Age at time of hepatitis Be antibody seroconversion in childhood chronic hepatitis B infection and mutant viral strain detection rates.

BACKGROUND: Investigations of adult patients have demonstrated that with seroconversion, changes occur from wild-type strains of the infecting virus to mutant strains. However, to date, there have been few reports and insufficient investigation of this issue in children. METHODS: The presence or absence of nucleotide base and amino acid sequence mutations in a portion of the X region containing the core promoter region, the pre-C region, and the C region of HBV genomic DNA were investigated using a polymerase chain reaction-direct sequencing method on serum samples collected from 14 children who were hepatitis Be antibody (HBeAb)-positive carriers. Samples from three children who were HBe antigen (HBeAg)-positive carriers served as the control subjects. RESULTS: When patients were grouped based on whether they had had documented seroconversion before age 6 or at age 6 or older, differences in mutant viral detection rates involving the core promoter region and the pre-C region were apparent. Specifically, a mutant strain showing a G-to-A substitution at nucleotide 83 in the pre-C region, or a mutant strain showing an A-to-T substitution at nucleotide 1762 and a G-to-A substitution at nucleotide 1764, was detected in only two of eight cases (25%) from the HBeAb-positive carriers with documented seroconversion before age 6. In contrast, these findings were present in six of six patients (100%) with documented seroconversion at age 6 or older. CONCLUSIONS: The results of the present study suggest that the mechanism of onset of HBeAb seroconversion differs between children aged less than 6 years and those who are aged 6 or more.     

Epidemiological features and visual prognosis of Beh?et's disease.

PURPOSE: Retrospective evaluation of epidemiological features and visual prognosis of patients with Beh?et's disease (BD) who visited the University of Tokyo Hospital between 1974 and 1993. OBSERVATIONS: During the survey period, more than 100 new patients with BD visited the uveitis clinic in each 5-year period. The number of new patients decreased in the most recent 5-year period from 1989 to 1993. Although BD has always been more prevalent in men, the percentage of women has increased to 24.7% (19/77) in the most recent 5-year survey period. The percentage of patients who initially manifested ocular symptoms in their third or fourth decade was more than 70%. The proportion of the incomplete type of BD gradually had increased to 62.3% (48/77) by 1993. Among the extraocular major symptoms, oral aphtha and skin lesions have been frequent and genital ulcer has become less frequent in the last 20 years. The patients whose visual acuity was better than 0.4 at the first visit in the 1984-1993 period had a significantly better visual prognosis than the patients in the previous 10-year period. The main drug therapy consisted of colchicine and cyclophosphamide in the earlier 10-year period, and of colchicine and ciclosporin in the later 10-year period. CONCLUSIONS: Beh?et's disease is still one of the most frequently encountered types of endogenous uveitis. There have been some changes in the epidemiological features of the patients with BD over the past 20 years. The introduction of ciclosporin in 1985 is probably responsible for the improvement of the visual prognosis in BD patients.     

The presence of atrial natriuretic peptide in canine cerebrospinal fluid and its possible origin in the brain

The presence of atrial natriuretic peptide (ANP) in canine cerebrospinal fluid (CSF) was clearly demonstrated and an attempt was made to determine its origin as either the brain or the atrium. The concentration of ANP in canine CSF was 0.78 +/- 0.37 pmol/l (n = 31) and showed no evident correlation with that in plasma (r = 0.12). Physiological doses of human alpha-ANP (alpha-hANP) were continuously infused intravenously into nine dogs, and ANP concentrations in CSF and plasma were examined six to eight times within a 120-min period following this. The ANP level in CSF was not influenced by the systemic administration of alpha-hANP up to 180 min. Only one low molecular weight peak corresponding to alpha-hANP could be obtained from the CSF samples, while both low and high molecular weight peaks were observed for plasma ANP by gel permeation chromatography. In the atrial and hypothalamic tissue extracts the same kinds of peaks were also evident. These results prove the presence of ANP in canine CSF and that it does not come from blood that has seeped across the blood-CSF barriers, but suggest that it may originate from the brain.     

High-resolution computed tomography patterns and immunopathogenetic findings in drug-induced pneumonitis

We tried to determine whether high-resolution computed tomography (HRCT) patterns correlate with the immunopathogenetic findings and whether they could provide helpful information for predicting the outcomes in non-neoplastic drug-induced pneumonitis. The HRCT images were classified as most suggestive of pneumonitis, diffuse alveolar damage (DAD), non-specific interstitial pneumonia, organizing pneumonia (OP), hypersensitivity pneumonitis, and acute eosinophilic pneumonia (AEP) in 34 patients with non-neoplastic drug-induced pneumonitis. The patients were analyzed for the bronchoalveolar lavage (BAL) cell findings and for the circulating levels of interferon-inducible protein 10 (IP-10) and macrophage-derived chemokine (MDC), which were measured by an enzyme-linked immunosorbent assay. The cumulative dose of corticosteroids received by the patients and the day when they required supplemental oxygen were calculated as outcome markers. There were no differences in the circulating chemokine levels and the BAL cell profiles except for the eosinophil percentages among the HRCT patterns. Most of the cases with pulmonary eosinophilia belonged to the OP and AEP groups, and the circulating MDC levels correlated with BAL eosinophil percentages. We could not find any relationship between the BAL cell profiles or the chemokine levels and the outcome markers. In contrast, the HRCT patterns rather predicted the outcomes because larger cumulative dose of steroids and longer oxygen supply were required for the patients in the DAD and OP groups. In contrast, all patients with AEP recovered without steroid administration. The present study suggests that HRCT does not predict cellular pathophysiology but it may predict the corticosteroid use in non-neoplastic drug-induced pneumonitis.     

NLRP3 Inflammasome Inhibitor OLT1177 Suppresses Onset of Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis

Digestive Diseases and Sciences - NLRP3 inflammasomes have been reported to have a key role in the initiation and perpetuation of inflammatory bowel diseases (IBD). Here we investigated the effects...     

Biodistributions of 201Tl in tumor bearing animals and inflammatory lesion induced animals

The accumulation of 201Tl in tumor and inflammatory tissues were small. However, this nuclide showed a high concentration in viable tumor tissue, less in connective tissue (containing inflammatory tissue), and was not seen in necrotic tumor tissue regardless of the time after administration of 201Tl(I)-chloride. In inflammatory lesions, 201Tl accumulated in subcutaneous tissue infiltrated with neutrophils and macrophages, and quite large amounts of this nuclide were accumulated in subcutaneous tissue and sites where neutrophils were crowded. Most 201Tl existed in a free form in the fluid of tumor and inflammatory tissues regardless of the time after administration. A small amount of this nuclide was localized in the nuclear, mitochondrial and microsomal fractions in these tissues, and the nuclide was bound to protein in these fractions. The distribution of 201Tl(III)-chloride in tumor bearing animals was essentially the same as that of 201Tl(I)-chloride.     

Effect of PSK on Th1/Th2 balance in tumor-bearing mice

We investigated the effect of PSK on Th1/Th2 balance in tumor-bearing mice. PSK was intraperitoneally administered to Meth A-bearing BALB/c mice, and PSK caused regression of the Meth A tumor. The results of Winn assay suggested that the effect of PSK was dependent on CD4+T cells. Furthermore, spleen cells were cultured with mitomycin C-treated Meth A, after which the cytokine concentration was measured by ELISA. IFN-gamma production was increased and IL-4 showed almost no change in PSK-administered mice. In another experiment, PSK was orally administered to colon 26-bearing mice in which tumors were inoculated into the subserosal space of the cecum. Mesenteric lymph nodes cells were cultured with mitomycin C-treated colon 26 cells. IFN-gamma production was increased, but not so much as to be statistically significant, and IL-4 was significantly decreased in PSK-administered mice. PSK increased IFN-gamma and IL-12 p70 production and decreased IL-4 production when spleen cells were stimulated with Con A together with PSK in vitro. As suggested from these results, PSK might induce cytokine production that works for Th1 differentiation, and suppress cytokine production that works for Th2 differentiation, and shift the Th1/Th2 balance toward Th1 dominance in tumor-bearing mice.     

Chemical radioprotectors

Basic mechanisms of radioprotection and clinical applicability of radioprotectors for low-and high-LET radiotherapy were reviewed and discussed here. Chemical radioprotectors are able to inhibit indirect radiation damage, to repair direct and indirect damage once they occur, and to facilitate the recovery of damaged cells on depleted cell populations. The vast majority of radioprotective agents that have been developed and tested are the aminothiols. WR-2721 or ethiofos represents a significant improvement in effectiveness, potency and reduction of toxicity over the early radioprotectors. WR-151327 provided substantial protection against neutron irradiation. Dose modification factors after single doses of cyclotron neutrons were 1.5 for both early and late skin damage and 1.5-2.4 for late muscle damage.