Accumulation of 7α-hydroxycholesterol in liver tissue of patients with cholesterol gallstones

Patients with cholesterol gallstones have a reduced pool of bile acids. This study was undertaken to clarify the mechanism by which bile acid biosynthesis does not increase to supranormal levels to cause a reexpansion of the pool. We investigated the first two steps of the bile acid biosynthesis pathway by assaying the activities of cholesterol 7α-hydroxylase, the rate-limiting enzyme in this pathway, and 3β-hydroxy-Δ⁵-C₂₇-steroid dehydrogenase/isomerase, and by measuring the concentrations of 7α-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one in liver specimens from ten patients with cholesterol gallstones and ten gallstone-free controls. In the patients with gallstones, cholesterol 7α-hydroxylase activity, 3β-hydroxy-Δ⁵-C₂₇ dehydrogenase/isomerase activity, and hepatic 7α-hydroxy-4-cholesten-3-one concentration did not significantly different from levels in controls, but hepatic 7α-hydroxycholesterol concentration was more than twofold that of controls (12.9 ± 2.6 vs 5.3 ±1.2 nmol/g liver,P<0.01). The concentration of 7α-hydroxycholesterol positively correlated with the ratio of cholesterol 7α-hydroxylase activity to 3β-hydroxy-Δ⁵-C₂₇ dehydrogenase/isomerase activity (r=0.93;P<0.005) in the gallstone-free controls. In contrast, this correlation disappeared in the patients with gallstones. These results suggest a derangement of the normal 7α-hydroxycholesterol metabolism in the patients with gallstones. The reason for the accumulation of 7α-hydroxycholesterol remains unclear; however, it is possible that, in patients with cholesterol gallstones, the accumulated 7α-hydroxycholesterol causes inappropriate suppression of cholesterol 7α-hydroxylase activity by product inhibition.     

Portal vein thrombosis following percutaneous ethanol injection therapy for hepatocellular carcinoma.

Percutaneous ethanol injection therapy was performed in a 66-year-old woman with hepatocellular carcinoma. She developed portal vein thrombosis that on color Doppler revealed no tumor vascular signal, and so was diagnosed as non-tumor thrombus. The thrombus resolved over 3 months.     

Systematic diagnostic method using magnetic resonance imaging to analyze viscero-bronchial-cardiovascular anomalies in pediatric patients with congenital heart disease

Segmental analysis of magnetic resonance imaging (MRI) was performed in 300 patients with congenital heart disease (CHD) (182 cyanotic CHD and 118 acyanotic CHD), between 20 days and 18 years of age. The usefulness of MRI in systematic diagnosis of CHD, which had previously been documented by angiography and echocardiography, was assessed. Electrocardiographyically gated MRI was performed by spin echo and gradient refocused imaging techniques operating at 0.5 tesla. In all 300 patients, not only cardiovascular anomalies of CHD but also viscerobronchial-cardiovascular anomalies were clearly visualized without serious complications due to MRI. In comparing 300 major cardiac anomalies and 1477 segments of the vein, the atrium, the ventricle, and the great arteries visualized by MRI and angiography, discrepancies were found in 7 anomalies (2.3%), and 22 segments (1.5%), respectively. Finally, in 86% (26/30) of patients manifesting atrioventricular valve regurgitation (AVVR), which had been evaluated by echocardiography, the AVVR was also detected on MRI. Based on these findings, segmental analysis of cardiac MRI was found to be safe and useful for systematic diagnosis of viscero-bronchial-cardiovascular anomalies in pediatric patients with CHD.Presented at the 36th Annual World Congress, International College of Angiology, New York, New York, July 1994     

A long-surviving patient with recurrences of hepatic alveolar echinococcosis after traumatic intra-abdominal rupture

Alveolar echinococcosis of the liver (AEL) takes a progressive and malignant course. Intra-abdominal dissemination of the parasite has a miserable outcome. Complete resection of the lesion is indispensable for the curative treatment of AEL. We experienced an extremely rare case of intra-abdominal rupture of AEL. The patient had repeated recurrences of AEL following the traumatic rupture of the lesion. After repeated resections of the lesions and appropriate medication, the patient is still alive more than 25 years since the initial onset of the disease. AEL differs from unilocular echinococcosis in terms of biological behavior. We compare the pathophysiology of the two conditions.     

The Fas antigen is detected on immature B cells and the representative cell lines show Fas-mediated apoptosis

The expression and functions of Fas antigen, a major regulator of apoptosis, in T-cell selection have been intensively investigated, but little is known about its expression in immature B cells which are also selected in the bone marrow, and plasma cells which are at the terminal stage of B-cell differentiation and are designed to die. We examined bone marrow cells and found Fas antigen on these cells at low levels. Next, we analysed Fas expression and susceptibility to anti-Fas antibody-mediated apoptosis on B-cell lines representing various stages of differentiation. We also examined the expression of Bcl-2 and Bax on these lines, which were intimately related to apoptosis. Fas antigen was almost negative on pre-pre-B cell lines and was detected on pre-B-cell lines at low levels. All plasma cell lines expressed Fas at a low to moderate level. Some cell lines with peripheral B-cell phenotype expressed Fas antigen. Except for the Burkitt cell lines and one plasma cell line, susceptibility to Fas-mediated apoptosis depended on Fas expression. Bcl-2 protein was detected on all but one cell line and Bax was detected on 15/23 lines, but neither were related to cellular differentiation or Fas expression.     

Substance P,vasoactive intestinal polypeptide,and gastrin catabolism in canine liver and kidney

No reports have described the catabolic mechanism of substance Pin vivo. We studied the effects of hepatic or renal transit on substance P, vasoactive intestinal polypeptide, and gastrin in anesthetized dogs. It was found that the liver plays a more important role in vasoactive intestinal polypeptide catabolism than the kidney and the kidney is more important in gastrin catabolism than the liver. Substance P was more rapidly degraded than the other two peptides in both organs. The transrenal substance P loss measured byC-terminal antiserum differed from that measured byN-terminal antiserum, although there was no difference in the liver. This suggested that there were different patterns of cleavage of substance P between the liver and the kidney, and that itsC terminal was degraded more strongly than itsN terminal in the kidney.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

Surgical experience with right atrial-aortic fistula and penetration of the superior vena cava by a protruding Accufix atrial J-shaped retention wire.

A 57-year-old woman who had a dual chamber pacemaker implanted in June 1990 for sick sinus syndrome had developed heart failure since 1993. Although fluoroscopy revealed that the proximal J-shaped retention wire of the lead had fractured and had protruded through the outer insulation in 1994, and also that the distal J-shaped retention wire of the lead had protruded through the outer insulation in 1997, a transthoracic echocardiographic examination diagnosed tricuspid valve regurgitation, suggesting that the right atrial-aortic fistula might have been overlooked. In an attempt to avoid migration of the J-shaped retention wire from the lead and to repair the tricuspid regurgitation, it was decided that an operation be performed; however, intraoperative transesophageal echocardiography showed a right atrial-aortic fistula. Intraoperative inspection also revealed that the right atrial-aortic fistula and penetration of the superior vena cava had been caused by the Accufix atrial J-shaped retention wire. Under total cardiopulmonary bypass and induced cardiac arrest, a right atriotomy was performed and the atrial and ventricular leads were removed from the tips. The atrial orifice of the fistula and the aortic orifice were closed. Finally, a new dual-chamber pacing system with bipolar epicardial pacing leads was implanted. Postoperative inspection revealed that the proximal retention wire had fractured, the tip of the retention wire had protruded through the outer insulation, and the distal J-shaped outer insulation was damaged.     

Autoradiographic study on healing process of cysteamine-induced duodenal ulcer in rat

The healing process of cysteamine-induced duodenal ulcer was studied by [³H]thymidine autoradiography. After the development of ulcer in the duodenum, cell proliferation was markedly activated not only in the crypts but also in the Brunner's glands near the ulcer. In the initial stages of ulcer healing, they both contributed to form the surface covering regenerating epithelium. Granulation tissue also proliferated at the base of the ulcer. In later stages of ulcer healing, new crypts were formed in the floor of the ulcer. New villi regenerated from these crypts and Brunner's glands regenerated by proliferationin situ. The ulcer base then was completely covered with new villi and granulation tissue was replaced by dense fibrous connective tissue. The present study suggested that the Brunner's glands, together with the crypts of Lieberkühn, play an important role in the healing process of cysteamine-induced duodenal ulcer.