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Biomedical subjects

T Hirohata

Publications and source records attributed to T Hirohata.

At least 37 records · Page 2Linked to original sources

The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene.

We examined the relationship between aryl hydrocarbon hydroxylase (AHH) and the frequency of a MspI mutation in the 3'-flanking region of cytochrome P450 (CYP) 1A1 (MspI polymorphism) and another mutation in exon 7 (Ile-Val polymorphism) in 84 healthy male subjects in Fukuoka, Japan. AHH inducibility (3-methylcholanthrene (MC)-induced AHH activity/non-induced AHH activity) was correlated with the MspI polymorphism (P < 0.0001) and age class (P = 0.015), whereas no correlation was found for the Ile-Val polymorphism (P = 0.509). Age-adjusted AHH inducibility (mean +/- SE) of the predominant homozygote (genotype A), the heterozygote (genotype B) and a homozygote rare allele (genotype C) genotypes was 4.89 +/- 0.36, 4.82 +/- 0.29 and 13.61 +/- 1.44, respectively. The genotype C showed much higher AHH inducibility than genotypes A and B (P < 0.001), while no significant difference was observed between genotypes A and B. Non-induced AHH activity was also correlated with these polymorphisms. The AHH activity of a homozygous mutant Val/Val genotype (0.076 +/- 0.010 pmol/min/10(6) cells) was significantly higher (P < 0.05) than that of the wild-type homozygous Ile/Ile (0.044 +/- 0.004 pmol/min/10(6) cells) and heterozygous Ile/Val (0.047 +/- 0.007 pmol/min/10(6) cells) genotypes. Our study suggests that the genotypes C and Val/Val, which are more frequent in smoking-related lung cancer, are closely related with high AHH inducibility and high non-induced AHH activity, respectively. Thus, the positive relationship between AHH inducibility and lung cancer is supported by our study. If our results are confirmed and the assessment of genotype becomes feasible on a population basis, identification of smokers who have genetically high susceptibility to lung cancer (genotype C or Val/Val) may become important for the prevention of lung cancer.

Adult↗

Second primary neoplasms in thyroid cancer patients.

To determine risk patterns for second primary neoplasms after the occurrence of thyroid cancer, we conducted a retrospective cohort study of 3321 thyroid cancer patients who were operated and histologically confirmed at the Noguchi Thyroid Clinic and Hospital Foundation between 1946 and 1985. They were followed from the date of operation through the end of 1990 with an observation period from 45 to 5 years. The average observation period of the patients was 13.4 years and the follow-up rate reached 98%. The standardized mortality ratio (SMR) was computed to assess possible risk increase by cancer site. In this computation, the time period less than 5 years after operation was omitted to reduce the influence of deaths related to the original thyroid cancer. A total of 103 deaths from malignant neoplasms other than thyroid cancer were observed during this time period (SMR = 1.6, 95% confidence interval [CI] = 1.3-2.0). Analyses of site-specific cancer mortality revealed significantly elevated risks for the central nervous system (SMR = 16.1, CI = 5.2-37.6) and respiratory organs (SMR = 2.6, CI = 1.5-4.1). Based on a review of available medical records with histological findings, we concluded that the risk increases for these sites were most likely to be attributable to second primary neoplasms. Whether or not the patients had received radiotherapy was not significantly associated with elevated risk. Further investigations are needed to clarify the risk factors responsible for the above findings.

Adolescent↗

Effect of surgery on gonadal function of premenopausal women with pituitary adenomas other than prolactinomas.

The effects of surgery on pituitary-gonadal function were investigated in women with pituitary adenomas other than prolactinomas. The subjects were 46 women of premenopausal age with a pituitary adenoma. Twenty tumors were GH producing, 19 were nonfunctioning, and 7 were adrenocorticotropin producing adenomas. The surgery was performed mainly via the transsphenoidal route, with the aim of eradicating the tumor and preserving pituitary function. The menstrual cycle was preserved postoperatively in 9 out of 10 (90%) patients with regular preoperative menstruation. Menstrual disturbance was seen in 36 (78.3%) cases preoperatively. The causative factors for menstrual disturbance were gonadotropin impairment and hyperprolactinemia in GH producing and nonfunctioning adenoma. Excessive hormonal secretion itself is a major causative factor for menstrual disturbance in GH and ACTH producing adenoma. Regular menstruation was restored following surgery in 20 out of 36 (55.6%) patients with menstrual problems. The predicting factors for postoperative recovery of menstruation are: size of adenoma less than 40 mm, period of amenorrhea less than 5 years, and preoperatively preserved gonadotropin secretion. In addition, preoperative hyperprolactinemia was also a predicting factor in women with nonfunctioning adenoma. Thus, even in patients with pituitary adenomas other than prolactinoma, the restoration of menstruation is highly achievable when surgery is performed with attention to preserving pituitary function.

Adenoma↗

Effects of surgery on testosterone secretion in male patients with pituitary adenomas.

The purpose of this study was to assess the effect of surgery on gonadal function in 42 male patients with pituitary adenomas Gonadal functions were evaluated by measuring total serum testosterone concentrations pre- and postoperatively. The subjects of the study were 20 patients with GH secreting adenoma, 7 patients with prolactinoma and 15 patients with nonfunctioning (NF) adenoma. Their ages ranged from 18 to 60 years (mean +/- SEM, 41 +/- 1.9). The serum testosterone concentration was low at less than 300 ng/dl preoperatively in 14 of 20 patients (70%) with GH producing adenoma, 6 of 7 patients (86%) with prolactinoma, and 7 of 15 patients (47%) with NF adenoma. Postoperatively, the total serum testosterone concentration was normalized in 9 of 14 patients (64%) with GH producing adenoma, one of 6 patients (17%) with prolactinoma, and 5 of 7 patients (71%) with NF adenoma. The normalization of serum GH and prolactin concentrations is indispensable for the restoration of gonadal function. It is very important to preserve the normal preoperative gonadotropin secretion by means of gentle surgery.

Adenoma↗

Epidemiological studies in Japan.

The present article provides an overview of epidemiological studies in Japan. The origin of modern epidemiology of Japan can be traced back into the late 19th century. Baron K. Takaki at that time made brilliant epidemiological studies on beriberi and was thus able to eradicate the disease long before vitamin B1 deficiency was identified as the cause of the disease. Epidemiological studies really began to flourish in Japan after the end of World War II. Since the most of infectious diseases have been controlled, epidemiological studies on cancer, heart disease, stroke, and other chronic diseases have become the main target of investigations. It may be cautioned that, among infectious diseases, tuberculosis is still a serious health problem today and HIV infection has become a threatening health issue although the number of AIDS patients reported was still about 1,000 for the whole country in 1995. In contrast to other industrialized countries, heart disease is far less common in Japan, probably reflecting still not-too-rich diet among Japanese. There are a number of unique or unusual epidemiological studies in Japan, including a long-term surveillance of those who were exposed to A-bomb irradiation in 1945. Readers are encouraged to refer to detailed description of each, specific topic presented in this volume. Essential vital statistics are also presented as background information of epidemiological studies in Japan.

Beriberi↗

Cancer occurrence among dyestuff workers exposed to aromatic amines. A long term follow-up study.

BACKGROUND: Although the occupational exposure to some aromatic amines is recognized to cause bladder carcinoma, the long term effect of such exposure on the risk for disease, including other malignant tumors, remains unknown. METHODS: A total of 442 dyestuff workers exposed to one or more substances including benzidine (BZ), beta-naphthylamine (beta-N), alpha-naphthylamine (alpha-N), and dianisidine were followed completely until December 1992 (average time since first exposure, 39.4 years). Besides the underlying cause of death, the incidence of urothelial carcinoma was determined by periodic urologic screenings. RESULTS: Analyses of site-specific cancer mortality revealed a remarkable increased risk for bladder carcinoma for those engaged in BZ manufacture (standardized mortality ratio [SMR] = 63.6), BZ use (SMR = 27.0) and beta N manufacture (SMR = 48.4), but not for those who were exposed to alpha-N. The increased risk of cancer mortality for other organs was not significant for any exposure classes. The crude incidence rate per 1000 person-years of bladder carcinoma was estimated to be 8.7 for those engaged in BZ manufacture, 2.9 in BZ use, 7.7 in beta-N manufacture and 1.0 in beta-N use. Regardless of the class or type of exposure, the adjusted incidence rate of urothelial carcinoma increased with the duration of exposure. The adjusted incidence rate for BZ manufacture remained high (3.8-12.8) during the entire observation period, whereas that for BZ use increased from 0.0 to 4.4 as the time since first exposure increased from less than 10 years to 30+ years. CONCLUSIONS: Occupational exposure to either BZ or beta-N demonstrated an extremely strong and prolonged effect on workers' risk for urothelial carcinoma, particularly for bladder carcinoma, but not for malignant neoplasms of other organs.

1-Naphthylamine↗

Risk factors for hepatocellular carcinoma among Japanese women.

To elucidate the risk factors for hepatocellular carcinoma (HCC) among women, we made a combined analysis of the data from three case-control studies conducted in high-risk areas of Japan. A total of 120 cases and 257 controls were included in the analysis. After adjustment for the study category, age, and other potential confounders, significantly increased risks were associated with chronic hepatitis-B virus infection (odds ratio [OR] = 42.4, 95 percent confidence interval [CI] = 11.2-160.2), a past history of blood transfusion (OR = 3.7, CI = 1.8-7.5), and a history of smoking (OR = 2.2, CI = 12-4.1). In addition, women with a history of heavy drinking experienced an elevated risk of borderline significance (OR = 4.2, CI = 0.9-20.4, P = 0.07). When these ORs were compared with the corresponding estimates among males from the same case-control studies, no significant differences were observed between the two genders. Among the factors examined in this analysis, drinking and smoking habits--which are more common among Japanese men than women--may partly account for a large male-predominance in the incidence of HCC. Further studies are needed to clarify the roles that sex-hormones and hepatitis-C virus infection might play in the large gender difference of HCC occurrence.

Adult↗

A high level of prostaglandin E2 (PGE2) in the portal vein suppresses liver-associated immunity and promotes liver metastases.

Prostaglandin E2 (PGE2) is generally accepted to be an immunosuppressant produced by cancer cells and their surrounding macrophages. Although several investigators have reported detecting high concentrations of PGE2 in the portal veins of patients with colorectal cancer, the relationship between these high concentrations of PGE2 in the portal vein and liver-associated immunity remains unclear. In this study, we attempted to determine if the portal administration of PGE2 suppresses the immune function of the liver in a rat model. Donryu rats were administered PGE2 via the portal vein for 7 days, following which the cytotoxic activity of hepatic sinusoidal lymphocytes (HSL) against natural killer (NK)-sensitive YAC-1 and rat syngeneic AH60C tumor cells was assessed. Purified HSL are spontaneously cytolytic; however, the continuous administration of PGE2 dramatically suppressed the cytotoxic activity of HSLs in a dose-dependent fashion. Flow cytometric analysis showed that the large granular lymphocyte (LGL) fraction, hepatic natural killer (pit) cells, and CD4-8+ killer/suppressor T cells were mainly reduced in number in the HSLs following PGE2 infusion. In this rat AH60C metastasis model, the continuous administration of PGE2 increased the number and size of metastatic tumor nodules in the liver, suggesting that high concentrations of PGE2 in the portal vein suppress liver-associated immunity and promote the formation of hepatic metastasis.

Animals↗

Analysis of the growth rate and cavernous sinus invasion of pituitary adenomas.

Pituitary adenomas generally are regarded as benign tumours, but a part of them can invade the cavernous sinus and recur. We examined 43 pituitary adenomas for the following factors: tumour volume, endocrinological function, cavernous sinus invasion, and growth rates examined by using anti-proliferating cell nuclear antigen (PCNA) and MIB1 (a novel anti-Ki-67) as markers. There was significant correlation between PCNA- and MIB1-positive cell rates and PCNA- and MIB1-positive cell rates were higher in the three cases with rapid regrowth than in the other cases. Staining was stronger and more distinct for MIB1 than for anti-PCNA; thus, MIB1-positive cells were easily distinguished by their intense immunoreactivity. MIB1 may be useful for detecting those rare cases with rapid regrowth even when initially regarded as benign tumours. Adenomas with cavernous sinus invasion were significantly larger than those demonstrating no invasion. However, no significant difference was found in the frequency of PCNA- or MIB1-positive cells between adenomas with and without cavernous sinus invasion. These findings suggest that cavernous sinus invasion and growth rate are independent biological factors. Therefore, cavernous sinus invasion may be due to chemical factors produced by the tumour itself rather than as a result of rapid tumour growth.

Adenoma↗

Effects of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in human lymphoblastoid cells on aryl hydrocarbon hydroxylase activity.

The separate and concurrent effects of polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) congeners on aryl hydrocarbon hydroxylase (AHH) activity in human lymphoblastoid cells were examined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) induced AHH activity about 9-fold acetone-treated AHH activity, while octachlorodibenzo-p-dioxin (octaCDD) did not affect the AHH activity and 2,4,6,8-tetrachlorodibenzofuran (2,4,6,8-tetraCDF) reduced the AHH activity by 34%. The concurrent effect of 2,3,7,8-tetraCDD with 1,3,6,8-tetraCDD on AHH inducibility was much smaller than expected. The concurrent effect of 2,3,7,8-tetraCDD with 2,4,6,8-tetraCDF, octaCDD or 3,3',4,4',5,5'-hexaCB was as much as the effect of 2,3,7,8-tetraCDD alone. There was a difference between 3-methylcholanthrene (MC) and 2,3,7,8-tetraCDD in the concurrent effects of 3-methylsulfone-3',4,4',5-tetraCB (3-MSF-3',4,4',5-tetraCB) on AHH activity. The concurrent effect of MC with 3-MSF-3',4,4',5-tetraCB on AHH activity was equal to the effect of MC alone while that of 2,3,7,8-tetraCDD and 3-MSF-3',4,4',5-tetraCB on AHH activity was inhibitory. These results imply that congeners of PCDD and PCDF are considered to be more or less effective and isozymes of cytochrome P450, key enzymes for the AHH, induced by them are differently inhibited.

Aryl Hydrocarbon Hydroxylases↗

Anterior pituitary function in patients with nonfunctioning pituitary adenoma: results of longitudinal follow-up.

Studies of anterior pituitary function in patients treated for nonfunctioning pituitary adenomas have been limited by their short duration. The purpose of the present study was to examine pituitary function longitudinally among three types of patients: those with complete tumor removal (group A); those with subtotal or partial adenomectomy (group B); and those in group B who underwent additional radiation therapy (group C). The subjects were 33 patients whose anterior pituitary function was evaluated by provocative tests such as insulin induced hypoglycemia, thyrotropin releasing hormone administration test and luteinizing hormone releasing hormone administration test. They underwent preoperative evaluation and postoperative reevaluations at 2 weeks, 3 months, 6 months and annually thereafter, for over 10 years. Anterior pituitary function was restored within a year after surgery, if at all. No additional function was restored after one year from treatment. In group A, no one developed impairment of anterior pituitary function after one year from surgery. In group B, however, new impairment was noted at intervals, due to tumor regrowth. In Group C, deficiencies developed after one year, irrespective of tumor regrowth. In conclusion, lifelong endocrinological follow-up is recommended for patients receiving postoperative irradiation, and for patients with potential for tumor regrowth. On the other hand, patients with total adenomectomy may be exempted from periodic endocrinological follow-up if they do not need postoperative hormonal replacement therapy.

Adenoma↗

[A case report of cranial bone defect with a porencephalic cyst in an adult].

A case of cranial bone defect with porencephalic cyst in an adult was reported. A 47 year-old male was admitted with epilepsy. He had a round lytic bone defect lesion in the left frontal skull. The porencephalic cyst was under the bone defect. The mechanism of bone defect is thought to be as follows. He had received some head trauma in childhood and the frontal skull bone had fractured. The contusioned brain changed to a porencephalic cyst. The linear bone fracture may have enlarged according to the mechanism of a growing skull fracture. Persistent pulsative pressure from the porencephalic cyst toward the fractured bone edge might be able to make the bone defect oval.

Brain Diseases↗

Blood polychlorinated biphenyls and manifestation of symptoms in chronic "Yusho" patients.

The correlation between blood PCB concentration and clinical manifestation of symptoms was investigated in 259 chronic "Yusho" patients, using the information obtained from the nationwide health examination conducted in 1988, twenty years after the outbreak. Concentrations of blood PCBs ranged 0.6-32.0 ppb (mean; 4.78), and they were categorized into approximate quartile for analysis. For general fatigue, odds ratios at 2.7+, 4.1+, and 6.1+ ppb were 2.4, 3.6, and 3.1, respectively, with a reference category of < 2.7 ppb (test for trend; p < 0.005). For numbness in extremities, the corresponding odds ratios were 2.8, 2.8, and 2.9(p < 0.005). For comedone, they were 1.4, 1.0, and 4.0 on face (p < 0.025); and 3.6, 4.6, and 9.5 on trunk (p < 0.005), respectively. A distinctive increase in odds ratio was observed at 2.7 ppb for these two subjective symptoms; and at 6.1 ppb for skin symptoms. The blood PCB concentrations among patients were relatively close to the normal subjects. Therefore, the observed correlations may be due to the effects of PCBs with a peculiar pattern in components, PCQs or PCDFs, taken and retained in the patients. Association with blood PCBs was also suggested for headaches; abnormal breath sounds; and acneiform eruptions in the genital region, but were statistically insignificant. None of the eye symptoms showed significant association with blood PCBs.

Adult↗

A case of Cushing's disease accompanied by Rathke's cleft cyst: the usefulness of cavernous sinus sampling in the localization of microadenoma.

A 42-year-old man presented with classical symptoms of Cushing's disease. Endocrinological examinations indicated the presence of a adrenocorticotropin-(ACTH) producing pituitary adenoma. Magnetic resonance imaging showed a cystic sellar lesion, which had features of a Rathke's cleft cyst, whereas the adenoma was not depicted. The ratio of blood ACTH concentration between cubital vein, left, and right cavernous sinus was 1: 1.4: 20. During transsphenoidal surgery, in addition to the Rathke's left cyst, a tiny adenoma was detected beneath the left pituitary lobe. Cavernous sinus sampling is a useful auxiliary in the localization of an ACTH-producing adenoma, as in this case.

Adenoma↗

Effect of packed red cell and whole blood transfusion on liver-associated immune function.

In order to clarify the effect of allogeneic blood transfusion on liver metastases from primary cancer, liver-associated immune function after blood transfusion was evaluated in a murine model. Hepatic sinusoidal lymphocytes (HSL) were strongly cytotoxic to conventional natural killer cell-sensitive target (YAC-1), as well as to natural killer cell-resistant solid adenocarcinoma cells (colon 26), compared with splenic lymphocytes. Allogeneic whole blood transfusion strikingly suppressed the cytotoxic activities of HSL. Red blood cell transfusions also suppressed cytotoxicity to the same degree. In an animal model, allogeneic transfusion increased the rate of liver metastases. Flow cytometric analysis showed that transfusion caused a temporary decrease in the class II antigen positive cell fraction, mainly Kupffer's cells. This phenomenon occurred in parallel with changes in hepatic antitumor activity, indicating the possible importance of the involvement of Kupffer's cell in the development of the killer activity of HSL. These results suggest that blood transfusion may be a significant risk factor for hepatic metastasis by transiently suppressing the immunocompetence of the liver.

Animals↗

Animal fat consumption and prostate cancer: a prospective study in Hawaii.

Whereas case-control studies have been very consistent in suggesting a positive association between intake of dietary fat, especially animal fat, and prostate cancer, the results from past cohort studies have been mostly inconclusive. In this study, we evaluated consumption of high-fat animal products, raw vegetables, and fresh fruits, as well as obesity, smoking, and drinking, in relation to subsequent occurrence of prostate cancer. We studied a cohort of 20,316 men of various ethnicities interviewed between 1975 and 1980 in Hawaii. As of December 1989, 198 incident cases with invasive prostate cancer were identified by computer-assisted linkage of this cohort to the statewide Surveillance, Epidemiology, and End Results registry. Relative risks (RRs) for prostate cancer computed by proportional hazards regression were elevated for intake of beef [RR for highest to lowest tertile of intake = 1.6; 95% confidence interval (CI) = 1.1-2.4] and milk (RR = 1.4; 95% CI = 1.0-2.1), and for a summary variable for intake of high-fat animal products (RR = 1.6; 95% CI = 1.0-2.4). Weight was not consistently associated with prostate cancer, but there was an association with height (> 167 cm) (RR = 1.8; 95% CI = 1.0-3.2 for the third and fourth quartiles relative to the lowest quartile in height). These associations were stronger in men diagnosed before age 72.5 years. The risk estimates for raw vegetable and fresh fruit intakes were close to 1.0. Smoking and alcohol drinking appeared to be unrelated to risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Obesity and adenomatous polyps of the sigmoid colon.

The relation between obesity and adenomatous polyps of the sigmoid colon was investigated in male self-defense officials who received a retirement health examination at three hospitals of the Self-Defense Forces in Japan between January 1991 and December 1992. Body mass index (BMI) and waist-hip circumference ratio (WHR) were used as indices of obesity. A total of 228 adenoma cases and 1484 controls with normal sigmoidoscopy were identified in 2228 men: cases having small adenomas (< 5 mm in diameter) and those with large adenomas (5 mm or greater) numbered 115 and 102, respectively. Smoking, alcohol use, physical activity, rank, and hospital were controlled for by multiple logistic regression analysis. BMI and WHR were classified into four levels using the 30th, 60th, and 90th percentiles of each distribution in the control as cut-off points. There was a significant two-fold elevation in the overall adenoma risk among men at the highest BMI level (> or = 26.95) compared with those at the lowest level (< 22.48), but the risk did not linearly increase: a similar increase was also noted for large adenomas. While WHR was only weakly related to the overall adenoma risk, the risk of large adenomas progressively increased with increasing levels of WHR; odds ratio (OR) 2.9 (95% confidence interval (CI) 1.4-5.9) for the highest (> or = 0.958) versus lowest (< 0.878) levels. BMI was not materially associated with adenoma risk after additional adjustment for WHR, but a positive association between WHR and large adenomas was independent of BMI: OR 3.4 (95% CI 1.5-7.6) for the highest versus lowest levels. These findings suggest that obesity is associated with an increased risk of colon adenomas, probably with adenoma growth.

Adenoma↗