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Biomedical subjects

T Usui

Publications and source records attributed to T Usui.

At least 199 records · Page 11Linked to original sources

Preliminary results of concurrent methotrexate, cisplatin and radiation treatment for locally advanced urothelial cancers.

Ten patients with invasive bladder cancer and one with locally advanced renal pelvic cancer were treated with concurrent methotrexate, cisplatin and radiotherapy. Methotrexate 30 mg/m2 was administered intravenously on the day of the initiation of radiotherapy and cisplatin 70 mg/m2 on the second day. The number of chemotherapy cycles delivered was 1 in 7 patients and 2 in 4. The median dose of radiation was 50 Gy. Of 11 patients, 7 (64%) achieved a partial response and 4 had no change in disease. The median duration of response was 16 months for patients with a partial response. Six patients with a partial response (55%) are alive for a median of 22.5 months and 2 of 4 with no change are alive for 4 and 15 months, respectively. Leukopenia less than 3000 cell/mm3 was observed in 4 (36%) and thrombocytopenia less than 100,000 cells/mm3 in 3 (27%). Local control could be achieved safely with concurrent methotrexate, cisplatin and radiation therapy in patients with locally advanced urothelial cancer who were unsuitable for surgery.

Aged↗

Two N-acetyl-D-galactosamine-specific lectins from Phaeolepiota aurea.

Two lectins, PAL-I and PAL-II, were isolated from the mushroom Phaeolepiota aurea by affinity chromatography on acid-treated Sepharose CL-4B followed by reverse-phase FPLC on ProRPC. Both of the lectins were tetramers of 16 kDa subunits. The lectins had little agglutination activity against native erythrocytes but Pronase treatment of erythrocytes increased the sensitivity to agglutination by the lectins. Both lectins exhibited slight preferences for type A compared with type B and O erythrocytes. In haemagglutination inhibition assays, N-acetylgalactosamine and both anomers of methyl N-acetylgalactosaminide were the best inhibitors.

Acetylgalactosamine↗

Intravesical instillation of epirubicin: effect on tumour recurrence in patients with dysplastic epithelium after transurethral resection of superficial bladder tumour.

OBJECTIVE: To evaluate whether the intravesical instillation of epirubicin is effective in preventing the recurrence of tumour in the bladder where dysplastic mucosa remains after transurethral resection of tumour. PATIENTS AND METHODS: Biopsy specimens were taken from apparently normal areas of the bladder mucosa in patients undergoing transurethral resection of the primary tumours. Of the 75 evaluable patients, 18 (24%) had abnormalities in at least one or more specimens. The patients were divided into two groups, 57 with normal and 18 with abnormal biopsy results. Intravesical chemotherapy with epirubicin (20 mg/40 mL saline) was randomized to patients in each group. Tumour recurrence rates were estimated and compared amongst the groups. Factors related to tumour recurrence were evaluated using univariate and multivariate analyses. RESULTS: The risks of tumour recurrence and progression were evaluated in 18 patients with concomitant mucosal abnormalities. All 10 patients with abnormal biopsy results who were treated with epirubicin had recurrence of tumour within a mean interval of 9 months, whereas six of eight controls had recurrence within a mean of 10.9 months. While there was progression in grade in four of 10 patients with abnormal biopsy results and treated with epirubicin, none of the recurrent tumours in six control patients with mucosal abnormalities progressed in grade. The overall recurrence-free rate of the patients with mucosal abnormalities was higher in controls than in those receiving epirubicin, but the difference was not statistically significant. There were no significant differences in recurrence rate for those treated with epirubicin and controls in the 57 patients with normal biopsy results. Univariate analysis showed that the recurrence-free rates were significantly influenced by tumour multiplicity and the mucosal biopsy results (P < 0.001 and P = 0.02, respectively). In a Cox proportional-hazards model, tumour multiplicity alone had prognostic significance for tumour recurrence (P = 0.002). CONCLUSIONS: The prophylactic intravesical instillation of epirubicin had no effect in preventing tumour recurrence and, conversely, it may promote tumour progression in bladders with dysplastic mucosal changes.

Administration, Intravesical↗

Immunohistochemical evaluation of proliferating cell nuclear antigen, prostate-specific antigen and alpha 1-antichymotrypsin in human prostate cancer.

OBJECTIVE: To determine the relationship between growth fractions defined by proliferating cell nuclear antigen (PCNA), prostate-specific antigen (PSA) and alpha 1-antichymotrypsin (ACT) staining in prostate cancer. MATERIALS AND METHODS: A total of 96 lesions, including 71 from prostate cancers and 25 from benign prostatic hyperplasia (BPH) were evaluated in microscopic sections of the prostatic tissues from 34 patients with prostate cancer. Immunohistochemical staining was performed with an avidin-biotin system using monoclonal anti-PCNA antibodies, polyclonal anti-PSA and anti-ACT antibodies. RESULTS: There was a significant difference in the mean PCNA labelling index between tissue from prostate cancer (4.2 +/- 7.1) and BPH (0.5 +/- 1.1) (P = 0.002). The mean labelling index of PCNA tended to increase with increasing Gleason score. The proportion of cells positive for PSA was significantly higher in tissue from BPH than from prostate cancer (P = 0.005). While the proportion of cells immunostaining for ACT was significantly higher in tissue from BPH compared to that from prostate cancer (P = 0.02), there was no significant difference in the proportion of ACT-positive cells among prostate cancers of differing Gleason score. The mean labelling index of PCNA decreased significantly with the increase in the proportion of PSA-positive cells (P = 0.013). There was a significant relationship between the proportion of ACT- and PSA-positive cells (P = 0.001). CONCLUSION: These results indicate a reciprocal relationship between cell growth and tumour differentiation in prostate cancer. Although the significance of ACT deserves further study, there was evidence for the complexing of PSA with ACT from the immunohistochemical studies.

Humans↗

Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis.

The hypothesis that dietary branched-chain amino acid (BCAA) supplementation improves the impaired protein turnover in male Donryu rats with carbon tetrachloride-induced liver cirrhosis was tested. We supplemented cirrhotic rats orally for 2 wk with BCAA solution [26.67 mg BCAA/(100 g body weight . d)], a conventional amino acid mixture [4.25 mg BCAA/(100 g body weight . d)] or saline and fed these three groups the AIN76 basal diet to have similar intakes of total energy and total nitrogen. Normal rats without liver cirrhosis were fed the basal diet similar to the above (noncirrhotic controls). After supplementation, rats were fed intravenous transthyretin (thyroxine-binding prealbumin) doubly labeled with 125I-tyramine-cellobiose and 131I. Kinetic indices including production rate of transthyretin were analyzed from plasma transthyretin disappearance curves. Tissue sites of transthyretin degradation were assayed using a trapped ligand technique by measuring 125I-tyramine-cellobiose levels. The production rate of transthyretin was significantly lower in cirrhotic rats supplemented with saline (mean 25.46 X 10(-3) . h(-1)) compared with noncirrhotic controls (45.08 X 10(-3) . h(-1)) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 X 10(-3) . h(-1), P < 0.05) but not with conventional amino acid mixture (22.49 X 10(-3) . h(-1)). The accelerated degradation of transthyretin in muscles of cirrhotic rats was improved by BCAA (P < 0.05). In conclusion, dietary supplementation with BCAA improves the impaired transthyretin turnover in rats with liver cirrhosis.

Administration, Oral↗

Convenient synthesis of beta-(1-->3)-galactosyl disaccharide alpha-glycoside and its analogs as mimic units of mucin-type carbohydrate.

beta-Galactosidase from porcine testes induced regioselective transglycosylation from lactose to the 3-position of 2-acetamido glycosides. When alpha-D-GalNAc-OC6H4NO2-p was used as an acceptor, the enzyme synthesized mainly beta-D-Gal-(1-->3)-alpha-D-GalNAc-OC6H4NO2-p with its (1-->6) linked isomer. The use of an inclusion complex of the glycoside acceptor with beta-CD increased the efficiency of transglycosylation by increasing the solubility of the acceptor. In the same way, the use of beta-D-GalNAc-OC6H4NO2-p as acceptor led to the preferential synthesis of beta-D-Gal-(1-->3)-beta-D-GalNAc-OC6H4NO2-p over that of its (1-->6) linked isomer. beta-D-Gal-(1.3)-beta-D-GlcNAc-OC6H4NO2-p was also synthesized with beta-D-GlcNAc-OC6H4NO2-p acceptor by the consecutive use of beta-D-galactosidases from porcine testes and Bacillus circulans. These enzyme reactions are efficient enough to allow the one-pot preparation of the desired disaccharide glycosides.

Alcaligenes↗

Reduction of intestinal apo A-IV mRNA levels in the cirrhotic rat.

In the present study, intestinal apo A-IV synthesis was investigated using a carbon tetrachloride (CCl4)-induced cirrhosis rat model. Triglyceride (TG) content in rat cirrhotic liver was increased markedly by 170% (P < 0.001) and apo B was increased by 20% (P < 0.05) compared with control levels. These results reflected the steatotic change in the liver. In contrast, TG levels in the small intestine of cirrhotic rats decreased significantly (P < 0.01). In addition, intestinal apo A-IV (jejunum P < 0.001; ileum P < 0.01) and its mRNA levels (jejunum P < 0.01; ileum P < 0.05) were also reduced. The decreased apo A-IV content in the jejunum was confirmed by immunohistochemical analysis. These results indicate that intestinal apo A-IV synthesis in cirrhosis is suppressed, at least under the condition of an overnight fast. Therefore, decreased intestinal apo A-IV synthesis may relate to the decreased ability to absorb fat in cirrhosis, but a fat-loading study will be necessary to confirm this hypothesis. It is unknown from the present study why serum apo A-IV level is not significantly decreased, despite a reduction in apo A-IV synthesis. The clearance of apo A-IV by the liver may be delayed or apo A-IV synthesis may be rather markedly enhanced during fat absorption in liver cirrhosis.

Animals↗

Acute changes in left atrial and left ventricular diameters after physiological pacing.

The present study examined alterations in left atrial diameter (LAD) and diastolic left ventricular diameter (LVDd) in 37 patients (72.2 +/- 9.8 years old) who received physiological pacemakers; 22 with atrioventricular (AV) block and 15 with sick sinus syndrome (SSS). After pacemaker implantation, LAD and LVDd were serially measured using echocardiography, and their diameters were expressed per body surface area (LADI and LVDdI; mm/m2). Pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured in ten patients with SSS and ten with AV block during both right ventricular and AV sequential pacing. After AV sequential pacing, CO increased in 19 of 20 patients (3.2 +/- 0.9 L/min to 3.9 +/- 1.0 L/min; P < 0.001). LADI decreased from 24.9 +/- 4.2 mm/m2 to 21.8 +/- 4.4 mm/m2 (P < 0.001) in 22 patients with AV block and from 24.1 +/- 3.4 mm/m2 to 20.4 +/- 3.8 mm/m2 (P < 0.001) in 15 SSS patients. However, LVDdI did not change significantly in either group of patients. The changes in LAD after the implantation of a physiological pacemaker occurred rapidly, i.e., LAD began to decrease within 1 minute after the procedure, and then reached a plateau. This plateau phase continued for at least 7 days during physiological pacing. There was a positive correlation between the changes in LADI after pacemaker implantation and those in PCWP observed during the AV sequential pacing performed prior to the implantation (r = 0.86; P < 0.001). The reduction in LAD following pacemaker implantation was rapid and seemed to be accompanied by improvement of cardiac function. Thus, it is suggested that the serial measurement of LADI is useful to predict the efficacy of physiological pacemaker implantation.

Aged↗

Effect of dose, sex and age on the drug disposition of incadronate, a new bisphosphonate, in rat bone.

We investigated the effects of dose, sex and age on the uptake and elimination of incadronate, a new biosphosphonate, in rat bone after intravenous administration. Following administration of 0.03-3 mg/kg to young male rats (age 7 weeks),intact drug concentration in humerus at 24 hr after administration (C24 hr) increased in a dose-dependent manner, indicating the linear uptake of the drug into bone. The estimated bone uptake clearance of 0.13 ml/min./g bone is comparable to the estimated plasma flow rate in bone, suggesting that uptake into bone is plasma flow-limited. Concentration from 24 hr after administration had declined bi-exponentially. Although t1/2 beta (350-444 days) was little altered among doses, t1/2 alpha was prolonged with increasing dose from 13.4 to 16.2 days. This effect seemed to be due to inhibition of bone resorption at higher doses resulting in the suppression of drug release from bone. No sex difference was seen on C24 hr in young rats, while the value in senescent (age 12 months) rats was 24% greater in females than in males. When comparing between ages it is seen that C24 hr values in senescent rats decreased to 50-66% of those in young rats. As for elimination from bone, t1/2 beta values in senescent rats were shortened to 76-79% of those in young rats. In contrast, little difference in t1/2 alpha was observed between ages or in either t1/2 alpha and t1/2 beta between sexes.

Aging↗

ERG campimetry using a multi-input stimulation technique for mapping of retinal function in the central visual field.

The m-sequence stimulation technique that has previously been described allows simultaneous recording of many local electroretinograms (ERGs). For topographical mapping of cone function in the central retina ERG traces from 61 retinal areas were recorded during a 4-min period in 20 normal volunteers and 4 patients with age-related macular degeneration, Stargardt's disease, choroidal atrophy, and polymyalgia associated with visual field loss. The local photopic luminance response was analyzed in each of the 61 areas. In the 2 patients with macular disease central defects were detected, in the remaining patients local defects were found outside the macular region. The method of multifocal ERG recordings provides the possibility of objective testing of visual fields when the outer retinal layers are affected.

Adult↗

Limitations of ureteroscopy in diagnosis of invasive upper tract urothelial cancer.

The efficacy of ureteroscopic evaluation of upper tract abnormalities was evaluated in 40 patients. Twenty-eight patients presented with a radiologic filling defect, 9 with a filling defect and hematuria and 3 individuals exhibited hematuria alone. Cold cup biopsies revealed transitional cell carcinoma in 7 of 9 patients with papillary tumors and in 2 of 3 with nonpapillary tumors. Four patients without ureteroscopic diagnosis of urothelial cancer were found to have invasive tumors on subsequent nephroureterectomy. Of 15 patients with upper tract urothelial cancer, 12 were treated with total nephroureterectomy. Three individuals with grade 1 neoplasms received conservative ureteroscopic ablative therapy. Ureteroscopy is effective when combined with biopsy in the diagnosis and treatment of papillary lesions, but exhibits a low sensitivity in patients with invasive lesions.

Adult↗

Fibroepithelial polyp in the renal pelvis.

Benign tumors in the renal pelvis are unique and rarely reported. We report a case of a benign polyp in the renal pelvis. A 68-year-old woman presented with a mass in the right renal sinus and underwent right nephrectomy. Histological investigations of the tumor revealed a polypoid angiofibromatous lesion of the renal pelvis which was benign in nature. Final pathological diagnosis was a benign fibroepithelial polyp.

Aged↗

Estramustine-binding protein in carcinoma and benign hyperplasia of the human prostate.

For the purpose of elucidating whether the biological characteristics of estramustine-binding protein (EMBP) are different in benign prostatic hypertrophy (BPH) and prostatic carcinoma (PC) and also to determine the clinical value of EMBP in the tissue, the EMBP concentration in 19 patients with BPH and 26 with untreated PC was measured by means of radioimmunoassay (RIA) using an antibody raised against EMBP obtained from the rat ventral prostate and compared simultaneously with the dihydrotestosterone (DHT) level in the same tissue. The level of serum prostate-specific antigen (PSA) was also measured in these patients. The EMBP concentration was significantly correlated with the tissue DHT level in BPH and well-differentiated PC (r = 0.745, p < 0.0001), whereas it did not correlate in moderately and poorly differentiated PC (r = -0.159, p = 0.542). By comparing well-differentiated PC with moderately and poorly differentiated PC, the EMBP concentration was significantly lower in the former than in the latter two conditions (p < 0.005) in spite of the highest tissue DHT level in well-differentiated PC. The ratio of the EMBP concentration to the DHT level in moderately and poorly differentiated PC was significantly higher when compared with that observed in either BPH or well-differentiated PC (p < 0.005, respectively). However, the level of serum PSA did not reflect the histological differentiation of PC. These results suggest that: (i) the correlation of the EMBP concentration to the DHT level changed with the progression of the histological grade, and (ii) the ratio of the EMBP concentration to the DHT level in the tissue is clinically valuable in elucidating the biological potential of individual tumors.

Aged↗

Association of nm23 protein levels in human prostates with proliferating cell nuclear antigen expression at autopsy.

OBJECTIVE: To investigate nm23-H1 gene expression in the human prostate. METHODS: The nm23-H1 protein levels of normal prostatic tissues, latent cancers of the prostate and primary and metastatic sites of clinical prostate cancers from autopsied men were evaluated using immunohistochemical analysis. Cell proliferation in serial sections using proliferating cell nuclear antigen immunoreactivity was also estimated. RESULTS: Intense nm23-H1 staining was observed in metastatic sites of clinical prostate cancers. The incidence of intense nm23-H1 staining cells in primary sites of clinical prostate cancers was significantly higher than that found in latent cancers and normal prostates (p < 0.01). The staining pattern of nm23-H1 was heterogeneous in latent cancers of the prostate. A significant relationship was observed between nm23-H1 staining and positive proliferating cell nuclear antigen staining (p < 0.01). CONCLUSIONS: These results seem to indicate that the nm23-H1 gene expression is related to cell proliferation and tumor metastatic potential, and appear to show the existence of a biologically different population of cells within the latent cancer.

Aged↗

Prostaglandin E receptor subtypes in mouse osteoblastic cell line.

PGE2 is one of the key molecules in the osteoblast. It is the major prostanoid in the bone, and its production is under the control of both systemic and local factors. PGE2 has been reported to have multiple actions in the osteoblast, such as growth promotion and cell differentiation. To better understand the action of PGE2 in the osteoblast, we determined the PGE receptor subtypes in MC3T3-E1, an osteoblastic cell line derived from the normal mouse calvaria. Northern blot analysis revealed that EP1 and EP4 subtypes are expressed in MC3T3-E1. In contrast, EP3 subtype was not detected by either Northern blot analysis or RT-PCR. The contribution of each subtype was evaluated by studying the effects of subtype-specific analogs on osteoblastic function at confluency and 5 days after confluency. An EP1 agonist, 17-phenyl-omega-trinor PGE2, increased DNA synthesis and decreased alkaline phosphatase activity. 11-Deoxy-PGE1, and EP2 and EP4 agonist, decreased DNA synthesis and increased alkaline phosphatase activity at both stages. Butaprost, an EP2-selective agonist, showed effects similar to those of 11-deoxy-PGE1 only at confluency. Another and more differentiated osteoblastic marker, osteocalcin production, was detectable and was stimulated by 11-deoxy-PGE1 only 5 days after confluency. The exposure of these cells to EP1 agonist changed the cell shape to a more fibroblastic appearance. These results indicate that EP1, EP4, and probably EP2 are present in MC3T3-E1 cells; EP1 promotes cell growth, and EP2 and EP4 mediate differentiation of the osteoblast. Furthermore, the decreased response to EP2-specific agonist 5 days after confluency suggests that the expression of PGE receptor subtype is dependent on the stage of osteoblastic differentiation. This is the first report to determine PGE receptor subtypes in the bone.

Alprostadil↗

Budd-Chiari syndrome caused by hepatic vein thrombosis in a patient with myeloproliferative disorder.

We report a 24-year-old Japanese female hospitalized with jaundice and ascites. She exhibited hepatosplenomegaly, severe liver dysfunction, and slight polycythemia with an increase in serum levels of beta-thromboglobin and platelet factor 4. Bone marrow was hypercellular with an increase in progenitor cells. The aggregation response of platelets to ADP and to collagen was markedly increased. Venography revealed narrowed hepatic veins with "spider web' sign. Liver biopsy revealed hepatic congestion. Budd-Chiari syndrome was diagnosed, and was thought to be due to thrombosis related to myeloproliferative disorder. Liver transplant was successful in relieving symptoms.

Adenosine Diphosphate↗

The distribution and architecture of lymphatic vessels in the rat stomach as revealed by an enzyme-histochemical method.

Enzyme-histochemical methods of staining for 5'-nucleotidase (5'-Nase) and alkaline phosphatase (ALPase) were successfully applied to study the distribution and architecture of lymphatic vessels and their relationships to blood vessels in the rat stomach. Extensively lymphatic capillary networks were found in the gastric wall, but there were significant differences in their extent, pattern, distribution and structure in the four different zones: esophagus-stomach (E-S), forestomach-corpus (F-C), corpus-antrum (C-A) and antrum-duodenum (A-D). 5'-Nase-ALPase double staining revealed that the 5'-Nase-positive lymphatic vessels run in close proximity to ALPase-positive arteries and veins. The fine blood capillary network was located superficially to the lymphatic network within the same layer in the gastric wall. The abundant lymphatic network located in the deep lamina propria and the lamina muscularis mucosa was always closely associated with the base of the lowest gastric glands, and yet no interglandular lymphatic capillaries were encountered in the corpus or antrum. In contrast, fewer lymphatic capillaries were present in the lamina propria beneath the squamous epithelium of the forestomach. The distribution of the well-developed lymphatic networks with valve-like structures in the submucosa and subserosa exhibited typical features, i.e., the distribution was annular in the submucosa and fan-shaped in the subserosa in the antrum near the duodenum. Open junctions of lymphatic endothelial cells were seen in the deep lamina propria and submucosa. Collecting lymphatics containing valves were mainly located deep in the submucosa and subserosa. The deep lamina propria and submucosa may play a key role in lymph formation and interstitial tissue fluid homeostasis as well as in pathological processes in certain diseases. The present findings obtained by interstitially injecting ultra-fine carbon particle suspensions or Evans blue showed that a great deal of lymph drained into the lymphatics accompanying the left gastric artery. The existence of a forestomach may explain the complicated organization and constitution of lymphatic networks in the rat stomach.

Animals↗