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Biomedical subjects

M Soda

Publications and source records attributed to M Soda.

At least 19 recordsLinked to original sources

Cancer incidence in children and young adults did not increase relative to parental exposure to atomic bombs.

We have examined whether parental exposure to atomic bomb radiation has led to increased cancer risks among the offspring. We studied 40,487 subjects born from May 1946 through December 1984 who were cancer-free in January 1958. One or both parents were in Hiroshima or Nagasaki at the time of the bombing and for childbirth. Using population-based tumor registry data we analyzed cancer incidence data from 1958 to 1997 by Cox regression models, and we examined the effects of both paternal and maternal irradiation with adjustment for city, sex, birth year, and migration. During follow-up, 575 solid tumor cases and 68 hematopoietic tumor cases were diagnosed. Median age at diagnosis was 39.7 years. Median doses were 143 millisierverts for 15,992 exposed (5+ millisierverts or unknown dose) fathers and 133 millisierverts for 10,066 exposed mothers. Cancer incidence was no higher for subjects with exposed parents than for the reference subjects (0-4 millisierverts), nor did the incidence rates increase with increasing dose. For 3568 subjects with two exposed parents, the adjusted risk ratio for all cancer was 0.97 (95% confidence interval 0.70-1.36). Because of the small number of cases, however, we cannot exclude an increase in cancer incidence at this time.

Adolescent↗

The effects of body mass index on age at menopause.

OBJECTIVE: We examined which of body mass index (BMI, kg/m(2)), serum cholesterol (mg/dl), or systolic blood pressure (SBP, mm Hg) affected age at natural menopause. DESIGN: A population-based follow-up program. METHODS: We determined the age at natural menopause in 1136 women followed biennially since their first examination in 1958-1959 through the 16th examination in 1988-1989. Four-hundred and ninety-three naturally menopausal women were classified into three groups by BMI, serum cholesterol and SBP measurement levels at age 40 or 41 y: the upper 25%, middle 50%, and lower 25%. We then studied whether there was a difference in age at menopause among the three groups thus classified. The 1136 natural menopausal women were also classified as early (n=454; 45-49 y at menopause (48.3+/-1.2 y)) or late (n=682; >or=50 y at menopause (52.3+/-1.6 y)) menopausal and compared for premenopausal trends in BMI, serum cholesterol and SBP in the early and late menopausal women by means of a longitudinal data analysis model. RESULTS: When women were classified into the three groups based on a BMI that was measured at 40 or 41 y, age at menopause in the upper 25% (50.4+/-2.8 y) was significantly higher (P<0.05) than that in the lower 25% (49.7+/-2.8 y). The entire premenopausal trend in BMI in late menopausal women shifted upward compared to that in early menopausal women. On the other hand, the premenopausal trend more than 4 y before menopause in serum cholesterol and the entire premenopausal trend in SBP in late menopausal women were identical to those in early menopausal women. CONCLUSION: Among the variables studied, only BMI is related to age at menopause, and the greater the BMI, the later the age at menopause.

Adult↗

An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin.

A putative G protein-coupled transmembrane polypeptide, named Pael receptor, was identified as an interacting protein with Parkin, a gene product responsible for autosomal recessive juvenile Parkinsonism (AR-JP). When overexpressed in cells, this receptor tends to become unfolded, insoluble, and ubiquitinated in vivo. The insoluble Pael receptor leads to unfolded protein-induced cell death. Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. Moreover, the insoluble form of Pael receptor accumulates in the brains of AR-JP patients. Here, we show that the unfolded Pael receptor is a substrate of Parkin, the accumulation of which may cause selective neuronal death in AR-JP.

Acetylcysteine↗

Mortality and cancer incidence among a population previously exposed to environmental cadmium.

OBJECTIVES: This paper evaluates the associations of previous exposure to environmental cadmium (Cd) and renal function with total mortality and cancer incidence. METHODS: The study population comprised 275 residents (aged 40-92 years at baseline) in a Cd-polluted area located on Tsushima Island, Nagasaki, Japan. In the study area, the dietary intake of Cd decreased because the soil of the Cd-polluted rice fields was replaced with new soil between 1980 and 1983. The mortality rate from 1982 to 1997 and cancer incidence from 1985 to 1996 were investigated. Standardized mortality and incidence ratios (SMR and SIR) were calculated by using regional reference rates. The associations of renal function and urinary Cd levels with total mortality and cancer incidence were evaluated with Cox regression models. RESULTS: The SMR for all subjects, and those with a urinary beta2-microglobulin (U-beta2M) concentration > or = 1,000 microg/g creatinine (Cr) and < 1,000 microg/g Cr was estimated at 90 [95% confidence interval (CI) 73-109], 138 (95% CI 101-183) and 66 (95% CI 49-87), respectively. After adjustment for age and other potential confounders, in men, serum beta2M (S-beta2M) (> or = 2.3 mg/l) and in women, serum Cr (> or = 21.2 mg/ 100 ml), relative clearance of beta2M (> or = 21%) and U-beta2M (> or = 1,000 microg/g Cr), were associated with a significantly increased risk of mortality, with hazard ratios exceeding 2.0. After further adjustment for log(U-beta2M), the rate ratio of deaths associated with, in men, increased S-beta2M was 2.53 (95% CI 0.97-6.65) and, in women, increased serum Cr (S-Cr) concentrations was 2.75 (95% CI 1.24-6.14). Urinary Cd concentrations (> or = 10 microg/g Cr) were not significantly associated with mortality. The overall SIR of all malignant neoplasms was 71 (95% CI 44-107). CONCLUSIONS: These findings suggest that renal tubule dysfunction and a reduced glomerular filtration rate are predictors of mortality among persons previously exposed to environmental Cd. However, the results also suggest that overall mortality rates in Cd-polluted areas are not necessarily increased, because of the low mortality among those with no, or only slight, signs of low-molecular weight proteinuria. Overall cancer incidence may not be increased among residents in Cd-polluted areas.

Adult↗

Effects of age at menopause on serum cholesterol, body mass index, and blood pressure.

Pre- and postmenopausal cholesterol (mg/dl), body mass index (BMI; kg/m(2)), and systolic blood pressure (SBP; mmHg) levels were compared in three age-at-time-of-menopause (ATM) groups to examine the relationship between the three risk factors and age ATM. Cholesterol, BMI, and SBP levels recorded 4 years prior to and 8 years after menopause were examined and increases in these risk factors between the two measurements were noted. The three age groups were: group A (n=49; age ATM [44+/-1]<45), group B (n=395; 45< or =age ATM [48+/-1]<50), and group C (n=578; age ATM [52+/-2]> or =50). Cholesterol levels in premenopausal groups A (169+/-31 mg/dl, 40 years) and B (174+/-31, 44 years) were lower than those in group C (179+/-30, 48 years) (0.05< or =P<0.1 and P<0.05). Because, the increases in cholesterol were greater in group A (41+/-28 mg/dl) than in groups B (32+/-28) and C (29+/-28) (0.05< or =P<0.1 and P<0.05), cholesterol levels were identical among groups despite age differences upon reaching the postmenopause phase: group A (210+/-34, 51 years), group B (206+/-35, 56 years) and group C (208+/-35, 60 years). BMI and SBP increases were not different in groups A, B, and C. Differences in BMI and SBP levels among groups in order of premenopausal age were still observed after menopause. These data suggest that the greater increase in cholesterol associated with early menopause may be related to a higher prevalence of ischemic heart disease (IHD) in younger menopausal women.

Aging↗

Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses.

Histological features of primary liver cancer among atomic-bomb survivors and their relationship to hepatitis B (HBV) and C viral (HCV) infections are of special interest because of the increased risk of liver cancer in persons exposed to ionizing radiation and the high and increasing liver cancer rates in Japan and elsewhere. We conducted a pathology review of liver cancers occurring from 1958 to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and Nagasaki residents. A panel of pathologists classified tumor histological types and defined accompanying cirrhotic changes of the liver. Archival tissue samples were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT) PCR was used to determine HCV status. We used unconditional logistic regression to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC) cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic changes occurred significantly more often among HCC than CC cases (76% in HCC and 6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV-positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV-positive (95% confidence interval: 1.1-20.5). No significant differences were found between HCC and CC cases in radiation exposures. The predominance of HCC in the atomic-bomb survivors follows the background liver cancer pattern in Japan. Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC with or without cirrhosis and are significantly less important in that of CC.

Aged↗

Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan.

The relation between fatty liver, detected by ultrasonography as a marker of visceral fat accumulation, and coronary risk factors was studied in 810 elderly men and 1,273 elderly women in Nagasaki, Japan from 1990 to 1992. The prevalence of fatty liver was 3.3% in the male and 3.8% in the female non-obese participants (BMI, body mass index < 26.0 kg/m2) and 21.6% in the male and 18.8% in the female obese participants (26.0 kg/m2 < or = BMI). Fatty liver was significantly (p < 0.01) related to hypercholesterolemia and hypertriglyceridemia in the men and to hypertension, hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and diabetes mellitus or impaired glucose tolerance (DM+IGT) in the women independent of age, obesity, smoking and drinking. Non-obesity with fatty liver, rather than obesity with or without fatty liver, had the highest odds ratio for hypertension and low-HDL cholesterol in the men and for hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and DM+IGT in the women. The prevalence of fatty liver is the same in elderly men and women, and fatty liver is an independent correlate of coronary risk factors in the elderly.

Aged↗

[Successful treatment of idiopathic pure red cell aplasia with antithymocyte globulin].

An 18-year-old woman was admitted to our hospital because of severe anemia on October 16, 1999. Laboratory data included hemoglobin 3.5 g/dl, reticulocytes 2,200/microliter, WBC 3,500/microliter, and Plt 38.5 x 10(4)/microliter. Bone marrow aspiration showed a normocellular marrow with severe erythroid hypoplasia, suggesting a diagnosis of pure red cell aplasia. Methylprednisolone pulse therapy was started on October 20, but there was no response. Administration of cyclosporine A (CyA; 400-450 mg) was begun on November 1, but again there was no response. Antithymocyte globulin (ATG; 800 mg/day for 5 days, 15 mg/kg) was started from December 1 in addition to prednisolone (60 mg/day) and CyA (450 mg/day). On day 7 of ATG therapy, the reticulocyte count began to increase, and reached a peak of 32.6 x 10(4)/microliter on day 20. The patient's hemoglobin level started to increase on day 13, and reached 8.5 g/dl on day 27. A complete response has been maintained up to the time of writing, and the hemoglobin level was 11.9 g/dl on December 14, 2000. This is the first detailed Japanese case report of successful treatment of pure red cell aplasia using ATG.

Adolescent↗

Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity.

Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations in the parkin gene. Parkin protein is characterized by a ubiquitin-like domain at its NH(2)-terminus and two RING finger motifs and an IBR (in between RING fingers) at its COOH terminus (RING-IBR-RING). Here, we show that Parkin is a RING-type E3 ubiquitin-protein ligase which binds to E2 ubiquitin-conjugating enzymes, including UbcH7 and UbcH8, through its RING-IBR-RING motif. Moreover, we found that unfolded protein stress induces up-regulation of both the mRNA and protein level of Parkin. Furthermore, overexpression of Parkin, but not a set of mutants without the E3 activity, specifically suppressed unfolded protein stress-induced cell death. These findings demonstrate that Parkin is an E3 enzyme and suggest that it is involved in the ubiquitination pathway for misfolded proteins derived from endoplasmic reticulum and contributes to protection from neurotoxicity induced by unfolded protein stresses.

Amino Acid Motifs↗

Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan.

The incidence of adult T-cell leukemia/lymphoma (ATL) and its impact on that of total non-Hodgkin lymphoma (NHL) were evaluated in Nagasaki, an area in southwestern Japan where human T-cell lymphotropic virus type I (HTLV-I) is endemic. The first study area comprised 4 towns located on the K Islands, which had a population of 26,870 in 1990. The overall HTLV-I seroprevalence estimated from the serologic survey of 18,485 subjects was 16.2%. By using the data from the Nagasaki Prefectural Cancer Registry (NPCR) and reviewing clinical and laboratory information, we identified 40 cases of ATL and 35 cases of other NHL diagnosed between 1985 and 1995. The crude annual incidence of ATL among 100,000 HTLV-I carriers aged 30 or older was estimated at 137.7 for men and 57.4 for women, with a significant sex difference after adjustment for age (rate ratio = 2.50, 95% confidence interval 1.32-4.73). The cumulative risk from 30 to 79 years of age was estimated at approximately 6.6% for men and 2.1% for women. Among the entire population, ATL accounted for 51 to 59% of the total NHL incidence, showing the strong impact of HTLV-I infection. The second study area comprised the whole of Nagasaki Prefecture (total population in 1990 = 1.56 million). Between 1985 and 1995, 989 cases of ATL and 1,745 cases of other NHL were registered in the NPCR. The world age-standardized annual incidence rate of ATL per 100,000 persons aged 30 or older was estimated at 10.5 for men and 6.0 for women, which accounted for approximately 37 to 41% of the total NHL incidence.

Adolescent↗

Birth cohort effects on incidence of lung cancers: a population-based study in Nagasaki, Japan.

Smoking prevalence remains high (around 60%) among Japanese males, but smoking initiation among males born in the 1930s decreased by approximately 10% due to economic difficulties following World War II. The present study was designed to examine whether this temporary decline in smoking initiation influenced the subsequent incidence of lung cancers, especially adenocarcinoma. Trends of lung cancer incidence by histological type in both sexes were investigated using data from the population-based cancer registry in Nagasaki, Japan, from 1986 through 1995. During this period, 5668 males and 2309 females were diagnosed as having lung cancer, and the overall incidence of lung cancers among both sexes remained stable. However, males aged 55 - 59 years showed a decrease in the age-specific incidence of adenocarcinoma and squamous-cell carcinoma (P < 0.05 and P < 0.01, respectively). In birth cohort analyses, the incidence of adenocarcinoma and squamous-cell carcinoma was lower in the 1935 - 1939 birth male cohort than in the successive cohorts. The incidence of lung cancers among females with low smoking prevalence did not change with birth cohort. The low smoking initiation among the 1935 - 1939 birth male cohort appeared to have resulted in a decreased incidence of adenocarcinoma and squamous cell carcinoma among middle-aged Japanese males. The present study suggests that smoking prevention has an effect in reducing the incidence of lung adenocarcinoma, as well as squamous-cell carcinoma, among smokers.

Adenocarcinoma↗

[A case of breast cancer with multiple organ metastases responding remarkably to combination therapy of CAF (cyclophosphamide, adriamycin and 5-FU), 5'-DFUR and MPA (medroxyprogesterone acetate)].

A 52-year-old woman complaining of breast tumor was diagnosed as having advanced breast cancer (T4bN1M1-Stage IV), with metastasis of multiple organs (lung, liver, mediastinal and unilateral axillary lymph nodes) after which she underwent tumorectomy. Postoperative adjuvant therapy was performed using combined chemoendocrine therapy (CAF + 5'-DFUR + MPA). Following the endocrine therapy, the metastatic lesions of the liver and lung had disappeared. The adverse effects were not remarkable. Complete remission was continued for 2 years and 3 months, and the patient enjoyed a favorable quality of life.

Antineoplastic Combined Chemotherapy Protocols↗

Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan.

The association between soya foods and breast cancer risk was investigated in a prospective study of 34759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969-1970 and/or in 1979-1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary breast cancer in 488989 person-years of observation. The risk for breast cancer was not significantly associated with consumption of soya foods: for tofu, relative risks adjusted for attained age, calendar period, city, age at time of bombings and radiation dose to the breast were 0.99 (95% CI 0.80-1.24) for consumption two to four times per week and 1.07 (0.78-1.47) for consumption five or more times per week, relative to consumption once a week or less; for miso soup, relative risks were 1.03 (0.81-1.31) for consumption two to four times per week and 0.87 (0.68-1.12) for consumption five or more times per week, relative to consumption once a week or less. These results were not materially altered by further adjustments for reproductive variables and were similar in women diagnosed before age 50 and at ages 50 and above. Among 17 other foods and drinks examined only dried fish (decrease in relative risk with increasing consumption) and pickled vegetables (higher relative risk with higher consumption) were significantly related to breast cancer risk; these associations were not prior hypotheses and, because of the large number of comparisons made, they may be due to chance.

Adult↗

Changes in bone mineral density after orchidectomy and hormone replacement therapy in individuals with androgen insensitivity syndrome.

Changes in bone mineral density (BMD) after orchidectomy and after hormone replacement therapy were reported in two patients with complete androgen insensitivity syndrome (AIS). Diagnosis of AIS was made by clinical features and confirmed by the presence of 46,XY karyotype and the presence of testis component in the removed gonads. BMD at the lumbar spine and at three sites of the femur was measured by dual energy X-ray absorptiometry (DXA). The Z scores of the lumbar spine BMD before orchidectomy were -0.8 and -3.1, confirming that patients with AIS have low BMD and that androgen plays an important role in bone mineralization in 46,XY individuals. Castration reduced BMD, but treatment with daily doses of 1.25 mg of conjugated oestrogen and 10 mg of medroxyprogesterone acetate increased BMD. These results indicate that both oestrogen and androgen play an important role in balancing BMD in men.

Adult↗

Human T-lymphotropic virus type-I infection, antibody titers and cause-specific mortality among atomic-bomb survivors.

There have been few longitudinal studies on the long-term health effects of human T-lymphotropic virus type-I (HTLV-I) infection. The authors performed a cohort study of HTLV-I infection and cause-specific mortality in 3,090 atomic-bomb survivors in Nagasaki, Japan, who were followed from 1985-1987 to 1995. The prevalence of HTLV-I seropositivity in men and women was 99/1,196 (8.3%) and 171/1,894 (9.0%), respectively. During a median follow-up of 8.9 years, 448 deaths occurred. There was one nonfatal case of adult T-cell leukemia/lymphoma (incidence rate = 0.46 cases/1,000 person-years; 95% confidence interval [CI] 0.01-2.6). After adjustment for sex, age and other potential confounders, significantly increased risk among HTLV-I carriers was observed for deaths from all causes (rate ratio [RR] = 1.41), all cancers (RR = 1.64), liver cancer (RR = 3.04), and heart diseases (RR = 2.22). The association of anti-HTLV-I seropositivity with mortality from all non-neoplastic diseases (RR = 1.40) and chronic liver diseases (RR = 5.03) was of borderline significance. Possible confounding by blood transfusions and hepatitis C/B (HCV/HBV) viral infections could not be precluded in this study. However, even after liver cancer and chronic liver diseases were excluded, mortality rate was still increased among HTLV-I carriers (RR = 1.32, 95% CI 0.99-1.78), especially among those with high antibody titers (RR = 1.56, 95% CI 0.99-2.46, P for trend = 0.04). These findings may support the idea that HTLV-I infection exerts adverse effects on mortality from causes other than adult T-cell leukemia/lymphoma. Further studies on confounding by HCV/HBV infections and the interaction between HCV/HBV and HTLV-I may be required to analyze the increased mortality from liver cancer and chronic liver diseases.

Adult↗

The long-term effect of menopause on postmenopausal bone loss in Japanese women: results from a prospective study.

The aim of this study was to elucidate perimenopausal bone loss in relation to menstrual conditions and to investigate the long-term effect of menopause on bone loss in aged women. The rate of change in bone mineral density (BMD) was measured twice at an exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine in 176 pre- and postmenopausal healthy women 41-65 years of age. Serum follicle-stimulating hormone, intact and N-fragment osteocalcin (OC), three types of vitamin D3, parathyroid hormone (PTH), and calcitonin were also determined. Women who exercised regularly or had anatomical changes at the lumbar spine were excluded from this study. The subjects were divided into eight groups based on their menstrual status and years since menopause. Annual bone loss at the lumbar spine of premenopausal women with regular menstruation was -0.2+/-1.9% (95% confidence interval, -0.9 approximately -0.4%) and was not statistically different from zero, while that of women with irregular menstruation or at menopausal transition was -2.1+/-3.4% (-3.4 approximately -0.8%), and -3.3+/-2.3% (-5.2 approximately -0.3%), respectively, and was significantly different from zero. Serum OC levels of women at menopausal transition were significantly higher than those of women with regular menstruation, suggesting that bone loss had commenced in these women. The rate of annual change in BMD of women who were menopausal for 1-3, 4-6, 10-12, and more than 13 years was -3.1+/-4.0% (-4.7 approximately -1.5%), -1.2+/-2.6% (-2.2 approximately -0.2%), -1.0+/-3.0% (-2.3 approximately -0.3%), and -2.3+/-2.1% (-3.7 approximately -1.0%), respectively, and was significantly less than zero. But the annual bone loss of women who were menopausal for 7-9 years was -1.5+/-2.6% (-3.0 approximately -0.1%) and was not statistically significant from zero. These results indicate that postmenopausal women lose BMD in two phases. The early bone loss is rapid and commences during irregular menstruation, then is attenuated within 6 years after the onset of menopause. The second bone loss commences after the attenuation of the first bone loss. Among bone metabolic hormones, intact PTH alone showed an age-related increase and was suggested as being a causal factor of bone loss in women who were menopausal for 13 years or more.

Absorptiometry, Photon↗

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/thymidine phosphorylase/platelet-derived endothelial cell growth factor and histological prognostic factor, and influence of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase activities and serum immunosuppressive acidic protein levels. A study group of oral anti-cancer drugs in Seiban/Tajima area].

PURPOSE: Among the pyrimidine nucleoside phosphorylases (PyNPase), thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, and is an enzyme which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor which was an antiogenetic factor, therefore. We think dThdPase may be a prognostic factor. METHODS: We investigated the possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, and examined influences of preoperative oral 5'-DFUR administration at a dose of 1,200 mg/body for 7 days on PyNPase activities and serum immunosuppressive acidic protein levels in patients with gastric cancer. RESULTS: Higher levels of PyNPase activities were especially observed in patients with v+ (p = 0.0161). PyNPase activities (p = 0.1668) and IAP (p = 0.0830) levels showed a decrease by 5'-DFUR administration. CONCLUSION: This study suggests that we must investigate in detail the possibility of PyNPase being prognostic factor, and 5'-DFUR administration may improve the prognosis of patients with gastric cancer.

Antineoplastic Agents↗