Splenosacral sinus after splenorrhaphy: case report.
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Abscess↗
Biomedical subjects
D Shibata
Publications and source records attributed to D Shibata.
Changes in the activity and mRNA of cinnamyl alcohol dehydrogenase during tracheary element differentiation in zinnia.
Changes in the enzymatic activity of cinnamyl alcohol dehydrogenase (CAD) and in the expression of a gene for CAD during tracheary element (TE) differentiation were investigated in cultures of single cells isolated from the mesophyll of zinnia (Zinnia elegans). In cultures in which TE differentiation was induced (TE-inductive cultures), CAD activity increased from h 36 after the start of culture (12 h before the start of thickening of the secondary cell wall) and peaked at h 72, when lignin was actively being deposited. In control cultures in which TE differentiation was not induced, CAD activity remained at a very low level for 5 d. Some isoforms of CAD were detected only in the TE-inductive cultures by native gel electrophoresis and subsequent staining for CAD activity. A cDNA clone for CAD, ZCAD1, was isolated from Z. elegans using a cDNA clone for CAD from Aralia cordata as the probe. RNA gel-blot analysis revealed that in the TE-inductive cultures the level of ZCAD1 mRNA increased from h 36 and peaked at h 48 to 60. No such increases were observed in control cultures. These results indicated that both the gene expression and the activity of CAD are strictly regulated, in association with lignification, during TE differentiation in Z. elegans.
Alcohol Oxidoreductases↗
Molecular tumour clocks.
Multistep tumour progression predicts that cancer arises through a series of mutations and cell divisions. This process has been difficult to document in humans because direct physical observations over time are impractical. Phylogenetic approaches, properly translated to cancer, offer opportunities to unravel the occult historical trail of mutations and clonal expansions inherent to multistep progression. Microsatellite loci in mutator phenotype tumours can function as molecular tumour clocks because they acquire single repeat unit additions or deletions at high frequencies. Differences in the number of somatic microsatellite mutations may indicate their relative ages.
Biological Clocks↗
Intestinal stem cell division and genetic diversity. A computer and experimental analysis.
Somatic mutations are expected to arise with age. This process is accelerated in mice lacking the DNA mismatch repair gene Pms2. The distributions of microsatellite alleles present in small patches of normal Pms2 -/- intestines revealed a general increase in genetic diversity or the number of mutations with age. However, the patterns were complex with different distributions and variances present within a single mouse. Computer simulations indicate that the experimental data are consistent with mutation rates between 0.0020 and 0.0025 mutations per division, nonrandom cell death, and an effective population size of 20 or fewer cells. Small numbers of cells exacerbate the random accumulation of mutations expected of a stochastic mutation process. The computer simulations and experimental data are consistent with known patterns of intestinal development and renewal by small numbers of stem cells and demonstrate relatively high mutation rates in histologically normal epithelium. These findings provide background for the analysis of microsatellite mutations in normal and tumor tissue lacking mismatch repair and further support the hypothesis that microsatellite loci can function as molecular tumor clocks.
Adenosine Triphosphatases↗
Molecular tumor clocks and dynamic phenotype.
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Adenoma↗
Telomerase activity in normal and neoplastic breast.
Telomerase activity is detected in the majority of human tumors and provides a mechanism to escape from proliferative limitations due to telomere loss. Similar to other studies, telomerase activity was detected with a modified telomeric repeat amplification protocol in the majority (76%) of 49 human breast cancer specimens, including most (75%) ductal carcinoma in situ specimens. There were no correlations between telomerase activity and tumor stage or estrogen/progesterone receptor status. In four of seven invasive tumors, telomerase expression seemed to be heterogeneous because not all microdissected regions were telomerase positive. Low levels of telomerase activity were also detected in a minority (17%) of breast specimens from patients without evidence of cancer. These findings suggest that telomerase activation can occur early in breast cancer progression and may be periodically down-regulated during subsequent progression.
Biomarkers, Tumor↗
The DCC protein and prognosis in colorectal cancer.
BACKGROUND: Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma. METHODS: The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy. RESULTS: The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03). CONCLUSIONS: DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients.
Aged↗
Induction of a novel cytochrome P450 (CYP93 family) by methyl jasmonate in soybean suspension-cultured cells.
We isolated a cDNA encoding a novel cytochrome P450 (CYP93A1) from soybean suspension-cultured cells that had been treated with methyl jasmonate (MeJA). The amino acid sequence of the gene product had 30-40% identity with those of other plant P450s. The protein contained the heme-binding domain which is highly conserved among plant P450s. Transcription of the cytochrome P450 gene in soybean cells was induced by 30 microM MeJA even in the presence of cycloheximide, and reached maximum level 6 h after MeJA treatment. This is the first report of a plant cytochrome P450 gene whose transcription is induced by MeJA even without protein synthesis.
Acetates↗
High-dose chemotherapy and autologous bone marrow plus peripheral blood stem cell transplantation for patients with lymphoma or metastatic breast cancer: use of marker genes to investigate hematopoietic reconstitution in adults.
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Adult↗
Molecular cloning and characterization of a gene that encodes a MYC-related protein in Arabidopsis.
In plants, MYC-related proteins function as transcription factors involved in anthocyanin production and trichome development. We cloned a gene, Atmyc1, and its corresponding cDNA, that encodes for a MYC-related protein from Arabidopsis thaliana. The putative protein has a basic/helix-loop-helix motif at the C-terminus and a highly homologous region with that of the maize B/R family at the N-terminus. The promoter region of Atmyc1 contains a Sph box (CATGCATG) that is known as a cis-regulatory element conferring seed-specific expression. In fact, Atmyc1 transcripts were more abundant in developing seeds than in stems and leaves where trichomes are normally expressed. Restriction fragment length polymorphism mapping demonstrated that Atmyc1 is located on the upper region of chromosome 4, which clearly indicates that Atmyc1 is distinct from the ttg (transparent testa glabrous) locus that affects both trichome development and anthocyanin biosynthesis.
Amino Acid Sequence↗
Somatic microsatellite mutations as molecular tumor clocks.
Microsatellite (MS) mutations can potentially unravel the past of mutator phenotype tumors, with greater genetic diversity expected in older regions. Rapid clonal expansions of xenografts were characterized by relatively homogenous MS alleles, whereas greater diversity was observed in a colorectal cancer with the greatest variation in its adjacent adenoma. A subcutaneous lung cancer metastasis demonstrated diversity consistent with its one-month clinical duration and evidence of active mitosis during dormancy. The genetic legacy inherent to multistep tumorigenesis provides direct estimates of tumor ages, with up to thousands of cell divisions and high death rates necessary to yield the observed diversities. MS molecular tumor clocks have the unique potential to systematically reconstruct the early and occult evolution of individual human mutator phenotype tumors.
Adenocarcinoma↗
Characterization and mapping of Ds-GUS-T-DNA lines for targeted insertional mutagenesis.
The transposition patterns of the Ds-GUS transposon T-DNA in 23 independent single-copy lines have been characterized and the map positions of 10 of them on three of the five Arabidopsis chromosomes are reported. Using overexpressed Activator (Ac) elements as a transposase source, it was found that the primary determinant of transposition frequency is the insertion site of the Ac-T-DNA. Neither the structure of the transposon T-DNA nor, in most cases, its insertion site have a significant effect on transposition frequency. Both the frequency and timing of transposition are influenced by the parent through which the transposon and transposase T-DNAs are transmitted. Overall, nearly 75% of plants in which excision has occurred bear a reinserted element and very short-range transpositions predominate, underlining the advantage of using mapped transposons for insertional mutagenesis.
Arabidopsis↗
Loss of DNA mismatch repair: life in the fast lane?
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Adaptor Proteins, Signal Transducing↗
Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer.
The major objective of the study was to determine if the contrasting frequencies (1.5% vs. 22%) of progression of cervical intraepithelial neoplasia (CIN) 3 lesions to invasive cervical carcinoma in two groups of patients in a previously published study from New Zealand had a virologic basis. Archival tissues on which the original diagnosis of CIN 3 was made were examined. Paraffin sections of 81 CIN 3 lesions from each group were tested for the presence of human papillomavirus (HPV)-6, -11, -16, and -18 DNA sequences by a combination of in of in situ hybridization for viral transcripts and polymerase chain reaction for viral DNA. The virologic profiles of the two groups were similar; HPV-16 and HPV-18 were identified, respectively, in 62% and 6% of CIN 3 lesions of group 1 and in 60% and 2% of CIN 3 lesions of group 2. additional tissues were examined for 17 women of group 2, who progressed from CIN 3 invasive cancer. Progression to invasive cancer was not associated with infection with specific HPV types. It is concluded that the contrasting frequencies of progression to invasive carcinoma in two groups of New Zealand women were not attributable to differences in HPV type distribution in the original CIN 3 lesions of these two groups.
Adult↗
Telomerase activity is commonly detected in hereditary nonpolyposis colorectal cancers.
Telomerase activity can be detected in most human cancers. These findings are consistent with the telomere hypothesis, which predicts telomerase expression after a number of mitotic divisions to prevent the progressive and catastrophic loss of telomeres. However, telomerase is not detected in a minority of colorectal cancers suggesting either alternative mechanisms of immortalization or that their telomeres have not yet shortened sufficiently to require telomerase activity. Colorectal cancers arising in patients with hereditary nonpolyposis colorectal cancer (HNPCC) were examined for telomerase activity because compared to sporadic tumors, HNPCC tumors are less likely to pass a telomere threshold as they occur in younger patients and exhibit "accelerated" progression, perhaps because of their characteristic mutator phenotypes and losses of mismatch repair. Primary, colorectal cancers, 13 in HNPCC patients, and 37 sporadic tumors (17 with mutator phenotypes) were examined for telomerase activity by the TRAP (telomeric repeat amplification protocol) assay. The majority of colorectal cancers contained detectable telomerase activity regardless of underlying phenotype (77 percent of HNPCC; 81 percent of sporadic tumors, 88 percent with mutator phenotypes and 75 percent without mutator phenotypes). Therefore, telomerase expression appears to be commonly acquired in the progression of both mutator phenotype and sporadic colorectal cancers.
Aged↗
Effects of mutation and growth rates on patterns of microsatellite instability.
The detection of somatic microsatellite (MS) alterations in tumors is often interpreted as a sign of underlying genomic instability. However, it is unclear why the proportions of altered MS loci vary between different mutator phenotype tumors. We present a simple mathematical analysis that can account for some of these differences, recognizing that the mutations accumulated in a tumor reflect both its mutation rate and number of cell divisions. Only a small proportion of mutated MS loci are expected in tumors with normal or low mutation rates. In contrast, tumors with high mutation rates may or may not acquire mutations depending on the numbers of divisions that proceed the onset of the mutator phenotype. The majority of MS loci should accumulate mutations if high mutation rates are acquired early in tumor progression. Somatic MS mutations provide clues to both the mode and tempo of tumori-genesis.
Adult↗
Role of zidovudine antiretroviral therapy in the pathogenesis of acquired immunodeficiency syndrome-related lymphoma.
The role of zidovudine and other antiretroviral agents in the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphomas has been somewhat controversial. In an attempt to elucidate the precise role of antiretroviral agents in the subsequent development of AIDS-related lymphoma, we performed a population-based, case-control study of human immunodeficiency virus (HIV)-seropositive patients with intermediate- or high-grade lymphoma in Los Angeles County, California, in which information regarding use of antiretroviral medications was ascertained. Diagnostic biopsy material was reviewed to confirm intermediate-or high-grade lymphoma. A structured interview, conducted with all cases and controls, included information about use of zidovudine and other antiretroviral agents. A total of 112 HIV-infected homosexual/bisexual men with lymphoma were matched to 112 homosexual/bisexual men with asymptomatic HIV infection; 49 of the lymphoma cases were also matched to 49 additional controls with AIDS, as defined by conditions other than lymphoma. Positive histories of zidovudine use were reported by 44 (39%) lymphoma cases, 24 (21%) asymptomatic HIV controls, and 21 (42%) AIDS controls. The average duration of zidovudine use up to 12 months before lymphoma diagnosis was 19.0 +/- 13.0 months (mean +/- SD) for the lymphoma cases, 12.6 +/- 10.5 months for the asymptomatic controls, and 11.0 +/- 7.1 months for the AIDS controls. When comparing the 49 HIV-positive lymphoma cases with their 49 matched AIDS controls, all of whom were diagnosed with AIDS during the same time period, the matched relative odds of lymphoma associated with prior use of zidovudine was 0.43 (95% confidence interval [CI] = 0.17 to 1.12). In comparing all 112 lymphoma cases with 49 AIDS controls, the unmatched relative odds of lymphoma associated with zidovudine use was 0.93 (95% confidence interval = 0.47 to 1.83). One lymphoma case and no AIDS control cases had a history of didanosine use; no lymphoma case or AIDS control cases had taken zalcitabine. We conclude that zidovudine is not associated with an increased risk of development of lymphoma among HIV-infected homosexual or bisexual men.
Acquired Immunodeficiency Syndrome↗
Elevated antibody titers to Epstein-Barr virus prior to the diagnosis of Epstein-Barr-virus-associated gastric adenocarcinoma.
Epstein-Barr virus (EBV) has recently been identified in the tumor cells of patients with gastric carcinoma. We tested pre-morbid serum samples from a carefully monitored cohort of Japanese men in order to investigate the possibility that patients with EBV-associated gastric cancer represent a sub-set of individuals with long-standing difficulties in appropriately managing EBV infection. From a serum bank, we obtained 108 samples derived from 54 patients destined to develop gastric adenocarcinoma and 54 controls. Samples were tested under code for antibodies to EBV-capsid antigen, early antigen and nuclear antigen. Individuals who were positive for IgA antibodies against EBV viral-capsid antigen (VCA) and IgG antibodies against the R component of EBV early antigen were at a 3.9-fold and 1.9-fold excess risk of disease, respectively. Antibody titers to EBV VCA were significantly higher in those destined to get EBV-associated gastric cancer than those subsequently developing non-EBV-associated gastric cancer or age-and-gender-matched controls. These findings suggest that the inability to control EBV infection on a long-term basis exists many years prior to the development of EBV-associated gastric cancer, and that EBV may play an etiologic role in this sub-set of malignancies.
Adenocarcinoma↗