Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 361 records · Page 20Linked to original sources

PubMed1996

Microsatellite instability in transitional cell carcinoma of the urinary tract and its relationship to clinicopathological variables and smoking.

To determine whether microsatellite instability is involved in the development of transitional cell carcinoma (TCC) of the urinary tract, a microsatellite instability assay was carried out using PCR with 9 microsatellite loci. Thirty-eight TCC samples (30 patients with bladder cancer, 5 with renal pelvic tumors and 3 with ureteral tumors) and 1 lymph node with metastasis were examined. Microsatellite instability was found in 8 of 38 tumors examined, and 3 showed alterations in more than 2 microsatellite loci. All 8 tumors were beyond grade 2 and stage pT2 advanced tumors. Stages pT1-2 and pT3-4 patients differed significantly. Microsatellite instability was greater in smokers than non-smokers, but the differences were not significant. Microsatellite instability in TCC of the urinary tract is rare in superficial tumors but more common in invasive tumors. Microsatellite alterations would thus appear to occur, and possibly be importantly involved, in the tumorigenesis of urinary tract TCC.

Carcinoma, Transitional Cell↗

PubMed1996

Recombinant human interferon alpha-2b (rh IFN alpha-2b) therapy for steroid resistant idiopathic thrombocytopenic purpura (ITP).

The efficacy of recombinant human interferon alpha-2b (rh IFN alpha-2b) in the treatment of steroid resistant idiopathic thrombocytopenic purpura (ITP) was studied in 50 cases. Forty-one patients treated with rh IFN alpha-2b three times a week, six of 18 (33.3%) in the low dose group (150 x 10(4)IU: 3 MIU) and four of 20 (20.0%) in the high dose group (300 x 10(4)IU: 3 MIU) responded with platelet counts increasing to above 50 x 10(9)/L. Because of the exacerbation of thrombocytopenia and nasal bleeding, treatment was discontinued within 2 weeks in three patients out of 41 cases. On the other hand, six of nine patients (66.7%) treated with 3 MIU of IFN alpha-2b once a week for 8 weeks showed satisfactory response. Treatment with either administration schedule did not result in sustaining platelet counts above 50 x 10(9)/L for a long time after treatment. The results indicate that once a week administration schedule of rh IFN alpha-2b is more efficacious for platelet counts increasing for short period in patients who failed to respond to steroid and other medications than other schedules. The maintenance of this treatment schedule will allow sustained increased platelet levels, resulting in relief of bleeding tendency, while also being cost effective in comparison with other IFN treatment schedules and achieving better patient compliance without flu-like symptoms.

Adolescent↗

PubMed1996

Risk of progression and dying of clinically localized prostate cancer in Japan.

Study was made of the conservative management of 107 men with clinically localized prostate cancer. Distant metastasis developed more frequently in patients with poorly differentiated tumors than in those with well- and moderately differentiated counterparts (P < 0.01). Poorly differentiated histology was strongly associated with cancer-specific death (P < 0.01). The progression-free and cancer-specific survival of patients with stage T1a disease was significantly better than that of patients with stages T1b, T2a-b, and T2c tumors (P < 0.05). Available data clearly demonstrate that prostate cancer is a progressive disease when managed conservatively. Long-term follow-up data indicate the natural history of prostate cancer not to differ significantly according to race, despite noteworthy differences in prevalence and mortality. Patients with localized prostate cancer would be candidates for expectant therapy if they had lower-grade tumors and a life expectancy of 10 years or less. For patients with a 10-year or greater life expectancy and any grade of disease definitive therapy should be applicable.

Aged↗

PubMed1996

The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: report of a case.

A 51-year-old woman was admitted to our hospital for further investigation of chest X-ray films which showed multiple shadows that had been growing slowly over 2 years. Her only symptom was hemosputa. The lesions were suspected of being metastasizing leiomyoma due to her past history of uterine leiomyoma. Just 1 week before undergoing scheduled open lung biopsy, the lung lesions increased remarkably in size and number. A thoracotomy was performed and six of the numerous nodules were removed. The resected specimens were pathologically diagnosed as metastasizing leimyosarcoma which was positive for the progesterone and estrogen receptors. Thus, 1 month postoperatively, a course of medroxyprogesterone (MPA), 600 mg daily, was commenced. The residual lesions in her chest started to diminish, shortly afterward. She has remained well on this MPA regimen for 45 months. The prognosis of patients with metastasizing leiomyosarcoma is poor because of its low sensitivity to chemotherapy; however, some types of leiomyosarcoma are hormone-sensitive. It is therefore important to examine the hormone receptors of excised tumors from patients suspected of having metastasizing leiomyoma or leimyosarcoma.

Antineoplastic Agents, Hormonal↗

PubMed1996

Inhaled nitric oxide improved the outcome of severe right ventricular failure caused by lipopolysaccharide administration.

OBJECTIVE: To evaluate the efficacy of nitric oxide (NO) inhalation against endotoxin-induced lung injury. DESIGN: Randomized prospective short-term study. SETTING: University school of Medicine Laboratory. INTERVENTIONS: Animal experiment (using 16 Japanese white rabbits). The animals inhaled NO at a concentration of 10 ppm. MEASUREMENTS AND RESULTS: The rabbits were randomly divided into the NO inhaling group (n = 7) and the control group (n = 9). Both groups received continuous infusion of 1200 mcg lipopolysaccharide (LPS) and the NO group inhaled 10 ppm NO during the LPS administration. In the control group, severe right ventricular (RV) failure was observed at 30-90 min of LPS infusion, and 4 of 9 animals died within 90 min of LPS infusion. In the NO group, none of the animals died and the early phase hemodynamic deterioration was milder than in the control group. But pulmonary gas exchange was not significantly different between the two groups throughout the study. At the end of the study there were no significant differences in any parameters of the surviving animals between the two groups. CONCLUSION: Although an improvement of pulmonary gas exchange was not demonstrated, NO inhalation (10 ppm) improved the outcome of severe RV failure caused by LPS infusion.

Analysis of Variance↗

PubMed1996

Mechanisms of bombesin on growth of gastrinoma (PT) in vivo.

The growth of the human gastrinoma model (PT) in athymic nude mice is stimulated by bombesin (BBS), an amphibian peptide homologous to both human gastrin-releasing peptide (GRP) and neuromedin B (NMB). The mechanism is not known, and a potent and specific GRP-R antagonist BIM26226, which has low affinity for NMB-R, was used in vivo in athymic nude mice bearing gastrinoma subcutaneously. Both the BBS and BIM26226 stimulated the growth of PT, and the growth stimulation was even greater when given together. RT-PCR study of gastrinoma revealed the presence of both GRP-R and NMB-R mRNA, but much more abundant NMB-R mRNA. We conclude that BBS-stimulated growth of gastrinoma involves both GRP-R and NMB-R, and our findings suggest that GRP-R mediates negative and NMB-R produces positive growth effects on gastrinoma.

Animals↗

PubMed1996

Effects of growth factors and gut hormones on proliferation of primary cultured gastric mucous cells of guinea pig.

Almost completely homogenous gastric mucous epithelial cells of guinea pigs were grown to confluence in the presence of 10% fetal calf serum (FCS). FCS, epidermal growth factor (EGF), and insulin significantly increased 5-bromo-2'-deoxyuridine (BrdU) uptake by the cells and EGF together with insulin increased the cells' [3H] thymidine uptake. Basic fibroblast growth factor (bFGF) enhanced EGF-induced DNA synthesis by the cells, but vasoactive intestinal peptide (VIP), secretin, prostaglandin E2 (PGE2), and dibutyryl cyclic AMP (dbcAMP) neither induced DNA synthesis nor enhanced the effect of EGF on DNA synthesis by the cells. Gastrin, cholecystokinin-octapeptide (CCK8), and carbamylcholine chloride (CCh) also did not enhance the effect of EGF on DNA synthesis. 125I-EGF, 125I-bFGF, and 125I-gastrin binding to the gastric mucous cells revealed the presence of high-affinity receptors for EGF and bFGF, but not for gastrin. Northern blot analysis showed the expression of EGF receptor mRNA, but not gastrin receptor mRNA. These results suggest that EGF, insulin, and bFGF may cooperatively regulate gastric mucous cell growth, but that gastrin and other gastrointestinal hormones do not have a direct stimulatory effect on mucous cell growth in the guinea pig.

Animals↗

PubMed1996

Mutagenic activation of N-nitrosobis(2-oxopropyl)amine by pancreatic juice and assessment of its ductal tumorigenicity following intraductal administration in dogs.

CONCLUSION: The results suggest that systemic administration (s.c. and i.p.) of BOP induces liver damage due to BOP itself and/or its metabolites which might be formed in the liver and that interaction of BOP itself in the pancreatic duct with pancreatic juice plays an important role for pancreatic duct tumorigenicity. METHODS: Mutagenic activation and pancreatic duct tumorigenicity of N-nitrosobis (2-oxopropyl)amine (BOP) administered s.c., i.p., and i.d. were studied in dogs. RESULTS: Following i.p. administration of BOP, N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP), but not BOP, were detected in pancreatic juice, while following i.d. administration, only BOP was detected. The pancreatic juice of one dog that received 100 mg of BOP i.d. showed positive mutagenicity towards Salmonella typhimurium TA100, but the pancreatic juice of two dogs that received 100 mg of BOP i.p. was not mutagenic. BOP showed clear mutagenicity in the presence of pancreatic juice from untreated dogs, but the pancreatic juice could not activate HPOP and BHP to mutagens. BOP administered sc for 2 wk (total dose: 600 mg) induced clinical toxicity, nausea, vomiting, and loss of appetite at 10 wk. BOP administered i.p. for 4 mo (total dose: 2000 mg) induced liver damage at 6 mo, but no pancreatic injury. BOP administered i.d. for 6.5 or 12 mo (total dose: 2500 or 4700 mg, respectively) induced papillary hyperplasia and dysplasia of duct epithelial cells and ductal proliferation with fibrosis.

Animals↗

PubMed1996

Comparative pharmacokinetics of KRN8602, a new morpholino anthracycline, and adriamycin in tumor-bearing mice.

It has been reported that KRN8602 shows antitumor effects similar or superior to those of Adriamycin (ADM) against several murine and human cell lines and has been found to be effective against multidrug resistant tumor cells. We investigated the pharmacokinetics of KRN8602, a new morpholino anthracycline, in comparison with ADM in mice bearing colon26 adenocarcinoma. After intravenous administration, both drugs disappeared triexponentially from the plasma and KRN8602 was eliminated faster than ADM. The rate of elimination of KRN8602 from tissues was also faster than than of ADM. The relative order of the area under the curve (AUC) of KRN8602 was spleen > tumor > small intestine > lung > kidney > heart > liver > brain > plasma, while that of ADM was spleen > kidney > lung > liver > heart > small intestine > tumor > plasma. ADM was not detectable in the brain. The AUC of KRN8602 was higher than that of ADM in the tumor and brain, but it was lower in other tissues. The tissue-to-plasma concentration ratio (KPapp) of KRN8602 was higher than that of ADM in the tumor, spleen, small intestine and brain. KRN8602 was metabolized to several metabolites. The concentrations of M1 and M2 (glycoside-type metabolites) was relatively high in the spleen. M3 (aglycone-type metabolite) showed a very high AUC ratio in the liver (34%). In tumor, M1 and M2 concentrations were low and M3 was not detected. KRN8602 had a greater activity than ADM and M2 had a cytotoxic activity similar to KRN8602 against colon26 cells in an MTT assay. These results suggest that the strong antitumor effect of KRN8602 against colon26 is due not only to its strong cytotoxic activity but also to its marked transferability into tumors. KRN8602 shows better selective toxicity than ADM, because KRN8602 is more selective for tumors than ADM and less is transferred to normal tissues.

Adenocarcinoma↗

PubMed1996

Inhibitory effect of a spicamycin derivative, KRN5500, on the growth of hepatic metastasis of human colon cancer-producing tissue polypeptide antigen.

The inhibitory effect of KRN5500, a spicamycin derivative, on the growth of hepatic metastasis of the tissue polypeptide antigen (TPA)-producing human colon cancer COL-1 was examined in severe combined immunodeficient (SCID) mice. Prior to this chemotherapeutic study, we confirmed the high correlation coefficient (r = 0.86, P < 0.01) between plasma TPA levels in athymic nude mice bearing COL-1 and tumor volume. In the chemotherapy of experimental hepatic metastasis induced by intrasplenic injection of COL-1 cells, KRN5500 at 12 mg/kg per day was administered i.v. three times at 4-day intervals. From the start of chemotherapy (day 1), plasma TPA levels in the mice were significantly decreased from 8332 U/l to a minimum of 494 U/l on day 16 and were within the range for intact SCID mice (409-634 U/l). The mean tumor weight was 4.87 g in the liver of untreated mice on day 19 and 0.74 g, in the liver of KRN5500-treated mice, a significant difference, representing a tumor growth inhibition rate of 85%. These results suggest the usefulness of TPA as a tumor marker in an experimental xenograft model. The chemotherapeutic efficacy of KRN5500 against experimental hepatic metastasis indicates that it may be a useful drug for the treatment of patients with hepatic metastases of colon cancer.

Animals↗

PubMed1996

Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK) I/glycogen synthase kinase-3 beta and cyclin-dependent kinase 5, a component of TPK II.

Using immunohistochemistry, we examined the localization of four types of proline-directed kinases in the brains of control rats and in the brains of non-demented aged human subjects, subjects with Alzheimer's disease and those with Down's syndrome. The four kinases were: cyclin-dependent kinase (cdk) 5, a component of tau protein kinase (TPK) II; TPK I/glycogen synthase kinase (GSK)-3 beta; GSK-3 alpha; and mitogen-activated protein kinase (MAPK/ERK2). Each of these kinases has been reported to promote the hyperphosphorylation of tau protein in vitro. The kinases were located essentially in neurons, although the intensity and distribution of labeling varied. Antiserum for cdk5 showed the most preferential and consistent labeling of intraneuronal neurofibrillary tangles (NFT). Antiserum for TPK I/GSK-3 beta also labeled intraneuronal NFT. Double immunolabeling for TPK I/GSK-3 beta and tau 1 showed that TPK I/GSK-3 beta was closely associated with NFT. Antiserum for GSK-3 alpha labeled neurons weakly, and the intensity of labeling did not differ between neurons with and without NFT. Antiserum for MAPK labeled neurons in superficial cortical layers, but NFT appeared in both superficial and deep cortical layers. These findings suggest that cdk5 and TPK I/GSK-3 beta are the critically important kinases for the generation in vivo of hyperphosphorylated tau, the main component of the paired helical filaments in NFT.

Aged↗

PubMed1996

The sites of origin and termination of afferent and efferent components in the lingual and pharyngeal branches of the glossopharyngeal nerve in the Japanese monkey (Macaca fuscata).

Afferent and efferent components in the lingual and pharyngeal branches of the glossopharyngeal nerve (Li and Ph) of the Japanese monkey (Macaca fuscata) were examined. After injecting wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) unilaterally into the central cut end of the Li and Ph, or into the stylopharyngeal muscle, labeled neuronal cell bodies and terminal labeling were observed in the medulla oblongata, peripheral ganglia of the glossopharyngeal and vagus nerves, and cervical ganglia of the sympathetic trunk. The following conclusions were deduced from the results. The Li contains efferent fibers from the inferior salivatory nucleus, and superior cervical ganglion. The afferent fibers in the Li are composed mainly of peripheral processes of ganglion neurons in the superior and petrous ganglia of the glossopharyngeal nerve, and additionally of those of ganglion neurons in the jugular ganglion of the vagus nerve. The afferent fibers in the Li terminate mainly in the lateral division of the nucleus of the solitary tract, and additionally in the dorsal aspect of the lateral marginal region of the interpolar spinal trigeminal nucleus. The Ph is mainly composed of efferent fibers from the ambiguous nucleus and superior cervical ganglion; only a small number of afferent fibers from the sensory ganglia of the glossopharyngeal and vagus nerves are contained in the Ph. Stylopharyngeal motoneurons are distributed in the retrofacial part of the ambiguous nucleus.

Afferent Pathways↗

PubMed1996

Enhancing effects of alpha-,beta-monoglycosylceramides on natural killer cell activity.

We examined the in vitro and in vivo natural killer (NK) cell activity enhancing effects of alpha-, beta-galactosylceramide (GalCer) and alpha-, beta-glucosylceramide (GluCer) which have the same ceramide moiety, and of other alpha-, beta-GalCer having a different ceramide portion, and found that alpha-types show stronger enhancing effects than beta-types and the alpha-GalCer possesses the most potent activity among GalCers and GluCers having the same ceramide moiety. When the comparison of tumor growth inhibitory effects of alpha, beta-GalCer on mice subcutaneously inoculated with B16 cells was performed, the alpha-GalCer showed stronger suppressive activity than its beta-type, paralleling their enhancing effects on NK cell activity. These results suggest that the manner of combination between sugar and ceramide plays an important role in antitumor activity as well as enhancing effect on NK cell activity of GalCers.

Animals↗

PubMed1996

Deoxyribonucleic acid ploidy status as no basis for pathologic stage prediction in clinically resectable prostate cancer.

OBJECTIVES: Assessment of deoxyribonucleic acid (DNA) ploidy status of a tumor as a means for predicting pathologic stages in prostate cancer. METHODS: DNA ploidy of each focus of a cancer in 70 radical prostatectomy specimens was determined by nuclear image analysis. DNA ploidy was compared with the pathologic features of tumors. RESULTS: One hundred three individual cancers in 70 patients were used for DNA ploidy analysis. Of these, 39 (38%) were diploid and 64 (62%), nondiploid. DNA ploidy was weakly correlated with increase in tumor volume (P = 0.049) but not tumor grade. The relationship between DNA content and extraprostatic spread was not statistically significant. Increase in tumor volume and grade promoted extraprostatic spread more than nondiploidy, as shown by multivariate analysis. CONCLUSIONS: The incidence of a nondiploid cell population in a tumor focus in prostate cancer is essentially the same, at least for Americans and Japanese. DNA ploidy of a tumor cannot serve as a means of pathologic stage prediction in clinically resectable prostate cancers, contrary to many previous studies. Thus, DNA content analysis would be of no use for deciding on the treatment strategy of prostate cancer.

DNA, Neoplasm↗

PubMed1996

Narrow photon beam dosimetry for linear accelerator radiosurgery.

The dosimetric characteristics of linear accelerator radiosurgery for 10-MV X-ray were measured. Measurement of the relative output factor and tissue maximum ratio with a microchamber produced results equivalent to those of measurement with X-ray film. The 80% isodose level width measured with the microchamber was significantly smaller than that measured with the X-ray film. For the measurement of relative output factor and tissue maximum ratio, a microchamber seems to be the more appropriate choice. X-Ray film was found to be suitable for beam profile measurement.

Phantoms, Imaging↗

PubMed1996

Production of amelogenin by enamel epithelium of Hertwig's root sheath.

OBJECTIVE: To study the multiple potentials of differentiating odontogenic epithelial cells. STUDY DESIGN: Bilateral first and second maxillary molars of 30 immature rats were perforated into the pulp chambers with a round bur. The pulps were observed histologically and immunohistochemically for amelogenin 3, 7, and 14 days after the perforation. RESULTS: On day 7, the enamel epithelium of Hertwig's root sheath migrated and formed oval-shaped epithelial islands that resembled epithelial rests of Malassez. On day 14, the islands consisted of epithelial cells with large nuclei and cytoplasm partially surrounded by a subsequently formed osteodentin and cementum. Immunoreactivity for amelogenin was observed in the large epithelial cells and in the area between the cells as well as the calcified tissues. Some of the enamel epithelium resembling columnar ameloblasts of the enamel organ were also positive for amelogenin. CONCLUSIONS: The enamel epithelium of Hertwig's root sheath appeared to differentiate into ameloblasts and produce amelogenin.

Ameloblasts↗

PubMed1996

Acute arterial thrombosis due to platelet aggregation in a patient receiving granulocyte colony-stimulating factor.

We describe a 44-year-old man with non-Hodgkin's lymphoma receiving granulocyte colony-stimulating factor (G-CSF) who developed an acute arterial thrombosis. The removed thrombus contained large amounts of platelet aggregation. A rapid increase of platelets and increased adenosine diphosphate (ADP)- and collagen-induced platelet aggregation were observed at the time of the thrombotic event. A challenge test of G-CSF showed an increase in the platelet count and an augmentation of ADP- and collagen-induced platelet aggregation. In the use of GCSF. patients who produce a rapid increase in platelet levels could be at greater risk for thrombotic events and need to be followed-up carefully.

Adult↗

PubMed1996

The CDKN2 gene alterations in various types of adult T-cell leukaemia.

The CDKN2 gene, encoding the cyclin-dependent kinase-4 inhibitor p16, is a putative tumour-suppressor gene because it is frequently altered in many malignant tumours. We analysed the CDKN2 gene in 44 cases of adult T-cell leukaemia (ATL) by Southern blot analysis, polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis, and direct sequencing. Southern blot analysis detected a homozygous deletion of the CDKN2 gene in 5/44 patients (11.4%). Mutational analysis by the PCR-SSCP method and direct sequencing showed one nonsense mutation at codon 72 (nucleotide 232), and two missense mutations at codon 43 (nucleotide 146) and codon 97 (nucleotide 309, 3/44, 6.8%). Therefore we found changes in the CDKN2 gene, including point mutations, in 18.2% of the patients with ATL. Interestingly, most of these patients had acute type ATL. Our results suggest that the CDKN2 gene is inactivated not only by homozygous deletion but also by point mutation, and these alterations contribute to the aggressiveness of ATL.

Adult↗