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Biomedical subjects

R Ueda

Publications and source records attributed to R Ueda.

At least 181 records · Page 10Linked to original sources
PubMed1996

Clinicopathologic study of PRAD1/cyclin D1 overexpressing lymphoma with special reference to mantle cell lymphoma. A distinct molecular pathologic entity.

Mantle cell lymphomas (MCLs) are frequently associated with the overexpression of PRAD1/cyclin D1, activated by 11q13 translocation and its molecular counterpart BCL-1 gene rearrangement. We recently described the correlation of positive nuclear staining using monoclonal antibody against a PRAD1/cyclin D1 product with mRNA overexpression in MCLs. In the present study, we immunohistochemically investigated the PRAD1/cyclin D1 protein in a large series of 334 lymphoproliferative disorders, including 39 cases of MCLs on paraffin sections. Based on the cyclin D1 positivity, CD5 expression, and the morphologic features of the tumor tissue, four groups of MCL-related lesions were identified among the B-cell lymphomas examined: 36 cases with cyclin D1 overexpression, 35 (95%) of which exhibited CD5-positivity and MCL-morphology (Group 1); four cases of lymphomas with MCL morphology and CD5 expression but lacking cyclin D1 overexpression (Group II); four cases of lymphomas without cyclin D1 overexpression and surface CD5 but that fall within the morphologic boundaries of MCLs (Group III); and 11 cases of CD5-positive diffuse large cell lymphomas without cyclin D1 overexpression (Group IV). The Group I cases demonstrated quite homogeneous clinicopathologic features identical to those of MCLs. This group showed a poor prognosis (11% had 5-year survival), which is highly contrasted with that of Group II (100%). Although the four groups of MCL-related lesions sometimes overlapped in their histologic or phenotypic spectrums, each appeared to show distinct clinicopathologic and prognostic profiles. Our study provides a basis for further clarification of the nature of the neoplasms of Groups II, III, and IV. Moreover, this comprehensive study may indicate that the overexpression of PRAD1/cyclin D1 is biologically essential to defining MCLs.

Aged↗
PubMed1996

Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers.

PURPOSE: This study was conducted to evaluate the prognostic significance of p53 abnormalities in primary, resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Methodologic validation of immunohistologic detection of p53 abnormalities in routine pathology sections was assessed using 31 lung cancer specimens for which p53 gene status was known from our previous molecular biologic studies. Applying the optimized cutoff value, we evaluated the prognostic significance of p53 abnormalities in an independent cohort of 208 NSCLC patients with complete follow-up data, whose resections were consecutively performed between January 1984 and December 1988. RESULTS: Immunohistologic detection of p53 abnormalities appeared to be reliable and showed approximately 90% concordance with the p53 gene status. Using the selected cutoff value of 10%, 46% of 208 NSCLCs showed p53 abnormalities. There was no relationship between p53 abnormalities and clinical outcome in the entire cohort, which represented all histologic subtypes of NSCLC (P = .58). Based on the reasoning that the influence of p53 abnormalities may have been obscured by distinct biologic roles depending on histologic subtypes, we also separately analyzed subsets of patients with adenocarcinomas (n = 100) and with squamous cell carcinomas (n = 88) and found that it may be a useful prognosticator only in adenocarcinoma patients (P = .04). CONCLUSION: p53 abnormalities are not a significant prognostic factor in primary, resected NSCLC when all histologic subtypes are combined, but may be a useful prognosticator for adenocarcinomas. Additional studies are warranted for further evaluation, specifically of adenocarcinomas.

Adenocarcinoma↗
PubMed1996

Evaluation of active oxygen effect on photosynthesis of Chlorella vulgaris.

The relationship between O2 and an active oxygen scavenging system in Chlorella vulgaris var.vulgaris (IAM C-534) was investigated. When Chlorella vulgaris was exposed to 2% O2, only traces of active oxygen scavenging enzymes were found. When the Chlorella vulgaris was treated with 20% or 50% O2, it was shown that the level of enzyme activity increased as the O2 concentration increased. An increase in enzyme activity was not found in any specific enzyme but in all of the enzymes, but the level of glutathione and ascorbate remained the same in all the cases. In addition, the photosynthetic efficiency also decreased as the concentration of O2 was increased. These results suggest that an O2 enriched environment can lead to an increase in the production of active oxygen species such as O2.- and H2O2 and to a decrease in the photosynthetic efficiency in Chlorella vulgaris. The hydroxyl radical (.OH) was detected directly in the Chlorella vulgaris suspension with a spin trapping reagent. It was also clear that the increase in the .OH intensity as the visible light intensity increased was unrelated to the O2 concentration. It was suggested that the conditions for producting .OH and the other active oxygen species were different, and that two types of oxygen stress should exist in the Chlorella vulgaris.

Antioxidants↗
PubMed1996

[Anemia in elderly patients with malignant tumors].

Complications, prognosis, and efficacy of treatments were retrospectively studied in elderly patients, some of whom had lung, stomach, colon, pancreatic, and liver cancers. Hemoglobin concentration and characteristics of erythrocytes were measured for up to sixty months. Eighty-eight patients died of cancer, and malignant tumors were detected before death in 57. The average survival periods were 11 months for patients with gastric cancer. 9 months for those with colon cancer, and 7 months for those with lung cancer. Malignancies of the digestive organs and lung were often detected in elderly patients with anemia. In elderly people who were without cancer for more than 78 months the hemoglobin concentration did not change significantly, but in those with a malignancy the hemoglobin concentration continuously decreased. Patients with colon cancer who were given blood transfusions survived longer than those who were not given the transfusions, but the same was not true of patients with gastric or lung cancers. Iron therapy, however, was generally effective in patients with malignant tumors of the gastrointestinal tract. Among those who were near death, the red cell distribution widths differed significantly between patients with different types of carcinomas, but differences in mean corpuscular hemoglobin and in mean corpuscular volume were not statistically significant. In conclusion, hemoglobin concentration and characteristics of erythrocytes should not be neglected in the diagnosis and treatment of cancers in the elderly.

Aged↗
PubMed1996

[Changes in erythrocyte structure and in platelets in elderly patients with disseminated intravascular coagulation].

We measured the platelet distribution width, the mean platelet volume, the volume percentage of platelets, and the platelet-to-large-cell ratio in 15 elderly patients with disseminated intravascular coagulation (DIC). Peripheral venous blood mixed with ehtylenediaminetetraacetic acid was analyzed with a Sysmex E-4000 analyzer. The underlying diseases were sepsis, pneumonia, pyelonephritis, and other inflammatory diseases. The mean duration of survival from the onset of DIC was 16.9 +/- 23.9 days. The distribution of red cell sizes before the onset of DIC did not differ significantly from that in patients without DIC, but fragmentation of erythrocytes on blood films was more common in the early stage of DIC (p < 0.01). Before the onset of DIC, the two groups did not differ significantly in the frequency of giant platelets on blood smears. At the onset of DIC, the platelet distribution width, the mean platelet volume, and the platelet-to-large-cell ratio were significantly higher than in patients without DIC. The concentration of glutamic-oxaloacetic transaminase and those of other serum enzymes did not change significantly, but the serum creatinine concentration and the blood urea nitrogen level increased as the platelet-to-large-cell ratio increased. No significant relation was evident between the levels of serum C-reactive protein and creatinine, between the platelet-to-large-cell ratio and the mean volume of red blood cells, or between the platelet-to-large-cell ratio and the distribution of red cell sizes. These data suggest that studies of platelets are more useful in the diagnosis of DIC at early stages of impaired organ function than are other indicators of inflammation such as the level of C-reactive protein.

Aged↗
PubMed1996

Expression of costimulatory molecules in human leukemias.

In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.

Antigens, CD↗
PubMed1996

Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia.

We have analyzed the frequency and clinical significance of the MLL gene rearrangements in 42 cases of infant acute leukemias; including 37 cases of acute lymphoblastic leukemia (ALL) and five cases of acute myeloid leukemia (AML). MLL gene rearrangements were found in 27 of the 37 ALL cases (73 percent), and in all five AML cases. Cytogenetic studies showed 11q23 abnormalities in 24 of 27 ALL cases with MLL gene rearrangements. MLL gene rearrangements were significantly correlated with absence of CD10 expression and poor prognosis, but not with age under 6 months, hyperleukocytosis, myeloid-associated antigen expression, or CNS leukemia. The 3-year overall survival rate for ALL cases with MLL gene rearrangements was 5.3 +/- 5.2 percent, compared with 88.9 +/- 10.5 percent for cases with germline MLL (P=0.0001). Absence of CD10 expression was also associated with poor prognosis (9.9 +/- 6.6 percent vs 85.7 +/- 13.2 percent, P = 0.0003). Of the five AML cases, three have remained alive for 27 months to 67 months. These findings suggest that infant ALL with MLL gene rearrangement is strongly associated with poor prognosis. We consider that infant ALL should be treated on different chemotherapy protocols according to the presence or absence of MLL gene rearrangement.

Antigens, CD↗
PubMed1996

[Myelodysplastic syndrome developed in a mother and her son whose bone marrow karyotype showed monosomy 7].

Two familial cases of myelodysplastic syndrome (MDS) are reported, one of whom had an abnormal karyotype of 45, XY, -7 (monosomy 7). Case 1 was a 60-year-old woman developed dizziness and nasal bleeding. She was treated with blood transfusion alone. About 11 months after diagnosis, she died of pneumonia. Case 2 was a 22 year-old man, who was the son of case 1, developed febrile disease because of recurrent skin and oral mucosa infections. He had a partial response to low-dose of cytarabine. Thirteen months after diagnosis, he died of severe pneumonia. Both cases were diagnosed as having refractory anemia with excess of blasts due to peripheral blood and bone marrow findings. Both patients had pancytopenia, erythroid hyperplasia in bone marrow, marked dyserythropoiesis, recurrent infectious diseases and severe pneumonia that resulted in death. These symptoms resembled to those reported for monosomy 7 syndrome. Familial MDS with monosomy 7 is rarely reported. These cases are of interest to investigate hereditary factors of MDS.

Adult↗
PubMed1996

Reduced expression of DNA topoisomerase II confers resistance to etoposide (VP-16) in small cell lung cancer cell lines established from a refractory tumor of a patient and by in vitro selection.

Cell lines, LC-5 and LC-172, were established from tumors of a small cell lung cancer patient prior to and after combination chemotherapy including etoposide (VP-16), when drug-resistant tumors developed in relapse. A VP-16-resistant cell line, LC-172/VP, was selected from the LC-172 cells in culture in multiple steps with VP-16. LC-172 cells were 3.5-fold resistant to VP-16 in growth inhibition, and 3.3-fold resistant to adriamycin as compared with LC-5 cells. LC-172/VP cells showed large differences in cross-resistance to topoisomerase II-targeting drugs such as VP-16, 200-fold, adriamycin, 10-fold, and MST-16, 4.3-fold; the cells were moderately refractory, 5.5-fold, to vincristine. VP-16 accumulation in the cells was similar in three cell lines. Topoisomerase II unknotting activity was reduced 7- to 10-fold in LC-172/VP and 1.5- to 2-fold in LC-172 cells compared with LC-5 cells, while relaxing activity of topoisomerase I appeared to be unchanged. Topoisomerase II protein was also reduced 5- to 10-fold in LC-172/VP and marginally so in LC-172 cells. Topoisomerase II alpha and II beta were each reduced 10-fold and 2-fold, respectively, in LC-172/VP cells, while they were both slightly decreased (-1.5-fold), respectively, in LC-172 cells compared with LC-5 cells. No apparent alteration in ATP requirement for catalytic activity and in sensitivity to VP-16 was observed for topoisomerase II from the three cell lines. Taken together, these results suggested that resistance to VP-16 in LC-172 and LC-172/VP is associated with a quantitative reduction in expression of topoisomerase II alpha of the parental type.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[A new strategy for treating small cell lung cancer].

Recent results from molecular biology have shown that lung cancer is characterized by multiple, sequentially appearing molecular changes that include genetic and epigenetic alterations. Among all types of lung cancer, small cell lung cancer (SCLC) is associated with the lowest rate of 5-year survival. In this symposium, we introduce our findings regarding the c-kit oncogenes in SCLC. We found that the c-kit gene is strongly expressed in SCLC. The c-kit gene was not expressed in normal bronchial epithelial cells, which indicates that this gene is abberantly transcribed in SCLC. In addition, c-kit-positive cases of SCLC showed autophosphorylation in response to recombinant human stem cell factor. Furthermore, adding rh stem cell factor of SCLC cell lines induced a significant chemotactic response and moderate in vitro cell growth. These results strongly suggest that abnormal expression of the c-kit gene may be involved in the pathogenesis of SCLC by autocrine/paracrine stimulation via the c-kit/SCF signal pathway. To overcome drug resistance, we assessed the efficacy of a chimeric toxin targeted to c-kit receptors.

Carcinoma, Small Cell↗
PubMed1996

Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria.

Deficiency of dihydropyrimidine dehydrogenase or dihydropyrimidinase, enzymes that catalyze the breakdown of pyrimidine chemotherapy agents such as 5-fluorouracil, may cause serious adverse reactions to these agents. We attempted to establish the reference range for urinary pyrimidines in adults to detect individuals with abnormal pyrimidine metabolism. We analyzed urinary pyrimidine levels in 1133 adults to establish a reference range for persons ages 20 years or older. Urinary dihydrouracil and uracil levels were determined by high-performance liquid chromatography with column switching. The reference range obtained was found to be 0-59.3 micromol/g creatinine for dihydrouracil and 0-129.8 micromol/g creatinine for uracil. In addition, an asymptomatic man with suspected dihydropyrimidinase deficiency was detected on the basis of dihydropyrimidinuria. Although only three cases of this disease have been found worldwide, including one infant reported previously by our group, it may not be so rare as has been thought. In this man, a 10 mg/kg oral uracil loading test yielded a peak blood dihydrouracil level of 192.1 micromol/liter and a peak uracil level of 67.8 micromol/liter. Eight h after loading, the uracil level was still 11.1 micromol/liter, about 17 times that in healthy subjects. Additional research on dihydropyrimininase deficiency may help to prevent adverse reactions to pyrimidine chemotherapy agents in susceptible individuals.

Adult↗
PubMed1995

Cloning and expression of a murine cDNA homologous to the human RCK/P54, a lymphoma-linked chromosomal translocation junction gene on 11q23.

The RCK/P54 gene was previously isolated from the chromosome translocation breakpoint region on 11q23 of a human lymphoma cell line, RC-K8, with t(11;14)(q23;q32). It was found to encode a 472-483-amino-acid (aa) polypeptide belonging to an RNA helicase/translation initiation factor family. The aim of the present investigation was the isolation and comparative sequence analysis of the mouse RCK/P54 cDNA from a BALB/c spleen cDNA library. Sequence analysis revealed an open reading frame (ORF) predicting a polypeptide of 483 aa showing 97.7% identity to human RCK/p54. Northern analysis demonstrated a 7.5-kb signal in all tissues tested and in vitro translation analysis showed a 54-kDa polypeptide. These results indicate that both mouse and human RCK/P54 are highly conserved.

Amino Acid Sequence↗
PubMed1995

Distinct mutational spectrum of the p53 gene in lung cancers from Chinese women in Hong Kong.

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies to search for risk factors in carcinogenic events. The lung cancer incidence for females in Hong Kong is unusually high, ranking among the highest in the world despite a low percentage with a history of smoking. To gain insights into possible etiological risk factors responsible for this high incidence, we examined p53 mutations in 35 lung cancer specimens from Chinese females living in Hong Kong and compared them with 35 matched cases from Japanese women as well as previously reported p53 mutations in the world literature. p53 mutations in exons 5-8 were present in 20 and 31% of the Hong Kong and Japanese cases, respectively. Notably, single-base deletions within runs of identical bases were observed in 3 (43%) of the 7 mutations in the Hong Kong cases, in contrast to the absence of such mutations in the controls and the extreme scarcity in the literature, suggesting that distinct environmental and/or genetic factor(s) might be involved. Although the frequent occurrence of characteristic single-base deletions could be a reflection of mutator mutations leading to inefficient mismatch repair of slipped strand mispairings, none of the lung cancer specimens exhibited such microsatellite instabilities.

Adult↗
PubMed1995

Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors.

The murine Unp proto-oncogene encodes a nuclear ubiquitin protease whose overexpression leads to oncogenic transformation of NIH3T3 cells. We have cloned cDNAs originating from the human homolog of this gene, designated herein as Unph (Unp, human), and have used these cDNAs to map the gene to 3p21.3, a region frequently rearranged in human tumor cells. Unph mRNA levels are consistently elevated in small cell tumors and adenocarcinomas of the lung, suggesting a possible causative role for the gene in the neoplastic process.

3T3 Cells↗
PubMed1995

Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers.

Accumulating evidence suggests that deregulation of the insulin-like growth factor II (IGF2) and H19 genes at 11p15, due to loss of imprinting (LOI), plays a role in the oncogenesis of Wilms' tumors. We previously reported LOI of IGF2 in carcinomas of the lung, a common cancer of adults. We show here that LOI of H19 is also a frequent event in lung cancer development, and correlated with hypomethylation of the promoter region. Furthermore, the present study also revealed that overexpression of H19 is often associated with LOI of H19 in lung cancers retaining both parental alleles, showing a contrast to LOI in Wilms' tumors. Interestingly, in contrast to frequent LOI of the imprinted genes at 11p15, LOI was not observed for the remaining gene known to be imprinted in man, SNRPN at 15q12.

Adult↗
PubMed1995

canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila.

The canoemisty1 (cnomis1) mutation was isolated by virtue of its severe rough eye phenotype from approximately 500 fly lines, each harboring a single autosomal insertion of a P element (Bm delta w). Excision of the P element generated a lethal, null allele, cnomis10, together with many revertants with normal eye morphology. Ommatidia homozygous for cnomis10, produced in an otherwise wild-type eye by somatic recombination, typically contain a reduced number of outer photoreceptors. Some cnomis1 homozygous adults bear extra macrochaetes on the head, notum, humerus and/or scutellum. cnomis1 hemizygotes often show conspicuous wing phenotypes such as a notched blade and the loss of a cross vein. The sequence of cno cDNA clones isolated from an embryonic cDNA library revealed a long open reading frame that potentially encodes a 1893-amino-acid protein with the GLGF/DHR motif, a conserved sequence in Discs large, Dishevelled, and some other proteins associated with cellular junctions. Flies doubly mutant for cnomis1 and scabrous1 (sca1) and those for cnomis1 and the split (spl) allele of Notch (N) always have rumpled wings curved downward. The spl; cnomis1 double mutant flies also exhibit a "giant socket" phenotype. These phenotypes are rarely observed flies singly mutant for either cnomis1, sca1 or spl. The wing vein gaps caused by Abruptex1, a N allele producing an activated form of N protein, are dominantly suppressed by cnomis1. Heterozygosity for shaggy and myospheroid promotes formation of extra wing veins in cnomis1 homozygotes. The genetic interactions suggest that cno participates with members of the N pathway in regulating adhesive cell-cell interactions for the determination of cell fate.

Amino Acid Sequence↗
PubMed1995

In vivo occurrence of p16 (MTS1) and p15 (MTS2) alterations preferentially in non-small cell lung cancers.

Frequent homozygous deletions of the p16 (MTS1) gene encoding a cyclin-dependent kinase inhibitor were recently reported in various tumor cell lines including examples derived from lung cancers, but direct evidence for their occurrence in lung cancer patients has not been reported thus far. In the present study, alterations of p16 and/or p15, a p16-related cyclin-dependent kinase, were observed not only in lung cancer cell lines but also in the corresponding tumor specimens in vivo, excluding the possibility of in vitro artifacts. Interestingly, a clear specificity was also noted in terms of the affected histological subtype; i.e., only non-small cell lung cancers carried alterations (6 of 20 as compared to 0 of 20 small cell lung cancer cell lines).

Base Sequence↗