Relation between serum hepatitis C virus-RNA levels and efficacy of interferon-β therapy

We performed two courses of interferon-β (IFN-β) to a child with chronic hepatitis C. A complete response was not obtained by the first interferon treatment, however, the results of the second treatment differed from those of the first. Hepatitis C virus (HCV)-RNA remained negative and both aspartate aminotransferase and alanine aminotransferase levels remained normal after completion of the second course. From these results we estimated that HCV-RNA levels before IFN therapy could be significantly associated with the efficacy of this treatment. The serum level of HCV-RNA was 10⁶ copies/50 μL before the first treatment, but was 10³ copies/50 μL before the second course. We conclude that IFN therapy to children with hepatitis C should always be directed at providing a cure. Even if the clinical effects of the first course are minimal decreasing quantities of HCV-RNA still offer hope for cure by subsequent readministration.     

Age-related endothelium-dependent vascular relaxation in rat thoracic aorta in response to colforsin

BACKGROUND: Colforsin, a novel water-soluble forskolin derivative, increases intracellular cyclic AMP by direct stimulation of adenylate cyclase and has strong positive inotropic and vasodilative effects. However, it is not known whether colforsin causes nitric oxide (NO) release and enhances endothelium-dependent vascular relaxation. METHODS: We studied NO production and relaxation on exposure to colforsin in thoracic aorta from rats aged 4, 12 and 60 weeks. RESULTS: When a low concentration of colforsin was added to a solution bathing ring segments of aorta from 12-week-old rats, relaxation was greater in the ring segments with intact endothelium than in those from which the endothelium had been removed. A high concentration of colforsin induced the same degree of relaxation of ring segments with or without endothelium, probably by a direct effect on vascular smooth muscle cells. Production of NO in response to colforsin by cultured endothelial cells from 12-week-old rat aorta was demonstrated by the electron paramagnetic resonance spin trapping method. A low concentration of colforsin relaxed aortic segments with intact endothelium from 4-week-old rats more than those from 12-week-old or 60-week-old rats. Reversal of relaxation by NG-nitro L-arginine, an NO synthesis inhibitor, was most significant in arteries from 4-week-old rats. Production of NO after exposure to colforsin was greater in aortic segments from 4-week-old rats than older rats, as detected by an NO-selective electrode. CONCLUSIONS: Colforsin induces vasodilation in part by releasing NO from the endothelium in rat thoracic aorta. In addition to a direct vasodilative effect on the vascular smooth muscle cells, an endothelium-dependent vasodilative effect is also important in younger arteries.     

昆明地区吸毒人群和异性性传播HIV-1的分子流行病学

目的探讨昆明地区吸毒人群和异性性传播感染者HIV-1的分子流行病学特点。方法收集1994~2002年26例昆明地区吸毒人群和异性性传播HIV-1阳性者的血浆,采用BigDye链终止反应试剂盒测定2.6-kb gag-RT区的核苷酸序列,确定HIV-1的基因型分布。结果CRF07_BC和CRF08_BC是吸毒人群中HIV-1的主要基因型;1例吸毒者感染了亚型B′。同样,大多数异性性传播HIV-1感染者的基因型也以CRF07_BC,CRF08_BC和亚型B'为主。结论昆明地区异性性传播HIV-1感染者中流行的病毒基因型来自当地吸毒人群。     

Lower Pacemaker in High Degree Atrioventricular Block is Modulated Electrotonically by Atrial Excitations

To see if the lower pacemaker in patients with atrioventricular (AV) block was modulated electrofonically by atrial excitation, we studied R-R intervals in two groups of AV block patients using a phase response curve (PRC). Group f consisted of 20 patients with high degree AV block, including seven patients in whom complete AV block was transiently observed in the course of acute inferior myocardial infarction. Group II consisted of 19 parents with complete AV block. In every patient, PRC was obtained from the continuous electrocardiogram by plotting each R₁-R₂ interval (response) on the ordinate as a function of the R₁-P_x interval (phase, x = 1, 2 …) on the abscissa, In Group I, the R-R interval was prolonged when the P wave fell in (he initial half of (he R-R interval, and was abbreviated when the P wave fell in the later half of the cycle. In Group II, the fluctuation of the R-R interval was minimum. In ten group I patients, with the improvement of the AV block, PRC became sharper and transition from prolongation to shortening occurred at shorter R-P intervals. We conclude that, in Group I, lower pacemaker was modulated electrotonicalIy by atrial excitations through decreased electrical coupling along the AV node.     

Imaging characteristics of papillary renal cell carcinoma by computed tomography scan and magnetic resonance imaging

AIM: To analyse the differences in the patterns between clear and papillary renal cell carcinomas using magnetic resonance imaging (MRI) and dual-phase helical computed tomography (CT). METHODS: We examined seven patients with papillary renal cell carcinoma, and six with clear cell carcinoma. The highest attenuation value of tumors in the corticomedullary phase (CMP) and the excretory phase (EP) was measured using the observer-defined region of interest (ROI). MRI consisted of T1-weighted and T2-weighted spin-echo imaging. RESULTS: All five tumors except for one with papillary renal cell carcinoma showed homogenous hypointensity, but all six tumors with clear cell carcinoma showed heterogeneous hyperintensity on their T2-weighted images. In the CMP, the mean CT numbers of the papillary renal cell carcinomas were significantly lower than those of the clear cell carcinomas. The mean enhancement of the papillary renal cell carcinomas in the CMP and the EP was significantly lower than that of the clear renal cell carcinomas. The mean CT numbers of the clear cell carcinomas in the CMP were markedly increased from those on the unenhanced CT; those in the EP were decreased gradually. But the mean CT numbers of the papillary renal cell carcinomas in the EP were still slightly more increased than those in the CMP. The enhancement patterns of the papillary renal cell carcinomas in the CMP and the EP were homogenous, but those of the clear cell carcinomas were heterogeneous. CONCLUSIONS: We can speculate the differential diagnosis from clear to papillary renal cell carcinoma using MRI and dual-phase helical CT.     

The close relationship between interleukin-1 and fibroblast proliferating factor from peripheral mononuclear cells of patients with chronic hepatitis and liver cirrhosis

The role of peripheral mononuclear cells (PMNC) was investigated in patients with hepatic fibrosis of chronic hepatitis or liver cirrhosis. PMNC from these patients released more fibroblast proliferating factor (FPF) in the conditioned medium than those PMNC from normal subjects in response to PHA stimulation. Production of FPF by PMNC from CAH patients was also observed in response to liver specific protein (LSP) which might act as a naturally occurring antigen in vivo. Analysis of FPF on gel permeation chromatography revealed two active components with molecular weight of 60000 (FPF-1) and 18000 (FPF-II). Both FPF-I and FPF-II exerted thymocyte proliferating activity, but not cytotoxic T cell line (CTLL) proliferating activity, indicating that they are closely related to interleukin-1 (IL-1). Isoelectrofocusing of FPF-I and FPF-II disclosed that each factor consisted of two peaks at similar pI: 5.3 and 7.0. Taking account of the fact the IL-1 consisted of two molecular forms of pI—5.4 (IL-1α) and 7.0 (IL-1β)—FPF-II is considered to be IL-1, which is a mixture of IL-1α and IL-1β, and FPF-I is probably the aggregated form of FPF-II. This assumption was further supported by the evidence that macrophages, which are the major source of IL-1 in patients with chronic hepatitis or liver cirrhosis, also released significantly higher amounts of FPF than those from normal subjects in response to stimulation by lipopolysaccharide. It was therefore concluded that in chronic hepatitis and liver cirrhosis, production of an IL-1, or a factor similar to IL-1, by PMNC is increased in response to mitogen or LPS.     

Measurement of carboxy terminal peptide of type I procollagen in sera of patients with viral hepatitis and liver cirrhosis

In the present investigation, a radioimmunoassay for carboxy terminal peptide of human type I procollagen (type 1 C-peptide) was developed. Its clinical implication for serodiagnosis of hepatic fibrosis in 85 patients with viral hepatitis, 45 patients with post-hepatitic liver cirrhosis and 37 patients with alcoholic liver diseases was evaluated in comparison with that of the previously established amino terminal peptide (type III N-peptide) assay. Anti-sera against type I procollagen was obtained by immunization of rabbit with purified type I procollagen from culture medium of IMR-90. The serum level of type I C-peptide in normal subjects was found to be 42 ng/ml (s.d. = 19). Type I C-peptide levels in patients with acute hepatitis were within normal range, while in chronic hepatitis, the mean type I C-peptide level increased as the grade of fibrosis advanced from grade I to III. However, there was no statistically significant difference between the mean type I C-peptide level of grade III and that of liver cirrhosis. Increments of type I C-peptide levels were also observed in alcoholic liver fibrosis (fatty liver with fibrosis and liver cirrhosis). On the other hand, type III N-peptide assay appeared to reflect not only the degree of hepatic fibrosis, but also the degree of hepatic inflammation, giving the high levels in acute viral hepatitis. Collectively, the results indicate the usefulness of type I C-peptide assay for monitoring hepatic fibrosis in viral hepatitis as well as in alcoholic liver disease.