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Biomedical subjects

S Kanoh

Publications and source records attributed to S Kanoh.

At least 55 records · Page 3Linked to original sources

Intra-arterial chemotherapy for bladder cancer.

Intra-arterial infusion chemotherapy with adriamycin (ADM) was carried out in 32 patients with bladder cancer prior to total cystectomy. An oblique incision approximately 12 cm long was made in the gluteal region to expose either the superior or inferior gluteal artery, into which a Teflon catheter was inserted and fixed. The distal end of the catheter was taken out from under the skin in the precordial region. Via this catheter, a single dose of 10 mg ADM was injected twice a week. Superior-gluteal-artery infusion chemotherapy was performed in 7 patients; the 5-year survival rate was 14.3%, which was not as high as expected. Inferior-gluteal-artery infusion chemotherapy was performed in 25 patients. Cisplatin (CDDP) was used with ADM in 8 patients. Radiation and/or hyperthermia were used in 11 patients. The 5-year survival rate in these 25 patients was 58.4%, which was considered to be satisfactory. Of these 25 patients, 5 were stage-T4 cases; for these, the treatment was ineffective, and all 5 died within 2 years. Of the 6 patients at stage T2, 1 died, as did 1 patient with carcinoma in situ (CIS). Of the 13 patients with bladder cancer at stage T3, 3 died; lymph-node metastases were found in all 3 of these cases. Of the 25 patients who received inferior-gluteal-artery infusion chemotherapy, 9 died of cancer; all 9 died within 2 years due to distant metastases. There was no evidence of recurrence in any patient who survived for 2 years or more after total cystectomy. Therefore, inferior-gluteal-artery infusion chemotherapy may be effective as a preoperative adjuvant therapy with no serious side effects.

Antineoplastic Combined Chemotherapy Protocols↗

Studies on platelet function in patients with prostatic cancer. Preliminary report.

Platelet function was evaluated as an index of the thromboembolic tendency in patients with untreated, advanced prostatic cancer. Patients with benign prostatic hypertrophy (BPH) and similar age distribution served as a comparison group. Platelet aggregations were elevated in both groups, but not significantly different from each other. Platelet serotonin level in patients with prostatic cancer was lower than in patients with BPH (p less than 0.01), whereas plasma serotonin level in patients with prostatic cancer (within normal ranges in our series) was lower than in patients with BPH (p less than 0.001). Levels of 2 intraplatelet proteins, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in the two groups of patients were similar. However, levels of beta-TG were elevated significantly in both groups of patients compared with those of healthy individuals. These studies revealed that the platelet serotonin levels in advanced prostatic cancer patients differed significantly from those in patients with BPH. The platelet serotonin level thus may provide an index of platelet activation in patients with prostatic cancer.

Aged↗

Establishment of a new prostatic carcinoma cell line (TSU-Pr1).

A new epithelial cell line, TSU-Pr1, from a human prostatic adenocarcinoma metastatic to lymph node has been established in long term tissue culture. The cultured cells show loss of contact inhibition, rapid growth in vitro and growth in athymic nude mice. Karyotypic analysis demonstrated an aneuploid karyotype with a modal chromosome number of 80 including a Y-chromosome and at least 10 marker chromosomes. The cells produced only a small amount of prostatic acid phosphatase, and heterotransplanted tumors did not have nuclear androgen receptors.

Adenocarcinoma↗

Physiology of the potentiation of lethal endotoxin shock by streptococcal pyrogenic exotoxin in rabbits.

Streptococcal pyrogenic exotoxin (SPE) dramatically potentiates the lethal shock induced by gram-negative bacterial endotoxin. To provide further understanding of the mechanism underlying the potentiating effect, the physiological basis for the toxic synergism of the two toxins was investigated. Pretreatment of rabbits with an intravenous (i.v.) dose (10 micrograms/kg of body weight) of SPE greatly enhanced the endotoxin lethality and reduced the 50% lethal dose to less than 5 micrograms of endotoxin per kg. The SPE pretreatment dose caused severe pathophysiological changes in combination with a small i.v. dose of endotoxin (1 microgram/kg). These changes included transient hyperglycemia followed by profound hypoglycemia, elevation of the blood lipoperoxide level, and an acute increase in plasma beta-glucuronidase activity. These changes were comparable with those in animals given a large i.v. dose of endotoxin (100 micrograms/kg) alone. An injection of SPE alone did not alter any of the parameters described above. These results suggest that SPE renders rabbits more sensitive to extensive pathophysiologic effects of endotoxin, and the potentiating effect on endotoxin lethality may thus involve a general potentiation of physiologic failures. The SPE pretreatment depressed the vascular clearance of a large dose of endotoxin (100 micrograms/kg) but failed to affect that of a small dose of endotoxin (1 microgram/kg). The data suggest that the potentiating effect is not readily explained solely on the basis of the decreased clearance of endotoxin.

Animals↗

Local bone resorption induced by serially transplantable human renal cell carcinoma in nude mice.

The high incidence of metastatic bone disease in urological cancer makes it necessary for clinicians to look for a valid experimental model to investigate the basic interactions between cancer cells and bone in order to improve the treatment. A new model of bone resorption was defined, namely the subcutaneous injection of tumor cell suspensions of serially transplanted renal cell carcinoma in nude mice after disruption of the periosteum of the calvaria. The tumor induced osteolysis associated with osteoclast proliferation with reactive bone formation. The X-p film from nude mice calvaria showed the same multiple osteolytic punched-out lesions as those of the patient's skull.

Aged↗

Malformations in rat fetuses induced by trypan blue.

Malformations of fetuses obtained from Wistar rat dams treated with trypan blue during gestation were studied. Fetuses were examined on day 20 of gestation. One hundred and twenty-seven fetuses showed abnormalities of the external features, skeleton and internal organs, separately or in combination. External malformations were found in 108 fetuses. The most frequent external malformation was anomaly of tail. Spina bifida, club foot, exencephaly and anal atresia were also observed frequently. Skeletal malformations were detected in 48 fetuses. Deformity of vertebrae in the lumbar, sacral and/or caudal regions was found in 46 fetuses. Internal malformations were observed in 27 fetuses. Anomaly of heart and/or great vessels, hydrocephaly and micro- or anophthalmia were observed frequently. About 90% of the fetuses with skeletal malformations also showed some external malformations. In contrast, about 48% of the fetuses with internal malformations also had some external malformations. These results suggest that, for teratological study, internal examination is more important in detecting malformations of fetuses than skeletal examination.

Abnormalities, Drug-Induced↗

Urophonographic studies of the lower urinary tract: a new approach to urodynamics.

The detection and recording systems for urethral sounds during micturition were developed. This procedure was termed as "urophonography" and its recording as "urophonogram". Classification of urophonograms was undertaken on the basis of analyzing normal healthy male volunteers, and patients with benign prostatic hyperplasia. Four types of urophonogram were demonstrated. Urophonography was useful for investigation of dysfunctional voiding, and lower urinary tract obstruction. Urophonography will be a new approach to urodynamic investigations.

Aged↗

Adjuvant activity of 6-O-acyl-muramyldipeptides to enhance primary cellular and humoral immune responses in guinea pigs: adaptability to various vehicles and pyrogenicity.

Thirteen 6-O-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamines (6-O-acyl-MDPs), including four inactive D-isoasparagine and L-isoglutamine analogs, were tested for their pyrogenicity and immunopotentiating activity to stimulate primary humoral and cellular immune responses in guinea pigs to a model protein antigen, ovalbumin, when administered in various vehicles. Among them, derivatives whose muramic acid residue was substituted by alpha-branched (and beta-hydroxylated) higher fatty acids at the carbon-6 position, especially 6-O-(2-tetradecylhexadecanoyl)-MDP (B3O-MDP) and, to a lesser extent, 6-O-(3-hydroxy-2-docosylhexacosanoyl)-MDP (BH48-MDP) and its L-serine analog [BH48-MDP(L-Ser)], were found to exert strong adjuvant activity in both the induction of delayed-type hypersensitivity and the stimulation of circulating precipitating antibody levels when combined with nonirritating vehicles (liposomes, squalene-in-water emulsion, and phosphate-buffered saline). These vehicles did not efficiently support the adjuvant activity of MDP, the parent molecule of the above lipophilic derivatives. Pyrogenicity tests showed that introduction of alpha-branched higher fatty acid groups but not of straight, long-chain fatty acids at the 6-position of the muramic acid residue resulted in marked decrease of the pyrogenicity inherent to MDP via intravenous administration.

Acetylmuramyl-Alanyl-Isoglutamine↗

Fluorescence study of renal cell carcinoma with antibodies to renal tubular antigens, intermediate filaments, and lectins.

A fluorescence study was performed in 16 renal cell carcinomas using antibodies to renal tubular antigens (RTA), two intermediate filaments, cytokeratin and vimentin, and two lectins, soybean agglutinin (SBA) and peanut agglutinin (PNA). We observed the presence of RTA, cytokeratin, and vimentin in all of our specimens. The expression of vimentin, the cytoskeletal protein of mesenchymal cells, was considered to be very interesting feature of the tumor. Binding sites of SBA, normally present in glomeruli, proximal and distal tubules, were detectable in the neoplastic cells in only 37.5% of our specimens. PNA did not react with the tumor except for the small area of 2 specimens. Lectins may be useful for estimating the characteristics or renal cell carcinoma including its malignant potentials, and antibodies to RTA and intermediate filaments seem to be available for the diagnosis of the tumor in metastatic lesions.

Antibodies↗

Antipyretic effect of indomethacin suppository in rabbits.

We have designed a thermistor rectal probe thermometer for measuring the antipyretic activity of suppositories. Using this thermistor probe, we tested the antipyretic effect of an indomethacin suppository in comparison with oral and intravenous administrations in rabbits (male, 2.5-2.9 kg). The rectal temperature of normal rabbits remained unchanged after rectal and intravenous administration of indomethacin, 25 mg/body and 10 mg/kg, respectively. The antipyretic effect was tested in febrile rabbits injected with bacterial pyrogen, lipopolysaccharide (LPS) 0.2 microgram/kg (i.v.). The dose-dependent antipyretic activities were observed in febrile rabbits administered with indomethacin by rectal (6.3-23.7 mg/body), intravenous (2.5-10 mg/kg) and oral (2.5-20 mg/kg) routes. When indomethacin was administered simultaneously or 1 h after LPS, the most potent antipyretic effect was observed in the case of rectal administration and the weakest effect was observed in that of oral administration. These data indicate that the rectal administration of drugs can produce a potent antipyretic activity, not inferior to that of the intravenous injection.

Administration, Oral↗

Antipyretic mechanism of indomethacin in rabbits.

The mechanism of the antipyretic effect of indomethacin (IM) on fever induced by bacterial pyrogen (LPS, 0.2 microgram/kg, i.v.), leukocytic pyrogen (LP, 2 ml/kg, i.v.) and 2,4-dinitrophenol (DNP, 20 mg/kg, i.m.) in male adult rabbits was studied. In plasma, the biological half lives of IM in normal and LPS-injected rabbits were estimated to be 24 and 21 min in the early phase and 72 and 51 min in the late phase, respectively. A potent antipyretic effect was observed with intravenous injection of IM in LPS- and LP-induced fevers, but not in DNP-induced fever. The antipyretic effect was also observed with intracisternal injection of indomethacin at doses of 0.025 and 0.013 mg/kg. The activity of endogenous pyrogen in serum after LPS injection was not suppressed by the injection of IM (10 mg/kg, i.v.). The production of LP by leukocytes in vitro was not inhibited by IM (10 micrograms/ml). In our previous report, it was ascertained that the rectal temperature of normal rabbits remained unchanged after intravenous injection of IM. These results suggest that indomethacin may inhibit only the pyretic processes in the central nervous system.

2,4-Dinitrophenol↗

Characterization of the pyrogenicity of two different lipopolysaccharides and their lipid A-bovine serum albumin complexes.

In order to elucidate the dependency of pyrogenicity of lipopolysaccharide (LPS) on the lipid A structure, we investigated the pyrogenicity of both LPS and lipid A prepared from Mima polymorpha var. oxidans which is deficient in 3-hydroxymyristic acids linked to the 3-hydroxy group of other fatty acids. LPS and lipid A were also prepared as reference compounds from Escherichia coli UKT-B. Furthermore, the establishment of reliable indices for pyrogenicity was undertaken. The following results were obtained. The correlation in linearity was demonstrated between maximal increase in body temperature (delta Tmax) and dose of LPS or lipid A complexed with bovine serum albumin (BSA). The dose-response curves based on delta Tmax were more reliable statistically than the Fever Index-4h representing the area under fever curves for 4 h. The minimum pyrogenic dose (MPD) of E. coli LPS was 1.6 X 10(-3) micrograms/kg i.v. In contrast, the MPD of M. polymorpha LPS was 7.0 X 10(-3) micrograms/kg i.v. By intracisternal injection, the MPD of E. coli LPS was 2.5 X 10(-6) micrograms/kg and that of M. polymorpha LPS 1.0 X 10(-4) micrograms/kg. The end points of Limulus amoebocyte lysate gelation were 10(-5) micrograms/ml in E. coli LPS and 10(-3) micrograms/ml in M. polymorpha LPS. The MPDs of lipid A/BSA complexes by i.v. injection were 0.15 micrograms/kg in E. coli and 2.5 micrograms/kg in M. polymorpha. The rabbits immunized with E. coli lipid A/BSA complex acquired pyrogenic tolerance to the parent LPS but the cross tolerance to M. polymorpha LPS was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acinetobacter↗

[Thermistor probe for testing an antipyretic suppository in rabbits].

The thermistor probe for estimating the effects of an antipyretic suppository after its administration into the rectum of the rabbit was studied. A thermistor probe with three rubber disk stoppers was confirmed to be able to prevent the leakage of drugs from the rectum of a rabbit restrained in a neck stock. By using this newly devised thermistor probe or the usual thermistor probe without a stopper, the febrile response was determined in rabbits injected with bacterial pyrogen. There was no difference in the ability to detect rectal temperature between the two thermistor probes. From these results, it could be concluded that this newly devised thermistor prove was useful in studying the effects of antipyretic suppositories in rabbits.

Animals↗

[Selection of treatment from a pathophysiological point of view. II: Studies on male urogenital tumors].

Testicular cancer is divided pathologically into two categories; seminoma and non-seminomatous germ cell tumor (NSGCT). Seminoma is a radio-sensitive tumor, so that radiation has been mainly used for stages I and II. Stage III seminoma is treated in the same way as NSGCT. Several years ago stages I and II NSGCT were treated primarily by retroperitoneal lymph node dissection. These days, chemotherapy, such as PVB, or VAB-6 therapy, is adopted as the first choice of treatment, followed by surgical intervention to elucidate the remaining bulky mass if present. Stage III NSGCT is also managed by chemotherapy. By these procedures 70-90% CR of patients with NSGCT is obtained. Prostatic cancer has been treated mainly according to its stages. As for stage A cancer palliative therapy has been shown to yield good results. However, in the case of poorly-differentiated tumors, local irradiation with anti-androgenic treatment should be employed. Stage B cancer should be treated by radical surgery. Local lymph node dissection is usually indicated. In addition local irradiation and anti-androgenic therapy should be considered. Most stage C or D patients do well for a while with antiandrogenic therapy. Within two or three years, however, drug resistance ensues, recessitating a change in the therapeutic modality. Treatments of choice include in chemotherapy, radiotherapy, and others. Treatment of penile cancer involves chemotherapy with bleomycin and irradiation, which result in considerable improvement.

Antineoplastic Combined Chemotherapy Protocols↗

Evaluation of potential nephrotoxicity of antibiotics.

In order to assess the potential nephrotoxcity excerted by various antibiotics in therapeutic doses, the effects of antibiotics administered to Wistar rats in vitro and in vivo were investigated in terms of protein synthesis, nucleic acid metabolism, and lysosome stability. In vivo experiment protein synthesis was inhibited by SM, KM, GM and CL. RNA metabolism and stability of lysosomal enzyme, acid-phosphatase, were also disturbed by the aminoglycosides. In vitro experiments yielded almost the same tendencies. In our studies cephalosporins and related antibiotics had no influence upon the metabolism of RNA, protein synthesis and lysosomal enzyme.

Aminoglycosides↗