtubule.

In order to clarify the role of the inner arms of the axoneme in sperm flagellar movement, we prepared an ATPase fraction (12S) from the outer arm-depleted axonemes of sea urchin sperm flagella. When both arm-depleted axonemes were incubated with the 12S ATPase, they exhibited the sliding disintegration of outer doublet microtubules. Electron microscopy revealed that the ATPase rebound to the original inner arm sites of the axoneme. Therefore, it is quite likely that the 12S ATPase is one of the components of the inner arms. We referred to it as "inner arm dynein".

Animals↗

Dose response study of N-nitrosodiethanolamine initiation of rat hepatocarcinogenesis.

Initiating activity of N-nitrosodiethanolamine (NDELA) for rat liver carcinogenesis was investigated using an 8-weeks bioassay system. Male F344 rats were initially treated with a single intraperitoneal injection of NDELA at one of five dose levels: 1,600, 800, 400, 200, or 100 mg/kg. Two weeks later, the rats were placed on 0.02% 2-acetylaminofluorene (2-AAF) or 0.05% phenobarbital (PB) containing diet for 6 weeks. All animals were subjected to 2/3 partial hepatectomy 4 weeks after the NDELA treatment, and killed at the end of the eighth week. NDELA itself exerted low toxicity in terms of body weight gain. Clear dose-dependent initiating activity of NDELA was observed in terms of development of glutathione S-transferase placental form (GST-P) positive liver cell foci, this being more apparent with PB promotion than with 2-AAF where the enhancing regimen itself caused multiple lesion development. Initiating potential of NDELA, however, was much lower than that observed for diethylnitrosamine in our previous work.

2-Acetylaminofluorene↗

Abnormal glucagon response to arginine and its normalization in obese hyperinsulinaemic patients with glucose intolerance: importance of insulin action on pancreatic alpha cells.

An excessive glucagon secretion to intravenous arginine infusion was found in obese hyperinsulinaemic patients with glucose intolerance. This study was designed to determine whether the glucagon hyperresponsiveness to arginine in these patients would improve by insulin infused at a high enough dose to overcome insulin resistance. By infusing high dose insulin during arginine infusion, the previously exaggerated glucagon response to arginine could be normalized. To normalize the abnormal glucagon response, insulin doses of 4.2 +/- 0.7 and 3.8 +/- 0.5 IU were required during arginine infusion in obese hyperinsulinaemic patients with impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus, respectively. This achieved plasma peak insulin levels 3 to 4 times higher than those observed in non-obese healthy subjects. Furthermore, we clarified whether or not the effect of normalizing insulin action and/or glycaemic excursions contributed to normalizing the exaggerated glucagon response to arginine in these patients. Blood glucose was clamped while high dose insulin was infused at the same levels as observed during the arginine infusion test with no insulin infusion. As a result, normalization of the exaggerated plasma glucagon response was achieved, whether hyperglycaemia existed or not. These results clearly demonstrate that, similar to non-obese hypoinsulinaemic Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients, the exaggerated Alpha-cell response to arginine infusion in obese hyperinsulinaemic patients with glucose intolerance is secondary to the reduction of insulin action on the pancreatic Alpha cell, and that the expression of insulin action plays an important part in normalizing these abnormalities.

Adult↗

Preclinical and clinical studies on immunogenicity and safety of the HIV-1 p17-based synthetic peptide AIDS vaccine--HGP-30-KLH.

Immunization with a synthetic HIV-1 p17 peptide analog (HGP-30; aa 85-115 of HIV p17), coupled to a carrier protein (KLH, keyhole limpet hemocyanin) given with alum as the adjuvant induces antibodies which cross-react with both HGP-30 and HIV p17 and clones of cytotoxic and helper T-cells which recognize HGP-30 and HIV p17. Proliferation of lymphocytes in response to HGP-30 has been observed in mice, in HIV-infected individuals and in healthy HIV-seronegative volunteers vaccinated with the p17-based synthetic peptide construct. Cytotoxic T-cell responses against EBV transformed, recombinant p17 pulsed targets were observed using antigen-expanded PBLs from HGP-30-KLH immunized individuals. These results are consistent with predictions that the HGP-30 domain of HIV p17 contains both T- and B-cell epitopes that are recognized by animals and humans. In preclinical toxicology studies in animals and in initial clinical trials in humans the synthetic peptide construct (HGP-30-KLH/alum) has been shown to be safe. This paper summarizes the preclinical immunogenicity and safety data for HGP-30-KLH and presents the initial results from the first Phase 1 clinical trial.

AIDS Vaccines↗

Efficacy of endoscopic retrograde cholecystoendoprosthesis (ERCCE) for cholecystitis.

Fourteen patients with cholecystitis were treated by endoscopic placement of an endoprosthesis into the cystic duct. In these patients the administration of antibiotics had failed to change the clinical picture of cholecystitis. Clinical and ultrasonographic findings before and two months after stenting were compared. There was an improvement in abdominal pain in 9 out of 14 cases (64%); fever, present in 5 patients, disappeared in all. No clinical complications were observed. Sonographic findings in terms of gallbladder wall thickening and sludge present within the gallbladder improved in 57% and 88%, respectively. Our results indicate that this endoscopic procedure may be effective in the treatment of cholecystitis.

Aged↗

Diagnosis of biliary diseases via a naso-biliary catheter.

Nasobiliary double contrast radiography and nasobiliary cytological diagnosis via nasobiliary catheter were performed in 30 patients with biliary diseases to assess the diagnostic usefulness and limitations of the procedures. The results showed that the contour and fine mucosal pattern of the extrahepatic bile duct could be demonstrated adequately (88%) by nasobiliary double contrast radiography. In contrast, the intrahepatic bile duct could not be fully demonstrated (56%) by nasobiliary double contrast radiography because of its anatomical structure. On the other hand the fine reticular pattern of the mucosa was defined in each section of the gallbladder by nasobiliary double contrast radiography. This procedure is thus a valuable method for detection of mucosal lesions of the extrahepatic bile duct and gallbladder, especially carcinoma. The cell collection rate was not as high (59%) using conventional nasobiliary cytological diagnosis. Brush cytology via a nasobiliary catheter was shown to be a useful adjunct to other diagnostic procedures.

Barium Sulfate↗

Synergistic enhancement of thyroid tumor induction by 2,4-diaminoanisole sulfate, N,N'-diethylthiourea and 4,4'-thiodianiline in male F344 rats.

Three thyroid carcinogens, 2,4-diaminoanisole sulfate (DAAS), N,N'-diethylthiourea (DETU) and 4,4'-thiodianiline (TDA), were simultaneously administered in the diet to male F344 rats at one-third the concentration of the reported TD50 levels (610, 200 and 46 p.p.m. respectively) for 52 weeks. The resultant incidence of thyroid adenocarcinomas in the combined treatment group (18/18: 100%) was significantly higher than those in each individual treatment group (DAAS, 0/21; DETU, 1/21; TDA, 2/20). Hepatocellular carcinomas (9/18, 50%) and lung adenomas (6/18, 33%) were also induced by the combined treatment, the incidences being higher than in the TDA group (3/20, 15% and 4/20, 20% respectively) to which these tumors were limited in the three groups treated with single chemicals. Thus, the results indicated that the three carcinogens exert apparent synergism in thyroid carcinogenesis when administered simultaneously.

Aniline Compounds↗

Combined effect of interleukin 2 and bacillus Calmette-Guérin in the therapy of mice with transitional cell carcinoma.

We investigated the effect of combination therapy with interleukin 2 (IL-2) and Bacillus Calmette-Guérin (BCG) on C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a local injection of BCG into the tumor at a dose of 1 mg/day for a total of 3 times and/or a 10-day continuous subcutaneous infusion of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of the tumor in mice treated with IL-2 alone was slightly suppressed, while tumor growth was hardly suppressed in mice treated with BCG alone. However, when IL-2 was administered with BCG, tumor growth was strongly suppressed and mean survival time was prolonged. Natural killer cell activity in the spleen cells was most elevated in mice treated with IL-2 and BCG, while lymphokine-activated killer cell activity was not observed in all groups. Lymphocyte subset analysis showed that there was little change in the ratio of Lyt2-positive lymphocytes or that of L3T4-positive lymphocytes. These findings suggested that clinical evaluation of combination therapy with IL-2 and BCG may be worthwhile.

Animals↗

Combined therapy of interleukin 2 with cyclophosphamide or bacillus Calmette-Guérin against implanted bladder cancer cells in mice.

1 x 10(5) cells of FAMFT-induced bladder cancer cell line (MBT-2) were injected into the right leg of the C3H/He mice. 10 days later, these animals with the same tumor size were divided into four groups. Group 1 is the control with no treatment. Group 2 underwent interleukin 2 (IL-2) treatment for 10 days since the 11th day after tumor inoculation. Group 3 received just one CPM injection on the 10th day. Group 4 had a combination therapy of CPM, followed by IL-2. Group 1 and 2 exhibited enlargement of tumor size, resulting in the death of all animals. Administration of CPM led to temporary disappearance of tumor, followed by local tumor recurrence in all cases. However, combined therapy with IL-2 showed complete remission of the tumors. Natural killer cell activity measured by the 51Cr release assay of the spleen cells using Yac-1 cells as target cells 20 days after tumor inoculation was found to be significantly higher in group 2 and 4, while lymphokine-activated killer cell activity of the spleen cells against P-815 cells showed no significant difference between the four groups.

Animals↗

Stone fragility--measurement of stone mineral content by dual photon absorptiometry.

We measured the mineral content of urinary tract stones by dual photon absorptiometry, which is widely used for the analysis of bone mineral content, and compared the values of the stones by dual photon absorptiometry (DPA values) with the results of an in vitro fracture study as well as those of an in vivo extracorporeal shock wave lithotripsy treatment study. The results of a preliminary experiment showed that the DPA values of 20 urinary tract stones reflected actual stone mineral content. As a result of the in vitro fracture study, the DPA value calculated by volume of a struvite stone, which was the most easily disintegrated, was the lowest (0.53 g/cm3). The DPA values of calcium oxalate monohydrate and apatite stones, which poorly disintegrated, were the highest (0.98, 1.01 g/cm3). The DPA value of calcium oxalate dihydrate, which moderately disintegrated, was 0.86 g/cm3. By the in vivo extracorporeal shock wave lithotripsy treatment study, the total DPA values of stones measured before extracorporeal shock wave lithotripsy treatment in 12 patients were 0.73 +/- 0.34 g in successful cases and 1.92 +/- 0.43 g in unsuccessful cases with a significant difference between the two (p less than 0.05). These results showed that the measurement of stone mineral content by dual photon absorptiometry was useful in predicting the fragility of stones against shock waves before performing extracorporeal shock wave lithotripsy treatment for patients with urinary tract stones.

Absorptiometry, Photon↗

Combined effect of tumor necrosis factor alpha and anticancer chemotherapeutic agents against human renal carcinoma cell lines.

Antitumor effect of recombinant human tumor necrosis factor alpha (TNF) alone or in combination with various anticancer chemotherapeutic agents was tested using an in vitro antiproliferative assay on four human renal carcinoma cell lines (VMRC-RCW, VMRC-RCZ, Caki-1 and A-498). When the dose-dependent effect of TNF was studied, none of the four cell lines showed a 50% or more inhibition even at a concentration of 10,000 U/ml of TNF, so that the susceptibility to TNF was low. An enhancing effect of TNF on the cytotoxic effect of almost all the chemotherapeutic agents tested was observed against VMRC-RCZ and A-498. Against VMRC-RCW and Caki-1, the combination of TNF with the chemotherapeutic agents did not result in an enhancing effect. Mitomycin C showed an enhancing effect of TNF against all four cell lines. These results suggested that the combined treatment of TNF with chemotherapeutic agents may have favorable results in clinical trials.

Antineoplastic Agents↗