The transition of fibrinogen to fibrin and to their degradation products within the arterial wall has been reported to be accompanied by atherosclerotic progression. A major step in the pathogenesis of atherosclerosis is the vectorial migration of vascular smooth muscle cells (SMCs) from the arterial media through the internal elastic lamina into the intima and their subsequent proliferation in the intima. I have been studying the effects of fibrinogen, fibrin and their degradation products on the behaviour, particularly migration, of SMCs. Fibrinogen/fibrin stimulates the adhesion and migration of SMCs and their effects are mediated by both the RGD-containing region of the α chain of fibrinogen/fibrin and integrin αvβ3 on the cell surface. SMCs migrate into fibrin gel even with no other chemotactic stimuli. SMCs displayed two-fold increase in migration into crosslinked fibrin gels compared to non-crosslinnked gels, suggesting the importance of fibrin crosslinking by factor XIIIa on its three-dimensional structure for the migration of SMCs. Fibrin gels prepared with batroxobin, which cleaves only fibrinopeptide A, with ACTS, which cleaves only fibrinopeptide B, and with protamine sulfate, which cleaves nothing, but forms a fibrin-like gel, induce migration of SMCs in a manner similar to the gel prepared with thrombin, suggesting that the cleavage of fibrinopeptides is not involved in the migration of SMCs. Both anti-fibrinogen fragment D and E antibodies inhibit the migration of SMCs into fibrin gel, suggesting that both D and E regions of fibrin are involved in the migration of SMCs into fibrin gel. The migration of SMCs into fibrin gel also depends on the RGD-containing region and integrin αvβ3. Both fibrinogen fragments D and E inhibit the migration of SMCs into fibrin gels, suggesting that these fragments may be involved in the regulation of SMC migration into fibrin gel as the result of fibrinolysis. Although subcultured SMCs usually show a synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. We employed an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. αvβ3 integrin and the RGD-containing region are involved in the migration of SMCs into the fibrin gels. SMCs which migrated from the explants showed positive staining with monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from a contractile to synthetic state. These findings show that fibrin (ogen) itself induces adhesion and migration of SMCs without other chemotactic or chemokinetic substances, suggesting a crucial role for fibrin (ogen) in the development and progression of such vascular diseases as atherosclerosis, thrombosis and restenosis following balloon angioplasty.
We investigated the pathogenesis and therapy of virus infection-induced senile bronchial asthma in vitro. To examine the effects of rhinovirus infection on the production of cytokines and intercellular adhesion molecule-1 (ICAM-1), human tracheal epithelial cells and submucosal gland cells were cultured, and infected with human rhinovirus. Rhinovirus upregulated the production of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α in supernatants of epithelial cells and submucosal gland cells, and IL-1α and granulocyte macrophage colony-stimulating factor (GM-CSF) in supernatants of submucosal gland cells. Rhinovirus upregulated the expression of ICAM-1 mRNA. Rhinovirus infection also increased epithelial permeability. These events may be important for the spread of airway inflammation after rhinovirus infection. Furthermore, we studied the effects of dexamethasone and erythromycin on the modulation of virus infection and induction of cytokines and ICAM-1 in tracheal epitherial cells. Both of them reduced viral titers of rhinovirus type 14, a major group rhinovirus, and cytokine production of supernatants, and ICAM-1 mRNA expression in the cells. Because it is known that acidic conditions by proton pumps are needed for rhinovirus entry into the cells, we studied the effects of H+ ATPase inhibitor bafilomycin A1. Bafilomycin A1 reduced the virus titers of both rhinovirus type 2 and 14 in supernatants. These findings in our in vitro study suggest that dexamethasone, erythromycin and bafilomycin A1 may inhibit rhinovirus infection and modulate airway inflammation induced by rhinovirus infection.
To determine the factors that influence acute hospitalization among long-term home care patients, all patients (N=59) who were provided home visiting nursing and/or medical care from a 169-bed community hospital in Saitama, Japan, between May 1989 and April 1993 were followed until November 1993. Data on patients concerning age, sex, diagnosis of primary disease, ability to perform activities of daily living (ADL), intellectual impairment, serum albumin, frequency of home visiting medical care, medical and nursing care provided at the patient's home were collected from the medical charts of each subject. The main outcome measure was onset of acute hospitalization during a one-year period after initiation of home visiting medical care. Thirty-five patients (59%) were admitted due to acute illness. Compared with patients who were not in need of acute hospitalization, Cox's proportional hazard model revealed that patients who were completely dependent for eating, dressing, and using the toilet (Hazard ratio (HR)=3.13, 95% confidence interval (CI)=1.34-7.35) and serum albumin less than 3.5g/dl (HR=3.05, 95% CI=1.37-6.77) were more likely to be hospitalized. Evaluating a patient's physical conditions at the beginning of home visiting care may allow us to predict whether the patients will have to be hospitalized during the following one-year period.
This study was conducted on a total of 358 normotensive (mean blood pressure<107mmHg) inpatients (182 men and 176 women, mean age: 67.8years) who had no cardiorenal or nutrition disorders that would affect blood pressure, lipid and glucose metabolism and who had not been given depressors or antilipidemic agents during the four years from September 1995 to August 1999. In addition to the known risk factors for atherosclerosis, the effects of pulse pressure and mean blood pressure on sclerotic changes of the carotid arteries were examined. These sclerotic changes were assessed by measuring the thickness of the combined intima-media of the common carotid artery (carotid arterial wall thickness) by ultrasonography (Hitachi EUB-565) and linear probe (7.5MHz). When the patients were divided into three groups based on pulse pressure (PP1, lower than 51mmHg; PP2, 51-65mmHg; PP3, higher than 65mmHg), the age of the group with higher pulse pressure was significantly higher (p=0.0011), women more (p=0.0315). However there were no differences in background factors such as body mass index, Brinkman index, lipid metabolism, uric acid, and glucose metabolism. There was observed a positive correlation between the mean blood pressure and the pulse pressure for both men and women (r=0.31, p<0.001, respectively). As for the relation between the pulse pressures and the blood pressure parameters, the systolic blood pressure, pulse pressure and the mean blood pressure were significantly higher in the group with higher pulse pressure (p<0.001, respectively), but the diastolic blood pressure was significantly lower (p=0.0275). As for the relation between the pulse pressure and the carotid wall thickness, the groups of both men and women with higher pulse pressures had significantly greater cartoid arterial wall thickness (p<0.001, p=0.0042, respectively). Logistic regression analysis of the carotid arterial wall thickness (defined as hypertrophic if greater than 1.0mm) as the object variable and various risk factors including pulse pressure as the explanatory variables revealed that pulse pressure and LDL-C were significant independent contributing factors for men. The age, Brinkman index, T-Chol and HDL-C were significant independent contributing factors for women. For all subjects, men, the age, Brinkman index, pulse pressure, TG and LDL-C were significant independent contributing factors. These facts suggest that pulse pressure is an important risk factor for thickening of the carotid arterial wall.
To examine the relationship between type A behavior pattern and hypercholesterolemia, we recruited 109 primary hypercholesterolemic patients without treatment for hyperlipidemia (30 males and 79 females) and then classified them according to Maeda's questionnaire into two groups; type A group (16 males and 35 females, aged 73.1±8.7) and type B group (14 males and 44 females, aged 71.3±8.7). We studied serum total cholesterol, serum triglyceride and BMI. Serum total cholesterol was shown significantly higher in type A group than that in type B (233.0±22.8 vs 223.9±14.2 p<0.01) and BMI lower (24.0±3.9 vs 25.4±3.9 p<0.05), however, there was no significant difference in serum triglyceride between two groups (148.9±8.2 vs 134.0±48.8). Although there was no significant difference in BMI, serum total cholesterol was significantly higher in the women's group and in the 60s. This study suggests that type A behavior pattern is related to lipid metabolism, however we should take gender and age into consideration to study the relationship between type A behavior pattern and lipid metabolism.
A 65-year old man was admitted with severe dysphagia, ataxia and aspiration pneumonia. Dysphagia and ataxia were caused by lateral medullary infarction (Wallenberg's syndrome). The swallowing abnormality was assessed by videofluorography and we attempted the balloon dilatation method for cricopharyngeal dysphagia. Three months after initiation of swallowing training, videofluorography (VF) showed that the magnitude of aspiration to the trachea had decreased and the patient began taking food by mouth. The balloon dilatation method is successful for chronic stage cricopharyngeal dysphagia and the VF test is useful for quantitative assessment of dysphagia and for deciding when to start oral intake in elderly patients.
A case of Klinefelter's syndrome with schizophrenia-like symptoms is reported. He was given a diagnosis of schizophrenia at the age of 39. After being treated with medication for many years, he stopped taking them at the age of seventy-two and involuntary movements appeared in his limbs and the trunk. Upon admission to our hospital, he was experiencing delusion and psychosocial exitement. A physical examination showed hime to be a thin man of 175.5cm height, suffering from a mild degree of gynecomastia, testicular atrophy. Serum LH and FSH were both high 10.9 and 47.8mU/ml respectively. Serum testosterone concentration was 0.2ng/ml, much lower than the normal range (2.7-10.7ng/ml). On the Wechsler adult intelligence scale (Revision), his total IQ was 103 (performance IQ 100, verbal IQ105). Karyotype analysis revealed an XXY pattern. Although slight auditory hallucinations remained, the delutional symptoms as well as the involuntary movemets diminished after the administration of psychotrophics. Personality changes such as apathy and abulia was subsided. The psychological symptoms were very simillar to these of cases in other reports of Klinefelter's syndrome associated with schizophrenia-like sympotoms. Some reports about the relationships between sex hormones and schizoprenia including other psychotic disorders suggestthat the X-chromosome plays an important part in the mechanism of psychosocial symptoms and in the prognosis in Klinefelter's syndrome.