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To assess the effect of antihypertensive drugs on aortic distensibility, we evaluated the aortic distensibility of 33 hypertensive patients before and after antihypertensive treatment by using cine magnetic resonance imaging. Thirty three hypertensive patients were divided into three groups and treated for 12 weeks with 2–4 mg trichlormethiazide per day (n = 10), 80 mg nicardipine per day (n = 13) and 50 mg alacepril per day (n = 10). There were no significant differences in mean age and mean blood pressure among the three groups. Cine magnetic resonance was performed at ascending and descending aortic levels. Aortic area was measured at the maximum and minimum frames. The effect of antihypertensive therapy on aortic distensibility was evaluated as the percent change from before treatment to after treatment. There were no significant differences in pulse pressure before and after treatment with trichlormethiazide, nicardipine and alacepril. After treatment with these drugs, mean blood pressure in all groups decreased (trichlormethiazide and nicardipine, P < .01; alacepril, P < .05), (the maximum area - the minimum area) and aortic distensibility in all groups increased significantly (each P < .01). Percent changes in aortic distensibility after treatment were significantly higher with nicardipine (ascending, 346.6 ± 255.9%; descending, 338.8 ± 246.5%, each P < .05) and alacepril (ascending, 369.7 ± 238.8%, P < .05; descending, 306.9 ± 123.3%, P < .01) than with trichlormethiazide (ascending, 146.0 ± 139.6%; descending, 129.3 ± 97.5%). In conclusion, nicardipine and alacepril have a beneficial effect on aortic distensibility.

It is well known that allergic reactions may sometimes occur in patients under treatment with β-lactam antibiotics. For the detection of antidrug antibodies in vitro, conjugation with human serum albumin has been considered to be essential. In this study, we found that cefotiam, cefpirome, and ceftazidime could be immobilized without conjugation to carrier protein to construct a solid-phase enzyme-linked immunosorbent assay (ELISA) system. We describe a patient (26-year-old female nurse) with contact urticaria induced by antibiotics. Using the serum of this patient, we successfully detected IgE antibody directed to the aminothiazolyl group of cephalosporins, which has not previously been reported. Results suggest that the simple ELISA using unconjugated antibiotics could be applicable to patients with allergy to some cephalosporins and the aminothiazole side chain of the cephalosporins could cause an IgE-mediated allergic reaction.

Although calcium-channel blockers and angiotensin-I-converting enzyme inhibitors are often used for treatment of hypertension in the elderly in Japan compared to those in the United States and in European countries, there have been few investigations on the prognosis of the elderly receiving these antihypertensive treatments. The Research Group for "Guidelines on the Treatment of Hypertension in the Elderly" collaborated with the Comprehensive Research Projects on Aging and Health group of the Ministry of Health and Welfare of Japan in performing a 3-year survey on the outcome of 700 hypertensive elderly outpatients (> or = 60 years) receiving treatment of antihypertensive drugs. Antihypertensive drugs including dihydropyridine-type calcium channel blockers, beta blockers, angiotensin-I-converting enzyme inhibitors, diltiazem, diuretics and old-type antihypertensives (hydralazine, budralazine, and centrally acting drugs such as clonidine, methyldopa and guanabenz) were administered to 71.3%, 30.4%, 26.2%, 14.0%, 8.6%, and 6.4% of the 642 elderly patients surveyed for three years, at the time of registration, respectively. Morbidity and mortality rates of total cerebro-cardiovascular diseases, stroke, and heart diseases, were 27.6 and 7.81/1,000 patient-years, 15.1 and 3.6/1,000 patient-years, 10.4 and 4.2/1,000 patient-years, respectively. These results were similar or even better than those of megatrials of antihypertensive treatments for elderly patients in Europe and United States. After adjustment for potential confounding factors, multiple logistic analysis revealed that a past history of ischemic heart disease, use of the old-type antihypertensive drugs, male gender, and diastolic high blood pressure were independent risk factors for the morbidity of cerebro-cardiovascular diseases taking the group of non-cerebro-cardiovascular disease as the reference group. We also identified 22 cases of newly occurred malignancies including 7 fatal cases. However, none of the antihypertensives was significantly related to the occurrence of malignancies. These results lead support to the tendencies in the use of antihypertensive drugs in Japan.

Background: Histopathological study in amyloid heart demonstrates that myocyte destructed by the extracellular deposition of amyloid protein together with viable myocyte is present. We hypothesized that rapid thallium washout may be found in amyloid heart as in regions which have a mixture of viable myocyte and scar tissue in patients with myocardial infarction. Thus, the purpose of this study was to evaluate the extent and severity of myocardial damage due to amyloid deposits using the washout rate of the tracer on rest-redistribution thallium-201 (201Tl) myocardial scans in cardiac amyloidosis patients. Methods: Rest-redistribution 201Tl myocardial scintigraphy was performed in 5 patients with biopsy-proved systemic amyloidosis with cardiac involvement (amyloidosis group). The initial and delayed images were obtained 15 min and 4 h, respectively, after intravenous injection of the tracer of 111 MBq. Washout rate of the tracer was calculated. Twelve patients with no apparent heart disease served as controls (control group). Results: Mean washout rate of the whole heart was higher in the amyloidosis group than in the control group (56 ± 9% vs 36 ± 6%, p < 0.001). Particularly, 4 of the 5 patients in the amyloidosis group presented a very high rate of thallium clearance which ranged from 57 to 61%, and died in less than a year. In the remaining 1 patient who had a normal washout rate of the tracer in the first study, it changed from 40 to 53% during the 5-year follow-up period. Conclusions: Washout rate in the setting of rest and delayed 201Tl images may represent the severity of amyloid depositions in the myocardium and may provide prognostic information.

BACKGROUND Apoptotic cell death is the major form of myocardial damage produced by coronary ischemic events. OBJECTIVE To assess whether circulating levels of soluble Fas (sFas), an inhibitor of apoptosis, and sFas ligand, an inducer of apoptosis, in patients with coronary artery disease are greater than normal. METHODS Forty-seven patients [acute myocardial infarction (AMI) in 17, old myocardial infarction (OMI) in 15, stable angina in 15] and 10 normal control subjects participated in this study. Serum levels of sFas and sFas ligand in all patients were measured, and cardiac catheterizations were performed. RESULTS Serum levels of sFas were greater than normal only in patients with AMI (4.6 +/- 1.6 ng/ml); the levels were significantly higher than those in patients with OMI (2.1 +/- 0.6 ng/ml) and stable angina (2.2 +/- 0.5 ng/ml), and in normal subjects (2.0 +/- 0.6 ng/ml; P < 0.0001). However, there was no difference among serum levels of sFas ligand for all groups. For patients with AMI, there was no significant correlation between serum levels of sFas and peak levels both of plasma creatine phosphokinase and of plasma myosin light chain type I as clinical indexes of infarct size. However, there were significant correlations between serum levels of sFas and both pulmonary artery wedge pressure (r = 0.767, P = 0.0003) and left ventricular end-diastolic pressure (r = 0.629, P = 0.03). CONCLUSIONS Circulating sFas increases in concentration in relation to the severity of hemodynamic conditions in patients with AMI, but it is independent from size of infarct. Therefore, circulating sFas could play an important role as the marker of pathophysiologic conditions associated with cardiomyocyte apoptosis in AMI.

Abstract —Platelet-derived growth factor (PDGF) and its receptors are widely expressed in several tissues in the stage of cellular growth and development. In adulthood, PDGF β-receptor (PDGFβR) is mainly detected in pathological conditions such as atherosclerotic lesions and injured vascular wall. The purpose of the present study was to elucidate the underlying mechanism of PDGFβR gene expression under pathological conditions in vascular smooth muscle cells (VSMC) and to identify the important cis elements responsible for tissue-specific gene transcription. Gel mobility shift assay and supershift assay indicated that the CCAAT motif located at −67 (C67) was mainly interacted with NF-YC, and this element drove the basal promoter activity of the gene as a putative promoter. On the other hand, another important sequence essential for the basal transcription was found at a 30-bp region (R30) spanning −150 to −121. To test whether R30 actually regulates the tissue-specific transcription of PDGFβR gene, electromobility shift pattern was compared between VSMC and hepatoma cell line (HTC). We obtained the result that DNA-protein complex seen only in nuclear extracts from HTC suppressed the promoter activity in HTC in a tissue-specific manner. Furthermore, cis element decoy transfection experiments for C67 and R30 also revealed that both elements were functionally important in mRNA expression of PDGFβR in VSMC. From these results, we concluded that the basal activity of PDGFβR gene expression was transactivated by the interaction or coordination of both C67 and R30, and the latter one mainly controlled the tissue-specific gene expression in VSMC.

Calponin has been implicated in the regulation of smooth muscle contraction. Basic calponin, one of the calponin isoforms, is expressed exclusively in smooth muscle cell (SMC)-rich tissues, and is considered to be a phenotypic marker of differentiated SMC. To define the molecular mechanism of SMC-specific gene transcription in humans, we isolated and characterized the 5′-flanking region of this gene. Sequence analysis revealed that several putative cis-acting elements were clustered within a 500-bp sequence upstream of the transcription start site. However, the 1.9-kb promoter region obtained herein lacked a completely matched consensus sequence of the CArG box that is commonly identified in the promoter region of other SMC-specific genes. A luciferase assay demonstrated that the 1.9-kb promoter region was sufficient to drive a basal transcriptional activity not only in human vascular smooth muscle cells (VSMC) but also in HeLa cells. In particular, the sequence between positions -1, 906 and -867 had a significantly higher transcriptional activity in VSMC than in HeLa cells. In contrast, the promoter activity was drastically decreased between positions -327 and -257 in both types of cells. These results indicate that the sequence spanning from position -327 to -257 contains an essential domain involved in the basal transcriptional activity of the human basic calponin gene, and that the distal region of the 1.9-kb 5′-flanking sequence presented herein may play a pivotal role in the phenotypic modulation of VSMC. (Hypertens Res 1999; 22: 187-193)

To compare the incidence of cough between two angiotensin converting enzyme (ACE) inhibitors, imidapril and enalapril, comparative crossover study was performed in 489 patients (228 men and 261 females) with essential or renal parenchymal hypertension. Patients were randomly assigned to one of two treatment groups, a group receiving imidapril for 12wk (Period I) followed by enalapril for 12wk (Period II), and a group in which the order of drugs was reversed. The occurrence of cough during treatment was monitored by questionnaire in all cases. There were no differences in background characteristics between the two groups. The incidence of cough during Period I was 15.2% (32/210) in the group initially treated with imidapril (Group IE) and 38.6% (85/220) in the group initially treated with enalapril (Group EI), the difference being statistically significant (p

Searching for early predictive markers of the therapeutic effects of high-dose corticosteroids ("pulse therapy") on patients with rapidly progressing idiopathic pulmonary fibrosis (IPF), we evaluated 14 such patients, who had received weekly pulse therapy for at least 3 wk. Eight patients responded to the treatment and survived. However, six patients failed to respond, and all of them died within 3 mo after treatment. Serum levels of KL-6 (MUC1 mucin), neutrophil elastase (NE), and lactate dehydrogenase (LDH) were measured before, and at 1 wk and 3 wk after treatment. Levels of KL-6 decreased significantly in patients who lived, whereas KL-6 levels tended to increase in patients who died. The values of NE did not change significantly. LDH levels decreased significantly at 1 wk, and tended to decrease at 3 wk in patients who lived. However, in patients who died, they did not significantly change. At the first cycle of treatment when clinical effects may not be evident, the decrease in KL-6 but not LDH levels was significantly related to a favorable outcome, whereas their increase was related to a poor outcome. Results suggest that monitoring with KL-6 may contribute to early clinical decisions for alternative therapy in the management of rapidly progressing IPF.

There are only a few reports concerning coexistent hypertrophic cardiomyopathy (HCM) and vasospastic angina. Clinical characteristics in patients with both diseases have not been clarified yet. This study was designed to elucidate the relationship between chest pain and coronary vasospasm in HCM patients and to delineate clinical characteristics in patients with both HCM and coronary vasospasm. First, 36 patients with HCM underwent acetylcholine provocation test for coronary vasospasm and were divided into two groups on the basis of presence or absence of coronary vasospasm. Next, the following risk factors for coronary artery disease were compared between the two groups: hypertension, smoking, hyperlipidemia, diabetes mellitus, and hyperuricemia. Coronary vasospasm was induced in 10 (28%) of 36 patients with HCM. There were no significant differences in age and male gender between the two groups. Smoking was more prominent in HCM patients with than without coronary vasospasm (80% vs 35%, p In conclusion, coronary vasospasm appears to play a significant role in the etiology of myocardial ischemia in Japanese patients with HCM, and smoking might be a major risk factor for coexistence of HCM and coronary vasospasm.

To investigate the pathophysiologic role of soluble interleukin-6 receptor (sIL-6R) in patients with rheumatoid arthritis (RA), serum sIL-6R levels were measured in 15 RA patients and 15 healthy control subjects using a sandwich enzyme-linked immunosorbent assay. Correlation analysis was performed between sIL-6R levels and clinical variables such as joint score, Lansbury’s index, C-reactive protein and platelet counts. Levels of sIL-6R and IL-6 were also measured in paired samples of serum and synovial fluid obtained at the same time from nine RA patients. Serum sIL-6R levels in RA patients (153.9±56.9 ng/ml) were significantly higher than those of control subjects (115.1±19.1 ng/ml;P

A 38-year-old man underwent pericardiectomy because of effusive-constrictive pericarditis. The gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging showed pericardial thickening separate from the effusion, which could not be shown by unenhanced computed tomography. Gd-DTPA enhanced magnetic resonance imaging could be useful for the early detection of effusive-constrictive pericarditis.

OBJECTIVE: To understand the regulatory mechanism of platelet-derived growth factor beta-receptor gene expression. METHODS: A 1.7 kb genomic fragment was obtained from a rat genomic library. After we had determined an entire sequence of this fragment, transcription start sites were determined both by primer extension analysis and by riboprobe mapping. We performed a functional promoter assay by using a dual-luciferase reporter system. Progressive 5'-deletions of the fragment and site-directed mutagenesis for the CCAAT motif located at -67 or -94 were used for the assay, and their promoter activities in vascular smooth muscle cells were assessed. Gel-mobility shift analysis was also performed for the CCAAT motif at -67. Effects of the upstream sequence spanning -310 through -120 on heterologous gene promoters were also investigated. RESULTS: Multiple transcription start sites were observed in the 5'-flanking region, and the 1.7 kb sequence was actually active as a functional promoter in vascular smooth muscle cells. Two important sequences responsible for the basal transcriptional activity were identified by the functional promoter assay. One was the CCAAT motif at -67 which acts as a promoter itself, and the other was the upstream region spanning -310 through -210 which positively regulates the basal promoter activity. CONCLUSION: The basal promoter activity of the rat platelet-derived growth factor beta-receptor gene is mainly regulated by the interaction or coordination of two sequences, the CCAAT motif and the upstream control element.

This study was designed to assess heart performance in young (10-week-old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, in terms of whole heart function in vivo and mechanics of isolated ventricular myocytes in vitro. The data suggest that left ventricular pressure (LVP) generation is greater, and the maximal velocities of LVP generation and decline are faster in SHR than in WKY. Two-dimensional morphologic measurements show that SHR myocytes are hypertrophied and that augmented contractile function is also present in isolated cells as determined by the extent of shortening and velocity of shortening. Relaxation is also faster at the myocyte level as determined by velocity of relengthening. However, the slope of the relationship between myocyte peak shortening and velocity of relaxation was similar in both groups. These results suggest that hyperdynamic myocyte relengthening may reflect changes in elastic recoil from increased shortening rather than intrinsic changes in cellular mechanisms, which are independent of shortening.

1. The aim of this study was to elucidate the pathophysiological role of adrenomedullin and the relation between adrenomedullin and other hormones in patients with hypertrophic cardiomyopathy. 2. Fourteen patients with hypertrophic obstructive cardiomyopathy (HOCM), 26 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) and 14 normal control subjects participated in this study. Radioimmunoassay for plasma adrenomedullin concentration was performed with adrenomedullin-M antibody. Plasma levels of endothelin-1, atrial and brain natriuretic peptides and noradrenaline were also measured. 3. Plasma levels of adrenomedullin were higher in patients with hypertrophic cardiomyopathy (8.43 ± 3.73 pmol/l) than in normal controls (5.24 ± 0.44 pmol/l, P < 0.005). There was no significant difference between HOCM and HNCM patients. There was a weak correlation between plasma levels of adrenomedullin and total 12-lead QRS voltage in patients with hypertrophic cardiomyopathy (r = 0323, P < 0.05) 4. Plasma levels of endothelin-1, atrial and brain natriuretic peptides were higher in hypertrophic cardiomyopathy than in normal controls. Endothelin-1 showed no significant difference between HOCM and HNCM patients, but atrial and brain natriuretic peptides were higher in HOCM than in HNCM patients. There was a positive correlation between plasma levels of adrenomedullin and endothelin-1 (r = 0.575, P < 0.0001), but no correlation between plasma levels of adrenomedullin and atrial natriuretic peptide, brain natriuretic peptide and noradrenaline. 5. Our results indicate that adrenomedullin may play an important role to maintain haemodynamics in patients with hypertrophic cardiomyopathy, and its action may be related to endothelin-1 but independent of atrial natriuretic peptide, brain natriuretic peptide and noradrenaline.

This study was conducted to quantify coronary blood flow (CBF) noninvasively according to the fractionation principle and to elucidate the relation between CBF and left ventricular hypertrophy. CBF/cardiac output (CO), estimated on the basis of the ratio of myocardial uptake/total injected dose of thallium-201 (% cardiac uptake), was determined in 14 control subjects and 40 patients with essential hypertension. CBF and CBF per 100 g of myocardium (unit CBF) were calculated according to the following formulas: CBF= % cardiac uptake x CO, and unit CBF = (CBF/LVM) X 100, where CO and left ventricular mass (LVM) are echocardiographically determined. There was good reproducibility of % cardiac uptake (r = 0.983, p < 0.0001). Percent cardiac uptake was greater in hypertensive patients (4.65+/-1.44%) than in control subjects (3.64+/-0.64%), and there was a positive correlation between % cardiac uptake and LVM. CBF (ml/min) was greater in hypertensive patients (240.7+/-80.5) than in control subjects (194.9+/-36.9), but unit CBF (ml/min/100 g) was less in hypertensive patients (102.2+/-26.7) than in control subjects (150.3+/-30.5). Multiple regression analyses showed that LVM was the most potent independent predictor of resting CBF in hypertension. Our results indicate that CBF, determined by thallium-201 myocardial scintigraphy, increases parallel to the increase in LVM, but unit CBF decreases even in the resting condition in patients with essential hypertension.

A 71-year-old woman was admitted to hospital because of malaise and bloody stool. Laboratory findings consistently showed anemia (Hb 9.2 g/dl) and occult blood in the stool. Although barium series and endoscopy of the upper and lower intestinal tructs were carried out, there was no evidence of bleeding from the gastrointestinal tract 99mTcO4- scintigraphy, which was performed to exclude bleeding from Meckel's diverticulum, also did not locate a significant lesion. Angiographic imaging of the superior mesenteric arteries (SMA) was performed to exclude lesions such as small intestine tumors with extraluminal growth and vascular abnormalities such as A-V malformation and it revealed the round encasement of arteries in the peripheral SMA region, strongly suggestive of a small intestine tumor. Surgery was performed and an extraluminally protruding tumor was found in the small intestine. The excised tumor was 4 x 3 x 3.5 cm in size, are was diagnosed histologically as aberrant pancreas. The postoperative laboratory findings showed that the anemia had improved and occult blood was not detected in the stools. Although aberrant pancreas of the small intestine is a common benign tumor, it is a very unusual cause of bleeding from the alimentary tract.

KL-6, a serum marker for interstitial pneumonitis, was evaluated in patients with Pneumocystis carinii pneumonia (PCP). Patient 1 was a 56-year-old woman with rheumatoid arthritis treated with immunosuppressive drugs and corticosteroids. Patient 2 was a 59-year-old man with a glioblastoma who received anti-cancer drugs and corticosteroids. In both patients, serum KL-6 showed an abnormally high level due to the complication of PCP, and it decreased following successful treatment. These results indicate that PCP is one of the diseases in which serum KL-6 increases.

Objectives To clarify whether the functional changes during the transition from compensatory myocardial hypertrophy to failure are associated with changes in sarcoplasmic reticulum gene expression. Methods We examined the gene expression of sarcoplasmic reticulum proteins [sarcoplasmic reticulum Ca 2+ -ATPase (SERCA), phospholamban, calsequestrin and ryanodine receptor] in Dahl salt-sensitive (Dahl-S) rats fed a high-salt (8%) diet from the age of 6 weeks. In-vivo contractile functioning was evaluated using echocardiography, and gene expression of sarcoplasmic reticulum proteins in the left ventricle was analyzed by Northern blotting for each stage of left ventricular hypertrophy. Results SERCA messenger RNA (mRNA) levels in Dahl-S rats with compensatory hypertrophy did not change significantly, whereas phospholamban mRNA levels were increased by 61% (P

In the search for markers of airway inflammation, we investigated the role of soluble interleukin-6 receptor (sIL-6R) in patients with bronchial asthma. Serum levels of sIL-6R were measured in 20 patients with stable asthma and in 18 healthy control subjects by means of a sandwich enzyme-linked immunosorbent assay. Such levels were also evaluated during a spontaneous attack of asthma (n = 10) as well as that after allergen inhalation (n = 7). Results were compared with those observed during the stable state and after the inhalation of methacholine. Serum levels of sIL-6R in asthmatic patients (132 +/- 31 ng/ml) significantly exceeded those of control subjects (111 +/- 16 ng/ml) (p < 0.05). These levels showed no correlation with such clinical variables as nonspecific bronchial hyperreactivity, atopic status, or serum concentration of IgE. Serum sIL-6R levels observed during an asthmatic attack versus those during the stable state (4 wk later) differed significantly. After a severe attack of asthma, such levels were significantly elevated on the second and third days, but not on Day 5. After challenge, circulating levels of sIL-6R were significantly increased 24 h after the inhalation of allergen but not of methacholine. Results suggest that serum levels of sIL-6R are increased in patients with asthma and are further increased during a spontaneous attack or that provoked by the inhalation of allergen. Thus, serum sIL-6R may reflect inflammation of the airway. Further studies are indicated to determine the clinical significance and the application of serum levels of sIL-6R in evaluating asthmatic patients.

In rheumatoid arthritis (RA), interstitial-pneumonitis is one of the major extraarticular complications that worsens a patient's prognosis. KL-6, a human MUC1 mucin, has been reported to be a sensitive serum marker for activity of interstitial pneumonitis. We investigated the clinical significance of serum KL-6 level in patients with RA. Serum levels of KL-6 and RA-associated inflammatory markers were evaluated in 177 RA patients. The diagnosis of active interstitial pneumonitis was made by clinical symptoms, pulmonary function tests, chest X-ray film, and high resolution CT. Serum KL-6 was increased in 8 of 9 (88.9%) RA patients with active interstitial pneumonitis but in only 1 of 168 (0.6%) RA patients without active interstitial pneumonitis. No significant correlation was found between KL-6 level and conventional clinical parameters. In RA, abnormal elevation of serum KL-6 strongly indicates the complication of active interstitial pneumonitis.

KL-6, a MUC1 mucin preferentially expressed in regenerating type 2 pneumocytes, has been reported to be a sensitive serum marker for evaluating the disease activity of interstitial pneumonitis (IP). Type III procollagen N-terminal peptide (PIIIP) and type IV collagen 7S (7S collagen) have also been reported to be useful in the serological evaluation of the activity. Their levels were measured and their serodiagnostic values were compared simultaneously in patients with IP and alveolar pneumonia. The study population was 45 patients with IP and 12 patients with alveolar pneumonia. Serum KL-6 levels were measured by a specific enzyme immunoassay, and both serum PIIIP and 7S collagen concentrations by their correspondent radioimmunoassay kits. There were no significant difference of serum C-reactive protein level, which was evaluated as an indicator of inflammatory process, between IP and alveolar pneumonia patients. In IP, the abnormally elevated rate of KL-6 [80% (3645)] was significantly higher than those of PIIIP [40% (1845)] and 7S collagen [40% (1845)]. In alveolar pneumonia, the rate of KL-6 [0% (012)] was significantly lower than those of PIIIP [33% (412)] and 7S collagen [25% (312)]. There were no significant correlations among serum levels of the markers. These observations indicate that the serodiagnostic value of KL-6 for IP is superior to that of PIIIP and 7S collagen, and that KL-6 has a characteristic to discriminate IP from alveolar pneumonia.

Pulmonary sequestration is a relatively rare anomaly. The arterial supply usually is derived from the aorta or its major branches. We present a 65-year-old female patient with pulmonary sequestration receiving arterial supply from the right coronary artery, complicated with sick sinus syndrome.

Inhaled beryllium induces specific sensitization and nonspecific effects leading to chronic beryllium disease (CBD). It is not known whether beryllium induces epithelial cell injury and increases alveolar-capillary leak. We hypothesize that lung injury is an early event in this disease and that markers of lung injury reflect severity of CBD. We measured serum and bronchoalveolar lavage fluid (BALF) KL-6 level, a marker of epithelial cell injury, and BALF/serum albumin, a marker of alveolar-capillary permeability, in 26 patients with CBD, 15 beryllium-sensitized subjects without disease (BeS), and 32 control subjects (Ctrl). We examined the association of these markers, BAL cellularity, pulmonary function, gas exchange, serum angiotensin-converting enzyme, chest radiograph, the effects of glucocorticoid therapy, and clinical course. BALF/serum albumin and serum KL-6 increased in CBD and were discriminative markers for CBD. BALF KL-6 and BALF/serum albumin reflected mainly lung cellular and granulomatous inflammation. Serum KL-6, like and BALF KL-6, was associated with permeability change and reflected functional and radiologic abnormalities. Serum KL-6 detected early lung injury in BeS. Epithelial injury and permeability changes occur early in CBD, indicating disease severity. Monitoring of these events with serum KL-6 may be useful for management of CBD.

To elucidate whether there is a difference in the progression of target-organ damage between primary aldosteronism and essential hypertension, we compared left ventricular hypertrophy and extracardiac target-organ damage in 23 patients with primary aldosteronism and 116 patients with essential hypertension. The severity of hypertensive retinopathy and the renal involvement in primary aldosteronism were subclinical and similar to those in essential hypertension without left ventricular hypertrophy but significantly milder than those in essential hypertension with left ventricular hypertrophy. There was a strongly significant correlation between the degree of left ventricular mass index and the severity of hypertensive retinopathy and renal involvement independent of office blood pressure in essential hypertension. In contrast, left ventricular hypertrophy markedly progressed despite the mild extracardiac target-organ damage in primary aldosteronism. Left ventricular end-diastolic dimension index in primary aldosteronism (3.16±0.50 cm/m 2 ) was significantly larger than in essential hypertension without (2.87±0.23) and with (2.88±0.22) left ventricular hypertrophy. On the other hand, there was no difference in extracardiac target-organ damage between 13 primary aldosteronism patients with eccentric left ventricular hypertrophy and the 26 essential hypertensive patients with eccentric left ventricular hypertrophy. The results suggest that predominantly volume load, be it due to aldosteronism or other mechanisms, resulting in eccentric left ventricular hypertrophy is less likely to cause extracardiac target-organ damage than hemodynamic or nonhemodynamic mechanisms resulting in concentric left ventricular hypertrophy.

CCAAT-enhancer binding protein-delta (C/EBP delta) is a transcriptional nuclear factor, and belongs to basic region-leucine zipper class DNA binding proteins. One genomic clone containing a 12-kb sequence of the C/EBP delta gene was isolated from a rat genomic library, and a 2,056-bp fragment containing the 5'-flanking region was characterized. Sequence analysis of this fragment revealed that there were a TATA-like sequence (TAGAAAA) and many transcriptional regulatory elements. The transcription start site of the gene was determined by both primer extension analysis and riboprobe mapping. Both analyses indicated that the transcription start site was located at 31-bp downstream of the TATA-like sequence. Transient transfection experiments showed that the fragment cloned in this study was able to act as a functional promoter in rat vascular smooth muscle cells. The 5'-deletion analysis of this fragment revealed that the sequence spanning -235 through -82, which was designated as an upstream control element (UCE), remarkably increased a basal promoter activity of the C/EBP delta gene, and was also able to act as a promoter by itself. In addition, we also studied effects of the UCE on the heterologous gene promoter including rat alpha-actin gene promoter or SV40 virus promoter. Interestingly, the UCE specifically increased the promoter activity of the rat alpha-actin gene suggesting that the C/EBP delta gene may be positively controlled by the UCE via a cell-type or promoter-type specific manner.

Cystic lesion, malignancy and interstitial pneumonia are well-known as pulmonary complications of patients with von Recklinghausen's disease. We report herein an unusual patient with distal acinar emphysema and interstitial pneumonia of prominent hypercellularity demonstrated by transbronchial biopsy and broncho-alveolar lavage fluid (BALF). Six months after quitting smoking, the total cell count of BALF was remarkably reduced. This patient remains stable under 5-year observation in terms of symptoms and findings of both BALF and pulmonary function tests. Quitting smoking may have facilitated a favorable prognosis for the particular lung disease complicated in this patient.

The aim of this study was to compare the effects of a calcium antagonist, nicardipine SR, with an angiotensin-converting enzyme (ACE) inhibitor, alacepril, on the regression of left ventricular hypertrophy (LVH) and function. Twenty patients with LVH, aged 42–73 years, were treated with nicardipine SR or alacepril. Ten patients were treated with nicardipine SR (40–80 mg) for 21 months, and the other 10 patients were treated with alacepril (25–100 mg) for 18 months. All patients underwent echocardiography to assess left ventricular structure and function before and after the treatment. After nicardipine SR or alacepril treatment, blood pressure was decreased significantly from 176.0 ± 13.9/97.0 ± 5.3 mmHg to 140.0 ± 14.0/77.4 ± 7.2 mmHg and from 168.2 ± 22.3/99.0 ± 5.5 mmHg to 138.4 ± 12.5/85.2 ± 9.7 mmHg, respectively (both p < 0.01), whereas heart rate did not change (73.8 ± 14.6 beats/min vs. 69.9 ± 13.5 beats/min and 71.6 ± 9.7 vs. 65.8 ± 8.1 beats/min, respectively). The left ventricular mass index decreased significantly from 133.2 ± 11.7 g/m2 to 114.4 ± 15.7 g/m2 with nicardipine SR and from 137.1 ± 14.8 g/m2 to 99.3 ± 23.0 g/m2 with alacepril (both p < 0.01). The fractional shortening, peak shortening rate, and peak lengthening rate all improved significantly after each treatment. The end-systolic wall stress/left ventricular end-systolic volume index, as an index of left ventricular contractility, was decreased significantly after treatment with nicardipine SR but was not changed after treatment with alacepril. In conclusion, both nicardipine SR and alacepril similarly reduced LVH and improved left ventricular systolic and diastolic function. However, alacepril did not alter left ventricular contractility, whereas nicardi-pine SR decreased left ventricular contractility.

In order to examine the current status of antihypertensive drug therapy for elderly hypertensive patients, and the effect of clinical characteristics and drugs on their prognosis, 1669 hypertensive patients in the Chugoku and Shikoku districts, aged between 65 and 84 years, were enrolled and followed for 3 years. Of the 1669 patients enrolled, 1459 were selected for evaluation and 1127 patients were followed. Group A comprised 955 patients who had not suffered from any accident, group B comprised 139 patients who had suffered from a cerebral, cardiac, renal or other non-fatal accident, and group C comprised 33 patients who died. The mortality rate was 10.7/1000 patient.years and the morbidity rate was 55.6/1000 patient.years. The number of patients who received monotherapy was 736 (calcium channel blockers: #436, beta blockers: #100, angiotensin converting enzyme inhibitors: #80, diuretics: #64, alpha blockers: #16; others: #13). In group C, there were more male, and the patients were older and showed a higher level of serum creatinine concentration at enrollment compared with other groups. The use of diuretics and beta blockers tended to be low in this group. Among the three groups, however, there was no difference in blood pressure, heart rate or the use of each drug at enrollment. In summary, it is suggested that the different antihypertensive drug therapies die not influence the prognosis of elderly hypertensive patients.

Autonomic nervous function in elderly essential hypertensive patients was investigated by power spectral analysis of heart rate variability. Fifty-seven essential hypertensive patients participated in this study. They were divided into two groups: the middle-aged group (ageor = 59 years, n = 30) and the elderly group (ageor = 60 years, n = 27). All examinations were performed during hospitalization. Power spectral analysis of R-R interval was performed from Holter electrocardiogram every 10 min by the maximum entropy method to obtain the low frequency band (LFB; 0.04 to 0.15 Hz), which is an index of both sympathetic and parasympathetic nervous activity. Twenty-four-hour blood pressure measurement was performed by the cuffoscillometric method to evaluate the nocturnal decrease in blood pressure. Nondipper patients were defined as those whose nocturnal decrease in systolic blood pressure was10% of daytime blood pressure. Both LFB and HFB were significantly lower in elderly hypertensive patients than in middle-aged patients (P.001 and P.05, respectively). Elderly nondipper patients had further reduced power spectral densities throughout the day. Both LFB and HFB showed a negative correlation with age. However, the age-related decline of power densities was more prominent in dipper patients and was not statistically significant in nondipper patients. These findings indicate that the nondipper phenomenon is superimposed on age-related attenuation of autonomic nervous function in essential hypertension.

Association between angiotensin-converting enzyme (ACE) gene polymorphism and essential hypertension in a Japanese population with the same socioeconomic back ground was investigated. Insertion-deletion (I/D) polymorphism of the ACE gene located on intron 16 was detected by polymerase chain reaction. Association between ACE gene polymorphism and family history of essential hypertension as well as the development of vascular damage in eye fundi were also investigated. Variation at ACE loci did not contribute to essential hypertension and the vascular damages in eye fundi. These results suggested that the ACE gene was not directly responsible for essential hypertension in this particular Japanese population with the same socioeconomic background.

Generation of soluble cytokine receptors is a general phenomenon, and the roles of several such receptors have been investigated in clinical settings. Unlike other soluble cytokine receptors, soluble interleukin-6 receptor (sIL-6R) can act as an agonist and thus is implicated as an important modulator in the acute-phase reaction of prolonged inflammation. The purpose of the present study was to determine the roles of pleural sIL-6R in both differential diagnosis of pleural diseases and in the induction of acute-phase protein. Specific sandwich enzyme-linked immunosorbent assays were used to determine sIL-6R and IL-6 in 19 tuberculous, 48 malignant and 10 transudative effusions. Although IL-6 levels in pleural effusions were strikingly different, no significant differences in pleural sIL-6R levels were found between the groups. Pleural levels of IL-6 were invariably much higher, whereas those of sIL-6R were invariably lower than serum levels. Furthermore, IL-6, but not sIL-6R, levels in effusions correlated significantly with serum C-reactive protein levels. These results suggest that: (1) pleural levels of sIL-6R are not increased even in strong inflammation such as tuberculous pleurisy, nor significantly different among pleural diseases; and (2) the local levels of sIL-6R are not as important as expected for the induction of acute-phase proteins in patients with pleural diseases.

1. We assessed the changes of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats (RHR). 2. Two-kidney, one-clip hypertensive rats (6-week-old male Wistar) were made and studied 6 (RHR-1) and 10 weeks (RHR-2) after the procedure. Regression of cardiac hypertrophy was induced by nephrectomy at 6 weeks after constriction, and the nephrectomized rats were maintained further for 4 weeks (nephrectomized rat: NEP). Sham operation was performed, and the rats were studied after 6 (Sham-1) and 10 weeks (Sham-2). Atrial natriuretic peptide and brain natriuretic peptide gene expression in the left ventricle was analysed by Northern blotting. 3. Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR-1 and RHR-2 than in Sham-1, Sham-2 and NEP. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in RHR-1 were approximately 7.2-fold and 1.8-fold higher than those in Sham-1, respectively, and the corresponding levels in RHR-2 were 13.0-fold and 2.4-fold higher than those in Sham-2, respectively. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized. Levels of atrial natriuretic peptide and brain natriuretic peptide mRNA were well correlated positively with left ventricular weight/body weight ratios. There was a significant positive correlation between the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA (r = 0.86, P 4. We conclude that the expression of atrial natriuretic peptide and brain natriuretic peptide genes is regulated in accordance with the degree of myocardial hypertrophy and that the augmented expression of these two natriuretic peptides may play an important role in the maintenance of cardiovascular haemodynamics in renovascular hypertension.

In order to evaluate aortic wall sclerosis in hypertension, the authors studied the following two parameters of carotid pulse tracing and ascending aortic wall distensibility by using cine magnetic resonance (MR) in 15 age- and sex-matched normal volunteers (NC) (mean age, fifty-four years old) and 15 hypertensive patients (HT) (mean age, fifty-four years old). As the parameters of carotid pulse tracing, they measured the interval from aortic second heart sound to dicrotic notch (A2-DN), and the height from dicrotic notch to top/total height of carotid pulse tracing (b/a ratio). Ascending aortic distensibility was calculated from the following formula: (max area - min area) / (min area x pulse pressure) A2-DN interval was lower in HT than in NC (18.4 ± 7.9 vs 31.5 ± 9.2 ms, P < 0.01). The b/a ratio was lower in HT than in NC (0.34 ± 0.07 vs 0.44 ±0.09, P < 0.01). Ascending aortic distensibility was lower in HT than in NC (2.08 ± 1.37 vs 7.26 ± 2.51 × 10-3 mmHg-1, P < 0.01). In conclusion, ascending aortic wall sclerosis is advanced in hypertension. A2-DN interval and b/a ratio measured by carotid pulse tracing are useful indicators in evaluating the ascending aortic wall distensibility in hypertension.

Familial nonobstructive hypertrophic cardiomyopathy in 78-year-old woman was diagnosed in 1988. Since then she has been treated with a beta-blocking drug and a calcium antagonist. Her clinical condition was NYHA I or II for several years. Echocardiography revealed asymmetric septal hypertrophy in 1988 (interventricular septal thickness = 21 mm, posterior wall thickness = 10 mm). Systolic anterior motion of the mitral valve was first observed at the end of 1992. The left ventricular pressure gradient also gradually increased; it was about 138 mmHg in 1993 (age 82 yrs). The left ventricular ejection time index increased from 376 msec in May, 1992 to 459 msec in May, 1994. In September, 1994, the patient's condition gradually deteriorated (NYHA IV), and she was admitted to our hospital. To attenuate the left ventricular pressure gradient, 150 mg of disopyramide was administered. Her condition markedly improved: the left ventricular pressure gradient decreased from 180 mmHg to 76 mmHg, and the left ventricular ejection time index decreased from 485 msec to 419 msec. These results indicate that a left ventricular pressure gradient can be generated rapidly even in a very old patient, and that disopyramide may be useful to attenuate the left ventricular pressure gradient.

We report the case of a 66-year-old woman with a patent ductus arteriosus and no significant progression of pulmonary arterial pressure over 17 years. She was admitted to our hospital in 1978 because of palpitations on exertion and chest discomfort. Cardiac catheterization was done, and she was given a diagnosis of patent ductus arteriosus. Because the left-to-right shunt was small (15%) and because there was no evidence of pulmonary hypertension (38/18 mmHg), she was treated medically. In 1995 she was admitted again, to determine the cause of a cerebral infarction. The cerebral infarction was believed to have been caused by an embolism due to atrial fibrillation. She underwent cardiac catheterization again. The left-to-right shunt had increased to 41%, but the pulmonary artery pressure had not changed (27/14 mmHg). Intravascular ultrasound imaging was used to evaluate the ductus arteriosus. The diameter of the ductus was 4.4 mm and calcification was not observed. During the 17 years of follow-up, heart size increased slightly, but pulmonary artery pressure did not change. In addition, intravascular ultrasound was very useful for evaluating the condition of the ductus arteriosus.

A 67-year-old woman with idiopathic orthostatic hypotension was presented. The patient started to experience faintness on standing since 1993. During a physical examination, her systolic blood pressure fell from 148 to 50 mmHg on standing. Blood pressure responses to the mental arithmetic test and hyperventilation stress were normal. However, cold pressor test failed to increase blood pressure. These observations, with the finding that phase IV response on Valsalva's maneuver was absent, indicate afferent sympathetic nervous dysfunction. Peripheral neuropathy including diabetes mellitus and involvement of central nervous system such as multiple system atrophy were excluded. Holter ECG examination revealed a 3.9 second sinus arrest and bradycardia (total beats 88901/day). the blunted responses of the heart rate to atropine as well as isoproterenol further suggested the presence of sick sinus syndrome. Amezinium administration significantly improved her orthostatic hypotension and eliminated sinus arrest. These findings indicate that sympathetic nervous dysfunction could account for at least a part of the sick sinus syndrome in this patient.

A 90-year-old man fell into a marsh and was rescued 18 hours later. When he was admitted to our emergency room, physical examination revealed no remarkable findings except for many abrasions on his skin. Laboratory examination revealed a serum CPK level of 46, 904 IU/L, which had further increased to 84,678 IU/L by the following day. Oliguria developed on the second day, along with an increase in serum creatinine to 5.5 mg/dt. Hemodialysis was considered for the treatment of acute renal failure, but his renal function recovered soon by the continuation of conservative fluid therapy. Fluid therapy may be an effective and easy treatment for acute renal failure due to the crush syndrome, even in very old patients.

老年者高血圧は, 成因および病態において若・中年期の高血圧と異なる特徴を示し, また診断および合併症, コンプライアンス, QOLへの注意などその管理上独特の配慮が必要となる. 高血圧の有病率は加齢とともに増加し, 老年者においても高血圧は心臓病, 脳卒中などすべての循環器疾患の共通で最も重要な危険因子である. 一方, 老年者高血圧患者を対象とした長期介入試験により, 降圧薬治療による心血管疾患発症予防に対する有効性が明らかにされた. 本報告は, 厚生省長寿科学総合研究事業「老年者の高血圧治療ガイドライン作成に関する研究」班の検討をもとに, 我が国における老年者高血圧の病態およびライフスタイルの特殊性を考慮し, また内外の長期介入試験の成果をも勘案し, 我が国における老年者高血圧に対する管理・治療指針の試案を提示する.1. 老年者の血圧値と血圧日内変動収縮期血圧は加齢とともに上昇, 拡張期血圧は老年期では逆に低下し, その結果, 脈圧は加齢とともに増大する. このような血圧値の加齢による変化は主として大動脈の伸展性の低下によって起こる. したがって, 老年者での高血圧の基準は別個に定める必要がある.老年者では血圧の調節機能が低下しており, この結果, 老年者では血圧の日内変動は大きい. これは大動脈の硬化に起因する圧受容体の機能低下が主たる原因である. 血圧日内変動測定の臨床的意義については, 血圧日内変動の平均値は随時血圧よりも高血圧の重症度や心血管疾患の発症とよく相関するなど, 高血圧の予後を評価する上で随時血圧よりも有用である. 老年者における血圧日内変動測定の適応としては, (1)外来での随時血圧が大きく変動する症例, (2)白衣高血圧の疑われる症例, (3)降圧療法に抵抗性の高血圧, (4)自律神経障害を有する症例, (5)起立性低血圧, 食後血圧低下の疑われる症例, (6)虚血性心疾患, 脳梗塞の既往を有する症例, (7)発作性高血圧を呈する症例などがあげられ, 老年者における高血圧の病態の解明のみならず, 白衣高血圧の診断, 降圧療法の良否の判定などに有用である.2. 診断に対する注意事項老年者高血圧の診断においては, 血圧基準自体は若・中年者と同じであり, JNC-V (1992年) およびWHO/ISH (1993年) いずれにおいても収縮期血圧140mmHg以上, 拡張期血圧90mmHg以上の両方またはいずれかを有するものとなる. しかしながら, 老年者では加齢に伴う種々の疾患特異性があり, 老年者の診療上それらに十分留意しなければならない. 分類上の特徴としては, 動脈硬化による Windkessel 効果減弱にもとづく収縮期高血圧が多い事がまずあげられる. 診断上の注意点としては, 各種2次性高血圧や脳, 心, 腎, 大血管, 末梢動脈などでの合併症を念頭において詳細な病歴をとる事は当然である. 循環調節機能低下による高度の血圧日内変動があるため, 血圧測定は繰り返し慎重に行うべさで,起立性低血圧もありうるため, 常に坐位, 臥位, 立位の3つのことなった体位で血圧を測る習慣をつけるべきである. 家庭血圧や24時間血圧測定も必要に応じて参考にすべきである. また, 二次性高血圧については, その分布, 原因等に若年者との相異点がみられ, 原発性アルドステロン症, 褐色細胞腫など内分泌性高血圧が少なく, 腎実質性や腎血管性高血圧が多いことが特徴となるため, 診断上特に注意を要する. 一方, 降圧利尿薬使用患者での原発性アルドステロン症や血圧変動性が特徴的な老年者における褐色細胞腫は薬剤による低K血症や病態上の特徴と紛らわしく, 見逃しやすくなるため特に注意を払い鑑別すべきである. 老年者では, 全身性に様々な疾患を有していることが多く, 心血管系をはじめとする高血圧による臓器障害の評価にあたっても慎重を期する.3. 治療の必要性海外における60～70歳以上を対象とした老年者の軽・中等症高血圧に対する介入試験により, 降圧薬治療による心血管疾患の予防効果が明らかにされている. 高血圧治療に際しては高血圧以外の危険因子の存在や標的臓器障害の有無も考慮に入れて降圧薬治療を開始する. 介入試験の成績から収縮期高血圧および拡張期高血圧いずれも降圧薬治療が必要であり, 特別な合併症がなければ収縮期血圧が160mmHg以上, 拡張期血圧が90～95mmHg以上であれば降圧薬治療の対象になると考えられる. 何歳までが治療対象になるかということについては介入試験からは80歳代前半までは新規治療の対象になると考えられるが, 老年者では個人差が大きいので一概に暦年齢だけで治療の適否を判断せず, 合併症がなくても高血圧の程度が強い場合や, 高血圧に伴う危機的合併症のみられる症例では, 年齢の上限を考慮せずに降圧治療を進めるべきであると思われる. 降圧に際しては過度の降圧による循環障害に注意して緩徐な降圧をはかるように心がける.

Abstract Autonomic nervous function was evaluated by means of power spectral analysis of heart rate variability in hospitalized dipper (n=31) and non-dipper (n=31) essential hypertensive subjects. Twenty-four–hour blood pressure (BP) measurement was performed by the cuff-oscillometric method to evaluate the nocturnal decrease of BP. The non-dipper subjects were defined as those whose nocturnal decrease of systolic BP was

The aim of this study was to elucidate the cause of T wave changes after ventricular pacing using thallium 201 single photon emission computed tomography (T1-SPECT). T1-SPECT was performed in 20 patients with sick sinus syndrome who had negative T wave after ventricular pacing and had had a ventricular demand pacemaker (WI) implanted. Patients who have stenotic coronary arteries were excluded from the study. From the analysis of Tl-SPECT, extent score was calculated as the ischemic region. Data in patients with SSS were compared with those in 20 normal controls (NC). Thallium perfusion defects in patients with VVI were observed and distributed mainly in apex and inferior regions on the polar map. The extent score in patients with VVI was significantly higher than that in NC (56.4 ±21.6% vs 3.2 ±6.4%, P < 0.01). The washout rate of thallium 201 in the defect area was significantly lower in patients with VVI than in NC (27.4 ±10.2% vs 46.8 ±12.3%, P These results suggest that T wave changes after ventricular pacing are closely related to myocardial ischemia.

Circulating interleukin-6 (IL-6) levels were determined using a sensitive enzyme immunoassay in adults with asthma in stable condition during naturally occurring attacks and before and after allergen inhalation tests. IL-6 was significantly elevated even in asymptomatic asthmatic subjects (n = 17) compared with normal control subjects (n = 17). During naturally occurring asthmatic attacks, serum IL-6 levels were significantly elevated in comparison with those in a symptom-free condition (4 wk interval; n = 8, p < 0.01). No significant difference was observed in serum IL-6 levels obtained from control asymptomatic asthmatic subjects during the period (n = 10). There was a significant elevation in circulating IL-6 levels in eight asthmatic patients following inhalation of allergen but not methacholine. These results suggest that IL-6 is involved in the pathophysiology of bronchial asthma.

To investigate the involvement of peripheral catecholamines in the development of Dahl-Iwai salt-sensitive (DIS/Eis) hypertension, we performed immunohistochemical staining of tyrosine hydroxylase (TH) in the superior cervical ganglia (SCG) of DIS/Eis rats and Dahl-Iwai salt-resistant (DIR/Eis) rats, and in situ hybridization histochemistry for demonstration of TH mRNA localization in the SCG of these rats. DIS/Eis and DIR/Eis rats were fed on a high (8%) salt diet or on a low (0.3%) salt diet for 4 weeks. Nerve cells in the SCG of DIS/Eis high salt rats exhibited more intense TH-immunoreactivity (P < 0.01) and hybridization signals (P < 0.01) than those of the other experimental groups. These findings suggest that activation of peripheral sympathetic nerves may account for hypertension in DIS/Eis rats on a high salt diet.

A 76-year-old female was referred to our hospital for examination of milky pleural effusion. We diagnosed her illness as chylothorax because of the high concentration of triglyceride in the effusion. There was neither obstruction nor damage of the thoracic duct. Systemic evaluation disclosed an abdominal mass in the umbilical region. Fasting with intravenous hyperalimentation followed by pleurodesis with minocycline successfully eliminated the effusion. On the other hand, the abdominal mass was diagnosed as mesenteric panniculitis by open biopsy. Since she also had chylous ascites, the tumor could have obstructed the intestinal lymphatics. Chylothorax was probably caused by damage to collateral lymph circulation.

軽症高血圧患者の治療について,「軽症高血圧の管理に関する1993年WHO/ISHガイドライン」を踏まえて,著者の経験を交えながら解説した.軽症高血圧であっても,高齢者はすでに心臓血管系疾患に対して高齢であるというリスクを有しているので,降圧薬療法に力点をおき,患者に適した降圧薬を用いて血圧を正常範囲にコントロールする.一方,青壮年者においては,著者らあるいは外国の成績からも明らかにされているように生活習慣の改善によって,約半数近くの患者は高血圧が正常化する可能性がある.したがって,生活習慣の改善に力点をおくが,降圧薬を投与した場合でも,積極的に減量,中止を試みる.ただし,心臓血管系疾患に対する独立したリスクである左室肥大を持った患者では,肥大の退縮作用のある降圧薬を用いて厳格に正常範囲に血圧をコントロールする.

It has been reported that ubenimex, a biological response modifier, has a direct anti‐tumor effect. To clarify the mechanism involved, we examined the effects of ubenimex on the growth and adhesive property of a breast cancer cell line YMB‐S. The cells proliferate in a floating manner without aggregation in normal complete medium. Ubenimex induced cell‐cell and cell‐surface adhesion of the cells accompanied with growth suppression. E‐Cadherin localized at cell‐cell contact sites of adhered cells, and anti‐E‐cadherin antibody inhibited the adhesion. Both Western blot analysis and binding assay disclosed that there was no apparent difference between E‐cadherin levels of the cells before and after the treatment with ubenimex. These results indicate that ubenimex inhibits the proliferation of YMB‐S cells and augments cell‐to‐cell adhesion through the induction of E‐cadherin ‐mediated adhesion resulting from the functional activation of pre‐expressed but inefficient E‐cadherin.

To elucidate the influence of aging upon the improvement of symptoms and cardiac size associated with surgical repair of atrial septal defect, clinical symptoms, cardiothoracic ratio and hemodynamic variables in older patients (group A; age at operation > or = 50 years old, n = 11) were compared with those in younger patients (group B; age at operation < 50 years old, n = 8). There were no differences in hemodynamic variables, i.e., peak systolic pulmonary pressure, pulmonary to systolic flow ratio (Qp/Qs), pulmonary to systolic vascular resistance ratio (Rp/Rs) and left to right shunt ratio between the two groups. Symptomatic benefits occurred in all patients, although 3 patients in group A who had atrial fibrillation preoperatively still displayed symptoms such as exertional dyspnea. The postoperative (after 3 months) cardiothoracic ratio improved in all patients except for 3 patients in group A who were operated at over 60 years of age. Although there was no significant difference in preoperative cardiothoracic ratio between the two groups, the postoperative cardiothoracic ratio in group B was significantly smaller than that in group A. These results indicate that operative closure of atrial septal defect is recommended for all patients aged 50 years old or older, but early improvement of symptoms and cardiomegaly in older patients is lower than that in younger patients.

To elucidate left ventricular (LV) cardiac structure and function in patients with mild to moderate essential hypertension, we studied the relationship between LV geometry and function. We evaluated LV diastolic and systolic functions by M-mode echocardiography in 91 age-matched normotensive control subjects (NT) and 124 patients with essential hypertension. Hypertensive patients were divided into two groups based on the WHO stage classification: WHO I (n = 76) and WHO II (n = 48). Patients in WHO I and WHO II were further categorized according to the relative wall thickness as normal left ventricle (n = 47), concentric remodeling (n = 29), concentric hypertrophy (n = 25), and eccentric hypertrophy (n = 23). LV diastolic function was significantly decreased in the hypertensive groups compared to NT. There was no significant difference in LV systolic performance among NT, WHO I and WHO II. LV contractility was significantly increased in WHO I compared to NT. In respect to ventricular geometric pattern, LV diastolic function was significantly decreased in both the concentric hypertrophy and eccentric hypertrophy groups. LV systolic dysfunction was noted only in the eccentric hypertrophy group. In conclusion, patients with concentric remodeling had normal systolic and diastolic functions. LV diastolic function was impaired in both the concentric and eccentric hypertrophy groups due to an increase in LVMi. Moreover, LV systolic impairment was noted in the eccentric hypertrophy group due to an inappropriate compensation to LV systolic load.