Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men : the Suita Study.

BACKGROUND: The Framingham Study recently revealed that the homozygous deletion polymorphism of the angiotensin-converting enzyme gene (ACE DD) is associated with increased risk for essential hypertension in a male-specific manner. However, this association has not been confirmed in races other than whites. METHODS AND RESULTS: Using a large number of Japanese subjects (n=5014) that were randomly selected from the general population (the Suita Study), we examined the association between ACE DD and hypertension. The frequency of DD (17.1%) in hypertensive men was significantly higher (P<0.0015) than that (11.8%) in other mildly hypertensive or normotensive men, and the estimated odds prevalence for hypertension (DD vs II) was 1.75 (95% CI 1.21 to 2.53). In contrast, no significant association was confirmed in women (OR 1.17, 95% CI 0.79 to 1.72). CONCLUSIONS: Despite the lower frequency of the DD genotype in Japanese than in whites, the ACE gene polymorphism was associated with increased risk for hypertension, suggesting that this polymorphism is a mild but certain genetic risk factor for essential hypertension in men.

Human prostacyclin synthase gene and hypertension : the Suita Study.

BACKGROUND: Prostacyclin (prostaglandin I(2)) is a strong vasodilator that inhibits the growth of vascular smooth muscle cells and is also the most potent endogenous inhibitor of platelet aggregation. Therefore, it has been considered to play an important roles in cardiovascular disease. On the basis of the hypothesis that variations of the prostacyclin synthase gene may also play an important role in human cardiovascular disease, we performed a screening for variations in the human prostacyclin synthase gene. METHODS AND RESULTS: We have detected a repeat polymorphism in the promoter region of the human prostacyclin synthase gene. The number of 9-bp (CCGCCAGCC) repeats in the promoter region, which encodes a tandem repeat of Sp1 transcriptional binding sites, varied between 3 and 7 in Japanese subjects. Luciferase reporter analysis indicated that the alleles of 3 and 4 repeats (R3 and R4, respectively) had less promoter activity in cultured human umbilical vein endothelial cells. We then investigated the possible association of this repeat polymorphism with blood pressure in a large population-based sample (the Suita Study), which consisted of 4971 Japanese participants. Multivariate models indicated that participants with the R3R3, R3R4, or R4R4 genotype (SS genotype, n=80) had significantly higher systolic pressure (P=0.0133) and pulse pressure (P=0.0005). The odds ratio of hypertension (140/90 mm Hg) for the SS genotype was 1.942 (95% confidence interval 3.20 to 1.19, P=0.0084). CONCLUSIONS: Repeat polymorphism of the human prostacyclin synthase gene seems to be a risk factor for higher pulse pressure and is consequently a risk factor for systolic hypertension in the Japanese population.

Strong and significant relationships between aggregation of major coronary risk factors and the acceleration of carotid atherosclerosis in the general population of a Japanese city: the Suita Study.

BACKGROUND: Carotid arterial intimal-medial thickness (IMT) measured by high-resolution B-mode ultrasonography has come to be used as a noninvasive surrogate end point to measure progression of atherosclerosis. However, there are no detailed data on the relationship between aggregation of coronary risk factors and carotid atherogenesis. METHODS: Cross-sectional assessment of the relationship between carotid atherosclerosis detected by high-resolution ultrasonography and integration of major coronary risk factors by age and sex. Subjects aged 30 to 86 years were randomly selected from Suita, located in Osaka, the second largest urban area of Japan, including 1896 men and 2102 women. Carotid atherosclerosis was evaluated by using our atherosclerotic indexes of IMT, plaque number, plaque score, and percentage of stenosis of the carotid artery assessed using ultrasonography by sex and age group classified by number of major coronary risk factors (ie, hypertension [diastolic blood pressure > or =90 mm Hg and/or systolic blood pressure > or 140 mm Hg or receiving medication], smoking [current smoker], and hypercholesterolemia [serum total cholesterol level > or =5.68 mmol/L [220 mg/dL] or receiving medication]). RESULTS: The mean carotid atherosclerotic index value, especially the mean IMT value, of the subjects with 1 major coronary risk factor was on average 0.028 mm (3.2%) higher for men and 0.025 mm (2.9%) higher for women than that of the subjects without major coronary risk factors; for subjects with 2 risk factors, 0.054 mm (6.3%) higher for men and 0.053 mm (6.2%) higher for women; and for high-risk subjects with 3 major risk factors, 0.135 mm (15.8%) higher for men and 0.137 mm (15.4%) higher for women. The percentage of the subjects with severe stenosis of at least 50% increased stepwise with increases in the number of coronary risk factors and showed a significant difference (P<.05) between men and women, ie, 2.4% vs 0. 6% (P =.01) among the subjects with no risk factors; 6.7% vs 1.5% (P<.001), subjects with 1 risk factor; 10.7% vs 2.7% (P<.001), subjects with 2 risk factors; and 18.6% vs 5.0% (P =.01), high-risk subjects. CONCLUSIONS: Aggregation of established major coronary risk factors strongly influenced carotid atherogenesis in both sexes. There were significant differences between sexes in the acceleration or progression of carotid atherosclerosis.

Potential of carotid enlargement as a useful indicator affected by high blood pressure in a large general population of a Japanese city: the Suita study.

BACKGROUND AND PURPOSE: Few studies have examined whether there is a relationship between carotid arterial diameter and cardiovascular risk factors in a large general population. The aim of this study was to investigate cross-sectionally whether, in a randomly selected general large population of a Japanese city, there is a relationship between common carotid artery (CCA) diameter and conventional cardiovascular risk factors. METHODS: The subjects of the present study were randomly selected from the residents of the city of Suita, located in the second largest urban area of Japan, and consisted of 2284 men and 2568 women aged 30 to 89 years. The outer and inner CCA diameters and intima-media thickness (IMT) of CCA were detected and measured by a single physician with high-resolution ultrasonography. We assessed cross-sectionally by age/sex group the relationships between IMT or CCA diameters and cardiovascular risk factors, especially blood pressure levels divided into 3 groups: the normal group of subjects had a diastolic blood pressure (DBP) <85 mm Hg and systolic blood pressure (SBP) <130 mm Hg and were not taking antihypertensive medication; the high group of subjects had DBP >/=90 mm Hg and/or SBP >/=140 mm Hg and/or were taking antihypertensive medication; and the moderate group consisted of all other subjects. RESULTS: The outer and inner CCA diameters for the high group were significantly (P:<0.05) enlarged in comparison with those for the moderate and normal groups in all age/sex groups of both sexes after adjustment for body mass index, pack-years of smoking, alcohol consumption, and total serum cholesterol. Multiple regression analysis showed that age, body mass index, SBP, pack-years of smoking, alcohol consumption, and IMT were positively and significantly (P:<0.005) related to both outer and inner CCA diameters in both sexes except for between alcohol consumption and outer CCA diameter in women and showed that only serum total cholesterol level was negatively and significantly (P:<0.01) related to inner CCA diameter in both sexes. CONCLUSIONS: Our present study showed that the outer and inner CCA diameters correlated with conventional cardiovascular risk factors, including high blood pressure and IMT. These findings suggest that the outer and inner CCA diameters may be a useful indicator of carotid atherosclerosis, particularly in relation to high blood pressure.

Low potentiality of angiotensin-converting enzyme gene insertion/deletion polymorphism as a useful predictive marker for carotid atherogenesis in a large general population of a Japanese city: the Suita study.

BACKGROUND AND PURPOSE: Some previous studies, almost all western, have investigated whether there is a relationship between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) and carotid atherosclerosis. The results, however, have not been consistently positive. Further, there have been few investigations based on a large, general population. Therefore, the present study aimed to clarify whether ACE gene deletion polymorphism was associated with carotid atherosclerosis in a large Japanese general population with a more homogeneous genetic background than Caucasian populations. METHODS: Subjects aged 30 to 86 years were randomly selected from Suita City, located in Osaka, the second largest urban area of Japan, and included 1894 men and 2137 women. With the aid of high-resolution ultrasonography, carotid atherosclerosis was evaluated using our atherosclerotic indexes of intimal-medial thickness (IMT), plaque number (PN), plaque score (PS), and percentage of stenosis of the carotid artery assessed using high-resolution B-mode ultrasonography. ACE gene I/D polymorphism was detected by polymerase chain reaction. RESULTS: There were no significant differences among the ACE genotypes for age and conventional cardiovascular risk factors, except for systolic blood pressure (SBP) and the percentage of hypertension in men. The values of IMT, PN, and PS as carotid atherosclerotic indexes were not significantly different among genotypes for either sex. After adjusting for age, body mass index, smoking habit, high-density lipoprotein cholesterol, triglycerides, presence of hypertension, presence of diabetes mellitus, and presence of hyperlipidemia, the estimated ORs for the presence of IMT >/=1.10 mm (defined as thickened IMT), according to ACE genotype (DD versus II, DD+ID versus II, and DD versus ID+II), for men were 0.80 (95% CI 0.60 to 1.23), 0.89 (0.62 to 1.29), and 0.89 (0.70 to 1.28), respectively. On the other hand, the ORs for women after the same adjustment were 0.92 (95% CI 0.58 to 1.35), 0.93 (0.59 to 1.45), and 0.91 (0.59 to 1.27), respectively. CONCLUSIONS: Our present data suggest that ACE I/D polymorphism is not potentially a useful predictive marker for carotid atherogenesis when investigated in a large and homogeneous general Japanese population of 4031 subjects, a finding similar to that in a Caucasian population study, the Perth Carotid Ultrasound Disease Assessment Study, an Australian study based on a general population using 1111 subjects.

Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese: the Suita Study.

Reduced plasminogen activity with a normal level of antigen is commonly observed in Japanese individuals. The first reported patient with plasminogen deficiency was accompanied with deep vein thrombosis. The present study examines whether heterozygous or homozygous deficiency of plasminogen is a risk factor for thrombotic disease. This study measures the plasminogen activity of 4517 individuals in the general population, determines the cut-off to define plasminogen deficiency, and identifies plasminogen deficiencies in the control groups and thrombotic disease groups. In another study, we examined the phenotypes of consecutive patients with homozygous plasminogen deficiency detected in our hospital. We found 173 and two of 4517 individuals to have heterozygous and homozygous deficiency with normal plasminogen antigen level, respectively, and 19 to have heterozygous deficiency with reduced antigen levels. The incidence of plasminogen deficiency in an age- and sex-matched control group (13/324, 4.01% for deep vein thrombosis or 13/330, 3.94% for stroke) selected from the 4517 individuals was not significantly different from those in patients with deep vein thrombosis (3/108, 2.78%) or cardioembolic stroke (6/110, 5.55%). Among 19 patients with homozygous plasminogen deficiency showing about 10% plasminogen activity, none had deep vein thrombosis. These findings indicate that neither heterozygous nor homozygous plasminogen deficiency constitutes a significant risk factor for thrombotic disease.

Development of approximate formula for LDL-chol, LDL-apo B and LDL-chol/LDL-apo B as indices of hyperapobetalipoproteinemia and small dense LDL.

Estimation of LDL-chol and LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia (normal LDL-chol with increased LDL-apo B), which is one of the most commonly occurring lipoprotein disorders associated with atherosclerotic cardiovascular diseases. The LDL-chol/LDL-apo B ratio reflects the level of small dense LDL, which is an important risk factor for IHD, CVD and ASO. In order to estimate LDL-apo B and LDL-chol/LDL-apo B ratio from blood chol, TG, HDL-chol and apo B values, we developed a formula for LDL-chol ¿0.94Chol- 0.94HDL-chol - 0.19TG¿, LDL-apo B ¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿, and LDL-chol/LDL-apo B [¿0.94Chol-0.94HDL-chol - 0.19TG¿/¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿] using ultracentrifugal data from 2179 subjects. These were calculated by the least squares method on the assumption that a certain compositional relationship exists between Chol, TG and apo B in VLDL, IDL and LDL. Friedewald's formula for LDL-chol (Chol - HDL-chol - 0.2TG) includes IDL-chol, but the present new formula theoretically excludes IDL-chol. It suggests a better estimation for the correct LDL-chol. Estimated LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia and detection of small dense LDL. Without performing ultracentrifuge, additional information is obtained for the quantitative and qualitative alteration of LDL, such as small dense LDL. The above formulae and a new classification of lipoproteinemia including apo B were applied to the analyses of lipoprotein profiles of subjects with cardiovascular diseases, which were compared with those in the general population. Hyperapobetalipoproteinemia with high TG was observed 2-3 times more frequently in subjects with CAD, MI and ASO than in the Suita population. Lower ratios of LDL-chol/LDL-apo B, reflecting preponderance of small dense LDL, were observed in the above three groups. Type IIb and combined low HDL-chol were also frequent phenotypes in CAD, A-Th and ASO. The present formulae are useful for the detailed analyses of lipoprotein disorders in both qualitative as well as quantitative aspects.

Second nation-wide study of atherosclerosis in infants, children and young adults in Japan.

This paper reports the results of the second nation-wide cooperative study of atherosclerosis in young Japanese, aged from 1 month to 39 years, who were autopsied between 1991 and 1995. Atherosclerotic lesions in 1066 aortas and 974 coronary arteries were classified into fatty streaks, fibrous plaques and complicated lesions and quantificated with the point-counting method. The results of this study were compared with those of the former study, which was conducted 13 years earlier in almost the same fashion as this study. Atherosclerosis of aorta, which was determined by surface involvement (SI) of atherosclerotic lesions and atherosclerotic index (AI), increased with age in both sexes of the former and the present studies and their tendency for the progression of the extent of atherosclerotic lesions appeared to be similar. In the coronary arteries, the mean values of SI and AI in the males of the present study were greater significantly than those in the male of the former studies and in the female of the both studies in the third and fourth decades. This difference suggests that atherosclerotic lesions are increasing in young Japanese males. It also suggests that these subjects may be increasingly susceptible to atherosclerotic cardiovascular disease with increasing age.

Increased incidence of follicular lymphoma in the duodenum.

The incidence of indolent lymphomas in the lymph nodes and extranodal regions is quite different. Follicular lymphoma (FL) is most common in the nodes, and it seems to be least common in the gastrointestinal (GI) tract, where mucosa-associated lymphoid tissue lymphoma arises most frequently. The authors report that the incidence of FL is unexpectedly high in the duodenum compared with other portions of the GI tract. FL was detected in only eight of 222 cases of GI lymphoma (3.6%). However, five cases of FL arose in the duodenum, which accounted for 38.5% of 13 duodenal lymphomas. Only in two patients did FL arise in either the stomach or the colorectum, and in the remaining patients FL was widespread with lymphomatous polyposis. Duodenal FL was composed of neoplastic follicles with small cleaved cells in dominance, and the immunophenotype of the lymphoma cells was CD10+, BCL-2+, CD20+, CD75+, CD79+, CD3-, CD5-, cyclin D1-, CD23-, and CD45RO-. All the patients were women age 37 to 66 years (average age, 52.4 yrs). In all patients the lymphoma was present around the ampulla of Vater, and four of five patients showed multiple small-size polyps. Although lymphoma cell infiltration was confined to the submucosa in the four patients examined, the regional lymph nodes were involved partially in two patients without distant metastasis. All patients are alive at 2 to 50 months of follow up (average, 27 mos), which is comparable with the prognosis for indolent nodal lymphomas. These results suggest that the duodenum has a distinct background of histogenesis of the lymphomas and that biopsy specimens from the duodenum with multiple polyps should be examined carefully.

Association analyses between genetic polymorphisms of endothelial nitric oxide synthase gene and hypertension in Japanese: The Suita Study.

OBJECTIVES: Endothelium-derived nitric oxide plays a key role in the regulation of vascular tone. Recently, endothelial nitric oxide synthase (eNOS) gene polymorphisms were reported to be associated with hypertension or coronary spasm. We investigated the association between the eNOS gene polymorphisms and hypertension in a large population-based sample of 4055 Japanese. DESIGN AND METHODS: We investigated two polymorphisms of the eNOS gene, Glu298Asp polymorphism of exon 7 and T(-786)C polymorphism of the promoter region. The genotype distribution in hypertensive subjects was compared to that in the other subjects. The influence of the genotype on blood pressure values was analyzed in the subjects not taking hypertensive medication. The promoter activities of the eNOS gene with the (-786)T or (-786)C allele were measured by a luciferase reporter gene assay. RESULTS: There was significant linkage disequilibrium between the two polymorphisms (P < 0.0001). The genotype distribution of the Glu298Asp or T(-786)C polymorphism did not differ between the hypertensive and the other subjects. No significant differences in the blood pressure of subjects not taking hypertensive medication were observed among the three genotypes of Glu298Asp or T(-786)C polymorphisms. No significant differences in the promoter activity were observed between bovine endothelial cells transfected with the (-786)T and (-786)C alleles. CONCLUSIONS: Our data suggested that these polymorphisms of the eNOS gene are unlikely to be major factors in the susceptibility to hypertension in the Japanese population studied.

Two cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) following diffuse large B-cell lymphoma.

Histiocytic necrotizing lymphadenitis (HNL) is often mistaken for malignant lymphoma clinically and is also sometimes difficult to differentiate from lymphoma even histopathologically. In this report, we describe the first 2 reported cases of HNL following non-Hodgkin's lymphomas. The patients were 27- and 30-year-old women who developed cervical and axillary lymph node swellings, respectively, in the course of remission of diffuse large B-cell lymphoma. The affected lymph nodes showed the typical histology of HNL: irregular-shaped "necrotic" foci with histiocytes engulfing apoptotic bodies intermingled with large-sized blastic lymphocytes. These findings mimicked the partial involvement of large-cell lymphoma. However, the blastic cells were almost exclusively T cells, and numerous apoptotic bodies were present, which excluded the possibility of recurrence of diffuse large B-cell lymphoma.

Histologic transformation of follicular lymphoma after allogeneic bone marrow transplantation.

A 38-year-old man with refractory follicular lymphoma underwent allogeneic BMT from an HLA-identical sibling donor. He had generalized lymphadenopathy, hepatosplenomegaly and lymphoma infiltration of the marrow, all of which disappeared within 3 months following transplantation. Six months post-transplant, progressive hepatomegaly developed in the absence of splenomegaly and lymphadenopathy, and he died from hepatic failure. Autopsy disclosed diffuse large B cell lymphoma of the liver, into which the follicular lymphoma had transformed. Future issues to be investigated should include the optimal timing of allogeneic BMT for low-grade lymphomas.

Clinicopathological features of gastric mucosa associated lymphoid tissue (MALT) lymphomas: high grade transformation and comparison with diffuse large B cell lymphomas without MALT lymphoma features.

AIMS: To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL). METHODS: Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected. RESULTS: Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL. CONCLUSIONS: The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.

The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: the Suita study.

Excessive alcohol consumption is a potent risk factor for high blood pressure. About half of Japanese show an extremely high sensitivity to alcohol, which is due to a genetic deficiency in an isoenzyme of aldehydede-hydrogenase with a low Km (ALDH2). It is possible that the effects of alcohol consumption on blood pressure differ according to the ALDH2 genotype. The purpose of the present study was to assess the influence of the ALDH2 genotype on the pressor effects of alcohol. The influence of the ALDH2 genotype on blood pressure was investigated in a large cohort (4,000 subjects) representing the general population in Japan. The genotype was determined by the TaqMan method. The genotype was significantly associated with alcohol consumption, gamma-GTP level, and HDL cholesterol level in both males and females. The odds ratio for the presence of hypertension for the Glu/Glu genotype in comparison to other genotypes was 1.67 (p< 0.0001, odds ratio=1.37-2.08, 95% confidence interval) among males. In contrast, the ALDH2 genotype had no significant effects on blood pressure among females. To investigate whether the ALDH2 genotype affected the sensitivity to the pressor effects of alcohol, we analyzed the effects of the ALDH2 genotype (Lys/Lys+Lys/Glu=0, Glu/Glu=1) and the level of alcohol consumption on blood pressure values after adjusting for age and BMI (residuals after adjusting for age and BMI). Among males, while the level of alcohol consumption significantly affected systolic, diastolic and pulse pressure, no significant interaction was observed between the ALDH2 genotype and the level of alcohol consumption in determining blood pressure levels. These results suggest that the Glu/Glu genotype is a potent risk factor for hypertension among males mainly through its association with the level of alcohol consumption, and that the ALDH2 genotype does not affect the sensitivity to the pressor effects of alcohol.

Lack of association between genetic polymorphism of CYP11B2 and hypertension in Japanese: the Suita Study.

Aldosterone synthase (CYP11B2) is a key enzyme in the biosynthesis of aldosterone. Recently, a polymorphism in the 5'-flanking region of the CYP11B2 gene [T(-344)C] has been reported to be associated with blood pressure and plasma aldosterone levels. We investigated the association between this polymorphism and hypertension in a large population-based sample of 4,000 Japanese. The genotype distribution in hypertensive subjects (n=1,535) was compared to that in normotensive subjects (n=2,514). In subjects not receiving antihypertensive medication, the influence of the genotype on blood pressure values adjusted for clinical covariates was analyzed. All analyses were performed separately for men and women. The genotype distribution did not differ between hypertensive and normotensive subjects in either men (frequency of C allele: 30.3% vs. 31.4%, p=0.48) or women (31.5% vs. 31.7%, p=0.93). There were no significant differences in systolic blood pressure, diastolic blood pressure, or pulse pressure among the three genotypes in either men or women who had not received hypertensive medication. Our data suggest that the T(-344)C polymorphism of CYP11B2 is unlikely to influence blood pressure status in the Japanese population.

Complete regression of advanced liposarcoma of the anterior chest wall with interferon-alpha and tumor necrosis factor-alpha.

This paper reports a case of complete regression of a liposarcoma in a 62-year-old Japanese man who, in August 1986, presented with a giant subcutaneous tumor of the right anterior chest wall. Local radiotherapy and conventional chemotherapy were initially performed; however, the tumor did not respond at all. He then received cytokine treatment (interferon-alpha and tumor necrosis factor-alpha). Nineteen months after cytokine treatment, the mass disappeared totally. The patient has been in complete remission for five years without recurrence and with no additional treatment. This suggests that the use of interferon-alpha and tumor necrosis factor-alpha in combination may be an effective and promising modality for liposarcomas which are refractory to the conventional anticancer treatments.

Cancer immunotherapy with surgery.

With the recent advances in the immunological surveillance system, an understanding of the role of host immunity has become essential to the management of carcinogenesis, tumor proliferation, recurrence and metastasis. Although it is important to continue chemical and surgical treatment of cancer, support of the anti-tumor immune system of the host should also be considered. Long term remission has been reported in leukemia by treating with BCG after chemotherapy whereas surgical treatment is usually more effective in preventing cancer recurrence in digestive organ cancer. The first step is extirpating the tumor as thoroughly as possible and the second step is chemo-immunotherapy. Cancer immunity, however weak, constitutes the basis for other treatments in selectively attacking cancer cells remaining after surgery, chemotherapy or irradiation. Immunotherapy should thus not replace chemotherapy or radiotherapy, but these methods should be employed in combination to attain more favorable results.

Comparison of the prevalence of asymptomatic carotid atherosclerosis detected by high-resolution ultrasonography in rural and urban middle-aged Japanese men.

BACKGROUND AND PURPOSE: We have recently shown that extracranial carotid atherosclerosis is not uncommon in urban regions of Japan. Rural data have, however, been scarcely reported. The aim of this study was to investigate the prevalence of asymptomatic extracranial carotid lesions in rural populations compared with urban populations. METHODS: The subjects in the rural region consisted of 249 men, aged 50 to 69 years. Urban subjects were 610 men of the same age range. Carotid ultrasound examinations were performed with 7.5-MHz high-resolution ultrasonography. RESULTS: Detection of severe atherosclerosis (stenosis of 50%) was significantly higher (P<.05) in rural subjects (9.6%) than in urban subjects (4.6%). Multiple regression analysis of carotid atherosclerosis showed significant relationships with age, fasting blood glucose, hypertension, pack-years of smoking, total serum cholesterol, and high-density lipoprotein cholesterol for the rural subjects as well as for the urban subjects (P<.05). CONCLUSION: The present cross-sectional study showed that, in middle-aged men, the prevalence of severe carotid atherosclerosis was higher in rural populations compared with urban populations of Japan. This was attributed to long-term exposure to hypertension.