Biomedical subjects

Shinichi Sato

Publications and source records attributed to Shinichi Sato.

At least 109 records · Page 6Linked to original sources

PubMed2003

Fat and protein intakes and risk of intraparenchymal hemorrhage among middle-aged Japanese.

The authors examined the relation between low intakes of saturated fat and animal protein and risk of intraparenchymal hemorrhage in a 14-year prospective study (ending in 1997) of 4,775 Japanese aged 40-69 years who undertook a single 24-hour dietary recall. Compared with the highest quartile of energy-adjusted saturated fat intake (median, 17 g/day), multivariate relative risks, after adjustment for age, sex, community, total energy intake, and known cardiovascular risk factors, were 0.77 (95% confidence interval (CI): 0.42, 1.42) for the second quartile (12 g/day), 0.66 (95% CI: 0.34, 1.25) for the third quartile (8 g/day), and 0.30 (95% CI: 0.12, 0.71) for the lowest quartile (5 g/day); p for trend = 0.005. An inverse relation was observed among both hypertensives and nonhypertensives; the respective relative risks with a one standard deviation increase in saturated fat intake (15.4 g/day) were 0.72 (95% CI: 0.52, 1.00) and 0.36 (95% CI: 0.14, 0.95). Intake of animal protein tended to correlate inversely with risk; the relative risk with a one standard deviation increase in animal protein intake (17.6 g/day) was 0.79 (95% CI: 0.61, 1.02); p = 0.07. Results are similar to those recently reported for US women and together help to explain the high rate of this stroke subtype in Asian countries, where intakes of these nutrients are low.

Adult↗

PubMed2003

Relative contributions of selectins and intercellular adhesion molecule-1 to tissue injury induced by immune complex deposition.

Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the relative contribution of adhesion molecules, including selectins and ICAM-1, in this pathogenetic process, the cutaneous passive Arthus reaction was examined in mice lacking E-selectin, P-selectin, or both L-selectin and ICAM-1 with anti-P- or E-selectin mAbs. Edema and hemorrhage were significantly reduced in P-selectin(-/-) mice compared with wild-type mice while they were not inhibited in E-selectin(-/-) mice. Combined E- and P-selectin blockade resulted in more significant reduction relative to L-selectin/ICAM-1(-/-) as well as P-selectin(-/-) mice. Remarkably, both E- and P-selectin blockade in L-selectin/ICAM-1(-/-) mice completely abrogated edema and hemorrhage. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells that expressed significant levels of P-selectin glycoprotein ligand-1. Similarly reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated partly with the decreased production of tumor necrosis factor-alpha and interleukin-6. The results of this study indicate that both endothelial selectins contribute predominantly to the Arthus reaction by regulating mast cell and neutrophil infiltration and that the full development of the Arthus reaction is mediated cooperatively by all selectins and ICAM-1.

Animals↗

PubMed2003

The frequency of type 2 CD8+ T cells is increased in peripheral blood from patients with psoriasis vulgaris.

Studies have suggested that psoriasis vulgaris is mediated by type 1 T cells. In this study, we examined both chemokine receptor expression and intracellular cytokine production by circulating T cells to check the type 1/type 2 balance in psoriasis. CCR4+ and CXCR3- T cells predominantly produced interleukin-4 and interferon-gamma, respectively. The frequency of interferon-gamma-producing cells and that of CXCR3+ cells in circulating CD4+ T cells were similar for psoriatic patients and healthy control subjects. By contrast, the frequency of CCR4+CD8+ T cells and CCR4/CXCR3 ratio in circulating CD8- T cells were significantly higher in psoriatic patients than in healthy control subjects. Analysis of intracellular cytokine production also indicated relative increase of type 2 CD8+ T (Tc2) cells in peripheral blood from psoriatic patients. The frequency of circulating Tc2 cells directly correlated with Psoriasis Area and Severity Index. Immunohistochemical analysis showed that not only CXCR3+CD8+ T cells but also a similar number of CCR4+CD8+ T cells infiltrated the psoriatic epidermis and dermis. Our findings suggest an increase in Tc2 cell number in blood from psoriatic patients, and the association of Tc2 cells with inflammation in psoriasis.

Adult↗

PubMed2003

Relationships of differential leukocyte and lymphocyte subpopulations with carotid atherosclerosis in elderly men.

To examine the relationship between systemic immune status and carotid atherosclerosis in elderly men, differential leukocyte counts and lymphocyte subpopulations were measured in 557 apparently healthy Japanese men aged 60-75 years. Each individual also underwent high-resolution ultrasonography for measurement of intima-media thickness (IMT) of the common carotid arteries. The increased numbers of circulating lymphocyte subpopulations, including memory T cells (CD4+CD45RO+T cells) and late-phase activated B cells (CD19+CD80+B cells) correlated significantly and positively with the mean IMT of the common carotid artery after adjustment for age, smoking, and other cardiovascular risk factors. The positive associations of CD19+CD80+B and CD4+CD45RO+ T cell counts with mean IMT were more evident among nonsmokers, hypertensives, and men with lower HDL-cholesterol levels. The present epidemiological study provided the evidence that alterations in lymphocyte subpopulations, in particular memory T cells and late-phase activated B cells concur with carotid atherosclerosis among free-living elderly men.

Aged↗

PubMed2003

Function blocking autoantibodies against matrix metalloproteinase-1 in patients with systemic sclerosis.

Systemic sclerosis is characterized by fibrosis and systemic autoimmunity; however, roles of autoantibodies in the development of fibrosis remain unknown in systemic sclerosis. The net accumulation of extracellular matrix is dependent on the balance between the synthesis and degradation of extracellular matrix components, the latter process regulated by matrix metalloproteinases. Matrix metalloproteinase-1 (interstitial collagenase-1) can initiate degradation of collagen types I-III that are major extracellular matrix constituents in affected skin of systemic sclerosis. In this study, we tested the hypothesis that systemic autoimmunity in systemic sclerosis induced anti-matrix metalloproteinase-1 autoantibodies that inhibited matrix metallo-proteinase-1 activity, resulting in collagen accumulation. Enzyme-linked immunosorbent assay using human recombinant matrix metalloproteinase-1 revealed that IgG anti-matrix metalloproteinase-1 autoantibody levels were significantly elevated in sera from patients with systemic sclerosis, but not patients with active systemic lupus erythematosus or dermatomyositis, relative to normal controls. IgG anti-matrix metalloproteinase-1 autoantibody levels were significantly higher in patients with diffuse cutaneous systemic sclerosis than those found in patients with limited cutaneous systemic sclerosis. Furthermore, IgG anti-matrix metalloproteinase-1 antibody levels significantly correlated with the extent of fibrosis in the skin, lung, and renal blood vessels. The presence of IgG anti-matrix metalloproteinase-1 autoantibody in sera from systemic sclerosis patients was confirmed by immunoblotting analysis. Remarkably, IgG anti-matrix metalloproteinase-1 autoantibody in sera from systemic sclerosis patients inhibited matrix metalloproteinase-1 collagenase activity. Collectively, the results of this study suggest that anti-matrix metalloproteinase-1 autoantibody contributes to the development of fibrosis by inhibiting matrix metalloproteinase-1 collagenase activity and reducing the extracellular matrix turnover and suggest that the presence of anti-matrix metalloproteinase-1 autoantibody in systemic sclerosis is the link between systemic autoimmunity and fibrosis.

Adult↗

PubMed2003

Serum levels of tumor necrosis factor and interleukin-13 are elevated in patients with localized scleroderma.

BACKGROUND: The enhanced production of some cytokines may be related to the pathogenesis of localized scleroderma (LSc). OBJECTIVE: To determine whether serum levels of tumor necrosis factor (TNF) and interleukin (IL)-13 are elevated, and whether they correlated with clinical or serological features in patients with LSc. METHODS: Serum levels of TNF and IL-13 were examined by ELISA in 45 patients with LSc and in 20 healthy controls. RESULTS: The frequency of serum TNF detection was significantly higher in patients with LSc (24%) compared with that in healthy controls (0%). The frequency of serum IL-13 detection was also significantly higher in patients with LSc (29%) compared with that in controls (0%). In patients with LSc, elevated TNF levels significantly correlated with the presence of IgM antihistone antibodies, anti-single-stranded DNA antibodies, elevated serum IL-6 levels, the number of linear lesions, and muscle involvement. Elevated IL-13 levels were significantly associated with the number of plaque lesions and the total number of lesions. CONCLUSIONS: These results suggest that TNF and IL-13 may be associated with the development of LSc.

Adolescent↗

PubMed2003

Smoking raises the risk of total and ischemic strokes in hypertensive men.

To examine the relation between cigarette smoking and risk of stroke and coronary heart disease among Japanese, we conducted a 14-year prospective study of 3,626 men aged 40-69, initially free from history of stroke and coronary heart disease. We identified 257 strokes (75 hemorrhagic and 173 ischemic strokes) and 100 coronary heart disease events. When we adjusted for age and other cardiovascular risk factors, a significant excess risk among current smokers of > 20 cigarettes/day vs. never-smokers was found for total stroke (relative risk (RR) = 1.6 (95% confidence interval (CI), 1.1-2.4)). The excess risk of total stroke was particularly evident among hypertensives (RR = 2.3 (1.2-4.4)). The multivariate RR of ischemic stroke was 1.6 (1.0-2.5) for total subjects, and 2.2 (1.0-5.0) among hypertensives. Significant excess risks among current smokers of > 20 cigarettes/day vs. never-smokers were also found for coronary heart disease (RR = 4.6 (1.6-12.9)) and total cardiovascular disease (1.9 (1.3-2.7)). The estimated proportion of the events attributable to current smoking was 30 (95% CI, 11-44)% for total stroke and 34 (5-54)% for coronary heart disease. In conclusion, current smoking of > 20 cigarettes per day increased the risk of both total stroke and ischemic stroke among Japanese middle-aged men, and particularly among middle-aged hypertensive men.

Adult↗

PubMed2003

Ankle-arm blood pressure index and cardiovascular risk factors in elderly Japanese men.

Low ankle-arm systolic blood pressure index (AAI) correlates with various cardiovascular risk factors and with risk of subsequent coronary heart disease and stroke in Western countries. However, few epidemiological data are available among Japanese, in whom the reported prevalence of peripheral artery disease is low. We examined the relationship between AAI and cardiovascular risk factors among 1,219 men aged 60 to 79 years in two Japanese communities in 1999 and 2000. The prevalence of AAI<0.90 was 5% in both communities. Hypertension, major ECG abnormality, current smoking, and history of stroke were associated with two- to four-fold higher prevalence of AAI<0.90. One-standard deviation increments of body mass index and high density lipoprotein-cholesterol levels were associated with 60% and 40% lower prevalence of AAI<0.90, respectively. Although the prevalence of low AAI in Japanese elderly men is lower than that reported in the Unites States and European studies, similar correlations of low AAI with cardiovascular risk factors were observed among different ethnic groups. Low AAI is suggested to be a predictor for stroke among Japanese men, which should be confirmed by a prospective study.

Age Distribution↗

PubMed2003

Improvement in Japanese clinical laboratory measurements of total cholesterol and HDL-cholesterol by the US Cholesterol Reference Method Laboratory Network.

BACKGROUND: Accurate and precise measurements of total cholesterol (TC) and HDL-cholesterol (HDL-C) are necessary for effective diagnosis and treatment of lipid disorders. We studied the impact of TC certification and HDL-C evaluation in Japanese clinical laboratories to standardize their measurements. METHODS: We selected 78 laboratories participated at least twice for TC and 46 laboratories participated twice for HDL-C in the standardization protocols developed by the Cholesterol Reference Method Laboratory Network (CRMLN). We compared the initial and subsequent results using the performance guidelines established by US National Cholesterol Education Program (NCEP). RESULTS: For TC, mean percentage bias of all participants was -0.93% and -0.49% for the initial and second rounds, respectively. Mean within-sample CV was 0.72% and 0.69% for the initial and second rounds, respectively. For HDL-C, mean percentage bias of all participants was -1.86% and -0.06% for the initial and second events, respectively. Mean among-run CV was 1.56% and 1.58% for the initial and second events, respectively. CONCLUSIONS: TC accuracy in the second round than the initial round tended to improvement although statistically not significant, however in the five years follow-up, mean absolute percentage bias was reduced over time. HDL-C accuracy was statistically improved in the second event than the initial event. The precision for both TC and HDL-C did not change. This study shows CRMLN protocols contribute effectively to improvement of TC and HDL-C performance.

Certification↗

PubMed2003

Evaluation of functional disability using the health assessment questionnaire in Japanese patients with systemic sclerosis.

OBJECTIVE: To assess whether the functional disability in Japanese patients with systemic sclerosis (SSc) can be adequately evaluated by the Health Assessment Questionnaire (HAQ) developed in the United States. METHODS: The HAQ was completed by 121 Japanese patients with SSc, in whom SSc-specific physical examinations and laboratory tests were performed at the same time. Clinical findings associated with the disability index (DI) and individual components of the HAQ were examined using Student's t tests and Pearson's correlation tests. Logistic regression analysis was used to identify clinical findings that independently contributed to the increase in the HAQ-DI score. RESULTS: Japanese patients with SSc had significant functional disability, especially in the categories of eating and gripping, but the degree of disability was much less than was reported in previous studies carried out in the US. The increase in the HAQ-DI score was strongly correlated with increased total skin score, reduced oral aperture, reduced hand extension, increased finger flexion, subcutaneous calcinosis, flexion contractures, increased erythrocyte sedimentation rates, decreased percent vital capacity, and vascular involvement (p < 0.001 for all correlations). Multivariate logistic regression analysis showed that hand extension was the most important and an independent correlate of the HAQ-DI. CONCLUSION: Our multicenter, cross-sectional study has demonstrated that the self-administered HAQ is a valuable assessment tool of functional disability in Japanese SSc patients, who have social customs different from Americans, but functional disability measured by the HAQ is potentially influenced by ethnic variability.

Adult↗

PubMed2003

[Neurobehavioral toxicity of acrylamide and IDPN (3,3'-iminodipropionitrile) in rats by 28-day oral administration--problems encountered in collaborative study and a commentary on conducting neurobehavioral testing].

In order to clarify technical problems in evaluating neurotoxicity of chemicals and to solve them, a collaborative study with a common protocol was conducted at 11 domestic safety research laboratories. In the collaborative study, acrylamide and IDPN (3,3'-iminodipropionitrile), which are known neurotoxicants, were used, and the chemicals were orally administered to rats for 28 days. In addition to the clinical observation done routinely, detailed clinical observation, sensory and motor function tests including grip strength and motor activity were performed to evaluate neurobehavioral toxicity with reference to Functional Observational Battery (FOB). In general, neurobehavioral toxicity of the two chemicals was detected in the collaborative study. However, we also encountered technical problems, since neurobehavioral testing was unfamiliar to us. In the present report, we describe the major problems and how to solve them, and briefly explain the neurobehavioral testing procedure.

Acrylamide↗

PubMed2003

Serum concentrations of the CXC chemokines interleukin 8 and growth-regulated oncogene-alpha are elevated in patients with systemic sclerosis.

OBJECTIVE: To determine whether serum concentrations of 2 CXC chemokines, interleukin 8 (IL-8) and growth-regulated oncogene-alpha (GRO-alpha), which are potent chemoattractants and activators for neutrophils, are elevated and whether they correlate with clinical features in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with diffuse cutaneous SSc (dSSc; n = 36), limited cutaneous SSc (lSSc; n = 42), systemic lupus erythematosus (SLE; n = 15), dermatomyositis (DM; n = 15), and healthy controls (n = 35) were examined by ELISA. RESULTS: Serum IL-8 was detected significantly more frequently in patients with dSSc (61%) and lSSc (55%) relative to healthy controls (6%), patients with SLE (7%), and those with DM (13%). Similarly, serum GRO-alpha concentrations in SSc patients were significantly increased compared with controls, patients with SLE, or those with DM. Elevated IL-8 concentrations significantly correlated with decreased % DLCO and rheumatoid factor positivity, while increased GRO-alpha levels were significantly associated with decreased % DLCO and % vital capacity, involvement of kidney and muscle, the presence of anti-topoisomerase I antibody, and increased serum IgG levels. CONCLUSION: Our results suggest that the elevation of serum levels of the CXC chemokines IL-8 and GRO-alpha is specific to SSc and that the elevation of CXC chemokines, particularly GRO-alpha, correlates with the involvement of internal organs, especially pulmonary damage.

Adolescent↗

PubMed2003

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). I. Susceptibility distribution].

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of September and December 2001. Then, the susceptibilities of them to a variety of antimicrobial agents were investigated. The number of them were 496 strains. The breakdown of these strains was Gram-positive bacteria as 29.6% and Gram-negative bacteria as 70.4%. Susceptibilities of these bacteria to antimicrobial agents were as follows; against Staphylococcus aureus, vancomycin (VCM) showed a strong activity, and this drug also had a strong activity against MRSA in preventing growth of all strains at 1 microgram/mL. In addition, arbekacin (ABK) showed strong activity with the MIC90 of 2 micrograms/mL against MRSA and prevented growth of all strains at 4 micrograms/mL. ABK also showed a strong activity against Staphylococcus epidermidis in preventing growth of all strains at 0.5 microgram/mL. Ampicillin (ABPC) and cefozopran (CZOP) showed a relatively strong activity against S. epidermidis (MIC90: 8 micrograms/mL). ABPC, imipenem (IPM), and VCM showed strong activities against Enterococcus faecalis. No increase of low-susceptible strains in E. faecalis was observed against these antimicrobial agents. Against Escherichia coli, carbapenems showed the highest activities: meropenem (MEPM) prevented growth of all strains at 0.25 microgram/mL; IPM prevented growth of all strains at 0.5 microgram/mL. CZOP and cefotiam (CTM) also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/mL; MIC90 of CTM was within 0.5 microgram/mL. Quinolone-resistant E. coli was detected at frequency of 9.3%, which was lower than that in the last year, and was higher level than those in up to 1999. MEPM showed the strongest activity against Citrobacter freundii in preventing growth of all strains at 0.125 microgram/mL. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/mL. Against Serratia marcescens, the MIC90 of gentamicin (GM) was the lowest value being 2 micrograms/mL, and those of IPM and carumonam were 8 and 16 micrograms/mL, respectively. Against Pseudomonas aeruginosa, almost all drugs were not so active. The MIC90 of GM was 8 micrograms/mL, those of IPM and amikacin were 16 micrograms/mL, and those of all other drugs were over than 32 micrograms/mL.

Anti-Bacterial Agents↗

PubMed2003

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). II. Background of patients].

Five-hundred thirty one bacterial strains isolated from 412 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between September and December 2001. Then, the clinical background of patients were investigated such as sex, age, and type of infections, infections and kind of bacteria, frequency of bacteria isolation by age and infections, bacteria and infections by timing of antibiotics administration, and bacteria and infections by surgical procedures. With regard to the relationship between age and sex of patients and type of infections, the number of cases aged lower than 50 years was few and complicated UTIs without indwelling catheter was the most frequent in male patients. In females, the number of patients aged lower than 20 years was few. Most of female patients aged lower than 80 years had uncomplicated UTIs. As for the relationship between type of infections and kind of bacteria, Escherichia coli decreased as the infections were more complicated, and Pseudomonas aeruginosa and Enterococcus faecalis increased as the infections were more complicated. In relation of these results to age of patients, isolation frequency of E. coli gradually decreased with aging in patients aged 20 years and older with uncomplicated UTIs. The isolation frequencies of E. faecalis decreased with aging in the patients with complicated UTIs without indwelling catheter while P. aeruginosa decreased with aging in the patients with complicated UTIs with indwelling catheter. E. coli was isolated a few after administration of antibiotics, and P. aeruginosa and E. faecalis were frequently isolated after administration in the patients with all types of infections. As for type of causative organisms in UTIs and with or without surgical operation, E. coli was frequently isolated in the patients without surgery in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter, while P. aeruginosa was frequently isolated in the patients who underwent surgery in the patients with uncomplicated UTIs and complicated UTIs with indwelling catheter. In uncomplicated UTIs, isolation frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were significant in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, S. aureus and Staphylococcus spp. were frequently isolated in the patients without surgery.

Adolescent↗

PubMed2003

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). III. Secular changes in susceptibility].

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 10 institutions in Japan were supplied between September and December, 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 2000. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter). The drug sensitivity of S. aureus in this year was comparable to those in up to the previous year, and S. aureus showed the best susceptibility to vancomycin (VCM). E. faecalis showed good susceptibility to ampicillin and imipenem, and the MIC90s were 2 micrograms/mL. The susceptibility of E. faecalis to VCM was also good. E. coli showed good susceptibility to the drugs except penicillins. Among cephems, the susceptibility to cefozopran (CZOP) was better (MIC90: < or = 0.125 microgram/mL). Just as the last report, the decreases in susceptibility of E. coli to quinolones were also observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all the test drugs did not significantly change in 2001 and was generally good but not to penicillins. Among cephems, Klebsiella spp. showed good susceptibility to flomoxef, cefpirome, cefixime, and CZOP with < or = 0.125 microgram/mL of MIC90s either in uncomplicated or complicated UTIs. Although the drug sensitivity of P. aeruginosa was generally low, the detection of the strains that showed good susceptibility to quinolones and carbapenems (MIC: < or = 0.125-2 micrograms/mL) were relatively frequent.

Anti-Bacterial Agents↗

PubMed2002

Cold-induced mitochondrial uncoupling and expression of chicken UCP and ANT mRNA in chicken skeletal muscle.

Although bird species studied thus far have no distinct brown adipose tissue (BAT) or a related thermogenic tissue, there is now strong evidence that non-shivering mechanisms in birds may play an important role during cold exposure. Recently, increased expression of the duckling homolog of the avian uncoupling protein (avUCP) was demonstrated in cold-acclimated ducklings [Raimbault et al., Biochem. J. 353 (2001) 441-444]. Among the mitochondrial anion carriers, roles for the ATP/ADP antiporter (ANT) as well as UCP variants in thermogenesis are proposed. The present experiments were conducted (i) to examine the effects of cold acclimation on the fatty acid-induced uncoupling of oxidative phosphorylation in skeletal muscle mitochondria and (ii) to clone the cDNA of UCP and ANT homologs from chicken skeletal muscle and study differences compared to controls in expression levels of their mRNAs in the skeletal muscle of cold-acclimated chickens. The results obtained here show that suppression of palmitate-induced uncoupling by carboxyatractylate was greater in the subsarcolemmal skeletal muscle mitochondria from cold-acclimated chickens than that for control birds. An increase in mRNA levels of avANT and, to lesser degree, of avUCP in the skeletal muscle of cold-acclimated chickens was also found. Taken together, the present studies on cold-acclimated chickens suggest that the simultaneous increments in levels of avANT and avUCP mRNA expression may be involved in the regulation of thermogenesis in skeletal muscle.

Animals↗

PubMed2002

The cutaneous reverse Arthus reaction requires intercellular adhesion molecule 1 and L-selectin expression.

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process highly regulated by expression of multiple adhesion molecules. To assess the role of L-selectin and ICAM-1 in this pathogenetic process, the cutaneous reverse passive Arthus reaction was examined in mice lacking L-selectin (L-selectin(-/-)), ICAM-1 (ICAM-1(-/-)), or both (L-selectin/ICAM-1(-/-)). Edema and hemorrhage, which peaked 4 and 8 h after IC challenge, respectively, were significantly reduced in L-selectin(-/-), ICAM-1(-/-), and L-selectin/ICAM-1(-/-) mice compared with wild-type littermates. In general, edema and hemorrhage were more significantly inhibited in ICAM-1(-/-) mice than in L-selectin(-/-) mice, but were most significantly reduced in L-selectin/ICAM-1(-/-) mice compared with ICAM-1(-/-) or L-selectin(-/-) mice. Decreased edema and hemorrhage correlated with reduced neutrophil and mast cell infiltration in all adhesion molecule-deficient mice, but leukocyte infiltration was most affected in L-selectin/ICAM-1(-/-) mice. Reduced neutrophil and mast cell infiltration was also observed for all mutant mice in the peritoneal Arthus reaction. Furthermore, cutaneous TNF-alpha production was inhibited in each deficient mouse, which paralleled the reductions in cutaneous inflammation. These results indicate that ICAM-1 and L-selectin cooperatively contribute to the cutaneous Arthus reaction by regulating neutrophil and mast cell recruitment and suggest that ICAM-1 and L-selectin are therapeutic targets for human IC-mediated disease.

Animals↗

PubMed2002

Trends in the incidence of coronary heart disease and stroke and the prevalence of cardiovascular risk factors among Japanese men from 1963 to 1994.

PURPOSE: To determine trends in the incidence of cardiovascular disease in Japan, we examined observational data on coronary heart disease, stroke, and cardiovascular risk factors among urban Japanese working men. SUBJECTS AND METHODS: The surveyed population included all male employees aged 40 to 59 years who worked for eight industrial companies in Osaka, the second largest metropolitan city in Japan. Surveillance for cardiovascular disease and risk factors was conducted from 1963 to 1994. RESULTS: The age-adjusted incidence of coronary heart disease increased from 0.4 per 1000 person-years during 1963 to 1970, to 1.5 per 1000 person-years during 1979 to 1986, and then plateaued until 1987 to 1994 (P for trend = 0.002), whereas the incidence of stroke declined from 1.2 per 1,000 person-years during 1971 to 1978, to 0.6 per 1,000 person-years in 1987 to 1994 (P for trend = 0.02). The age-adjusted mean (+/- SD) total cholesterol level, which was 4.87 +/- 2.88 mmol/L during 1963 to 1966, increased to 5.11 +/- 0.62 mmol/L during 1982 to 1983 (P <0.001), and 5.09 +/- 0.75 mmol/L during 1990 to 1991. Both mean systolic and diastolic blood pressures increased by 1 mm Hg between the periods of 1966 to 1967 and 1982 to 1983, and declined below the 1966 to 1967 levels during 1990 to 1991. The prevalence of smoking declined from 72% during 1975 to 1976, to 58% during 1990 to 1991 (P for trend <0.001). CONCLUSION: Although these findings were limited to urban middle-aged men, the increase in serum cholesterol is likely to attenuate the reduction in future rates of coronary heart disease in Japan that would have been expected to result from the declining prevalence of smoking.

Adult↗