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The object of this study is to evaluate the usefulness of the ATP sensitivity assay for appropriate selection of anticancer drugs for prophylactic bladder instillation therapy in patients with superficial bladder cancer.The ATP assay was performed using the method reported previously. The anticancer drugs examined were ADM, MMC, THP-ADM and EPI. The 5-year rate of non-recurrence in group A (32 cases) which had been treated using the results of ATP assay, was compared with that of group B (37 cases), for which the ATP assay was not performed.The most sensitive anticancer drug was THP-ADM. The 5-year rate of non-recurrence in group A (80.9%) was significantly higher than that in group B (39.4%) (p0.001). Tumor recurrences in group A was observed within 2 years post-operatively in all cases. When the ATP assay was re-performed in 3 cases with recurrent disease, altered antitumor sensitivity was observed.These findings suggested that ATP assay was useful for choosing effective anti-cancer drugs for prophylactic instillation, especially for patients with primary or solitary tumor, grade 2 disease or tumor of a certain size (or = 1 cm). It also appeared that the ATP assay should be performed for patients with primary superficial bladder cancer as a screening test for the selection of drugs for prophylactic instillation therapy.

Seven steroids in normal adrenal gland and those of patients with aldosteronoma or Cushing's adenoma were measured by liquid chromatography/mass spectrometry with an atmospheric pressure ionization interface system. Using this system, quasi-molecular ions [M + H]+ of standard cortisol, corticosterone, 17α-hydroxyprogesterone, 11β-hydroxyandrostenedione and Δ4-androstenedione and [(M + H) − H2O]+ ions of aldosterone and dehydroe-piandrosterone were observed as their base peaks, and quasi-molecular ions [M + H]+ and [(M + H) − H2O]+ ions of seven steroids were clearly observed in chromatograms of biological samples. The ratio of glucocorticoid (cortisol) to mineralocorticoid (corticosterone) content was measured, and found to be significantly lower for aldosteronomas and higher for Cushing's adenomas than for normal adrenals. These findings indicate that the method had suffficient sensitivity for the identification and simultaneous measurement of a variety of adrenal gland steroids.

The distribution of S-100 protein positive dendritic cells (S100-DCs) inside the cancer nest and the expression of HLA-DR alpha antigen (HLA-DR) and blood group antigen (BGA) on cancer cells in 90 cases of transitional cell carcinoma (TCC) of the urinary bladder were immunohistochemically investigated in relation to the degree of malignancy and its prognosis. A dense infiltration of S100-DCs inside the cancer nest ("many", i.e. more than 10DCs/HPF) was detected in 47 (52%) out of 90 cases. The HLA-DR positive cancer cells (DR-CCs) were detected in 24 cases (27%), including in the 16 most dense cases ("many", i.e. more than 100DR-CCs/HPF). BGA positive cancer cells (BGA-CCs) were detected in 49 cases (54%) ("positive", i.e. more than 100BGA-CCs/HPF). In connection with the degree of malignancy and with the number of cases affected by S100-DCs infiltration. HLA-DR expression and BGA expression. A statistical analysis showed significant correlation between the number of cases affected by S100-DC and each clinicopathological factor including G, pT, ly, v, and showed also between that affected by BGA expression and each clinicopathological factor including G, pT, INF, but showed no significant correlation between that affected by HLA-DR and each clinicopathological factor. As regards the prognosis, the 10-year survival rates for all 90 cases were 60.4%. In the 10-year survival rate, S100-DCs "many'' (77.7%) and "few'' (39.0%), DR-CCs "many'' (85.7%) and "no'' (56.9%), DR-CCs "many'' and "few'' (43.8%), BGA-CCs "positive'' (74.3%) and BGA-CCs "negative'' (46.5%) were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

The distribution of S-100 protein positive dendritic cells (S100-DCs) in cancer nests and the expression of HLA-DR antigen on cancer cells in 90 patients with transitional cell carcinoma of the urinary bladder were studied immunohistochemically. A dense infiltrate of S100-DCs (more than 10 S100-DCs/high power field) was detected in 47 out of 90 cases, while in the remaining tumours the infiltrate was sparse. HLA-DR positive cancer cells (DR-CCs) were detected in 24 cases, including 16 with dense DR-CCs (more than 100 DR-CCs/high power field); no expression was observed in the remaining tumours. In terms of the numbers of S100-DCs infiltrating the following statistically significant differences were observed: tumour grading G1G3, depth of penetration pT0pT3; (p0.05), G2G3, lymphatic invasion -+ and venous invasion -+; (p0.01). A multivariate analysis demonstrated that the most important factor affecting prognosis was distant organ and/or lymph node metastasis (p0.01) the number of S100-DCs, with a hazard ratio (HR) of 0.26 (p0.01), and the number of DR-CCs with HR of 0.18 (p0.05); these were statistically significant. S100-DCs and DR-CCs may be regarded as independent prognostic factors of tumour growth and progression.

Standard sulphur amino acids and various cystathionine metabolites in the urine of a patient with cystathioninuria were analysed using liquid chromatography/mass spectrometry with an atmospheric pressure ionization interface system. Very intense quasi-molecular ions ([M + H]+) of synthetic cystathionine, N-monoacetylcystathionine, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, S-(3-hydroxy-3-carboxy-n-propyl)cysteine, S-(2-carboxyethyl) cysteine, S-(2-hydroxy-2-carboxyethyl)homocysteine, S-(carboxymethyl)homocysteine, N-acetyl-S-(3-hydroxy-3-carboxy-n-propyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine were observed by this method. Quasi-molecular ions ([M + H]+) of these sulphur amino acids were observed in the urine sample of the patient with cystathioninuria, and N-acetyl-HCPC and N-acetyl-beta-CEC as N-substituted sulphur amino acids were also identified in the urine of the same patient.

Analyses of amino acids in the urine of a normal human and of patients with heterozygous and homozygous cystinuria have been carried out, using liquid chromatography-mass spectrometry with an atmospheric pressure ionization interface system. A kidney cystine stone was also analysed by this system. Very intense quasi-molecular ions ([M + H]+) of standard cystine, arginine, lysine and ornithine were observed on mass chromatograms as base peaks. Mass chromatograms of the urine samples from a normal human and from patients with heterozygous and homozygous cystinuria were easily distinguishable. The retention times in the mass chromatogram and mass spectrum of kidney stone cystine was almost the same as that of authentic cystine.

Polymorphonuclear leukocytes (PMNs) play an important role in host defense system. Upon interaction with soluble or particulate matter, PMNs generate active oxygen species (AO), which act on killing of bacteria. In urinary tract infection, urinary PMNs are assumed to have bactericidal activity in urine. Basal experiments were studied on the AO generation of urinary PMNs, monitored by mainly the luminol-dependent chemiluminescence. It was indicated that urinary PMNs, isolated from patients with urinary tract infection, generated AO in physiological medium. This activity of urinary PMNs was found to be significantly inhibited rather than that of PMNs in blood, and this suppression was suggested to be time-dependent. PMNs were affected significantly by osmolarity of reaction medium. These changes were associated with intracellular free calcium. PMNs exposed in hyposmotic medium generated AO, just as they were stimulated. However PMNs exposed in hyperosmotic medium did not generate AO. The stimulation-dependent AO generation of PMNs was increased in hyposmotic solution, while in PMNs incubated at 37 degrees C for 60 min in hyposmotic solution, this generation was decreased than controls. On the other hand, the stimulation-dependent generation was decreased in hyperosmotic solution, while incubated in hyperosmotic solution, this generation was increased. These results suggest that ability of urinary PMNs is regulated by urine osmolarity and retaining time or many other factors, however urinary PMNs are primed and maintain bactericidal activity.

Intravesical instillation of anti-cancer drugs for superficial urinary bladder cancer is generally carried out with the aim of prophylaxis against recurrence and chemotherapy against tumor. But since sensitivity of tumor cells to each anti-cancer drug differs individually, the anti-cancer drug to be used should also be decided individually. We selected a new sensitivity test, ATP-sensitivity-assay, which measures intracellular adenosine triphosphate (ATP) volume by Luciferin-Luciferase reaction, for the decision of the anti-cancer drug. In this paper, we evaluated the direct anti-tumor activity of the drugs that were decided by ATP-sensitivity-assay of intravesical chemotherapy. Six drugs, that are Doxorubicin (ADM), Mitomycin C (MMC), Pirarubicin (THP-ADM), Cytarabine (Ara-C), Bleomycin (BLM) and Cisplatin (CDDP) were tested in this research and size of tumors of six patients reduced to 34-93% after 6 times' installation. A woman got cystitis induced by ADM after 3 times' instillation but instillation was completed. ATP-sensitivity-assay is useful for deciding the anti-cancer drugs for intravesical chemotherapy and prophylaxis for superficial bladder cancer.

The first case was a 63-year-old man with edema in the lower extremities, and the second case was a 78-year-old man complaining of general fatigue and loss of appetite. Both cases had bilateral hydronephrosis and renal failure due to ureteric obstruction. Both patients with histologically proven idiopathic retroperitoneal fibrosis were studied by magnetic resonance imaging (MRI). MRI was performed using a superconducting magnet operating at 0.5 tesla and spin echo images were obtained. The retroperitoneal fibrous plaque appeared at an intermediate intensity on T1 weighted image and at a high intensity on T2 weighted image. They underwent intraperitoneal ureteral transposition and postoperative administration of prednisolone. Although their renal functions and hydronephrosis improved after the treatments, the fibrous plaque was still observed on MRI. It was considered that MRI was an excellent method of choice in the diagnosis and follow-up of retroperitoneal fibrosis.

Electrical resistivity has been measured under magnetic fields parallel to the CuO2 planes in LSCO single crystals, where Josephson vortices form in the region between the CuO2 planes. In the crystals over the wide Sr content from the under-doped to the over-doped the vortex glass melting transition is observed in the field range of 1–17.5 T. The glass transition curves strongly depend on the anisotropy of the system, that is, it is suppressed to the low field in the under-doped crystal with large anisotropic parameter. The Josephson vortex glass transition is discussed in terms of the anisotropic parameter.

A rare case of leiomyosarcoma of the renal vein that was incidentally detected is reported, and the literature on such tumors is reviewed.

We reported the clinical results of radical surgeries for 44 patients with prostate cancer performed between November 1984 and December 1992. The patients were aged from 57 to 79-year-old (mean 67.2) and classified as clinical stage A2 (6 cases), B1 (7), B2 (12), C (16) and D1 (3) respectively. Radical prostatectomy was performed in 42 cases and radical cystoprostatectomy with urinary diversion in 2 patients, and thirty-nine of 44 cases underwent endocrine or chemoendocrine therapies prior to the surgeries. In all patients with stage A2-B1, the operations were curative, on the other hand, more than 80% of clinical stage B2 patients had pT3 tumors and 33.3% of them had lymph node involvements. With regard to stage C patients, the incidence of lymph node metastasis and positive margin was more frequent. Postoperative adjuvant therapies were added to the patients with pT3,4 tumors and nodal involvements. Patients without residual tumors (n = 20) remained disease-free for 8-89 months (mean 32.8). Of 24 patients who had incomplete resection of tumors, 2 died of other diseases, other 2 were alive recurrent and 20 were alive free from disease for 3-99 months (mean 33.8). The surgical indication for low-stage (A2-B2) prostate cancer has been widely accepted, however that for high-stage cancer (C,D1) has remained controversial. It was our belief that radical surgeries for high-stage cancer could become a potentially curative therapeutic modality in combination with pre- and post-operative adjuvant therapies.

The HPLC system was used to separate and measure 10 kinds of corticoids in adrenal tissues. Calibration curves were drawn as straight lines that ranged from 1.25 to 20ng, or 1.25 to 200ng by peak area calculated with the chromatointegrator. The samples for the assay were extracted from homogenized tissues and treated with methanol to remove non-steroidal contaminants which may interfere with the ultraviolet absorption monitor. The recovery rate during the assay procedure was calculated using testosterone as the internal standard, because testosterone was not detected in any adrenal tissue examined in the present study. Contents of corticoids were measured in normal adrenal glands obtained during radical nephrectomy for renal cancer and in functioning adrenal adenomas. Steroid levels in the adrenal glands and tumors have been measured by radioimmunoassay until now, and the data obtained in the present study were compared with those in previous reports. Main steroids in normal adrenals were cortisol (F) and corticosterone (B), and there were certain amounts of 11-deoxycortisol (S), 11-deoxycorticosterone (DOC) and precursor steroids. 11 beta-hydroxy-androstenedione was the main androgen in the adrenal gland. Mineralocorticoids other than B and DOC were very low in the normal adrenals. There was a certain balance between the production of cortisol and corticosterone in normal adrenals. In functioning adenomas, the levels of F, B and aldosterone, and F to B ratios (F/B) varied according to their biological features. Although with the HPLC system it was possible to obtain the production balance of each steroid clearly in the chromatogram, we could not detect the delta 5-3 hydroxysteroids such as pregnenolone and dehydroepiandrosterone using the ultraviolet absorption monitor.

Upon stimulation by various ligands, freshly isolated human peripheral neutrophils (PMN) respond in a variety of ways, such as Superoxide (O − 2 ) generation, phagocytosis, enzyme release, migration etc. Chemotactic peptide formylmethionyl-leucyl-phenylalanine (FMLP) and opsonized zymo- san activate neutrophils by a receptor-mediated mechanism, while phorbol myristate acetate and dioctanoylglycerol activate the cells by a mechanism involving Ca 2+ - and phospholipid-dependent protein kinase (PKC). Receptor-mediated but not PKC-mediated O − 2 generation in PMN was enhanced by the priming of recombinant human granulocyte colony stimulating factor (G-CSF). FMLP-dependent luminol chemiluminescence was also enhanced by G-CSF. However, no appreciable enhancement was observed in FMLP-induced intracellular calcium ion concentration ([Ca 2 +] i ). Enhancement of FMLP- induced generation of O − 2 by G-CSF was inhibited by genistein or α-cyano-3-ethoxy-4-hydroxy-5- phenylthiomethylcinnamamide (ST 638), inhibitors of tyrosine kinase (TK), and was stimulated by staurosporine and 1-(5-isoquinolinesulfonyl)-3-methyl-piperazine (H-7), inhibitors of PKC. The ED 50 values of genistein and ST 638 for the inhibition of the FMLP-induced O − 2 generation from G-CSF were 0.5 and 5 muM, respectively. In contrast, O − 2 generation by PKC activation without G-CSF priming was inhibited by stauroporine and H-7, but was stimulated by genisten and ST 638. These results suggested that the enhancing effect of G-CSF on receptor-mediated generation of the O − 2 might be regulated by protein kinases, such as TK and PKC and that the TK inhibitor selectively inhibited the G-CSF-primed receptor-mediated O − 2 generation of neutrophils.

Superconducting characteristics have been studied from the viewpoint of the annealing condition on single crystals of the Nd1-x PrxBa2Cu3Oy system grown by the travelling solvent floating zone (TSFZ) method. An anneal as the first step in Ar at 850–900°C gives the best superconducting characteristics in contrast to the anneal in O2. It is suggested that the annealing at high temperature in Ar causes the redistribution between the Pr(Nd)/Ba sites and strongly suppresses the occupancy to the Ba site by the Pr(Nd) ions.

A 64-year-old man with sudden onset of quadriplegia due to marked hypokalemia was referred to our clinic with suppressed plasma renin activity in the presence of a low aldosterone level. Computerized tomography demonstrated a left adrenal adenoma, shown on adrenal scintigraphy to be functioning. The elevated basal level of plasma corticosterone and its increased response to 1-24 adrenocorticotropic hormone suggested the tumor produced corticosterone. The surgical specimen was a benign adrenocortical adenoma with excess content of corticosterone and 18-hydroxycorticosterone.

In order to examine its clinical efficacy, recombinant human interferon-β (rIFN-β) was instilled intravesically into 51 patients with superficial bladder cancer. Ten patients, who received intermittent intravesical instillation at a dose of (3−36) × 106 U rIFN-β on days 1–3 every week, showed no response. Thirty-two patients received intravesical instillation at a dose of (3−36) × 106 U every day for 10–20 days. Eight patients showed partial response, indicating an efficacy rate of 25%. Nine patients received divided doses of 18 × 106 U twice a day every day for 10–20 days. Six patients showed partial response, indicating an efficacy rate of 67%. This value was significantly higher than that obtained by administering divided doses. The response to intravesical instillation therapy with rIFN-β varies with treatment protocol. Frequent and longer exposure to rIFN-β may induce better regression of superficial bladder cancer. Six incidences of side-effects were found in five cases (9.8%): pollakiuria in one, pain on micturition in two, fever in two, and eruption in one case. All of these side-effects were slight and reversible after drug withdrawal. Laboratory tests showed only a few changes with low severity. Thus, rIFN-β is potentially a new drug for instillation therapy of superficial bladder cancer, in view of the absence of adverse effects.

We investigated natural killer (NK) activity and T-lymphocyte subsets in peripheral blood and regional lymph nodes in order to examine the host's defence mechanisms against cancer. The materials were obtained from 26 patients with genitourinary cancer and 9 patients with benign diseases, who were used as controls. NK activity was measured by ATP-chemiluminescence (ATP) assay, a new method which is well correlated to the 51Cr-release assay, and T-lymphocyte subsets were stained with anti-Leu-2, -3, -4, -7, and -11 monoclonal antibody. The NK activity of regional lymph nodes was lower than that of the peripheral blood in all 35 cases, and the percentage of Leu 7+ and Leu 11+ cells was in agreement with that of the NK activity detected by ATP assay. In the peripheral blood, the percentage of Leu 3+ cells was lower in high stage patients than it was in low stage patients and controls, but in the regional lymph nodes it was paradoxically higher. The NK activity of regional lymph nodes against autologous tumor cells was low in 8 patients with bladder cancer. It appears from this study that the regional lymph nodes have no function as immunological barriers for metastasis and we therefore conclude that they should be dissected during surgery.