Differential expression of Gh1 and Gh 2 genes by competitive RT-PCR in rainbow trout pituitary.

The expressions of the GH1 and GH2 genes were examined by competitive RT-PCR and whole-mount in situ hybridization of pituitary of starved rainbow trout (Oncorhynchus mykiss). lambda RNA having GH primers at both 5' and 3' sites of the gene was used for the competitive RT-PCR, and thermostable reverse transcriptase produced a reasonable band when authentic RNA was examined. The amount of GH1 gene expression was significantly (P < 0.05) greater than that of GH2. Although almost the same amount of GH1 gene expression was obtained during the day, it was significantly (P < 0.05) decreased at midnight. However, there was no significant change in GH2 gene expression in the daily cycle. There were also some differences in gene expression in the pituitary: GH2 gene was more widely expressed than GH1. However, the signal intensity of the GH1 gene was greater than that of GH2.

[A case of MPO ANCA associated glomerulonephritis with interstitial pneumonitis complicated with lung tuberculosis and pericarditis].

The main target organs of myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA)-related disease are the kidney and lung. This report describes a 71-year-old man with rapidly progressive glomerulonephritis (RPGN) and interstitial pneumonitis associated with MPO ANCA. The patient was admitted to our hospital because of bloody sputum, low grade fever and appetite loss on October, 1998. He was diagnosed as having interstitial pneumonitis from the findings of chest X-ray and CT examinations. Moderate proteinuria and hematuria, renal dysfunction(serum creatinine: 5.6 mg/dl, BUN: 58.0 mg/dl) and positivity for MPO ANCA were noted. He was negative for anti-glomerular antibody and PR3-ANCA. Renal biopsy was performed and revealed crescentic glomerulonephritis without deposition of immunoglobulins. Therefore, the diagnosis of pauci immune type RPGN was made. Pulse therapy with methylprednisolone(1.0 g/day x 3 days) following oral administration of prednisolone (60 mg/day) found marked improvement of renal function maintenance and interstitial pneumonitis, respectively. However, he died because of lung tuberculosis and acute tuberculous pericarditis during treatment with prednisolone. In this case, MPO ANCA might have been directly associated with both RPGN and interstitial pneumonitis. Furthermore, chronic lung disease, such as interstitial pneumonitis, is important as a preceding disease of RPGN. MPO ANCA-related disease is more frequent in aged persons, therefore particular attention should be paid during their treatment with an immunosuppressant.

A case report of intravenous leiomyomatosis extending into the heart.

The patient was a 47-year-old woman who underwent total hysterectomy for uterine leiomyoma in 1994. Two years later, intracaval and intravenous tumors were found by ultrasonic cardiography, magnetic resonance imaging, enhanced chest computed tomography, and venography. The patient underwent total removal of these tumors. Pathological findings indicated that these tumors were leiomyomas. After comparing the present findings with those of similar cases in the literature, we concluded that our patient had intravenous leiomyomatosis extending into the heart.

[Left cardiac output curve and pulmonary venous return curve in patients with various heart diseases].

This study assessed the cardiac function of humans by drawing simultaneous left cardiac output and pulmonary venous return curves using radionuclide angiocardiography and right heart catheterization which allows recording of the pressure-flow relationship. Thirty-one subjects with various cardiac diseases were divided into two groups [18 patients with New York Heart Association (NYHA) functional class I and 13 patients with NYHA classes II or III]. Mean pulmonary filling pressure (Pmp) was calculated from the formula of Guyton, using pulmonary arterial compliance which was measured by Reuben's method and pulmonary venous compliance measured as reported previously. On the pressure-flow plane, the down slope of the pulmonary venous return curve was drawn by joining the points of (Pmp, 0) and (mean pulmonary capillary wedge pressure, cardiac output). To construct the cardiac output curve, two levels of lower body negative pressure were used to regulate the venous return to the heart. Pmp and the resistance to pulmonary venous return in NYHA II or III patients were significantly higher than those in NYHA I patients (Pmp: 16.3 +/- 1.5 vs 9.0 +/- 0.5 mmHg, p < 0.01; resistance to pulmonary venous return: 0.75 +/- 0.09 vs 0.43 +/- 0.04 mmHg/l/min, p < 0.01, respectively). The slope of pulmonary venous return curve in NYHA II or III patients was smaller than that in NYHA I patients and the pulmonary venous return curve in NYHA II or III patients shifted rightward. The slope of cardiac output curve in NYHA II or III patients was significantly smaller than that in NYHA I patients. This curve in NYHA II or III patients shifted downward and rightward. These results indicate that simultaneous cardiac output and pulmonary venous return curves may be a useful method for assessing the cardiac function in patients with various heart diseases.

Enhanced presence of thrombomodulin in the glomeruli of lupus glomerulonephritis.

The intraglomerular presence of thrombomodulin (TM) was examined in 19 patients with lupus glomerulonephritis (GN). TM is a cell surface glycoprotein found on endothelial cells and plays a key role in the protein C anticoagulant pathway. Renal biopsy specimens of patients with lupus GN and several kinds of renal disease other than lupus GN, i.e., membranous GN, IgA GN, minimal change nephrotic syndrome (MCNS) and hemolytic uremic syndrome (HUS) were examined by indirect immunofluorescence, using three kinds of monoclonal antibodies against human TM: KA-2, KA-3 and KA-4. It has been reported that KA-3 and KA-4 bind to enzyme-digested TM as well as intact TM, while KA-2 recognizes intact TM only. In the glomeruli from both normal subjects and patients with MCNS, only very weak staining of TM was found. Patients with HUS showed negative TM staining in the glomeruli. In contrast, positive to strongly positive staining of KA-2 as well as of KA-3 and KA-4 was observed mainly along the capillary wall of glomeruli from patients with lupus GN. Some patients with non-lupus GN showed positive staining of these monoclonal antibodies, but the staining was far more intense in most patients with lupus GN than in the patients with non-lupus GN. Staining of albumin and transferrin by the indirect method was negative in all cases of lupus GN that showed positive staining of TM. There was no relationship between the intensity of TM staining and the degree of proteinuria, creatinine clearance or histologic types of lupus GN.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma thrombomodulin in primary glomerular disease and lupus glomerulonephritis.

Although thrombomodulin (TM) in circulating blood is regarded as an indicator of vascular endothelial disorders, blood TM levels are also known to be affected by renal dysfunction. We measured plasma TM levels in primary glomerular disease (PGD) and lupus glomerulonephritis (GN) with the EIA method, and assessed the extent to which renal dysfunction and endothelial disorders contribute to plasma TM levels in these diseases. The plasma TM/serum creatinine (TM/Cr) ratio was significantly higher in lupus GN patients than in PGD patients or normal controls. A significant positive correlation was found between plasma TM and serum Cr levels in both PGD and lupus GN patients, but the slope (A) of the regression line (TM = A.Cr+B) in lupus GN patients was significantly steeper than in PGD patients. We conclude that plasma TM levels are greatly influenced by renal dysfunction, but that not only renal dysfunction but endothelial disorders may be an important determinant of increased plasma TM levels in diseases such as lupus GN.

Cardiovascular response and red cell membrane sodium transport in hypertensive cardiac hypertrophy.

To investigate the involvement of the sympathetic nervous system and cell membrane sodium transport in hypertensive cardiac hypertrophy, we divided 51 middle-aged male patients with essential hypertension into cardiac hypertrophy and noncardiac hypertrophy groups. We then compared the plasma noradrenaline concentration after exercise, the cardiovascular response to exercise and sympathomimetic agents, and cell membrane sodium transport in the two groups. There were differences between the cardiac hypertrophy and noncardiac hypertrophy groups with regard to the pressor response to exercise and noradrenaline (i.e. the response to sympathetic alpha-receptor stimulation) as well as the intracellular sodium concentration and cell membrane sodium transport. We concluded that there were abnormalities of the pressor response to alpha-receptor stimulation and of intracellular sodium concentration and cell membrane sodium transport in patients with hypertension and cardiac hypertrophy. These abnormalities might play some role in the pathogenesis of hypertensive cardiac hypertrophy.

Prognostic significance of posturally induced crackles. Long-term follow-up of patients after recovery from acute myocardial infarction.

We found that on pulmonary auscultation, fine crackles could be induced by changing the posture from sitting to supine and/or from supine to supine with passive leg elevation in patients without obvious congestive heart failure. We named these crackles "posturally induced crackles (PIC)." To investigate the relationship between PIC and long-term prognosis after myocardial infarction, we followed up 262 patients who recovered from acute myocardial infarction for a mean period of six years. Cardiac death occurred in three of 78 PIC-negative patients and in 28 of 143 PIC-positive patients. PIC-negative patients had a significantly better long-term prognosis than PIC-positive patients according to the Kaplan-Meier survival curves for cardiac death (p < 0.01). In a multilogistic model based on 70 appropriate cases, PIC was the third most important prognosticator after recovery from myocardial infarction and the number of diseased coronary vessels and the pulmonary capillary wedge pressure ranked first and second, respectively.

Thallium-201 myocardial SPECT findings at rest in sarcoidosis.

In 41 patients with sarcoidosis (diagnosed according to criteria recommended by the Committee on Diffuse Pulmonary Disease, Ministry of Health and Welfare, Japan 1988), thallium-201 (201Tl) myocardial SPECT was performed to investigate: (1) the ability of 201Tl SPECT to detect cardiac involvement of sarcoidosis with images recorded at rest and 2 hours later, and (2) the relationships between 201Tl myocardial SPECT findings and the activity of sarcoidosis or endomyocardial biopsy findings. As to the abnormal findings in 201Tl myocardial SPECT, (1) a low density area was seen in 13 of 41 cases (31.7%) and non-uniform uptake was found in 17 cases (41.5%), (2) the mean washout ratio (n = 39) was 16.5 +/- 7.4%, which is significantly (p < 0.05) lower than that found in normal subjects, 23.9 +/- 7.5% (n = 10). Of the 19 patients judged visually to be normal, 5 patients had a reduced mean washout ratio less than 12%. Thus, the incidence of abnormal findings including all types of abnormality, on 201Tl myocardial SPECT in sarcoidosis was 63.4% (26/41 cases). In studying the relationship between 201Tl myocardial SPECT findings and the activity of sarcoidosis (as measured by the serum ACE (angiotensin converting enzyme) or lysozyme level, or the presence of more than 30% symphocyte fraction in BALF (broncho-alveolar lavage fluid)), 20 (80%) of 25 cases with 201Tl abnormality were judged to be active sarcoidosis, while only 6 (37.5%) of 16 cases with normal findings on 201TI SPECT were judged to be active.(ABSTRACT TRUNCATED AT 250 WORDS)

Extravascular lung water measured with 99mTc-RBC and 99mTc-DTPA is increased in left-sided heart failure.

Extravascular lung water (EVLW) was quantitatively measured in 81 patients consisting of 10 subjects with normal cardiac function and 71 patients with left-sided heart diseases, using 99mTc-RBC as a non-diffusible indicator and 99mTc-DTPA as a diffusible indicator in the equilibrium phase. EVLW averaged 3.0 +/- 1.4 (ml/kg, mean +/- SD) in subjects with normal cardiac function (n = 10), 4.3 +/- 1.7 in New York Heart Association functional class I patients (n = 30), 4.8 +/- 2.4 in NYHA functional class II patients (n = 33) and 9.4 +/- 5.4 in NYHA functional class III (n = 8) patients. EVLW was greater in NYHA class III than in normal controls or NYHA classes I or II (p < 0.01). Lung thermal volume (LTV) was also measured in 31 of the 81 patients using a double indicator dilution technique with sodium and heat. LTV averaged 6.0 +/- 1.2 (ml/kg) in normal subjects (n = 4), 8.6 +/- 2.0 in NYHA functional class I patients (n = 11), 9.7 +/- 3.0 in NYHA functional class II patients (n = 13), and 15.9 +/- 8.2 in NYHA functional class III patients (n = 3). The correlation between EVLW and LTV was significant (EVLW = 0.79 x LTV - 72.8, r = 0.80, p < 0.01). There were significant differences in EVLW/LTV ratio between NYHA class III (0.93 +/- 0.16) and NYHA class I (0.62 +/- 0.22). Thus, it was shown that EVLW was increased in left-sided heart failure and that LTV overestimated the EVLW.

[The influence of pulmonary "venous" compliance on the static pulmonary compliance: a study of patients with left-sided heart disease with normal respiratory function].

In heart diseases, such as mitral stenosis and angina pectoris, the static pulmonary compliance has been reported to be decreased. By definition, the pulmonary "venous" system consists of the pulmonary veins and the left atrium. It plays an important role as the reservoir for the left ventricle. In this laboratory, the pulmonary "venous" compliance (Cp"v") has been evaluated as delta V/delta P of a short segment of the P"V" volume-pressure curve. To evaluate the influence of Cp"v" on the static pulmonary compliance and to speculate about the mechanisms of the reduction in static pulmonary compliance in left-sided heart disease, hemodynamic data and static pulmonary compliance (Cst) were measured in 27 patients with left-sided heart disease. Cst was measured with esophageal balloon technique in a sitting position. The static volume-pressure curve was fitted by a sigmoid model: V = Vm/(1 + e(A-P)/kappa), where kappa is a shape constant and an index of the lung stiffness. The pulmonary blood volume (PBV) was estimated with our own method, using radionuclide (RN) angiocardiography. The mean pulmonary artery wedge pressures (PAW) were measured using a floating catheter. Cp"v" was calculated as the delta V/delta P from the increment of pulmonary "venous" volume (delta V) and that of PAW (delta P) that occurred during passive elevation of the legs. Pulmonary arterial compliance (Cpa) was obtained from an analysis of the diastolic decline in pulmonary arterial pressure wave forms.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of primary cardiac amyloidosis with amyloid A protein].

A case of cardiac amyloidosis in a 46-year-old male is reported. He was admitted for dyspnea. Physical examination revealed third and forth heart sound and hepatomegaly. Radiographic heart-thoracic ratio was 53%. Electrocardiogram showed first degree A-V block, rS pattern in V1-V4 leads, and ambulatory electrocardiogram showed ventricular tachycardia. Echocardiogram revealed hypertrophy and highly refractile echoes of the left ventricular wall. Endomyocardial biopsy was performed and it demonstrated amyloid fibrils, which were characterized immunohistochemically as Amyloid A (AA) protein, which is generally a constituent in secondary amyloidosis. Urine protein electrophoresis showed lambda type Bence-Jones protein, but bone marrow biopsy was normal. There was no evidence of malignancy, chronic inflammatory disease, or collagen disease. This case was diagnosed as primary amyloidosis with AA protein. It is rare that, in spite of its being a case of primary amyloidosis, its constituent protein is AA protein.

Enhanced coagulation and fibrinolysis during treatment with recombinant human erythropoietin in patients undergoing chronic hemodialysis.

Twenty-two patients on regular hemodialysis treatment suffering from renal anemia were treated with intravenous recombinant human erythropoietin (rhEPO) for more than 8 weeks. Before and 4 and 8 weeks after the start of rhEPO administration, we measured prothrombin time, activated partial thromboplastin time, fibrinogen (FBG), antithrombin III activity (ATIII), plasminogen activity (PLG), alpha 2-plasmin inhibitor activity (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (alpha 2 PIC), and cross-linked fibrin degradation products (XL-FDP) in citrated plasma to determine whether rhEPO treatment enhances coagulation and fibrinolytic activity. The pretreatment values of FBG, alpha 2 PIC, and XL-FDP were significantly higher than the normal control values. The pretreatment values of ATIII, PLG, and alpha 2 PI were significantly lower than the normal control values. Platelet count and FBG were significantly increased 4 and 8 weeks after treatment with rhE-PO. The prothrombin time was significantly shortened 8 weeks after rhEPO treatment, but the activated partial thromboplastin time did not change. PLG was significantly decreased 4 and 8 weeks after rhEPO treatment, and ATIII and alpha 2 PI were significantly decreased 8 weeks after rhEPO treatment. alpha 2 PIC was significantly increased 8 weeks after rhEPO treatment, and XL-FDP was significantly increased 4 and 8 weeks after rhEPO treatment. These data suggest that in patients on regular hemodialysis treatment coagulation and fibrinolysis are already enhanced before the start of rhEPO treatment and that rhEPO administration further enhances these disorders.

Coagulation and fibrinolysis in patients with chronic renal failure undergoing conservative treatment.

Eighteen patients with chronic renal failure due to primary glomerular disease undergoing conservative treatment (CRF patients) were studied to evaluate whether coagulation and fibrinolytic activity in plasma are enhanced in the patients. We measured plasma levels of coagulation-fibrinolysis parameters including thrombin-antithrombin III complex (TAT) (an index of thrombin formation), alpha 2-plasmin inhibitor (alpha 2 PI)-plasmin complex (alpha 2 PIC) (an indicator of plasmin production) and cross-linked fibrin degradation products (XL-FDP) (an index of fibrinolysis secondary to coagulation). There was no correlation between plasma levels of TAT, alpha 2PIC and XL-FDP and serum creatinine levels in CRF patients. Both fibrinogen and TAT were found to be significantly higher in CRF patients than in normal controls. TAT was negatively correlated with serum albumin or total protein. Antithrombin III (ATIII) activity was significantly lower in CRF patients than in normal controls. CRF patients showed significantly but slightly higher alpha 2 PIC and XL-FDP when compared to normal controls. These results suggest that TAT, alpha 2PIC and XL-FDP are good indicators of coagulation-fibrinolysis even in patients with decreased renal function. Coagulation activity is significantly increased in CRF patients but fibrinolysis secondary to coagulation is only slightly enhanced.

Exercise-loaded blood pressure and Li-Na countertransport system in the erythrocyte membrane as predictors of mild essential hypertension prognosis.

1. The blood pressure response to exercise loading, Na concentration in the erythrocyte and Li-Na countertransport (Li-Na CT) system in the erythrocyte membrane in 40 male volunteers and 98 patients with mild essential hypertension were investigated. Subjects were divided into a juvenile group (less than 36 years) and a middle-aged (greater than 36 years and less than 65 years) group. Exercise-loaded blood pressure in patients with mild essential hypertension was followed up for more than 5 years. 2. Systolic blood pressure (SBP) at 6 min during exercise loading was significantly higher in the mild hypertension group compared with the control group. 3. Patients with high SBP at exercise loading in the mild hypertension group transferred more often to the moderate hypertension group within 5 years. 4. No difference in the haemodynamic parameter at rest was noted in the transferred group for moderate hypertension and the non-transferred group. 5. A higher blood pressure response to noradrenaline was noted in the transferred group compared with the non-transferred group of the juvenile group. 6. High Na concentration in the erythrocyte and acceleration of the Li-Na CT system in the erythrocyte membrane were noted in the mild hypertension group compared with the volunteer group. 7. A correlation between SBP at exercise loading and Li-Na CT system in the erythrocyte membrane was noted. This correlation was strongly noted in subjects less than 50 years old. 8. From these results it was concluded that SBP at exercise loading and Li-Na CT system in the erythrocyte membrane are useful as indicators for the prognosis of mild essential hypertension.

Effect of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics in essential hypertension.

The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics were studied in essential hypertension. A 4-week study was performed in eight patients with essential hypertension who were given a regular sodium diet in the first and third weeks, and a sodium-restricted diet in the second and fourth weeks. Nicardipine, 60 mg/d, was administered in the third and fourth weeks. The urinary sodium excretion rate (UNaV) was plotted on the y-axis against the mean arterial pressure (MAP) on the x-axis before and after the administration of nicardipine. Assuming the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure across the glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar resistance (RA) and efferent arteriolar resistances (RE), glomerular pressure (PG), and gross filtration coefficient (KFG) were calculated. Although the MAP on regular salt diet was lowered from 125 +/- 3 to 109 +/- 2 mm Hg by nicardipine, neither the renal blood flow rate (RBF) (670 +/- 40 mL/min) nor the glomerular filtration rate (GFR) (79 +/- 2 mL/min) was altered. The RA was estimated to be reduced from 9,300 +/- 900 to 7,400 +/- 700 dyne.s.cm-5 (P less than 0.01), while no changes were noted in RE (4,900 +/- 400 dyne.s.cm-5), PG (50 +/- 1 mm Hg), or KFG (0.180 +/- 0.041 [mL/s]/mm Hg). Essential hypertension has been characterized by a prominent increase in RA, resulting in maintenance of normal PG. This Ca-entry blocker worked to normalize intrarenal hemodynamics in essential hypertension by dilating afferent arterioles alone.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of systemic and pulmonary hemodynamics in genesis pleural effusion in congestive heart failure].

We tried to make an estimate of how pleural effusion occur in congestive heart failure, using right atrial pressure (RA) and pulmonary arterial wedge pressure (PAW) as variables. We calculated the following equation by quoting the data in the past. RA greater than -0.02 x PAW + 13.3. We speculated that when this relationship is satisfied, pleural effusion will appear. We also studied the patients with severe congestive heart failure, dividing them into 2 groups, ie the pleural effusion group (EF) and pulmonary edema group (ED). Compared with ED, EF has a significantly higher RA (RA = 6.1 +/- 1.33 mmHg in EF and 13.3 +/- 2.21 mmHg in ED, mean +/- SE, p less than 0.02) and a significantly lower cardiac index (3.17 +/- 0.26 l/min/m2 vs 2.23 +/- 0.16 l/min/m2, mean +/- SE, p less than 0.01). Therefore, we thought that it was adequate to treat RA and PAW as independent variables. These equations appear to be useful in predicting the development of pleural effusion that's based in the plots of our patients on RA-PAW plane and their relationship to our equations.

Plasma von Willebrand factor and thrombomodulin as markers of vascular disorders in patients undergoing regular hemodialysis therapy.

Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are regarded as reflecting the release reaction by vascular endothelial cells and/or endothelial cell injury, and increased levels of thrombomodulin (TM) antigen as reflecting damage to endothelial cells. We investigated changes in plasma vWF:Ag and TM antigen levels during the course of regular hemodialysis treatment (RDT) in 14 patients undergoing RDT in order to evaluate the effect of hemodialysis (HD) on endothelial cells. vWF:Ag and TM were both measured by the sandwich EIA method. Predialysis levels of vWF:Ag and TM in RDT patients were both significantly higher than normal control values. Neither patient age nor blood pressure was not correlated with predialysis vWF:Ag and TM levels. Both vWF:Ag and TM levels significantly increased during a single HD session. There was a positive correlation between predialysis TM levels and duration of HD and an inverse correlation between the amount of vWF:Ag released during HD and duration of HD. It appears that HD procedures induce stimulation and damage of endothelial cells and that long-term, recurrent HD treatment may predispose to vascular disorders.