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.     

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.     

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.     

Distribution of Significant Changes in QRST Area Compared to Supraventricular Complex

To assess the effects of right ventricular (RV) pacing on body surface QRST distributions, we recorded QRST isointegral mops (I-maps) during sinus rhythm and RV pacing in 25 patients with anterior myocardial infarction (MI), 19 with inferior MI, and 14 without MI. The QRST values at each lead point recorded during sinus rhythm and RV pacing with an 87-lead system were analyzed with a paired t-test in each patient. An abnormal decrease in the QRST value of the I-map was assessed by the difference map, which indicated a −"2SD area," where the QRST integral value was less than the normal range (mean – 2SD) caiculated from 608 normal individuais. The I-maps were similar during the two activation sequences in patients with and without MI. However, during RV pacing, QHST values significantly decreased over the upper right anterior chest and increased over the lower left anterior chest and back. The ΣDMs (sum of QRST integral vaiues beiow the normal range) for both activation sequences were strongly correlated in patienis with anterior MI and with inferior MI (r = 0.91 and r = 0.92, respectively; P < 0.001). Although small but significant changes in QRST values were detected, the distribution of the "-2SD area" and the ΣDM were similar during both activation sequences in patients with prior MI. Thus, these findings demonstrate that an altered activation sequence produces small but significant changes in QRST values but that I-maps still provide information that is useful for the diagnosis of MI during RV pacing.     

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.     

Dispersion Method for Safety Research on Manufactured Nanomaterials

Nanomaterials tend to agglomerate in aqueous media, resulting in inaccurate safety assessment of the biological response to these substances. The present study searched for suitable dispersion methods for the preparation of nanomaterial suspensions. Titanium dioxide (TiO₂) and zinc oxide (ZnO) nanoparticles were dispersed in a biocompatible dispersion medium by direct probe-type sonicator and indirect cup-type sonicator. Size characterization was completed using dynamic light scattering and transmission electron microscopy. A series of dispersion time and output power, as well as two different particle concentrations were tested. Microscopic contamination of metal titanium that broke away from the tip of the probe into the suspension was found. Size of agglomerated nanoparticles decreased with increase in sonication time or output power. Particle concentration did not show obvious effect on size distribution of TiO₂ nanoparticles, while significant reduction of secondary diameter of ZnO was observed at higher concentration. A practicable protocol was then adopted and sizes of well-dispersed nanoparticles increased by less than 10% at 7 d after sonication. Multi-walled carbon nanotubes were also well dispersed by the same protocol. The cup-type sonicator might be a useful alternative to the traditional bath-type sonicator or probe-type sonicator based on its effective energy delivery and assurance of suspension purity.