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T Uchida

Publications and source records attributed to T Uchida.

At least 505 records · Page 28Linked to original sources
PubMed1995

[Use of ultrasonography in the diagnosis of cystic lesions in seminal vesicles and prostate].

Transrectal ultrasonography (TRUS) has been used extensively to evaluate the lower urinary tract in males, including the prostate gland, seminal vesicles and ejaculatory ducts. Of 475 males who underwent TRUS at Kitasato University Hospital, 43 (9.1%) were found to have cystic changes of these structures. Most of these cystic changes could be identified as being of prostate origin, Wolffian duct origin or Müllerian duct origin by their sonographic appearance and location. Although most patients were asymptomatic, 8 of the 30 men with a complaint of hematospermia had a sonographic finding of cystic changes in the prostate (3 patients) or ejaculatory ducts (5 patients). Inflammation and allergic reaction have been suggested to be related to hematospermia, however, their mechanism remains to unclear. These findings suggest that cystic changes in the ejaculatory duct contribute to hematospermia.

Adolescent↗
PubMed1995

[Chylothorax in a patient with 9-year remission of malignant lymphoma].

We describe a 69-year-old man who developed chylothorax after a 9-year remission of malignant lymphoma. The patient was admitted to our hospital and received exploratory laparotomy for ileus in February 1986. Bulky masses in the posterior mediastinum and the retroperitoneum, and also a jejunal tumor were observed. Fibrosis of the liver was also observed. The jejunal tumor was removed and histological findings revealed diffuse large B-cell malignant lymphoma. He was treated by combination chemotherapy and remission was achieved. He was discharged in June and remained in remission, but was readmitted for right pleural effusion in October 1994. Effusion was chylous and the chylomicron level was estimated to be 181 mg/dl. Liver cirrhosis also developed but there was no chylous ascites. Chylorrhea disappeared after continuous aspiration, but recurred in December. Continuous aspiration was ineffective, therefore 10 KE of OK-432 was administered twice into the pleural cavity, and chylorrhea again disappeared. No findings suggestive of malignant lymphoma were not detected by computerized tomography and gallium scintigram. He was discharged in March 1995 and chylothorax has not recurred since. These findings suggest that the fragility of the thoracic duct which had been infiltrated by malignant lymphoma might increase, resulting in rupture, even if in remission.

Aged↗
PubMed1995

[Hepatitis E].

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Genes, Viral↗
PubMed1995

KRN7000, a novel immunomodulator, and its antitumor activities.

KRN7000, a compound with a novel alpha-galactosylceramide structure, showed potent tumor growth inhibitory activities in B16-bearing mice and markedly stimulated lymphocytic proliferation in allogeneic mixed leukocyte reaction, suggesting that KRN7000 is a biological response modifier. To confirm this suggestion, we examined the abilities of KRN7000 to enhance in vitro and in vivo natural killer (NK) activities, and found that KRN7000 enhanced in vitro and in vivo NK activities, and its potency on in vivo NK activity was much stronger than those of Poly I:C, which is a positive control, or the representative BRMs OK432 and Lentinan. In addition, since spleen cells intravenously treated with KRN7000 also showed potent cytotoxic activities against B16 and EL-4 cells, we evaluated the capability of KRN7000 to prolong the survival period of mice intravenously inoculated with B16 cells or mice intraperitoneally inoculated with EL-4 cells. In these models, KRN7000 (100 micrograms/kg) significantly prolonged the lifespan of mice, and its potency was stronger than that of Mitomycin C, a typical chemotherapeutic agent, in two models. These results demonstrate that KRN7000 would be a useful agent for cancer therapy.

Adjuvants, Immunologic↗
PubMed1994

Precursor of cdk5 activator, the 23 kDa subunit of tau protein kinase II: its sequence and developmental change in brain.

Tau protein kinase II (TPKII) is shown by immunoprecipitation to be a complex composed of two subunits, a catalytic subunit, cdk5, and regulatory subunit, p23. By sequence analysis of p23 cDNA, p23 was found to occupy a region from the 99th amino acid residue to the C-terminus of a novel protein with a molecular weight of 34,000 Da, suggesting that this 34 kDa protein is a precursor of p23 (pre-p23). These findings suggest that p23 results from the processing of the precursor protein, pre-p23. The precursor mRNA was expressed most abundantly in rat brain just before and after birth. Expression of pre-p23, but not of cdk5, mRNA changed, coinciding with the developmental change of TPKII activity, suggesting that its expression controls the phosphorylation of tau by the TPKII/TPKI system in the neonatal brain. p23 appears to be a cdk5 activator in neuronal cells.

Amino Acid Sequence↗
PubMed1994

The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin.

The expression of the murine double minute-2 (MDM2) gene, the product of which binds to and inactivates p53, was studied in 60 patients with B-cell chronic lymphocytic leukemia (B-CLL) or non-Hodgkin's lymphoma (B-NHL). Northern blot analysis showed that the level of MDM2 gene expression was low in normal human B-cells, whereas 17 of the patients (28.3%) with B-CLL or NHL had more than 10-fold higher levels of MDM2 gene expression than that observed in normal B cells. Immunohistochemical analysis confirmed MDM2 overexpression at the cellular protein level. MDM2 gene overexpression was found more frequently in patients with the low-grade type of lymphoma (56.5%) than in those with intermediate-/high-grade types (10.8%) (P = .001). Moreover, MDM2 overexpression was found significantly more frequently in patients at advanced clinical stages. Simultaneous analysis of p53 gene mutation showed that three patients had both MDM2 gene overexpression and p53 gene mutation. The results of the present study suggest that MDM2 gene overexpression may play an important role in the tumorigenicity and/or disease progression of CLL and low-grade lymphomas of B-cell origin.

Adult↗
PubMed1994

Src kinase tyrosine phosphorylates PTP1C, a protein tyrosine phosphatase containing Src homology-2 domains that down-regulates cell proliferation.

PTP1C is a non-transmembrane-type protein-tyrosine phosphatase and contains two Src homology-2 (SH2) domains. PTP1C was tyrosine-phosphorylated in SR-3Y1, a v-Src-transformed rat fibroblast cell line. Tyrosine phosphorylation of PTP1C was more prominent when PTP1C was overexpressed in SR-3Y1 cells. PTP1C lacking SH2 domains was also tyrosine-phosphorylated in SR-3Y1 cells, indicating that SH2 domains of PTP1C are not required for tyrosine phosphorylation of PTP1C by v-Src kinase. V-Src kinase catalyzed the phosphorylation of PTP1C in a cell-free system. The growth rate of SR-3Y1 was reduced by the expression of PTP1C in the low-serum medium. Furthermore, overexpression of PTP1C suppressed the anchorage-independent colony formation of SR-3Y1 cells. These results suggest that PTP1C is a direct target for v-Src kinase and may down-regulate the proliferation of cells.

Animals↗
PubMed1994

Down-regulation of mitochondrial gene expression by the anti-tumor arotinoid mofarotene (Ro 40-8757).

To understand the mechanism of action of the antitumor arotinoid mofarotene (Ro 40-8757), differential screening of cDNA libraries with cDNA probes prepared from treated or untreated breast-cancer cells was performed. Several genes were identified that appeared to be regulated by mofarotene, including a mitochondrial gene encoding a subunit of NADH dehydrogenase (NDI). This gene was down-regulated in the breast-cancer cell line MDA-MB-231 after treatment with the arotinoid for 3 to 6 hr. Down-regulation of NDI was detected in 2 other breast-carcinoma cell lines (ZR-75-I and MCF-7) and a pancreatic cancer cell line (BxPC3), but not in the normal fibroblast cell line Wi-38 or several other tumor cell lines. This effect was blocked by addition of cycloheximide to the medium. The retinoids, all-trans and 9-cis retinoic acids, did not affect the expression of NDI in MDA-MB-231 cells, demonstrating that mofarotene was not acting through the nuclear retinoic-acid receptors. In the estrogen-receptor-expressing breast-cancer line ZR-75-I, tamoxifen had no effect on NDI expression. The cytotoxic drugs doxorubicin, 5-FU and vincristine also had no effect on regulation of this gene. Two mitochondrial proteins encoded in the nucleus, ATPase beta subunit and mitochondrial transcription factor I, were not down-regulated by mofarotene. Addition of mofarotene to cells incubated in glucose-free medium led to their death. These results indicate that down-regulation of mitochondrial gene transcription is specific to mofarotene and may explain, in part, the anti-proliferative effects of this compound.

Antineoplastic Agents↗
PubMed1994

Block of Na+ channel by moricizine hydrochloride in isolated feline ventricular myocytes.

The effect of moricizine hydrochloride, a potent class I antiarrhythmic agent, on Na+ current (INa) of single feline ventricular myocytes were studied using whole cell patch clamp techniques. Moricizine inhibited INa in a concentration-dependent manner without altering the current-voltage relationship for INa. INa inhibition was expressed by the Hill equation with a Hill coefficient of 1.3 and dissociation constant of 105 microM in the resting state (holding potential = -140 mV). Moricizine 30 microM shifted the steady state inactivation curve for INa toward more negative potentials by 7.3 +/- 2.4 mV without causing significant changes in the slope factor. Recovery of INa from inactivation was retarded (time constant = 8 s) at a holding potential of -140 mV in the presence of 30 microM moricizine. When the start of INa block was studied in experiments using a double pulse protocol, moricizine reduced INa by only 4% after a 4-ms prepulse, but strongly inhibited it after prepulses longer than 200 ms. Intracellular application of 100 microM moricizine did not produce significant resting or use-dependent INa block. These results suggest that (1) moricizine blocks INa by binding to the Na+ channel with a 1:1 stoichiometry, (2) the drug has a higher affinity to the inactivated state than to the activated and resting states of the Na+ channel, (3) recovery kinetics of moricizine from Na+ channel inactivation, or drug dissociation observed during the transition from inactivated to resting state was relatively slow, (4) the drug binding site appeared to be located on the external side of the membrane.

Animals↗
PubMed1994

Genomic instability of microsatellite repeats and mutations of H-, K-, and N-ras, and p53 genes in renal cell carcinoma.

Thirty-six primary renal cell carcinoma samples and one metastatic lymph node DNA sample were examined for mutations of H-, K-, and N-ras and p53 genes, and genomic instability at (AC)n, (CA)n.(GT)n, and (TA)n.(GT)n repeats. No mutations were noted for H-, K-, and N-ras genes and only 2 of all the samples (5.6%) showed mutations at exon 8 of the p53 gene. Differences in unrelated microsatellites for tumor and normal DNA were detected in 9 (25.0%) of the cases examined. Somatic alterations in seven microsatellites, D3S1228, D3S643, D5S107, LPL5GT, D9S63, D17S261, and DCC, were found in 1 (2.8%), 3 (8.3%), 2 (5.7%), 5 (14.7%), 3 (8.3%), 3 (8.3%), and 3 (8.3%) cases, respectively. Five of 26 (19.2%) clear cell type and 4 of 10 (40.0%) non-clear cell type patients showed DNA instability. Two of 11 (18.2%) grade 1, 5 of 20 (25.0%) grade 2, and 2 of 5 (40.0%) grade 3 patients showed abnormal patterns. One of 2 (50.0%) stage pT1, 4 of 24 (16.7%) stage pT2, and 4 of 10 (40.0%) stage pT3 patients were shown to have microsatellite instability. In 4 of 9 alteration-positive cases (44.4%), mutations in multiple microsatellites were observed. Alterations in microsatellite instability may be more common in non-clear cell type, high-grade, and high-stage renal cell carcinoma patients.

Base Sequence↗
PubMed1994

[The usefulness of 201TlCl scintigraphy for the diagnosis of breast tumor].

The usefulness of 201TlCl SPECT (Tl SPECT) for the diagnosis of breast cancer was evaluated in 14 patients with various breast tumors (9 with invasive ductal carcinoma, 2 with fibroadenoma and 3 with benign process). These tumors ranged in size from 1.5 cm x 1.5 cm to 15.0 cm x 14.0 cm. Tl SPECT was carried out 2 hours after the intravenous injection of 201TlCl (185 MBq). For quantitative study, ROIs were set in the tumor (T), normal tissue of the opposite breast (B) and myocardium (M). Count ratios of T/B and T/M were calculated. Eight patients with breast cancer and a case of fibroadenoma showed intense accumulation of 201TlCl in the tumors. The T/B ratio was 1.20 +/- 0.68 and the T/M ratio was 0.68 +/- 0.31 in the 9 cases. Lymph node metastasis was detected in 2 of 6 cases that were confirmed at operation. No remarkable accumulation of 201TlCl was seen in 4 patients with benign process. One patient with benign tumor showed a false positive result. The rates of accuracy of mammography and ultrasonography for the same subjects were 82% and 84%, respectively. The results suggest that 201TlCl SPECT might be useful to assess breast cancer in cases in which the findings of other modalities are equivocal.

Adult↗
PubMed1994

Genomic instability of microsatellite repeats and its association with the evolution of chronic myelogenous leukemia.

Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor-suppressor genes. Investigation of genomic instability of microsatellites has indicated a new mechanism for human carcinogenesis in hereditary nonpolyposis colorectal cancer and sporadic cancer and this instability has been shown to be related to inherited predisposition to cancer. This study was conducted to determine whether such microsatellite instability is associated with the evolution of chronic myelogenous leukemia (CML) to the blast crisis. Nineteen CML patients clinically progressing from the chronic phase to accelerated phase or blast crisis and 20 other patients in the CML chronic phase were studied. By polymerase chain reaction assay, DNAs for genomic instability in five separate microsatellites in chromosome arms 5q (Mfd27), 17p (Mfd41), 18q (DCC), 3p (CI3-9), and 8p (LPL) were examined. Differences in unrelated microsatellites of chronic and blastic phase DNAs in 14 of 19 patients (73.7%) were demonstrated. Somatic instability in five microsatellites, Mfd27, Mfd41, DCC, CI3-9, and LPL, was detected in 2 of 19 (10.5%), 8 of 19 (42.1%), 11 of 19 (57.9%), 4 of 17 (23.5%), and 4 of 17 (23.5%) cases. In 10 of 19 cases (52.6%), genetic instability in at least two of five microsatellites was observed and was categorized as replication error (RER+) phenotype. CML evolution cases with myeloid, lymphoid, and mixed phenotypes and the blast crisis and accelerated phase showed somatic instability in a number of microsatellites. No alterations in leukemic cells at the chronic phase could be detected in any microsatellites. These data indicate instability of microsatellites (RER+) but not familial predisposition to possibly be a late genetic event in the evolution of CML to blast crisis. In the microsatellite of the DCC gene, complicated alterations in band patterns caused by instability as well as loss of heterozygosity (LOH) were observed in 13 of 19 cases (68.4%): instability in 9 cases, instability plus LOH in 2 cases, and only LOH in 2 cases. These highly frequent alterations in microsatellites, including instability and LOH, suggesting that secondary events due possibly to loss of fidelity in replication and repair machinery may be significantly associated with CML evolution.

Adult↗
PubMed1994

Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains.

PTP1C is a non-transmembrane protein-tyrosine phosphatase and contains two Src homology-2 (SH2) domains. Insulin stimulated the tyrosine phosphorylation of PTP1C in human 1M-9 lymphoblast cells, in rat H35 hepatoma cells and in Chinese hamster ovary cells over-expressing both insulin receptors and PTP1C. Insulin also stimulated the tyrosine phosphorylation of a mutant PTP1C lacking SH2 domains in Chinese hamster ovary cells, suggesting that the SH2 domains are not required for insulin-stimulated tyrosine phosphorylation of PTP1C. The insulin receptor tyrosine kinase catalyzed the tyrosine phosphorylation of PTP1C in a cell-free system. Peptide mapping of phosphorylated PTP1C showed that Tyr538 in the C-terminal region was phosphorylated in response to insulin. The tyrosine phosphorylation of PTP1C by the insulin receptor kinase increased phosphatase activity. Furthermore, PTP1C was shown to bind to autophosphorylated insulin receptors through its C-terminal region, but PTP1C did not bind to unphosphorylated receptors. These results suggest that PTP1C is a target protein for the insulin receptor tyrosine kinase and that the C-terminal region of PTP1C may function both in the regulation of phosphatase activity and in the association of PTP1C with autophosphorylated insulin receptors.

Amino Acid Sequence↗
PubMed1994

Expression of adult and fetal natural killer cell markers in sinonasal lymphomas.

The majority of sinonasal non-Hodgkin's lymphomas (NHLs) are thought to originate from T-cell lineage. However, they often express natural killer (NK)-cell markers so that their origin still remains obscure. In this study, cell type of sinonasal NHLs were characterized by immunohistochemical and Southern blot analyses. We examined nine patients with sinonasal NHL. Six patients with tonsillar or pharyngeal non-B-cell lymphomas served as a control group. Immunohistochemical study showed that all nine cases of sinonasal NHL were CD56+CD2+, whereas controls were CD56-CD2+. According to the rearrangement of T-cell receptors (TCRs) and expression of CD3 markers, the sinonasal NHL cases were classified into three groups: TCR-CD56(Leu-19)+CD3(Leu4)- NHL (three patients), TCR-CD56+CD3+ NHL (five patients), and TCR+CD56+CD3+ NHL (one patient). In contrast, control patients' NHLs were TCR+CD56-CD3+. These results imply that eight cases of TCR-CD56+ sinonasal NHL are of NK-cell lineage. Among these eight cases, TCR-CD56+CD3+ cases (five of eight patients) were rather similar to the phenotype of fetal NK cells. From these results, the majority of sinonasal NHLs seem to originate from varying maturation stages of NK-cell lineage.

Adult↗
PubMed1994

Identification of the 23 kDa subunit of tau protein kinase II as a putative activator of cdk5 in bovine brain.

Tau protein kinase II (TPKII) was reported previously to be composed of a neuron-rich cdc2-related kinase (PSSALRE/cdk5) and 23 kDa subunit. Here we show that the 23 kDa subunit is a putative activator for the kinase activity. Amino acid sequence analysis revealed that the protein was novel and included a partial similarity of amino acids to a cyclin box important for the interaction with cdc2-related kinase. These results suggest that the 23 kDa subunit, but not cyclin, activates cdk5 in neuronal cells, which no longer exhibit cell cycling but are terminally differentiated cells.

Amino Acid Sequence↗
PubMed1994

Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and its expression in gastrointestinal cancers.

To determine the expression of various protein-tyrosine phosphatases (PTPs) in human gastric cancers, cDNAs encoding conserved PTP domains were amplified by reverse transcriptase polymerase chain reaction from KATO-III cell mRNA and sequenced. Among 72 polymerase chain reaction clones, one of the cDNA sequences encoded a novel potential PTP (stomach cancer-associated PTP, SAP-1). The full length (3.9 kilobases) of the SAP-1 cDNA was further isolated from the KATO-III cell cDNA library and the WiDr cell cDNA library. The predicted amino acid sequence of the SAP-1 cDNA showed that mature SAP-1 consisted of 1093 amino acids and a transmembrane-type PTP, which possessed a single PTP-conserved domain in the cytoplasmic region. The extracellular region of SAP-1 consisted of eight fibronectin type III-like structure repeats and contained multiple N-glycosylation sites. These data suggest that SAP-1 is structurally similar to HPTP beta and that SAP-1 and HPTP beta represent a subfamily of transmembrane-type PTPs. SAP-1 was mainly expressed in brain and liver and at a lower level in heart and stomach as a 4.2-kilobase mRNA, but it was not detected in pancreas or colon. In contrast, among cancer cell lines tested, SAP-1 was highly expressed in pancreatic and colorectal cancer cells. The bacterially expressed SAP-1 fusion protein had tyrosine-specific phosphatase activity. Immunoblotting with anti-SAP-1 antibody showed that SAP-1 is a 200-kDa protein. In addition, transient transfection of SAP-1 cDNA to COS cells resulted in the predominant expression of a 200-kDa protein recognized by anti-SAP-1 antibody. SAP-1 is mapped to chromosome 19 region q13.4 and might be related to carcinoembryonic antigen mapped to 19q13.2.

Amino Acid Sequence↗
PubMed1994

Culture of a prostatic cell line in basement membrane gels results in an enhancement of malignant properties and constitutive alterations in gene expression.

Interaction of a transformed rat prostate epithelial cell (NbMC-2) with basement membrane gels (Matrigel) has been evaluated using a long-term matrix culture system. NbMC-2 cells, and single-cell clonal derivatives, formed spheroidal multicellular structures (aggregates) on Matrigel surfaces and were weakly invasive or noninvasive during a 1 week period. During subsequent 2-4 week periods, invasive cells originating from the aggregates and exhibiting a fusiform morphology became evident and increased in number in the matrix cultures. This biphasic pattern of behavior did not occur on laminin, type I or type IV collagen, or fibronectin substrates, but it did occur on Matrigel in serum-free medium. Characterization of sublines enriched in fusiform cells indicated that they maintained their distinct morphology with continuous culture. Further, they exhibited significantly greater invasive potential, saturation density, and random motility (chemokinesis) than the parent cell line. Steady-state levels of fibronectin mRNA were highly elevated in the fusiform variants, demonstrating a constitutive alteration in patterns of gene expression coinciding with the altered morphology. These results indicate that clonal NbMC-2 cells differentiate at a reproducible frequency into a more aggressive cell type in response to culture in the basement membrane-like matrix. The altered phenotypic properties appear to be stable since they can be inherited by daughter cells and because they are evident in the absence of matrix. These observations suggest a cell-specific mechanism for promotion of malignant growth by matrix-mediated induction of novel cell properties.

Animals↗