Autoantibodies against a 210kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis

It has been reported that the presence of anti-nuclear antibody against a 210kDa glycoprotein of nuclear pore complex (anti-gp210) is highly speci?c for primary biliary cirrhosis (PBC). The aim of the present study was to investigate the signi?cance of anti-gp210, especially as a prognostic marker. The presence of anti-gp210 was ascertained in 113 patients with PBC and 162 controls by indirect immuno?uorescence assay using HepG2 cells and immunoblotting analysis using nuclear extracts from HeLa cells. Anti-gp210 was detected in 25 of the 113 (22.1%) patients. None of the 162 controls was positive for anti-gp210. The appearance and titre of anti-gp210 in the patients with PBC did not vary from the time of diagnosis and through their clinical course. Anti-mitochondrial antibodies (AMA), including antibodies against pyruvate dehydrogenase complex, branched chain α-ketoacid dehydrogenase complex and α-ketoglutarate dehydrogenase complex, were not detected by enzyme-linked immunosorbent assay in ?ve of the 113 (4.4%) patients with PBC. However, anti-gp210 alone was positive in one of these ?ve patients. The difference in prognosis was statistically signi?cant; patients with PBC positive for anti-gp210 died from hepatic failure more frequently than those who were negative (P < 0.01), although there were no statistically signi?cant differences in the frequency of jaundice and the histological stage at the time of diagnosis between the two groups. We suggest that the presence of anti-gp210 is one of the independent prognostic markers able to predict, at the time of diagnosis, a poor outcome in patients with PBC.     

Coexistence of proguanylin (1–15) and somatostatin in the gastrointestinal tract

In order to identify proguanylin-secreting cells, we have raised an antiserum against the synthetic fragment of human proguanylin (1–15) and have examined the proguanylin-positive cells in the human and rat gastrointestinal tract by immunohistochemical methods. Numerous proguanylin (1–15)-immunoreactive cells were found in the gastrointestinal tract. They were either pyramidal or spindle shaped in the stomach. Spindle-shaped cells, frequently possessing long slender processes, were located at the base of the pyloric epithelium and did not extend to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in shape and often had a slender process towards the lumen. The immunostaining was completely blocked by the human proguanylin (1–15) fragment. Paneth and goblet cells were negative against this antiserum. The number of serotonin-positive cells was much larger than that of proguanylin-positive cells in all the segments tested. The number of proguanylin-positive cells decreased from the jejunum to the ileum and very few cells were observed in the colon. In contrast to serotonin-positive cells, most somatostatin-positive cells were also positive for proguanylin. Thus, proguanylin (1–15) or its related protein appears to coexist with somatostatin in intestinal endocrine D cells which may be a source of circulating proguanylin. Proguanylin, like somatostatin, may also regulate intestinal function as a local regulator.     

Decreased arteriovenous flow resistance in the left gastric venous area in cirrhotic patients

Abstract. To assess the relationship between the fluid mechanics in the left gastric venous area and the portal trunk, manometric measurements were made in patients with or without cirrhosis of the liver. In ten normal subjects, temporary portal vein occlusion produced comparable elevation in both the occluded left gastric venous pressure (OLGP) and the portal vein pressure (PVP); 152–4129 mm of water in OLGP and 115–452 mm of water in PVP. In sixty cirrhotic patients, however, the portal vein occlusion resulted in far less increase in OLGP than that in PVP; 281–365 mm of water in OLGP and 281–540 mm of water in PVP. In other words, regarding pressure measurements, the relationship was 'separated' in cirrhotics, but 'continuous' in normal subjects. Mathematical analysis of the data using a modification of Wheat-stone bridge model suggested that the arteriovenous flow resistance in the left gastric venous area of cirrhotics was reduced to less than one fifth of that in the controls. It would appear that the increased flow capacity as a result of a reduced arteriovenous flow resistance is responsible for the functional 'separation' from the portal trunk.     

A ROLE FOR APOPTOSIS INDUCED BY ACUTE HERPES SIMPLEX VIRUS INFECTION IN MICE

Acute herpes simplex virus (HSV) infection causes apoptosis in the adrenal cortex and myenteric plexus of the gut, ovary, pituitary gland, and liver of mice. Apoptosis of infected cells is increased in immunosuppressed regions of the adrenal cortex and liver of macrophage-depleted mice. HSV carries the US3 gene which interferes with host cell apoptosis. When the livers of macrophage-depleted mice are infected with a US3-null virus, apoptosis occurs in the narrow areas of inflammatory cell infiltration, restricting viral replication and spread. Thus, these data suggest that apoptosis may function as a primitive immune response to HSV infection in mice.     

Successful uses of magnesium sulfate for torsades de pointes in children with long QT syndrome

BACKGROUND: Administration of magnesium sulfate (MgSO4) is an effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. As for children, there are few reports focusing on it. The authors discuss the efficacy of MgSO4 for TdP in children with congenital and acquired LQTS. The authors also discuss the optimal administration dosage and serum magnesium (SMg) concentration during MgSO4 therapy. METHODS: The authors studied seven consecutive LQTS children undergoing MgSO4 therapy for TdP. Of the seven children, five were congenital LQTS and two were acquired LQTS. A bolus injection of MgSO4 was given intravenously over 1-2 min followed by continuous infusion for the next 2-7 days. RESULTS: Of the seven patients, six responded completely to the initial bolus. The bolus dosage was 5.9 +/- 3.8 mg/kg (range, 2.3-12 mg/kg) in these six, and the other remaining one (neonate with congenital LQTS) required a total of 30 mg/kg until complete abolishment. The continuous infusion was given at rates of 0.3-1.0 mg/kg per h and patients did not show recurrence of TdP. The SMg concentration was 3.9 +/- 1.0 mg/dL (2.9-5.4 mg/dL) immediately after bolus injection. The mean corrected QT (QTc) interval before and after bolus injection did not show significant difference. CONCLUSION: Intravenous infusion of MgSO4 was effective for TdP in children with LQTS, and MgSO4 abolished TdP without shortening the QTc interval. The optimal bolus dosage, infusion rates and SMg concentration were 3-12 mg/kg, 0.5-1.0 mg/kg per h and 3-5 mg/dL, respectively.     

CUTANEOUS B-CELL LYMPHOMA CONSISTING OF LARGE CLEAVED CELLS WITH MULTILOBATED NUCLEI

A 65-year-old man was seen at the Ushioda Hospital in Au-gust 1989, because of a 1-month history of a tumor on the scalp. The tumor was excised and the diagnosis was malig-nant lymphoma. The patient was then referred to our de-partment in September 1989. Several nut-sized lymph nodes wvepa-b and m-fepa for 2 months. Since then, the patient has been free of disease up to the time of writing, July 1992, a period of 2.5 years. Biopsy samples taken from the tumor on the scalp showed a monomorphous infiltrate of large lymphoid cells throughout the entire dermis and subcutis, with a definite clear zone (Fig.1). A high-power view showed diffuse large lymphoid cell infiltration. Numerous mitotic figures were also seen. The lymphoid cells had multilobated nuclei and distinct nucleoli (Fig. 2). Monoclonal antibodies such as Leui (CD5), Leu2a (CD8), Leu3a (CD4), Leu4 (CD3), MT-1 (CD43), Leu14 (CD22), LN1 (CDw75), and Leu26 (CD20), and polyclonal antibodies such as anti-kappa, anti-lambda, anti-IgG, anti-lgA, anti-IgM, and anti-lgD were purchased from commercial sources. Optimal dilutions of the monoclonal antibodies and heteroantisera were assessed beforehand by titration on suitable tissue samples. The antigens recognized by the monoclonal anti-bodies and heteroantisera were investigated by either the avidin-biotin peroxidase complex (ABC) method on cryostat sections or the peroxidase-antiperoxidase complex (PAP) method on paraffin sections, as described elsewhere.¹ The immunologic properties of the infiltrating cells were determined using skin biopsied in August 1989, and October 1989. Large lymphoid cells, which formed the major popu-lation of infiltrating cells, were positive for CD20, CD22, and HLA-DR and negative for CD3, CD4, CD43, and CD45RO. From these findings the patient was diagnosed as hav-ing primary cutaneous B-cell lymphoma, diffuse large non-cleaved cell type, as classified by the Working Formulation.²     

Left renal pelvis of male neonates is predisposed to dilatation

Dilatation of the renal pelvis has been observed as an ultrasonographic finding of ureteral reflux as well as hydronephrosis. However, little information is available on the prevalence of renal pelvis dilatation in neonates. We measured the inner pelvis dimension of the kidneys in 511 apparently healthy neonates (279 boys and 232 girls) using an ultrasound scanner to determine the prevalence of renal pelvis dilatation. Ninety per cent of the neonates had an inner dimension of both renal pelvises below 5 mm. The prevalence of left renal pelvis dilatation of 5 mm or more was significantly higher in the boys than in the girls, 25 (9%) compared to 5 (2%). In contrast, no significant difference was found in the prevalence of right renal pelvis dilatation between the sexes. In the boys, the prevalence of renal pelvis dilatation of 6 mm or more was significantly higher on the left side than on the right. Moreover, the left renal pelvis dilatation of the male neonates had a tendency to persist at 1 month of age. These findings suggest that the left renal pelvis of the baby boy may be predisposed to dilatation.     

Further studies on the resolution of human mercapt- and nonmercaptalbumin and on human serum albumin in the elderly by high-performance liquid chromatography

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520 showed at least two peaks, the principal component corresponding to human mercaptalbumin (HMA) and the secondary one to nonmercaptalbumin (HNA). HPLC analysis of HSA on Asahipak ES-520 N showed three peaks, the principal component corresponding to HMA, the secondary one to HNA having mixed disulfide with cysteine or glutathione and the tertiary one to HNA oxidized higher than mixed disulfide. Two kinds of rapid HPLC for the resolution of HSA into HMA and HNA were developed by the present authors. Using these HPLC, the present authors found a significant decrease in the fraction of HMA in the elderly.