Hepatic HCV-RNA as a predictor of outcome after interferon therapy in patients with chronic hepatitis C

Measurement of serum HCV-RNA is a useful index for evaluating the antiviral effect of interferon therapy in chronic hepatitis C. In the present study, we investigated whether the detection of hepatic HCV-RNA after interferon treatment, using a polymerase chain reaction assay, predicted long-term response to therapy in patients with chronic hepatitis C. Thirty-three patients underwent liver biopsies before and after interferon therapy. Histology and clinical courses were compared after treatment. Before therapy, serum and hepatic HCV-RNA was detected in specimens from 32 (97%) and 33 (100%) patients, respectively. Serum HCV-RNA became undetectable in samples from 22 (67%) patients; however, in 10 of these patients (45%), serum HCV-RNA levels relapsed after therapy. Hepatic HCV-RNA became undetectable in 14 patients after therapy and the serum aminotransferase concentration remained within normal limits during and following (24–92 weeks) therapy in 12 of these patients (86%). All 11 patients with detectable hepatic HCV-RNA also had serum HCV-RNA and elevated aminotransferase concentrations refractory to therapy. The absence of hepatic HCV-RNA at the end of interferon treatment thus predicted a long-term complete response to therapy with a sensitivity of 100%, a specificity of 90% and an accuracy of 94%. We conclude that hepatic rather than serum HCV-RNA is a more useful index for the prediction of the long-term efficacy of interferon therapy.     

Stromal Cell‐Derived Factor 1α Induces Accumulation of Intraveneously Administered Marrow‐Derived Stromal Cells in the Partially Obstructed Rat Bladder

Objectives: We investigated the time course of the stromal cell‐derived factor 1α (SDF1α) expression and behavior of intravenously administered bone marrow‐derived stromal (BMS) cells in the urinary bladder of partial bladder outlet obstruction (PBOO) rats. Methods: Study 1: Recombinant SDF1α or saline was directly injected into the bladder wall of female rats followed by intravenous administration of BMS cells isolated from green fluorescent protein (GFP) transgenic rats. The bladder was examined with immunohistochemistry to determine whether SDF1α would enhance migration of BMS cells to the bladder. Study 2: Following surgery of PBOO or sham in female rats, bladders were removed on days 1–14, and expression of hypoxia inducible factor 1α (HIF1α) and SDF1α were examined with real‐time polymerase chain reaction (PCR) to determine if PBOO preferentially increased their expression. Study 3: Female rats underwent PBOO or sham surgery followed by intravenous administration of GFP‐positive BMS cells. Bladders were examined with immunohistochemistry on days 1–14 to determine whether BMS cells preferentially accumulated in the bladder. Results: BMS cells were accumulated in the injection site of SDF1α but not saline in the bladder. SDF1α and HIF1α increased at day 1 after PBOO compared to sham. More BMS cells accumulated in the bladder of PBOO on day 1, and some BMS cells expressed smooth muscle phenotypes by day 14. Conclusion: SDF1α induced with ischemia/hypoxia due to PBOO is implicated in the accumulation of BMS cells in the bladder and regeneration of the bladder for PBOO.     

Double ventricular responses during extrastimulation of atrioventricular nodal reentrant tachycardia

In patients with dual atrioventricular (AV) nodal pathways,double ventricular responses to a single atrial depolarizationhave been shown to occur, but virtually only during a trialpacing in sinus rhythm. We report on a patient with a slow-fastform of AV nodal reentrant tachycardia who exhibited doubleventricular responses following extrastimulation during AV nodalreentrant tachycardia. The phenomenon of double ventricularresponses during the tachycardia was demonstrated by ex trastimulationfrom the proximal coronary sinus. Retrograde unidirectionalblock in the slow pathway, and an anterograde effective refractoryperiod that was shorter in the fast pathway than that in theslow pathway, are suggested.     

Class IC Antiarrhythmic Drugs, Flecainide and Pilsicainide, Produce ST Segment Elevation Simulating Inferior Myocardial Ischemia

ST Elevation with Flecainide and Pilsicainide . Flecainide and pilsicainide, Class IC antiarrhythmic drugs with slow kinetics, were administered to a 64-year-old man experiencing ventricular tachycardia. Both drugs suppressed the arrhythmia, but caused ST segment elevation in leads II, III, and aVF. No evidence of ischemic heart disease was detected. Withdrawal of the drugs eliminated the ST change. Because these drugs frequently are used to treat tachyarrhythmias in patients who may present with chest pain, this rare ECG manifestation of Class IC drugs should he recognized to avoid misdiagnosis of acute interior myocardial infarction.     

Synthesis and stabilization of amino and carboxy terminal constrained collagenous peptides

Short collagenous peptides cross-linked at their amino and carboxy termini with Lys-Lys-dimer template(s) were synthesized, and the effect of the cross-linking on their stabilities was investigated by thermal denaturation experiments. Two chemoselective ligations were used for the construction of the amino and the carboxy cross-linked peptides. The thermal transition temperature (T_m) and the standard free energies (ΔG°) of the cross-linked collagenous peptides increased, and the thermal stabilization effect corresponded to an elongation by two units of the Gly-Pro-Hyp triad. The van't Hoff enthalpy (ΔH°) and the entropy (ΔS°) values of the cross-linked peptides increased with chain elongation, although the increments were smaller than those of the linear peptides. When the same chain lengths were compared, the ΔH° was increased and the ΔS° was nearly the same or increased by the cross-linking. These results suggest that the cross-linking of the collagenous peptides with the Lys-Lys-dimer template(s) for stabilization contributes to the enthalpic effect, rather than the entropic effect.     

Expression of Lewis X-related antigens in adenocarcinomas of lung

Fifty primary lung adenocarcinomas were examined immunohistochemically using monoclonal antibodies to determine changes in the expression of N-acetyl-lactosamine (blood group type-2 chain), Le^x, Le^Y and sialyl Le^x-i. These antigens were expressed in 60%, 70%, 90% and 94% of carcinomas, respectively; in 8%, 12%, 56% and 86% of normal broncho-bronchiolar epithelium; and in 32%, 0%, 100% and 0% of normal alveolar epithelium. The greater the complexity of the antigenic structure, the greater the incidence of positive staining in the adenocarcinomas. Although the more complex antigens such as sialyl Le^x-i and Le^Y have also been demonstrated in the sera of lung cancer patients, they were not always cancer-selective in our immunohistochemical study. In contrast, the less complex antigens such as N-acetyl-lactosamine (type-2 chain) and Le^x seem to be cancer-selective, as they showed low positivity in normal lung tissue.