Histological findings in asymptomatic hepatitis C virus carriers

There is controversy about clinical management of individuals who persistently have hepatitis C virus antibodies (HCVAb) but who have no symptoms or signs of liver disease. Liver biopsy samples were taken from 15 individuals, all of whom had normal alanine aminotransferase (ALT) levels, to determine the prevalence of liver disease and whether HCVAb and HCV-RNA correlate with histological findings. Eleven patients with hepatitis C viremia had histological evidence of chronic hepatitis on biopsy. On the other hand, four HCV-RNA-negative individuals had almost normal liver histology. These findings indicate that serum HCV-RNA is a sensitive and specific marker of liver disease in HCVAb-positive subjects, independent of ALT levels. Furthermore, these results suggest that there are very few histologically healthy carriers of HCV among HCV-RNA-positive individuals.     

Clinical significance of red blood cell distribution width in the elderly: a potential indicator of bone marrow stimulation by erythropoietin

Summary To investigate the clinical significance of red blood cell distribution width (RDW) and haemoglobin distribution width (HDW) in the elderly and their relationships with erythropoietin (EPO) secretion, we measured red cells parameters using a Technicon HI system and serum EPO using a radioimmunoassay in 247 elderly subjects (normal: n= 150; preanaemic iron deficiency: n= 24; iron deficiency anaemia: n= 8; senile anaemia: n= 65). RDW was slightly higher in the elderly subjects with preanaemic iron deficiency (14.1 ± 1.1%) than in the normal elderly subjects (13.5±0.7%). It was highest in iron deficiency anaemia (16.1 ± 1.3%), while the increase in senile anaemia was limited (13.9 ± 1.2%). The HDW increased only in iron deficiency anaemia. There was a strong positive relationship between EPO and RDW in iron deficiency anaemia (r= 0.817, P<0.01). Moreover, this correlation was also found in preanaemic iron deficiency (r= 0.456, P < 0.05), but not in senile anaemia, suggesting that bone marrow hypoactivity may partly play a role in the pathogenesis of senile anaemia. All the eight subjects with iron deficiency anaemia had a RDW ≥ 14.9% (mean + 2SD of normal subjects), while 55 (85%) of the 65 with senile anaemia had a RDW < 14.9%. Both the RDW and EPO levels of six anaemic subjects with high RDW values (≥ 14.9%) after oral iron therapy for 56–78 days decreased significantly. Our results suggest that RDW is useful to distinguish iron deficiency anaemia from senile anaemia, and may be a potential parameter of bone marrow stimulation by EPO.     

A Novel Missense Mutation Causing a G487R Substitution in the S2–S3 Loop of Human ether‐à‐go‐go‐Related Gene Channel

hERG(G487R) Channel . Introduction: Mutations of human ether‐à‐go‐go‐related gene (hERG), which encodes a cardiac K⁺ channel responsible for the acceleration of the repolarizing phase of an action potential and the prevention of premature action potential regeneration, often cause severe arrhythmic disorders. We found a novel missense mutation of hERG that results in a G487R substitution in the S2–S3 loop of the channel subunit [hERG(G487R)] from a family and determined whether this mutant gene could induce an abnormality in channel function. Methods and Results: We made whole‐cell voltage‐clamp recordings from HEK‐293T cells transfected with wild‐type hERG [hERG(WT)], hERG(G487R), or both. We measured hERG channel‐mediated current as the “tail” of a depolarization‐elicited current. The current density of the tail current and its voltage‐ and time‐dependences were not different among all the cell groups. The time‐courses of deactivation, inactivation, and recovery from inactivation and their voltage‐dependences were not different among all the cell groups. Furthermore, we performed immunocytochemical analysis using an anti‐hERG subunit antibody. The ratio of the immunoreactivity of the plasma membrane to that of the cytoplasm was not different between cells transfected with hERG(WT), hERG(G487R), or both. Conclusion: hERG(G487R) can produce functional channels with normal gating kinetics and cell‐surface expression efficiency with or without the aid of hERG(WT). Therefore, neither the heterozygous nor homozygous inheritance of hERG(G487R) is thought to cause severe cardiac disorders. hERG(G487R) would be a candidate for a rare variant or polymorphism of hERG with an amino acid substitution in the unusual region of the channel subunit. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1246–1253, November 2012)     

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.     

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.     

Experience With the Atrium Advanta Covered Stent for Aortic Obstruction

Introduction

We sought to assess the efficacy, safety and clinical outcomes of the Advanta V12? covered stent in management of coarctation of the aorta (CoA).

Materials and Methods

Stent functionality was assessed by review of angiographic imaging, clinical data at admission, discharge and at the last clinic visit, stent configuration on chest roentgenogram, radiation exposure, and complications.

Results

Between October 2009 and February 2012, 17 patients underwent stent implantation. There were 9–12, 2–14, and 6–16 mm diameter stents deployed. Balloon angioplasty after implantation was required in 2 patients. Mean percent recoil in the middle of the stent for the 12, 14, and 16 mm implants was 14%, 24%, and 24%, respectively. There was improvement in CoA diameter from 6.6 ± 3.2 to 11.5 ± 1.7 mm (P < 0.0001) and a reduction in the peak pressure gradient from 23.1 ± 10.1 to 0.8 ± 3.3 mmHg (P < 0.0001). No patient had a symptomatic complication. Left arm cuff blood pressure fell 24 hours after implantation and left arm to leg blood pressure gradient fell to <20 mmHg in all (P < 0.0001). Follow‐up was a median 242 days and at the last clinic visit there were no statistically different findings from discharge. Five children (33%) required antihypertensive medications but 3 were off medication at latest follow‐up. Three patients (18%) required reintervention.

Conclusion

The implantation of the Advanta? V12 stent for the treatment of CoA is safe and effective in the early term. However, further study is required to determine longer‐term stent efficacy.

     

A Monoclonal Antibody, H2, Defines a New Surface Antigen Expressed on Human Lymphocytes

We have previously described a monoclonal antibody (MoAb), H2, which recognized a tumour-unique antigen on a human T-cell chronic lymphatic leukaemia (T-CLL, CD3,4+). However, further characterization of H2 has revealed a reactivity with the majority of T lymphocytes and a minority of B lymphocytes, some malignant T cells and a few cell lines of leukaemia or of hematopoietic tumour origin. The molecular weight of the antigen (80,000) precipitated by the MoAb H2 from the cell lines NALM-6 and Reh corresponded to that previously found. When PBL were stimulated with PHA, IL-2, or Con A a reduced reactivity of H2 could be seen. The MoAb H2 was submitted to the Fourth International Conference on Human Leucocyte Differentiation Antigens, Vienna, 1989. H2 did not cluster in any of the 78 clusters of differentiation (CD 1-78) discussed at the conference, indicating its unique reactivity. This suggests that we have defined a new antigen on lymphocytes with a possible role along the resting-proliferating axis.     

A New Surface Antigen on Human Lymphocytes Defined by the Murine Monoclonal Antibody IVF7

The murine monoclonal antibody (MoAb) IVF7 was produced against tumour cells from a patient with a CD3+, CD4+, CD8- T-cell chronic lymphatic leukaemia (T-CLL). The MoAb IVF7 showed reactivity with subpopulations of normal peripheral blood lymphocytes (PBL), as well as with a few cell lines of haematopoietic origin. Thirty-six per cent of PBL were stained with IVF7. Analysing subpopulations, we found that 80% of NK cells, 25% of T cells, and 10-20% of B cells were positive. The myelomonocytic cell line KG-1 was also stained. The molecular weight of the molecule was 40 kDa under reducing conditions. The antigen was found to be trypsin-sensitive. MoAb IVF7 could modulate the antigen from the cell surface. The antibody did not stimulate PBL to DNA synthesis, nor did it significantly influence NK cell-mediated killing.