Loss of Secreted Frizzled-Related Protein-1 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.

AIMS: Secreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)-ß-catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt-ß-catenin pathway. METHODS: Fifty IHCC patients who had liver resection were enrolled in this study. SFRP1 protein expression was examined by immunohistochemistry in tumor tissues. The patients were divided into two groups: SFRP1 positive (n = 30) and negative (n = 20). Clinicopathological characteristics were analyzed. RESULTS: SFRP1 significantly correlated with curability (Cur A, B vs. C, p = 0.029); and recurrent pattern (intrahepatic vs. extrahepatic, p = 0.010). The negative SFRP1 group had significantly poorer prognosis, and 5-year survival rates were 8.1% of the negative SFRP1 group and 44.6% of the positive SFRP1 group, respectively. Moreover, the disease-free survival rate in the negative SFRP1 group was significantly poorer (p < 0.001). Multivariate analysis revealed that loss of SFRP1served as an independent prognostic factor in IHCC for both overall (HR, 2.923; 95% CI, 1.30-6.56; p = 0.009) and disease-free (HR, 2.631; 95% CI, 1.31-5.27; p = 0.006) survival. In addition, SFRP1 expression negatively correlated to ß-catenin expression (p = 0.005). CONCLUSIONS: Those results suggested that the loss of SFRP1 could be a poor prognostic factor for IHCC, through the Wnt-ß-catenin pathway.

Long-term effects of LDL apheresis on carotid arterial atherosclerosis in familial hypercholesterolaemic patients.

OBJECTIVES: To assess the long-term effect of LDL apheresis on carotid arterial atherosclerosis in severe familial hypercholesterolaemic (FH) patients. DESIGN: Changes in existing plaque, new plaque formation and annual progression rate of carotid early plaque were evaluated by B-mode ultrasonography. SUBJECTS: LDL apheresis group: two homozygous FH and nine heterozygous FH patients received a combination of LDL apheresis and cholesterol-lowering drug therapy for a mean of 7.8 years. CONTROL GROUP: 10 heterozygous FH patients were maintained by medication only for a mean of 5.5 years. RESULTS: As a result of LDL apheresis treatment, LDL cholesterol levels reduced from 16.0+/-3.60 to 6.43+/-0.07 mmol L(-1) in homozygous FH patients and from 11.5+/-2.46 to 4.32+/-1.2 mmol L(-1) in heterozygous FH patients. During the long-term treatment period, the existing plaque tended to progress and new plaque formation in carotid arteries was also observed in both groups. The annual progression rate of mean maximum intima-media thickness in the common carotid artery was a mean of -0.0023+/-0.0246 mm year(-1) in heterozygous FH patients in the LDL apheresis group, suggesting regression. This was significantly lower when compared with the control group, which had a mean of 0.0251+/-0.0265 mm year(-1) CONCLUSION: The results suggest that the long-term treatment with combined LDL apheresis and drugs may delay the progression of the atherosclerotic process and prompt the stabilization of atheromatous plaque in severe FH patients.

Structure of the rat methionine adenosyltransferase 2A gene and its promoter.

In this study, to understand the regulation of methionine adenosyltransferase (MAT) gene expression, we isolated the rat MAT2A gene encoding MAT alpha2, the catalytic subunit of non-hepatic-type enzyme MAT II and characterized its structural organization and 5'-flanking region. The gene spans approximately 7 kbp and consists of nine exons interrupted by eight introns. The transcription initiation site, as demonstrated by primer extension analysis, is located 123 bp upstream of the translation start codon. Comparison of the structural organization of the rat MAT2A gene to that of the mouse MAT1A gene encoding MAT alpha1, the subunit of liver-type enzymes MAT I and III, shows that the exon structure of two genes is very similar and the insertion sites of all corresponding introns are identical. A canonical TATA box and a GC box, the potential Sp1-binding site, are found 32 bp and 70 bp upstream of the transcription initiation site, respectively. The 5'-flanking region also contains potential recognition sites for various transcription factors including AP-1, AP-2 and NF-IL6 (C/EBPbeta), and a large G+C-rich domain with the characteristics of a CpG island. The 5'-flanking sequence of the rat MAT2A gene has no significant similarity with those of the MAT1A genes. Transient transfection experiments using a luciferase reporter gene showed that the first 820-bp sequence of the 5'-flanking region directed high levels of luciferase activity in cultured rat kidney fibroblast (NRK-49F) and hepatocellular carcinoma (FAA-HTC1) cells, but not in primary rat hepatocytes. Deletion analysis suggested that the first 343 bp of the 5'-flanking region contained cell-type-specific promoter elements of this gene.

[Early diagnosis and management of acute pulmonary embolism: clinical evaluation those of 225 cases].

To contribute for making early diagnosis and treatment of acute pulmonary embolism (APE), we investigated on clinical pictures of 225 patients with APE. Common underlying factors were heart disease, prolonged bed rest, post-surgical state, thrombophlebitis, malignant tumor and post-catheterization state in this order. Dyspnea, chest pain, tachycardia and shock were frequently seen as initial symptoms and signs. Blood screening showed leukocytosis, hypoxemia, hypocapnia and elevated serum LDH. Electrocardiographic findings highly demonstrated were ST.T abnormalities, such as T inversion with ST elevation in V1-3, ST depression in V4-6 and sinus tachycardia. Chest X-rays showed diminished pulmonary vascular marking and pulmonary artery dilation. Right ventricular dilatation were frequently seen on 2-dimensional echocardiograms. Pulmonary artery pressure were elevated up to 49/20 (30) mmHg. Twenty-five percent of the patients died, and the recurrence was seen in 4%. Thus, as soon as APE is suspected by above clinical findings, definitive diagnosis should be obtained by the lung perfusion scan and pulmonary arteriography, then oxygen and thrombolytic agents should be given immediately to prevent the fatal outcome.

A fast Fourier transform analysis of coronary reperfusion-induced ventricular fibrillation and the modification by dibutyryl cyclic AMP in a cat model.

To investigate the effect of dibutyryl cyclic AMP (dbcAMP) on ventricular fibrillation after coronary reperfusion, the proximal portion of the anterior descending branch of left coronary artery was reperfused 20 min after ligation in 24 cats. McFee X Y Z electrocardiograms were recorded and ventricular fibrillation was analyzed using a fast Fourier transform analysis (FFT). Ventricular fibrillation occurred in 20 of 24 cases. Sixty seconds after the occurrence of ventricular fibrillation, an intracardiac infusion of dbcAMP was administered. Nine of the 20 were defibrillated and converted to sinus rhythm or junctional rhythm after the administration of dbcAMP. The amplitude and frequency of the main power spectrum of the ventricular fibrillation waves were analyzed by FFT before and after the infusion of saline or dbcAMP. In the saline group there was no significant change in FFT. However, in the dbcAMP group, the amplitude increased significantly from 0.036 +/- 0.015 (MV--2) to 0.054 +/- 0.013 (MV--2) (p < 0.01) and the frequency decreased significantly from 4.22 +/- 1.37 (Hz) to 1.33 +/- 0.91 (Hz) (p < 0.01). Those results indicate that dbcAMP increased the amplitude and decreased the frequency of the main power spectrum of ventricular fibrillation analyzed by FFT. These distinctive changes in FFT analysis were associated with defibrillation in 9 of 20 cases.

Alcohol intake and nonfatal acute myocardial infarction in Japan.

The relation between alcohol and nonfatal acute myocardial infarction (AMI) was examined in a case-control study of 89 male patients and 271 control subjects in Fukuoka, Japan. Patients admitted for the first AMI at 2 hospitals in Fukuoka City were aged 40 to 69 years, and control subjects were recruited based on the telephone directory of the city. Information on alcohol drinking and potential coronary risk factors was obtained by using a self-administered questionnaire, and past drinkers were separated from lifelong abstainers in the analysis. After adjustment for age, occupation, cigarette smoking, strenuous exercise, body mass index, hypertension, diabetes mellitus and parental heart disease, the risk of AMI was progressively less with increasing levels of alcohol consumption. With those who never drank as a referent, adjusted odds ratios for current drinkers consuming less than 30, 30 to 59, and greater than or equal to 60 ml/day of alcohol were 1.11 (95% confidence interval 0.51 to 2.42), 0.31 (0.11 to 0.83), and 0.13 (0.05 to 0.36), respectively. These findings add to the body of data showing that alcohol drinkers are less likely to have AMI.

Effects of dibutyryl cyclic AMP on ventricular vulnerability during atrioventricular block in dog.

The effects of dibutyryl cyclic AMP (DBcAMP) on ventricular vulnerability during complete atrioventricular block (CAVB) were studied one week after transarterial electrical ablation of the AV junction in 18 closed-chest dogs. All dogs exhibited CAVB and a stable ventricular escape rhythm with a mean cycle length of 1812 +/- 638 ms. After the administration of DBcAMP at a rate of 0.1 mg/kg/min for 30 min, the ventricular cycle length was significantly shortened, and the QTc interval was slightly prolonged, although the QT interval did not change. The ventricular fibrillation threshold after the administration of DBcAMP was significantly increased (from 12.2 +/- 3 84 to 18.4 +/- 5.08 mA, p less than 0.01). Thus, it was demonstrated that DBcAMP exhibited suppressive effects on the ventricular vulnerability in the experimentally induced CAVB.

[A case of myxedema with diffuse myocardial fibrosis proven by endomyocardial biopsy].

We report a middle-aged woman with myxedema heart who presented both clinical features resembling dilated cardiomyopathy and the diffuse myocardial fibrosis proven by endomyocardial biopsy. Thirty years previously, when she was 36 years old, partial thyroidectomy had been performed after a diagnosis of hyperthyroidism was made. Four years later, she experienced dry skin and peripheral edema, and hypothyroidism was diagnosed. Several months after, replacement therapy for hypothyroidism improved her symptoms. However, the therapy was discontinued because of her ignorance of the disease. Twenty six years later (64 years old), she felt exertional dyspnea, and was admitted to Fukuoka University Hospital for evaluation of her cardiac state. Thyroid function test revealed primary hypothyroidism with low T3, low T4 and high TSH levels. Cardiothoracic ratio on chest X-ray film was 69%. Electrocardiogram showed low voltage in the limb leads and intraventricular conduction disturbance. Echocardiogram demonstrated marked dilatation and severely reduced wall motion of the left ventricle and pericardial effusion. Left ventriculogram showed diffuse hypokinesis with 27% of the ejection fraction. No significant stenosis was observed on coronary arteriogram. Seventeen-month replacement therapy did not improve these cardiac findings significantly. Transvenous right ventricular endomyocardial biopsy demonstrated diffuse myocardial fibrosis without inflammatory infiltrate, which was interpreted as a sequel of interstitial lesions of the myxedema heart such as edema or mucoid infiltration. This pathological finding suggests that long-standing untreated hypothyroidism can cause irreversible myocardial damage.

Plasma fibrinogen levels as an independent indicator of severity of coronary atherosclerosis.

The relationship between plasma fibrinogen levels and the severity of coronary atherosclerosis was examined in 229 patients, aged 25-82 years (162 men and 67 women), undergoing coronary angiography. Severity of coronary atherosclerosis was assessed in terms of the number of vessels with a 75% or greater stenosis and Gensini's severity score. Fibrinogen levels increased progressively with the severity of coronary atherosclerosis, determined by both the number of involved vessels and Gensini's severity score in men, and the relationships were statistically significant. Similar patterns were noted among women, but the trends were not statistically significant. The association was evident even after adjustment for age, hypertension, total cholesterol, cigarette smoking, alcohol intake, high density lipoprotein cholesterol and body mass index. These results provide evidence that in the Japanese also plasma fibrinogen levels can serve as an independent indicator of the progression of coronary atherosclerosis.

A case of cross stimulation.

Cross stimulation in a dual chamber pacing system, in which the atrial stimulus intermittently captured the right ventricle, occurred immediately after pacemaker implantation in a 71-year-old man. It was prevented temporarily by reducing the pacing rate so that P wave synchronous ventricular (VDD) pacing resulted and by reducing the output of the atrial circuit from 5 to 4 volts. Cross stimulation disappeared spontaneously 14 days after surgery.

[Two cases of malignant cardiac tumors attached on the anterior mitral valve].

Two cases were reported in which malignant cardiac tumors attached to the mitral valve were diagnosed during their lifetimes using two-dimensional echocardiography. Case 1 was a 29-year-old man with speech disturbance and left hemiparesis. Histological examination of the specimen excised from the cardiac tumor during the operation revealed mesenchymal chondrosarcoma, which is extremely rare etiologically and has never been reported so far. Case 2 was a 62-year-old woman complaining of paroxysmal nocturnal dyspnea and chest pain. The diagnosis of malignant histiocytosis was made from the pathological examination of biopsy specimen taken from the rib metastasis. Using two-dimensional echocardiography, characteristic findings for the cardiac tumor were obtained. The tumor echo in Case 1 showed, unlike to that reported for myxoma, two different echogenic layers; the outer dense and the inner light in the echo density. On surgery, tumor echo was revealed to reflect the cystic lesion. In Case 2, two-dimensional echocardiography on admission revealed two separate tumor echoes which attached to the mitral valve and left atrial wall region, respectively. Within two months, they grew rapidly and finally fused into one mass resulting in so-called ball valve syndrome. Phonocardiographically, the tumor plop in Case 1 was high-pitched in quality, and was extinguished completely after the tumor was resected. The tumor plop in Case 2 was not audible on admission, but became evident after fusion of the tumor echoes and was associated with a presystolic murmur.

An accelerated hypertension with neither malignant nephrosclerosis nor elevation of plasma renin activity.

A case of accelerated hypertension, which was unique in a resistance to an angiotensin antagonist, and a lack of the elevation of plasma renin activity (PRA) is reported. Non-elevated PRA was coincided with non-malignant nephrosclerosis in renal histology. The acceleration was attributed to the neurological cause i.e., cerebral hemorrhage in the right hypothalamus which extended to the ventricle and subarachnoid space. The case therefore clinically seemed malignant-like, but it was not malignant hypertension in the sense of Volhard's classical definition. This does not conflict with the usefulness of the determination of PRA in the diagnosis of malignant hypertension with nephrosclerosis.