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.

Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS.

An antirat monoclonal antibody (mAb) against inducible nitric oxide synthase (iNOS), ANOS11, was used for immunohistochemistry to examine the expression of iNOS in various organs and tissues of adult rats in experimental endotoxic shock induced by lipopolysaccharide (LPS) injection. The phenotype of iNOS-expressed cells was also examined immunohistochemically using various mAbs. In control rats, very few cells were positive for ANOS11 except in the thymus. After intravenous injection of LPS, the number of iNOS-positive cells increased rapidly in almost all organs, except the thymus and brain, peaked 6 h after the injection, and decreased slowly. Of the numerous inflammatory cells that infiltrated the lungs, liver, and spleen after LPS injection, many were positive for ANOS11. Besides inflammatory cells, hepatocytes and endothelial cells of the aorta were also positive for ANOS11 but only around 6 h after injection. The cellular composition of iNOS-positive infiltrated cells changed along with the progression of endotoxic shock. At 4 to 6 h after injection, most iNOS-positive cells were considered polymorphonuclear leukocytes judging by their positive reactivity to OX42 and their nuclear morphology. The population of iNOS-positive macrophages positive for ED1 or ED2 increased with time. After 24 h, many iNOS-positive macrophages were found around the focal necrosis in the liver and spleen. These results indicate that the expression of iNOS in neutrophils, endothelial cells, and hepatocytes precedes that of macrophages in experimental endotoxic shock. The expression of iNOS in various cells and organs is closely associated with the progress and pathological changes of endotoxic shock.

Isolation of dendritic cells in the rat liver lymph.

Lymphadenectomy of the regional lymph nodes of the rat liver resulted in the direct influx of peripheral hepatic lymph into the thoracic duct after regeneration of lymphatic vessels. Thus, we could obtain the dendritic cells in the hepatic lymph by cannulating the thoracic duct. By the double immunostaining, dendritic cells in cytosmears could be easily determined as non-B, non-T, and MHC class II-positive cells. The yield of dendritic cells after enrichment by the metrizamide density gradient was about 5 x 10(5)/first 16 hr collection/rat, with viability of more than 95% and purity of more than 70%. About 80% of dendritic cells were positive for OX62, which recognized the rat dendritic cell subpopulation. They showed strong stimulating activity in the primary allogeneic mixed leukocyte reaction. The method presented here should be applicable to studies of the roles of liver dendritic cells, especially in transplantation immunity.

Increased vascular permeability of Brucella abortus bacilli in the thymus of NZB/W F1 mice.

Various amounts of the bacterium, Brucella abortus (BA) were injected intravenously into autoimmune NZB/W F1 mice and non-autoimmune BDF1 mice and then the localization of BA in the thymus was traced using an immunohistochemical method at 30 min and 3 h after injection. The results showed that a greater amount of BA became consistently localized in the thymic parenchyma in a free form or in a phagocytized form in NZB/W F1 mice in comparison with BDF1 mice, indicating a marked increase of vascular permeability in the thymus of NZB/W F1 mice. The extravascular leakage of BA was clearly dose-dependent. The significance of invasion of bacterial antigens from the general circulation into the thymic parenchyma is discussed in relation to autoimmune states.

Plasma levels of leukotriene E4 during clinical course of bronchial asthma and the effect of oral prednisolone.

To investigate the relationship between circulating leukotriene E4 and bronchial asthma, we tried to measure the concentration of leukotriene E4 during the clinical course of bronchial asthma with or without oral prednisolone treatment. Additionally, we investigated the relationship between the LTE4 levels and FEV1 (percent predicted) and PaCO2 (mm Hg) concomitantly. Two milliliters of blood were drawn from the femoral artery of eight patients on three occasions: (1) during remission; (2) during an attack treated without prednisolone; and (3) during an attack treated with prednisolone. Leukotriene E4 was detected by high-pressure liquid chromatography and radioimmunoassay. In eight asthmatic patients, mean (SD) leukotriene E4 levels on the three occasions were 11.8 (2.61), 48.4 (18.2), and 32.6 (8.28) pg/ml, respectively. In contrast, the mean leukotriene E4 level of ten normal control subjects was 11.8 (4.49) pg/ml. Leukotriene E4 levels differed significantly between remission and attack treated without prednisolone, and between attacks treated with and without prednisolone. Mean FEV1 values were 85.5 (3.07), 50.5 (9.58), and 65.9 (7.44) on the three occasions, respectively; corresponding mean PaCO2 values were 31.7 (2.74), 55.5 (5.81), 48.9 (2.56), respectively. Leukotriene E4 was significantly correlated with FEV1 and relatively with PaCO2 during an attack without prednisolone. We suggest that leukotriene E4 levels in arterial blood reflect the severity of asthmatic attacks and orally administered prednisolone may affect the leukotriene E4 levels.

Expression of the fibroblast growth factor family and their receptor family genes during mouse brain development.

The fibroblast growth factor (FGF) family is composed of nine members and four genes encode protein tyrosine kinase receptors for them. To gain insight into the involvement of FGFs and their receptors in the development of nervous system, their expression in brains of perinatal and adult mice was examined by semi-quantitative reverse transcription-linked polymerase chain reactions and in situ hybridization. Although all the genes, with the exception of FGF-4, were found to be expressed, FGF-3, FGF-6, FGF-7 and FGF-8 genes demonstrated higher expression in the late embryonic stages than in postnatal stages, suggesting that these members are involved in the late stages of brain development. In contrast, expression of FGF-1 and FGF-5 increased after birth. Interestingly, FGF-6 expression in perinatal mice was restricted to the central nervous system and skeltal muscles, with intense signals in the developing cerebrum in embryos but in cerebellum in 5-day-old neonates. Furthermore, FGF-receptor (FGFR)-4, a cognate receptor for FGF-6, demonstrated similar spatiotemporal expression, suggesting that FGF-6 and FGFR-4 plays significant roles in the maturation of nervous system as a ligand-receptor system. The results indicate that individual member of the fibroblast growth factor and their receptor family are expressed either sequentially or simultaneously in brain development, strongly suggesting their involvement in the regulation of a variety of developmental processes of brain, i.e., proliferation and migration of neuronal progenitor cells, neuron and glia differentiation, neurite extensions, and synapse formations.

Congenital sensory neuropathy with anhidrosis.

Congenital sensory neuropathy with anhidrosis (CSNA) is a well-defined entity among a group of sensory deficiency syndromes. Children with this genetic disease are insensitive to pain and temperature, do not sweat, and suffer from mental retardation. Self-mutilation may be severe and may lead to insoluble orthopedic problems. We treated a girl with CSNA, who was born to nonconsanguineous Japanese parents. This disease is important in the dermatological field, since the degree of anhidrosis and self-mutilation influence the prognosis of patients with CSNA.

Effects of in situ freezing and stress-shielding on the ultrastructure of rabbit patellar tendons.

The effects of in situ freezing and the combination of in situ freezing and stress-shielding on the microstructure and ultrastructure of the patellar tendon were studied with use of 20 mature rabbits. The patellar tendon was frozen in situ with liquid nitrogen to kill fibroblasts and then was completely released from stress by chronically pulling a stainless-steel wire installed between the patella and the tibial tubercle. Microstructurally, the freezing treatment induced separation of collagen fiber bundles and fibroblast necrosis at 3 weeks, although the separation disappeared at 6 weeks. Ultrastructurally, small collagen fibrils with a diameter of less than 90 nm were predominant; at 6 weeks, the area occupied by collagen fibrils had decreased. In the frozen-shielded tendon, numerous large spaces were observed in the matrix at 3 weeks. This treatment increased the number of fibrils with a diameter greater than 360 nm and decreased the number of collagen fibrils per unit of area and the area occupied by collagen fibrils at 3 weeks. This study demonstrated that in situ freezing and the combination of in situ freezing and stress-shielding leads to a smaller volume of collagen fibrils per unit of cross section of the patellar tendon by mechanisms that remain to be defined.

Abdominal actinomycosis: barium enema and computed tomography findings.

A case of abdominal actinomycosis is described in a woman with recurrent right lower abdominal pain and low-grade fever without history of appendectomy. Past history included the use of an intrauterine device (IUD) until 10 years before manifestation of these symptoms. We followed up the patient, via diagnostic imaging, for 7 months. On initial barium enema, a polypoid lesion was visualized at the bottom of the cecum and there was constriction of the sigmoid colon; the appendix was not seen. Seven months later, poor extension at the cecum, severe constriction in the sigmoid colon, and narrowing of the terminal ileum were also visualized. On computed tomography (CT), the lesion was initially localized only in the ileocecal region adjacent to the sigmoid colon. After 7 months, the lesion had infiltrated adjacent anatomic components and showed direct infiltration of the pelvic space. Differential diagnosis was difficult, as it was not obvious whether this was a pelvic abscess due to inflammation or appendiceal carcinoma. Laparotomy was performed. Macroscopically, the lesion was not limited to the ileocecal region, but involved the right ureter, tubes the Fallopian and ovary, bladder, psoas muscle, and abdominal wall. Pathology findings showed, chronic inflammatory tissue with evidence of actinomycosis. Although previous reports have described a lack of specific findings in this disease. When actinomycosis is suspected, CT is recommended to define its extent.

Systemic and local immunological features of atopic dermatitis patients with ocular complications.

AIMS: Clinical factors and data from recent cases of atopic dermatitis (AD) (with or without ocular complications) and non-AD cases were examined to evaluate the mechanism of atopic ocular complications. METHODS: IgE-RAST for eight allergens including rice, egg, and mite and serum total IgE were measured in 216 patients with AD (70 ocular type, 146 non-ocular type) and 69 non-AD individuals. Tear histamine and leukotriene B4 (LTB4) levels were also measured. RESULTS: The serum levels of IgE were significantly increased in AD patients with ocular complications compared with those without ocular complications. The positive rates of IgE-RAST for rice and wheat were significantly higher in ocular type AD than in non-ocular type AD. In ocular type AD, serum IgE was significantly increased in patients with cataract compared with that in those without cataract. Tear histamine and LTB4 levels in AD patients with ocular complications showed significant elevations compared with those in patients with pure AD and controls. CONCLUSIONS: These results suggest that ocular type AD belongs to the most severe end of the spectrum of AD, and that some food antigens may contribute to the pathogenesis of severe AD resulting in ocular complications.

Interaction of surfactants with vesicle membrane of dipalmitoylphosphatidylcholine. Effect on gel-to-liquid-crystalline phase transition of lipid bilayer.

The gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine (DPPC) vesicle membrane was observed in the presence of various types of surfactants; sodium alkylsulfates, alkyltrimethylammonium bromides, alkanoyl-N-methylglucamides, and hexaethyleneglycol mono n-dodecyl ether. The phase transition was monitored by a change in scattered light intensity of the lipid suspension. For all the surfactants examined, the phase transition temperature was depressed linearly with the surfactant concentration in the measured concentration range, from which the partition coefficient, K, of the surfactant between bulk solution and lipid membrane was estimated. Except alkyltrimethylammonium bromides, log K and log CMC showed a linear relationship, which indicates that the driving force to transfer the surfactant from bulk solution to lipid membrane is a hydrophobic interaction. The addition of surfactants increased the transition width. The extent of widening the transition width was in the order of sodium alkylsulfate greater than alkyltrimethylammonium bromides greater than hexaethyleneglycol mono n-dodecyl ether; in the case of alkanoyl-N-methylglucamides, the transition width was not affected by the addition. These effects on the transition width was interpreted qualitatively in terms of the cooperativity of the transition.

Follow-up results of surgical treatment for chronic pancreatitis. Present status in Japan.

The results of surgical treatment for chronic pancreatitis at our clinic and in the eight leading institutions of Japan were reviewed in a total of 328 cases. Abdominal pain disappeared or was alleviated in about 90 percent of the patients who survived more than 6 months after operation. There was no significant differences in the effect of pain among the three main types of operations: pancreaticoduodenectomy, distal resection and pancreatic ductal drainage. In the collected cases, however, complete disappearance of pain was reported more often in patients subjected to Puestow's operation than in those who underwent Nardi's operation. The patients who underwent pancreatic ductal drainage had a greater postoperative weight gain than those without drainage, in both our patients and the collected cases. In the collected cases, Puestow's operation was predominantly linked to postoperative weight gain. Evidence of pancreatic functional improvement, either in endocrine or in exocrine, was very meager.

Diabetic mastopathy: a case report with reference to the findings of enhanced computed tomography.

We report a case of insulin-dependent diabetic fibrous mastopathy with special reference to the findings of computed tomography (CT). The patient was a 27-year-old woman with a history of insulin-dependent diabetes mellitus from childhood who presented with a right breast tumor. Physical examination showed a stony-hard, ill-defined but freely movable mass under the nipple of the right breast without nipple discharge. Mammography revealed a high-density mass shadow without microcalcifications or spicular formation. Ultrasonographic examination revealed an irregularly-shaped hypoechoic lesion with marked posterior acoustical shadowing. Contrast-enhanced CT revealed poor early phase contrast enhancement and slight delayed phase heterogeneous enhancement. Since core needle biopsy revealed fibrocystic disease, the lesion was suspicious for diabetic mastopathy. Incisional biopsy of the right breast lump was performed. On histopathological examination, the lesion showed fibrosis with dense lymphocytic infiltration around the lobules. Diabetic fibrous mastopathy was diagnosed. Physicians should be aware of the association of long-standing diabetes mellitus with the development of fibrous mastopathy. CT is considered a useful tool to differentiate diabetic mastopathy from breast cancer.

Contrast-enhanced computed tomography for diagnosing the intraductal component and small invasive foci of breast cancer.

It is important to eliminate local residual cancer to avoid local recurrence after breast conserving treatment. Many efforts have been made to detect extensive intraductal components (EICs) and small invasive foci of breast cancer by diagnostic imaging including MRI and contrast-enhanced computed tomography (CE-CT). The abilities and limitations of CE-CT are reviewed in this article. The sensitivity of EIC detection by CE-CT ranges from 76% to 88%, and specificity from 79% to 89%. The sensitivity for detecting EIC and cancerous lesions were significantly higher for CE-CT than for US or MMG. The enhanced patterns of CE-CT demonstrating EIC and small invasive foci were classified into diffuse, spotty, linear and multiple types. The differences of the size of cancerous extension by CE-CT from the pathological EIC were within 2 cm in almost all cases. CE-CT is useful for visualizing EIC and small invasive foci of breast cancer.

Two special types of breast cancer presenting as progressive disease after neoadjuvant chemotherapy with docetaxel plus doxorubicin.

Seventy-eight patients with primary breast cancer over 3 cm in diameter in stages II A, II B, III A and III B according to the UICC classification received neoadjuvant chemotherapy from August 1, 1998 to June 30, 2000 at the Breast Division of the National Cancer Center Hospital. Neoadjuvant chemotherapy consisted of doxorubicin (Adriamycin: ADM) 50 mg/m(2) and docetaxel (Taxotere: DOC) 60 mg/m(2) every three weeks. The overall clinical response to this regimen was 88% (69/78). Although neoadjuvant chemotherapy with this regimen achieved good responses in patients with breast cancer, 2 patients presented with progressive disease (PD) after treatment. One patient had inflammatory breast cancer (IBC) and the other had primary squamous cell carcinoma (SCC) of the breast. There were 4 cases of IBC and one case of SCC of the breast who received neoadjuvant chemotherapy in this series. Our observations suggest that this regimen might not be effective for these types of breast cancer.

Mechanisms of blood pressure oscillation caused by central nervous system ischemic response.

The experimental results on the hemodynamics and mechanisms of the systemic arterial pressure oscillation (SAPO) produced by the side pressure exertion procedure (SPEP) are presented. The SAPO has revealed us the existence of reciprocal structure at the base of the nervous integration of the cardiovascular system. The reciprocity is found between the type I and type II vasomotor neurons in the bulbar cardiovascular center. The latter is in charge of making the hierarchical set-up in the cardiovascular system, in which blood is supplied to the brain and the cardiac muscle at the expense of blood supply to the other organs. The former is in charge of building antihierarchical set-up, in which blood is provided to the other organs including the cardiac muscle at the sacrifice of blood supply to the brain. During the SAPO, the two groups of the reticular vasomotor neurons alternately discharge, and the two set-ups appear by turns in the cardiovascular system. Thus the animal can survive the SPEP for hours. The SAPO is caused by the coupling of the existing reciprocity with a newly generated central oscillator. The central oscillator has a segmental structure. It is composed of unit oscillators combined in series. This structure works as a ruler of the powerful CNS ischemic response and endows the SAPO with both rigidity and plasticity. It has shown the existence of segmental organization in the CNS in the chronological aspect also and the role of the CNS as that more than mere reflex centers. The study on the SAPO has opened a way to the physiology on emergence of a new order in the animal body.

Blood mobilization by regional vascular beds during cerebral ischemic pressor response in rabbits.

The mobilization of blood volume from regional vascular beds during cerebral ischemic pressor response was studied in anesthetized rabbits. The visceral beds of the kidney, jejunum, and liver served as volume reservoirs from which blood was mobilized during cerebral ischemia. The renal bed gave the largest volume decrease, from 24 to 13%. The magnitude of weight change in the renal and intestinal regions varied in parallel to the volemic state of the animal. Superimposition of pressure oscillation on the systemic pressor response was created by progressive restriction of the blood supply to the brain. Regional tissue weights also oscillated with a period equal to that seen in arterial pressure but almost 180 degrees out of phase. Such variations gave evidence of active venoconstriction in the reservoir response of all regional beds except the hind paw. The responses noted in the hind paw were passive except during complete restriction of the blood flow to the brain. Autoregulation of skeletal muscle and especially liver volume was present with moderate elevations in systemic arterial pressure.

Hemodynamic characteristics of regional vascular beds in cerebral ischemic pressor responses.

The mode of participation of three vascular beds of the kidney, intestine and skeletal muscles during blood pressure oscillation elicited by what is called a "side pressure exertion experiment" was investigated in anesthetized rabbits. The effect of varied circulating blood volume on their participation was also studied. The route of the blood supply to the brain was surgically restricted to one common carotid artery and the artery was compressed by exerting side pressure on a segment of it. When the side pressure was elevated in steps, the systemic arterial pressure also rose in steps from normal to the maximum, superimposed by an oscillation. During the course of graded elevation of systemic arterial ,ressure, the regional blood flow in the three vascular beds indicated characteristic changes as follows. The mean renal blood flow indicated simply an exponential decrease, the mean intestinal blood flow showed an initial slight augmentation which was followed by an expontential decrease, and the mean skeletal muscle blood flow exhibited a marked increase of up to 120 mmHg of mean arterial pressure, succeeded by an exponential decrease. Hemorrhaging and volume loading diminished the range of the changes in renal and intestinal resistance. Muscle resistance change was strongly intensified by hemorrhage. It is concluded that "post-ischemic reactive hyperemia" distinctly characterized the response of the three peripheral vascular beds in addition to the neurogenic control.

Neurogenic constriction of the superior mesenteric and femoral veins during systemic blood pressure oscillation in rabbits.

Behavior of the mesenteric and femoral veins was studied in rabbits during an arterial pressure oscillation elicited by a method that we call the "side pressure exertion experiment." A segment of the mesenteric or femoral vein with intact innervation was vascularly isolated and was perfused under an isovolumetric condition. The force of the isovolumetric constriction of the segments was recorded in terms of the intrasegmental pressure duirng arterial pressure oscillation. The intrasegmental pressure of the superior mesenteric vein indicated an alternation of marked rise and fall during the oscillation. On the other hand, the response of the femoral segment during oscillation was less phasic but was better maintained at the higher range of initial pressures than that of the superior mesenteric segment. Simultaneously with the maximum rise of systemic arterial pressure, maximum elevation by 6.1, 6.1 and 6.4 mmHg was obtained in the mesenteric vein segment at initial intrasegmental pressures of 6, 10 and 14 mmHg, respectively. In the same circumstances, the femoral vein segment indicated a maximum rise of 8.1 to 9.3 mmHg at initial pressures of 10, 18, 26 and 34 mmHg. It can be concluded that there are marked differences between the mesenteric and femoral segments in behavior during systemic arterial oscillation and in the range of bearable intrasegmental pressure. The characteristics of the two veins might be related to the difference of specific circumstances in which the respective veins send blood back to the heart.

Vascular resistance of intestine, muscle and skin during blood pressure oscillation.

After the blood supply to the head was surgically limited to one common carotid artery in rabbits, the artery was compressed by exertion of stepwise elevated side pressure on a segment of the artery. Systemic arterial pressure rose and began to oscillate when the side pressure was increased to 50 to 60 mmHg. The oscillations were regular and occurred at a rate of 3 to 4 per minute with a wave height of 15 to 45 mmHg. Concomitant with systemic pressure oscillations, and in near synchrony were undulations in the perfusion pressures recorded during constant flow from the vascularly isolated abdominal skin, skeletal muscle and small intestine. With the graded elevation of side pressure on the common carotid artery, mean systemic pressure and perfusion pressure showed a nearly exponential relation. The ratio between the two variables was slightly less than one below the systemic pressure of 120 mmHg and rapidly increased above this level. At ratios greater than one, the peripheral resistance undulations in the isolated areas gave a larger minimum and maximum, a sharper contour and, particularly in the skin, a phase lag in the period of the wave form when compared to the systemic pressure oscillations. These observations highlight the differences in response characteristics of peripheral resistance vessels and those of cardiac output and different consecutive parts of the systemic arteries during periods of intense sympathetic activation.