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Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 613 records · Page 34Linked to original sources

Differential effect of submandibular gland resection on the growth of pancreatic cancer in cheek pouch and subcutaneous tissue.

Exogenous administration of epidermal growth factor (EGF) enhances tumor growth of H2T, a hamster pancreatic cancer that is inoculated in the cheek pouch. The effect of endogenous EGF on tumor growth, however, is not known. The main source of EGF in the body is the submandibular glands. This study examined the influence of submandibular gland resection (SMx) on H2T tumor growth in the cheek pouch and compared it to the growth in SC tissue. Bilateral SMx or sham operation was performed on male Syrian golden hamsters. In 30 hamsters (n = 15 for each operation group), 5 x 10(4) and 5 x 10(5) H2T cells were inoculated in the bilateral cheek pouches and intrascapular SC tissue, respectively (Exp. 1). In another 30 hamsters (n = 15 for each operation group), 5 x 10(5) and 1 x 10(6) H2T cells were inoculated at the same sites (Exp. 2). Two longest perpendicular diameters of the tumor were measured once a week for 12 wk (Exp. 1) or 8 wk (Exp. 2), and the tumor area was calculated. The tumor area in the cheek pouch became significantly smaller in the SMx group than the sham-operated group after the 8th wk (Exp. 1) or the 7th wk (Exp. 2). On the other hand, the tumor area in the SC tissue did not show any difference between groups through the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PGE2 protects isolated cells against injury through multiple mechanisms.

In order to clarify how PGE2 regulates gastric mucosal integrity, we examined the effects of PGE2 on ethanol-caused injury of isolated gastric chief cells, cultured gastric mucous cells from guinea pigs and Balb/c 3T3 fibroblasts. Pretreatment of these cells with PGE2 reduced ethanol-caused injury of the cells. Furthermore, pretreatment of gastric mucous cells with indomethacin enhanced ethanol-caused injury, suggesting that endogenous PGE2 may be involved in the cell protection. PGE2 stimulated an increase in diacylglycerol (DG) accumulation in chief cells and treatment of chief cells with synthetic DG reduced the injury of the cells. However, DG accumulation was not observed in gastric mucous cells treated with PGE2. Therefore PGE2 may protect the cells from injury through a variety of mechanisms. In addition, PGE2 enhanced the survival of the quiescent fibroblasts cultured in the absence of serum, while PGE2 had no survival enhancing effect on gastric mucous cells. These results suggest that the mechanism by which PGE2 preserves the cell viability may depend on not only cell types used but also how the cells are injured.

Animals↗

Long-term impact of conservative management on localized prostate cancer. A twenty-year experience in Japan.

The clinical outcome of 107 patients with localized prostate cancers over the past twenty years was analyzed retrospectively. Immediate endocrine therapy was administered in 55 patients after diagnosis. The other group of 52 patients did not receive any anti-tumor treatment until progression. Overall, 22 patients (21%) died of prostate cancer, while 45 (42%) died of other known causes. During a mean observation period of thirty-seven months, 27 (25%) experienced progression of the disease (local in 9, distant metastasis in 25, and both in 7 patients). The cancer-specific survival rates for these 107 patients were 78 percent at five years and 71 percent at ten years. The timing of endocrine therapy and age at diagnosis did not influence patient's prognosis. Tumor stage failed to demonstrate any prognostic significance after being controlled for other factors including tumor grade. Poorly differentiated histology appeared to be the sole and the strongest predictor for both tumor progression and cancer death. Prostate cancer may not differ significantly among races once it becomes clinically manifest. Expectant management for localized prostate cancer in well and moderately differentiated cancer may be justified because of the higher probability of dying of other intercurrent causes especially in the elderly group of patients. However, definitive forms of therapy should be considered for the group of patients with poorly differentiated tumor who have reasonably long life expectancy.

Age Factors↗

Morphological and electrophysiological changes induced by calcium ionophores (A23187 and X-537A) in spontaneously beating rabbit sino-atrial node cells.

1. Effects of calcium ionophores (A23187 and X-537A) on the spontaneously beating sino-atrial (SA) node cells of rabbit heart were examined using electron microscopic and an electrophysiological techniques. 2. During exposure to A23187 or X-537A (2 x 10(-5) M), the cycle length was significantly prolonged by 11% (n = 12) or 118% (n = 11), respectively. But neither ionophore affected other action potential parameters. 3. X-537A (2 x 10(-5) M) induced irregular rhythm (dysrhythmia), probably due to cellular calcium overload. Similarly, ouabain (3 x 10(-7) M) also elicited dysrhythmia. In the presence of isoproterenol (ISP, 10(-7) M), X-537A potentiated dysrhythmia, and A23187 newly induced it. 4. In ultrastructural analyses, X-537A caused swelling of the cisternae of Golgi apparatus within 10 min, whereas A23187 and ouabain did not produce any changes even after 30 min-application. 5. Addition of high Ca2+ (10 mM) and/or ISP (10(-7) M) to X-537A produced a further dilation and vacuolization. In A23187 or ouabain, however, the addition of Ca2+ and ISP did not cause any changes, even during dysrhythmia. 6. These results indicate that X-537A elicited a more potent calcium overload than A23187, and that a discrepancy between ultrastructural damages and electrical changes exists.

Animals↗

Infrequent involvement of p53 mutations and loss of heterozygosity of 17p in the tumorigenesis of renal cell carcinoma.

Restriction fragment length polymorphism (RFLP) analysis and the polymerase chain reaction of the single-strand conformation polymorphism (PCR-SSCP) method were conducted to assess the loss of heterozygosity of chromosome 17p and mutations of the p53 gene in 30 surgical specimens of human renal cell carcinoma. Six of 29 tumors (20.6%) showed loss of heterozygosity on chromosome 17p in RFLP analysis, and in none of 21 tumors could a mutation be found on exons 5 to 8 of the p53 gene in PCR-SSCP analysis. We conclude that the p53 gene mutation does not play a role in the development of the majority of cases of renal cell carcinoma and that there may be another tumor suppressor gene on 17p.

Carcinoma, Renal Cell↗

Detection of precore/core-mutant hepatitis B virus genome in patients with acute or fulminant hepatitis without serological markers for recent HBV infection.

To confirm the possibility that some hepatitis B virus (HBV) variants do not induce HB s antigen (HBsAg), anti-HB core antibody (anti-HBc) and anti-HBc IgM in a transient infection, polymerase chain reaction (PCR) was performed in 20 patients with acute hepatitis and 7 patients with fulminant hepatitis. Patients were diagnosed with non-A, non-B hepatitis by serological markers at admission. PCR successfully amplified the precore/core gene in 5 (25%) of the patients with acute hepatitis and 2 (29%) of the patients with fulminant hepatitis. Subsequent sequencing revealed frequent mutations including precore-defects in the precore/core gene.

Acute Disease↗

Comparative effects of neurotensin and neuromedin N on growth of human pancreatic cancer, MIA PaCa-2.

Neurotensin (NT), an important regulatory hormone of the gut, stimulates growth of the human pancreatic cancer cell line MIA PaCa-2 in vitro. The purpose of our study was to compare the stimulatory effects of NT and neuromedin N (NMN), a structurally related hexapeptide, on the growth of MIA PaCa-2. In addition, the effects of NT on the growth of MIA PaCa-2 xenografts and normal GI tissues were assessed in athymic nude mice. MIA PaCa-2 cells, plated in serum-free media, were treated with either NT (10(-12)-10(-6) M) or NMN (10(-11)-10(-7) M) and cells were counted. For the in vivo study, MIA PaCa-2 cells were inoculated sc into 30 athymic nude mice and then randomized to two groups to receive either NT (600 micrograms kg-1, sc, tid) or vehicle. At sacrifice (day 35), the xenografted tumours, as well as normal host pancreas, jejunum and ileum were removed, weighed, and assayed for DNA, RNA and protein. Both NT and NMN stimulated the growth of MIA PaCa-2 cells in vitro with maximal (approximately 30%) increases occurring with dosages of 10(-9) M. In vivo, NT had a transient effect on xenografted MIA PaCa-2 tumour area with increases noted on days 21 and 25 of the study. Conversely, NT significantly stimulated the growth of jejunum and ileum, with a more pronounced effect noted in the jejunum. NT and NMN have similar growth-stimulatory effects on MIA PaCa-2 cells in vitro, which suggests an interaction through the same receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Infrequent involvement of p53 gene mutations in the tumourigenesis of Japanese prostate cancer.

A study was made of the incidence of p53 mutations in Japanese males with prostate cancer or benign prostatic hyperplasia. Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) was used as a primary screening technique with gene sequencing being carried out in positive cases. Two out of 21 prostate cancers (9.5%) were found to have p53 mutations. These were stage B2 and D2 prostate cancers. No abnormalities were found in the remaining cases or benign prostatic hyperplasia. Mutations of the p53 gene would thus appear infrequent in the tumourigenesis of primary prostate cancer.

Adenocarcinoma↗

Differentiation of Rickettsia japonica by restriction endonuclease fragment length polymorphism using products of polymerase chain reaction amplification with Rickettsia rickettsii 190-kilodalton surface antigen gene primers.

Restriction fragment length polymorphism of polymerase chain reaction (PCR) amplification products differentiated Rickettsia japonica, a causative agent of Oriental spotted fever, from other spotted fever group (SFG) rickettsiae. Primer pair Rr190. 70p and Rr190. 602n of R. rickettsii 190-kDa antigen gene sequence primed genomic DNAs obtained from R. japonica, type strain YH and strains NT, NK, YKI, and TKN. The products were cleaved by PstI but not by AfaI restriction endonuclease. The PstI digestion pattern of PCR-products amplified from all strains of R. japonica was identical and easily differentiated from that of other SFG rickettsiae. The present study demonstrated a genotypic difference between R. japonica and other pathogenic SFG rickettsiae.

Animals↗

Effects of AE0047 on renal haemodynamics and function in anaesthetized dogs.

1. The effects of AE0047, a newly developed calcium channel blocker, on renal haemodynamics and function were investigated and compared with those of nicardipine in anaesthetized dogs. 2. Intravenous injection of AE0047 (10 and 30 micrograms/kg) caused a dose-related fall in blood pressure (BP). The AE0047-induced fall in BP was of slow onset and long lasting. AE0047 at 10 micrograms/kg elicited a slight increase in renal blood flow (RBF) and urine formation. 3. When AE0047 was infused intrarenally at non-hypotensive doses (25 and 50 ng/kg per min), there was no significant increase in RBF. However, the glomerular filtration rate increased significantly after drug infusion. Intrarenal arterial (i.r.a.) infusion of AE0047 led to dose-related increases in urine flow (UF), urinary excretion of electrolytes (Na+, K+ and Cl-) and fractional excretion of electrolytes. The AE0047-induced increase in urine formation was of very slow onset and progressed even after the cessation of the AE0047 infusion. 4. The intrarenal arterial infusion of nicardipine at same doses as AE0047 produced significant increases in urine formation, but these effects were immediately restored to the control values after cessation of the nicardipine infusion. 5. It was shown that AE0047 has a long-lasting diuretic effect and that AE0047-induced diuresis may be due to inhibitory effects on sodium and water reabsorption in the renal tubules.

Anesthesia↗

An epidemic outbreak of hepatitis E in Yangon of Myanmar: antibody assay and animal transmission of the virus.

An epidemic outbreak of hepatitis E occurred in an army recruit camp of Yangon, Myanmar, in October 1989. One hundred and eleven patients among 600 residents were hospitalized. As high as 83.7% of these patients were positive for the acute phase antibody against hepatitis E virus by an enzyme-linked immunosorbent assay developed in our laboratory. Also, 30.6% of 49 symptom-free residents examined were positive for the antibody. We prepared a stool extract from six patients and inoculated it into 10 rhesus monkeys for a series of three sub-passages. All of them developed acute biochemical hepatitis along with an elevation of antibody levels. A rechallenge with viruses of the present outbreak failed to provoke hepatitis in two monkeys that had previously recovered from acute hepatitis caused by an isolate of sporadic hepatitis E of the same area. Similarly, the rechallenge of the sporadic strain did not induce hepatitis in two monkeys that had been previously infected with the epidemic virus. These data suggested that the subjects would obtain neutralizing antibodies against the hepatitis E virus once infected, and many adult inhabitants of the endemic area had no protective antibodies and were still susceptible to hepatitis E infection.

Adult↗

Histological difference between complete responders and non-responders to interferon therapy of the livers of patients with chronic hepatitis C.

Liver histology was compared in patients with chronic hepatitis C to note the differences between responders and non-responders to interferon treatment. Fifty-eight patients were administered interferon in varying doses and over various periods, and were then followed up for 1 year. According to the improvement status of serum alanine aminotransferase (ALT) levels during this period, the patients were classified into complete responders who showed complete normalization of ALT; partial responders who exhibited a significant decrease, but not complete normalization of ALT; and non-responders who did not reveal any significant decrease of ALT. Before application of the interferon treatment, liver biopsies were analyzed in four parameters and given scores from 0 to 5 for three groups in cord with no prior knowledge of the efficacy. The parameters included necroinflammation, fibrosis/lobular distortion, portal lymphocytic reaction and portal (or fibrous septal) outline destruction. Results indicated that there were no significant differences in the score of necroinflammation and portal lymphocytic reaction between the complete responder group and the non-responder group. In contrast, the complete responder group exhibited weaker fibrosis/lobular distortion and less portal outline destruction than the non-responder group. The partial responder group was more akin to the former group in these parameters. Thus, it is safe to conclude that liver histology may predict the efficacy of interferon treatment.

Adult↗

Tau protein kinase II is involved in the regulation of the normal phosphorylation state of tau protein.

To study the phosphorylation state of tau in vivo, we have prepared antisera by immunizing rabbits with synthetic phosphopeptides containing phosphoamino acids at specific sites that are potential targets for tau protein kinase II. Immunoblot experiments using these antisera demonstrated that tau in microtubule-associated proteins is phosphorylated at Ser144 and at Ser315. Almost all tau variants separated on two-dimensional gel electrophoresis were phosphorylated at Ser144 and nearly one-half of them at Ser315. Phosphorylation at Ser144 and at Thr147 of tau isolated from heat-stable brain extracts was shown to be developmentally regulated, with the highest level of phosphorylation found at postnatal week 1. In vitro phosphorylation of tau by tau protein kinase I, a kinase responsible for abnormal phosphorylation of tau found in paired helical filaments of patients with Alzheimer's disease, was enhanced by prior phosphorylation of tau by tau protein kinase II. Thus, we suggest that tau protein kinase II is indirectly involved, at least in part, in the regulation of the phosphorylation state of tau in neuronal cells.

Aging↗

A brain-specific protein p25 is localized and associated with oligodendrocytes, neuropil, and fiber-like structures of the CA3 hippocampal region in the rat brain.

Developmental expression and cellular localization of a novel brain-specific 25-kDa protein (p25), a substrate of tau protein kinase II, were investigated in the rat brain using polyclonal antibodies raised against peptides synthesized based on the p25 amino acid sequence. By western immunoblotting, p25 was found to be expressed only slightly in the embryonic period; the expression increased from 11 days up to 5 weeks of age, and continued to increase gradually until 1-2 years of age. Immunohistochemistry revealed distinct staining of glial cells in most regions of the central nervous system in the adult rat brain. These positively immunostained cells were especially abundant in the white matter, such as the corpus callosum, cingulum, external capsule, and internal capsule. The glial cells were identified as oligodendrocytes, and the nuclei of the cells remained unstained. Whereas the neuropil in most parts of the brain was immunostained less intensely than glias, the neuropil in the first and second layers of the cerebral cortex and the dentate gyrus was relatively strongly stained. Fiber-like structures were also stained in the CA3 region of hippocampus.

Aging↗