CD36 mediates long-chain fatty acid transport in human myocardium: complete myocardial accumulation defect of radiolabeled long-chain fatty acid analog in subjects with CD36 deficiency.

Long-chain fatty acids (LCFA) are the major energy substrate for heart and their oxidation is important for achieving maximal cardiac work. However, the mechanism of uptake of LCFA by myocardium has not been clarified. We previously reported that bovine myocardial LCFA transporter has a sequence homology to human CD36. Clinically, total defect of myocardial uptake of radiolabeled long-chain fatty acid analog [123I-BMIPP: Iodine-123 15-(p-iodophenyl)-(R,S)-methylpentadecanoic acid] has been reported in some restricted cases, but the etiology has not been clarified. In the present study, we analyzed CD36 expression and CD36 gene in subjects who showed total lack of myocardial 123I-BMIPP accumulation, and, vice versa, evaluated myocardial 123I-BMIPP uptake in subjects with CD36 deficiency. Four unrelated subjects were evaluated, Two were found to have negative myocardial LCFA accumulation by 123I-BMIPP scintigraphy, after which the expression of CD36 on their platelets and monocytes was analyzed. Remaining two subjects were identified as CD36 deficiency by screening, then 123I-BMIPP scintigraphy was performed. Expression of CD36 on platelets and monocytes was measured by flow cytometric analysis. The molecular defects responsible for CD36 deficiency was detected by allele-specific restriction enzyme analysis. CD36 expression was totally deficient in all 4 subjects on both platelets and monocytes. Two subjects were homozygous for a 478C-->T mutation. One was heterozygous for the dinucleotide deletion of exon V and single nucleotide insertion of exon X, and remaining one was considered to be heterozygous for the dinucleotide deletion of exon V and an unknown gene abnormality. All cases demonstrated a completely negative accumulation of myocardial LCFA despite of normal myocardial perfusion, which was evaluated by thallium scintigraphy. In addition, all cases demonstrated apparently normal hepatic LCFA accumulation Thus, these findings suggested that CD36 acts as a major myocardial specific LCFA transporter in humans.

Atrial natriuretic peptide as a preload depressor in acute renal failure secondary to congestive heart failure.

The present study was undertaken to verify the hypothesis that infusion of atrial natriuretic peptide (ANP) might lower preload and be beneficial in the treatment of pulmonary congestion even without a diuresis in patients with acute renal failure (ARF) secondary to severe congestive heart failure (CHF). We studied 22 patients with ARF secondary to CHF. The mean age of the patients (14 men and 8 women) was 72 years (range 36 to 85 years). Seven of the patients had dilated cardiomyopathy, ten had ischemic heart disease, and five had valvular heart disease. ANP was infused intravenously and the following data before and 1 hour after the start of ANP infusion were recorded; urinary output, systemic blood pressure (SBP), pulmonary blood pressure (PBP), right atrial pressure (RAP), cardiac index (CI), heart rate (HR), and arterial blood oxygen partial pressure. Diastolic PBP were employed as pulmonary capillary wedge pressure. Urinary output did not change. Mean SBP decreased from 92 to 85 mmHg (p < 0.05), and mean PBP decreased from 34 to 28 mmHg (p < 0.01). Mean RAP decreased from 11 to 9 mmHg (p < 0.01) and diastolic PBP decreased from 25 to 19 mmHg (p < 0.01). HR did not change significantly and CI increased 2.4 to 2.5 mi/min/m2 (p < 0.05). Arterial blood oxygen partial pressure increased significantly from 71 to 82 mmHg (p < 0.05). In conclusion, ANP decreased preload and improved arterial blood oxygen partial pressure, though diuretic response to ANP is attenuated in ARF secondary to CHE. Infusion of ANP will be very beneficial in cases in which dyspnea and pulmonary edema due to elevation of preload are the principal clinical problems.

[Indication for percutaneous transluminal coronary angioplasty based on quality of life of patients with angina pectoris].

The changes in quality of life (QOL) before and after percutaneous transluminal coronary angioplasty (PTCA) were investigated to establish criteria for determining whether patients with angina pectoris should undergo PTCA. The QOL was surveyed twice by self-completed questionnaire for QOL by Iida and Kohashi (QUIK) before and about 4 months after PTCA in 84 patients (mean age 62.8 +/- 10.1 years) with angina pectoris. High QUIK score reflects a poor QOL, of which the internal consistency was 0.86, demonstrating high reliability. The subjects were classified into three groups according to the changes of total QUIK score before and after PTCA (I: QOL improved 31.0%, II: QOL unchanged 48.8%, III: QOL worsened 20.2%). Age, gender, total QUIK score prior to PTCA, presence of anginal pain, complications extent and degree of coronary artery stenosis, and left ventricular ejection fraction were compared between the three groups. The total QUIK score prior to PTCA in the improved QOL group was higher than that in the worsened QOL group (11.6 vs 5.1, p < 0.01). Most patients showing a poor QOL prior to PTCA demonstrated an improvement in their QOL after PTCA. The number of patients with anginal pain prior to PTCA was high in the improved QOL group (35.8%, p < 0.05). Percutaneous transluminal coronary angioplasty might not aggravate QOL (12.1%, p = 0.1) in patients with single-vessel disease. In patients with multivessel disease, PTCA might not improve (35.3%) but also might aggravate QOL (25.5%). Multivariate analysis showed that PTCA improved QOL in male or sixty-ager patients and in patients with a total QUIK score of 10 or more prior to PTCA (p < 0.01). The total QUIK score, presence of anginal pain and extent of coronary artery stenosis prior to PTCA, gender and age are factors predicting QOL after PTCA. The adaptation of PTCA for those patients should be prudently and inclusively taken into consideration to extend their QOL.

[Intravascular ultrasound in determining the end point of percutaneous transluminal coronary angioplasty].

Intravascular ultrasound (IVUS) imaging was used to measure internal luminal area immediately after percutaneous transluminal coronary angioplasty (PTCA) in 83 patients (59 males, 24 females, mean age 63 +/- 12 years) with angina pectoris to determine the need for additional intervention. The effectiveness of these interventions to prevent restenosis was also studied. Thirty-five patients (42%) with insufficient dilatation revealed an internal luminal area less than 5 mm2 or luminal stenosis greater than 60% as evaluated by IVUS imaging following the procedure. The luminal area increased from 4.5 +/- 1.1 to 7.9 +/- 2.8 mm2 and the percentage luminal stenosis improved from 66 +/- 9% to 54 +/- 9% in patients who underwent further dilatation with a larger size balloon, longer dilatation time, directional coronary atherectomy, or stenting. The insufficient dilatation group exhibited hard plaque and calcification more frequently than in the other group (48 patients, 58%) in whom sufficient dilatation of the target lesion was achieved. The incidence of restenosis in the sufficient dilatation group was 25%, compared to 33% of the patients receiving additional treatment after IVUS imaging and 42% in the 192 patients who underwent PTCA without IVUS imaging. IVUS imaging is a useful method for evaluation of complex luminal morphology to decrease the incidence of restenosis and for determination of the end point and the extent of dilatation required.

[A case involving coronary dissection caused after PTCA that was observed with intravascular echocardiography].

We encountered a case that was observed on coronary angiography (CAG) during coronary dissection after coronary angioplasty (PTCA) in which the dissected cavity disappeared on CAG but thrombolytic obstruction in the dissected cavity could be observed by intravascular echocardiography (IVUS). A 67-year-old woman was admitted with a diagnosis of acute myocardial infarction with ST elevation when experiencing chest pain. PTCR was performed for obstruction of the left circumflex artery (LCX) and the stenosis was improved to 90 percent. One month later PTCA was performed on an obstruction lesion in LCX and the feature of the dissected section at the same site was observed by CAG after PTCA. CAG showed that the dissected cavity had disappeared a year and a half later, but IVUS indicated thrombolytic obstruction in the dissected cavity.

Usefulness of serum CA125 measurement for monitoring pericardial effusion.

To investigate the clinical significance of carbohydrate antigen 125 (CA125), an antigen related to ovarian cancer, in patients with pericardial effusion, we examined the relationship between serum levels of CA125 and the presence or severity of pericardial effusion. Fifty-seven patients (25 with heart failure, 22 with pericardial metastasis, 4 with hypothyroidism, 4 with renal failure, and 2 with other diseases) in whom pericardial effusion was confirmed by echocardiography or autopsy, were used as subjects. Thirty-seven of these patients (65%) tested positive for CA125 in the serum. Of these, no significant differences in serum levels of CA125 were found between patients with benign and those with malignant underlying diseases or between those with, or without, pericarditis. However, CA125 values were higher in the patients with larger pericardial effusions and the serum level decreased when the pericardial effusion reduced. In some cases, the serum level normalized before the effusion resolved. Pericardial drainage was performed on 6 patients with cardiac tamponade. Four of these 6 patients had high serum CA125 levels and recurrent pericardial effusion. The other 2 patients had normal serum CA125 levels and no recurrence of effusion. An immunohistological study showed that a positive stain of pericardial tissues reacting to CA125 antibodies correlated to higher serum and pericardial fluid levels of CA125 than the levels of groups staining negative to the antibody. These results suggest that CA125 can be useful in assessing the status and clinical course of this disease.

[Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy: one simulates hypertrophic and the other dilated cardiomyopathy].

Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy were presented. In case 1 (a 68 year-old woman), moderate pericardial effusion and myocardial hypertrophy were observed on admission. In case 2 (a 69 year-old woman), dilation of the left ventricle, hypokinesis of the interventricular septum and the left ventricular free wall, and reduced left ventricular systolic function were observed on admission. These echocardiographic findings were similar to hypertrophic or dilated cardiomyopathy. In the two cases, after recovery to euthyroid state, these echocardiographic abnormalities returned to normal. We concluded that hypothyroidism led to a reversible hypertrophic or dilated cardiomyopathy, and that echocardiographic study was useful for diagnosis and for following up cardiac manifestations of hypothyroidism.

Eurystatins A and B, new prolyl endopeptidase inhibitors. I. Taxonomy, production, isolation and biological activities.

Eurystatins A and B, were isolated from the cultured broth of Streptomyces eurythermus R353-21. They showed specific and potent inhibitory activity against prolyl endopeptidase and did not show antimicrobial activity. No lethal toxicity was observed for the two compounds after ip administration in mice at 200 mg/kg.

Eurystatins A and B, new prolyl endopeptidase inhibitors. II. Physico-chemical properties and structure determination.

The structures of eurystatins A and B, new prolyl endopeptidase inhibitors, have been elucidated by chemical degradation and spectral studies. They have in common a unique 13-membered cyclic peptide core composed of L-leucine, L-ornithine and (S)-3-amino-2-oxobutyric acid, and differ from each other in the alpha,beta-unsaturated fatty acid attached to the alpha-amino moiety of the ornithine.

[The effect of acebutolol and metoprolol on noninvasive ambulatory blood pressure monitoring system in essential hypertension].

We compared the antihypertensive effects of acebutolol and metoprolol during 2-4 weeks of treatment in patients with mild to moderate essential hypertension. Acebutolol (n = 12) significantly decreased conventionally measured blood pressure from 173/100 mmHg to 148/86 mmHg (p less than 0.005), and metoprolol (n = 11) decreased it from 164/106 mmHg to 138/87 mmHg (p less than 0.01). Based on data derived from automated 24-hour ambulatory blood pressure monitoring, both drugs significantly decreased the blood pressure in the early morning (5:00-10:00). Moreover, in the metoprolol group, there were significant falls in day-time blood pressure (7:30-19:30) and night-time blood pressure (23:00-7:00). In contrast, acebutolol showed significant antihypertensive effect on day-time blood pressure, but not effect on night-time blood pressure. The study confirmed the efficacy and character of metoprolol and acebutolol. We must choose an effective beta-blocker when using an automated 24-hour ambulatory blood pressure monitoring system to get adequate blood pressure reduction for the whole 24 hours.

Butyrolactols A and B, new antifungal antibiotics. Taxonomy, isolation, physico-chemical properties, structure and biological activity.

New antifungal antibiotics, butyrolactols A and B, have been isolated from the culture broth of Streptomyces rochei S785-16. They are novel type of molecules containing a common 2,3-dihydroxybutyrolactone nucleus substituted with a different long hydroxyalkyl side chain. Butyrolactol A showed good antifungal activity against Aspergillus fumigatus and Trichophyton mentagrophytes, and moderately inhibited the growth of yeasts.

New antiviral antibiotics, cycloviracins B1 and B2. II. Structure determination.

The structures of novel antiviral antibiotics, cycloviracins B1 and B2 have been determined by means of chemical and spectroscopic methods including 2D NMR correlation spectroscopy. The antibiotics are unique macrocyclic diesters consisting of two D-glucoses, three 2-O-methyl-D-glucoses and two (C24 and C26) hydroxy fatty acids.

New antiviral antibiotics, cycloviracins B1 and B2. I. Production, isolation, physico-chemical properties and biological activity.

Kibdelosporangium albatum No. R761-7 (ATCC 55061) produced new antiviral antibiotics, cycloviracins B1 and B2. They show weak activity against Gram-positive bacteria and potent antiviral activity against herpes simplex virus type 1. Unique acylsaccharide structures were established for cycloviracins B1 and B2 by degradation and spectroscopic analysis.

Quartromicin, a complex of novel antiviral antibiotics. I. Production, isolation, physico-chemical properties and antiviral activity.

A strain of Amycolatopsis orientalis No. Q427-8 (ATCC 53884) was found to produce a complex of new antiviral antibiotics, quartromicin which consisted of at least six components A1, A2, A3, D1, D2 and D3. Structural studies suggested that they are a novel type of molecules unrelated to any known antibiotics. Each component of quartromicin exhibited antiviral activity against herpes simplex virus type 1, influenza virus type A and human immunodeficiency virus.

[A case of anomalous origin of circumflex artery from right sinus of valsalva recognized by transesophageal echocardiography].

A 56-year-old man visited our hospital for further examination of resting electrocardiographic abnormality. Positive exercise stress resulted in mild chest discomfort and 1.5 mm ST depression in II.III.aVF leads. Myocardial imaging perfusion with thallium-201 was normal and an anomalous origin of the left circumflex coronary artery from the right aortic sinus was observed by coronary angiography. MRI showed that the vessel running behind the aorta was connected to the right Valsalva's sinus. Furthermore, transesophageal echocardiography revealed that the vessel connected to the lateral wall of the left ventricle was running from the right Valsalva's sinus between the aorta and left atrium. The above results indicated that this vessel was the left circumflex artery. Although myocardial infarction or sudden death in patients with coronary anomaly has been discussed, the mechanism is still unknown. The present case is a rare one in which the anatomical relation between the anomalous coronary and the great vessels was directly detectable by transesophageal echocardiography. Transesophageal echocardiography is useful for the assessment of this type of coronary anomaly.

Pure red cell aplasia associated with non-Hodgkin's lymphoma and hemolytic anemia.

Pure red cell aplasia (PRCA) rarely occurs in non-thymic lymphoproliferative disorders. The present article describes a patient with non-Hodgkin's lymphoma (follicular, mixed type), who concurrently developed PRCA and warm type autoimmune hemolytic anemia during the clinical course. The PRCA and hemolytic anemia were successfully treated with prednisolone (60 mg/day). The patient died two years later, however, from advanced lymphoma without any recurrence of the PRCA or hemolytic anemia. To our knowledge, only 20 cases of PRCA associated with malignant lymphoma have been reported. The pathogeneses of the PRCA and hemolytic anemia in our patient are discussed.

[A case of multiple myeloma with heart failure improved remarkably by chemotherapy alone].

A rare case is reported, in which heart failure in a patient with multiple myeloma without amyloidosis was improved following chemotherapy for the myeloma. The patient, a 50 year-old man, came to our hospital for examination because of anemia and hematuria. He was diagnosed as having an IgG kappa type of myeloma with the relatively rare complication of renal cancer. A chest X-ray revealed cardiomegaly and pulmonary congestion. An echocardiogram revealed an enlarged left ventricle with decreased wall motion. No cardiac amyloid deposits were detected upon endomyocardial biopsy. Chemotherapy for the myeloma which was carried out before the operation for renal cancer was not only effective for control of the myeloma, but also decreased the pulmonary congestion and improved the heart function. It is suggested that the lowering of heart function in this patient was not due to amyloid infiltration as is relatively frequent in heart failure but was due to increased blood viscosity due to the multiple myeloma.

Protective effect of coenzyme Q10 on thyrotoxic heart in rabbits.

An excess of thyroid hormone is known to produce cardiac dysfunction and failure, i.e., thyrotoxic heart. We studied the protective effect of coenzyme Q10 (CoQ10) on the thyrotoxic heart in 29 rabbits. A group treated with 1-thyroxine sodium salt (T4; 167 micrograms/kg) for 3 weeks showed marked decreases in the myocardial content of norepinephrine (NE) and ATP (0.5 +/- 0.2 microgram/g wet weight, P less than 0.05 and 31.1 +/- 2.6 nmol/mg protein, P less than 0.05, respectively) as compared with a group treated with CoQ10 solvent (2 ml/kg) for 3 weeks (1.1 +/- 0.1 microgram/g wet weight and 45.7 +/- 4.7 nmol/mg protein). The mitochondrial Ca2+ content of the T4 group showed significant increases (21.3 +/- 0.6 nmol/mg protein, P less than 0.05) compared with the solvent group (18.2 +/- 0.8 nmol/mg protein), while the total tissue Ca2+ content of the T4 group was unchanged compared with the solvent group. These biochemical derangements suggest that T4-treated rabbits were in a state of cardiac dysfunction. In contrast, a group which was assigned to concomitant treatment of T4 and CoQ10 (5 mg/kg) for 3 weeks showed no reductions in NE and ATP (0.9 +/- 0.2 micrograms/g wet weight and 44.6 +/- 1.9 nmol/mg protein, respectively) and protected an increase in the mitochondrial Ca2+ content (18.2 +/- 1.2 nmol/mg protein). A group treated with CoQ10 (5 mg/kg) for 3 weeks showed no changes in myocardial NE, ATP, and Ca2+ content in the mitochondria. These results suggest that exogenously administered CoQ10 may protect against biochemical derangements in the thyrotoxic heart.

Collagen species in human aorta: with special reference to basement membrane-associated collagens in the intima and media and their alteration with atherosclerosis.

Collagen species, especially basement membrane or short chain types, of human aorta extracted by limited and repeated pepsin digestions were investigated as to their type dependent solubility by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after differential salt precipitation and cyanogen bromide cleavage. Basement membrane-associated collagens, i.e., types IV, V and VI, were more extractable in the earlier limited pepsin digests than in the later repeated ones, whereas type I collagen was continually extracted. The content of collagen type IV as well as that of type V increased with the proliferative fibrotic process in the intima including the media. Basement membrane collagen type IV showed heterogenous molecular sizes, including alpha 1(IV) and alpha 2(IV) chains. The alpha 3(V) chain of type V collagen was found in addition to the alpha 1(V) and alpha 2(V) chains. Short chain collagen type VI was detected in the intima and media at a position corresponding to 145 Kd and was reduced to fragments of around 45 Kd.