Induction of unscheduled DNA synthesis by half-nucleus irradiation of HeLa cells with an UV-microbeam in combination with hydroxyurea treatment.
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Biomedical subjects
Publications and source records attributed to R Yatani.
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A series of 25 primary prostate cancers in Japanese were screened for loss of heterozygosity and microsatellite instability using twelve microsatellite markers containing APC, DCC, TP53, BRCA1, and BRCA2. Frequent loss of heterozygosity was observed for D8S201 (48%), LPL (48%), and DCC (26%). In contrast, the incidence did not exceed 15% at BRCA1 and BRCA2 loci. Microsatellite instability was observed in 28% of stage B, C, and D cancers. These data suggest that microsatellite instability and loss of unidentified genes on chromosome 8p may be involved in carcinogenesis of the prostate; however, BRCA1 and BRCA2 may not be largely involved in the development of prostate cancer in the Japanese population.
While pancreaticobiliary maljunctions (PBM) are clearly associated with biliary tract tumor development, little is known about their molecular mechanisms. This study was conducted to assess the contributions of microsatellite instability (MSI), mutations of transforming growth factor type II receptor (TGF-beta RII) and insulin-like growth factor type II receptor (IGF RII) genes and loss of heterozygosity (LOH) of hMSH2 and hMLH1 in 23 biliary tract tumors using PCR methods. MSI was detected by 13 markers in 16/23 samples (69.6%). TGF-beta RII mutations were detected in eight of these (50%), and of the IGF IIR gene in two (12.5%). LOH was detected in 4/16 (25%) at the hMSH2 locus, and 2/16 (12.5%) at the hMLH1 locus. No TGF-beta RII mutations or LOH of hMSH2 and hMLH1 were detected in MSI-negative samples. These findings suggest that MSI plays an important role in carcinogenesis of the biliary tract epithelium with PBM cases.
Vitamin D receptor gene (VDR) polymorphisms have been reported to be related to prostate cancer risk in the USA. We analyzed the distribution of TaqI RFLP and poly(A) of VDR in 100 prostate cancer patients and 202 urological controls. Among the control, 79.2% were homozygous (TT) for the absence of a TaqI RFLP, while 17.8% were heterozygous (Tt) and 3.0% homozygous (tt) for its presence. The distribution was almost the same in the cancer group; 80% were homozygous TT, 18% heterozygous Tt, and 2.0% homozygous tt. Polymorphism of poly(A) sizes was categorized as a long allele (> or = 18 As) and a short allele (< 18 As). The distribution did not vary between the cancer and control groups; 80, 79.2% were LL, 18, 17.8% LS and 2.0, 3.0% SS, respectively. These results showed no significant association of two VDR polymorphisms with prostate cancer risk, however a different distribution of VDR polymorphisms between Japanese and non-Japanese men.
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Prostate cancer was diagnosed in life among 274 of 8006 (3.6%) members of a cohort of Japanese men in Hawaii between 1965 and 1990. Only 55 (20%) of the 274 diagnosed cases died with prostate cancer, and they accounted for only 2% of the 2893 deaths that occurred among the men during this period. None of the 61 men whose tumor was found incidentally to a transurethral resection died as a result of this cancer, while it was the cause of death of 9 of 106 (8%) men with clinical cancer localized to the prostate. Forty-six of the 107 (43%) men with more extensive disease at the time of diagnosis died from prostate cancer. Step sectioning of the prostate identified prostate cancer in 80 of 293 (27%) autopsied Hawaii Japanese men who died after 50 years of age, reaching a frequency of 63% (10 of 16) among men over 80 years of age. The volume of 48 (60%) of these cancers was less than 150 mm3. These small tumors would probably not have been discovered in a screening program. Tumors larger than 1000 mm3 would probably be discovered using modern diagnostic procedures but were found in only 13 (4.4%) of the autopsied men. It is likely that a screening program to detect and treat such large, unsuspected tumors in this population would have had little impact upon the already low proportion of deaths due to prostate cancer among these Japanese men.
A case of acinar cell carcinoma of the pancreas was diagnosed by fine needle aspiration cytology during surgery. The cytologic characteristics of this neoplasm are described. Electron microscopy disclosed numerous zymogen granules in the tumor while histochemistry demonstrated the presence of elastase-1. Serum elastase-1 levels were markedly elevated. The cytologic differential diagnosis of pancreatic tumors is discussed.
Two hundred and eighty four bone marrow sections obtained at autopsy from the United States and 304 from Japan were evaluated. Patients who died of malignancy were excluded from the study. There was a significant increase in the incidence of lymphoid aggregates in the bone marrow with increasing age. After the age of 40, the incidence increased to 26.5 percent and 13.8 percent in the USA and Japan, respectively. After age 70, the frequencies reached 45.2 percent (USA) and 18.9 percent (Japan). There was a significant difference in the frequency of lymphoid aggregates between Americans and Japanese, and between females and males. The frequencies are 41.5 percent (females) and 35.1 percent (males) in the USA, and 18.7 percent (females) and 15.2 percent (males) in Japan. Bone marrow necrosis is more frequent in the old age group. The average frequency of marrow necrosis is 38 percent (USA) and 43.1 percent (Japan). Bone marrow fibrosis also increased with increasing age, reaching 16.1 percent (USA) and 19.5 percent (Japan) after the age of 70.
Significant elevation in the peripheral granulocyte count (more than 20,000) and the absence of overt infection are commonly associated with a wide variety of human neoplasms. Robinson demonstrated a dose correlation between the amount of the serum and urine levels of granulocyte-macrophage colony stimulating factor (GM-CSF) and the peripheral neutrophil counts. In vivo assessment of hematopoietic activities induced by GM-CSF has not been explored owing to the complexity, time consuming, and ill-defined specific results. This experiment is designed to understand the pathophysiology of the hematopoiesis induced by GM-CSF released from tumor of Chinese Hamster Ovary (CHO) cell line in nude mice. To our knowledge, this experiment is the first one to describe detailed histopathological changes induced by GM-CSF. Three to five months old nude mice inoculated subcutaneously with the CHO cell line developed local tumor with or without metastasis and hepatosplenomegaly. Active granulopoiesis is demonstrated in bone marrow, spleen, liver, and some of the tumors. Lymph nodes show histiocytic proliferation, however, without active granulopoiesis. Peripheral granulocytosis seems to be not linearly but step-wisely coordinated with tumor growth.
Bone marrow necrosis is a poorly understood and frequently an unrecognized finding in routine bone marrow biopsies. Previous reports indicate the incidence of bone marrow necrosis ranges from 0.5 percent (rare) to approximately one-third of all bone marrow biopsies examined. Our studies indicate that the presence of bone marrow necrosis depends on the clinical condition of the patient. Overall, our incidence of bone marrow necrosis was 37 percent of the bone marrow biopsies examined. Of these, 26.4 percent was mild. 7.5 percent moderate, and 3.1 percent severe necrosis. The mechanism in most cases had an identifiable underlying etiology such as a malignancy, or vascular or cytotoxic damage, with a small percentage being unexplained. Bone marrow necrosis is seen across a wide range of conditions, including sickle cell diseases, AIDS, leukemia, lymphoma, metastatic carcinoma, anemia, sepsis, and other systemic diseases. Patients at the extremes of age, less than 20 years and greater than 70 years, usually demonstrate only small foci of necrosis (Grade I). Moderate (Grade II) and severe (Grade III) bone marrow necrosis are often associated with life threatening illnesses, with most of these being hematologic malignancies or bone marrow metastases. The prognosis associated with bone marrow necrosis seems to be dependent on the underlying primary clinical condition regardless of the degree of necrosis observed.
To evaluate a possible correlation between tissue hormone levels and the development of latent prostatic carcinoma, levels of testosterone, estradiol, and prolactin were measured in homogenates of prostates by radioimmunoassay. One hundred and thirteen prostates obtained at autopsy from males over age 50 were morphologically classified into three groups; benign prostates, prostates with latent well differentiated type carcinoma (LWTC), and prostates with latent moderately or poorly differentiated type carcinoma (LMPTC). As detected by double antibody radioimmunoassay, tissue prolactin levels were statistically elevated (P less than 0.05) in prostates classified as LMPTC compared to benign prostates only. No statistical differences were noted for prostatic tissue levels for testosterone and estradiol in the three groups. Results suggest the possibility that prolactin may relate to the promotion and/or manifestation of prostatic carcinoma at the tissue level.
Prostates obtained at autopsy from five different ethnic groups were serially step-sectioned and examined microscopically using identical techniques and diagnostic criteria. The groups consisted of African-American and white males from the United States of America, Japanese immigrants in Hawaii, and Japanese men in Japan. The prostates were collected between 1965 and 1979. The fifth group consisted of newly collected prostates from indigenous Japanese between 1982 and 1986. The frequency of latent prostatic carcinoma from men under 50 years of age was compared to each other and with those from men over 50 years of age. Latent carcinoma was not found in men between 30 and 39 years old in any groups except indigenous Japanese men (6%) who died from 1982 to 1986. The frequency of latent carcinoma in the patients in fifth decade varied from 0 to 20%. Latent tumor was not found in the African-Americans in the fifth decade. There was an age-dependent increase in prostate cancer in all groups. The Japanese prostates from 1982 to 1986 had a higher rate of latent cancer than the ones from 1965 to 1979 in each decade. International comparison of the latent prostatic carcinoma from the patients under 50 years of age showed similar tendency as those from over 50 years old, Japanese men had a marked increase in the frequency of latent prostate cancer from 1965-1979 to 1982-1986. These data suggest that the prevalence of prostate cancer may be increasing worldwide.