This study was conducted to clarify if the long-term notype is important clinically because it is one of the histological outcome among patients with chronic hepa-predictive markers of the response to interferon thertitis C differs according to whether they are infected apy in patients with chronic hepatitis C. 16,17 with genotype 1 or 2 hepatitis C virus (HCV). We examSeveral investigators have reported that the HCV ined 140 patients with chronic hepatitis C. The HCV ge-genotype is associated with the stage of type C chronic notype was determined by the enzyme-linked immuno-liver disease. 18,19 However, it has not been sufficiently sorbent assay (ELISA) based on genotypes 1 and 2 clarified whether the prognosis differs among hepatitis specific recombinant proteins; genotype 1 was found in C patients infected with different genotypes. In this 100 patients (96 were 1b and 4 were indeterminate) and study, we compared the long-term histological outcome genotype 2 in 36. The two groups showed no significant of chronic hepatitis in patients infected with HCV genodifference for any clinical background features. Deterioration of the grade of liver histology during the follow-up type 1 with that in patients infected with HCV genoperiod was seen in 68.0% of the patients with genotype 1 type 2 to clarify the difference of pathogenicity between as compared with 41.7% of those with genotype 2 (P these genotypes.õ .01). Similarly, the deterioration of the stage of liver histology was more common in the former group than PATIENTS AND METHODS in the latter (63.0% and 38.9%, respectively; P õ .05). The mean serum HCV-RNA titer was significantly higher inPatients. The subjects were 140 patients (100 men and 40 the patients with genotype 1 than in those with genotype women aged 18 to 59 years) selected from among a total of 758 2 (P õ .001), and multivariate analysis showed the titer patients with chronic hepatitis C who underwent histological was one of the independent factors of the deterioration examination of the liver between 1966 and 1988 at Shinshu of the stage (P Å .0044). This phenomenon may be related University Hospital. All patients meeting the following critein part to the difference in pathogenicity between the ria were included in this study: histological reexamination two HCV genotypes. In conclusion, our results suggest performed at least 5 years after the initial examination; that more severe progression of chronic hepatitis C is younger than 60 years of age at the time of the initial exami- titis B surface antigen, and antibody to human immunodefiAddress reprint requests to: Kendo Kiyosawa, M.D., The Second Departciency virus were measured using commercially available en-

The quantitation of hepatitis C virus (HCV) viremia RNA is measured by molecular techniques such as comcan be helpful in the diagnosis, therapy, and monitoring petitive reverse-transcription polymerase chain reacof patients with chronic hepatitis C. A sensitive and tion and branched DNA (bDNA) signal amplification. 5,6 quantitative fluorescence enzyme immunoassay (FEIA) More recently, a sensitive and quantitative fluoreshas recently been developed for assaying HCV core pro-cence enzyme immunoassay (FEIA) has been developed tein in serum. To assess the utility of measurements of to measure serum HCV core protein, which may also serum HCV core protein during the course of treatment correlate with levels of HCV viremia. 8 We have evaluof chronic hepatitis C, we studied 27 patients who were ated the clinical usefulness of serum HCV core protein treated with a single schedule of interferon alfa (IFN-a) measurements in patients with chronic hepatitis C be- This study was conducted at Shinshu University 27 patients (93%). The initial serum concentration of Hospital and affiliated hospitals between July 1993 and Sep-HCV core protein was significantly (P õ .01) higher in tember 1994. Informed consent was obtained from all pathe nonresponders versus the responders. Two weeks tients. Twenty-seven Japanese patients with chronic hepatiafter initiating IFN-a therapy, HCV core protein was not tis type C who were treated with IFN-a therapy (19 men detectable in any of the 11 responders, but was detected and 8 women aged 32 to 65 years; mean, 50.6 years) were in 8 of 16 nonresponders (P õ .01). All responders, but evaluated. All had antibodies to HCV and HCV RNA in senone of the nonresponders, remained negative for core rum, and were negative for hepatitis B virus surface antigen protein after IFN-a therapy. The measurement of HCV and antibodies to human immunodeficiency virus. Chronic core protein by FEIA may be useful for predicting the hepatitis was diagnosed on the basis of persistence of serum response to IFN-a and for monitoring its therapeutic alanine transaminase (ALT) elevations, determined in serum efficacy. (HEPATOLOGY 1996;23:1330-1333.) tests performed monthly for at least 6 months, and by liver biopsy taken within the previous 6 months. Seven patients had mild, 6 had moderate, and 14 had severe chronic hepatiInfection by hepatitis C virus (HCV) can lead to tis. 9 chronic hepatitis and cirrhosis, and may also be inRecombinant IFN-a 2a (Roche, Tokyo, Japan, and Takeda, volved in the pathogenesis of hepatocellular carci-Osaka, Japan) was administered in a dose of 9 million units intramuscularly daily for 2 weeks, followed by three times a noma. 1,2 Treatment with interferon alfa (IFN-a) is efweek for 22 weeks. Patients were seen 2 and 4 weeks after fective in some patients with chronic hepatitis C, the initiation of therapy, and then every 4 weeks for at least resulting in a rapid decrease in aminotransferase activ-24 weeks after its completion. Serum samples were collected ities into the normal range and a clea...

The stabilities Be,, and B,l clusters (4 5 n 5 8) based on the vibrational analysis were investigated by ab initio MO calculations. The computations were performed by using a 3-21G basis set at the R(U)HF level and at the R(U)MP4 level with the HF optimized structures. Spin-multiplicities were also considered up to quintet states (n 5 7 ) . Of the 120 species that were treated, half of them were considered stable and some of these stable species were obtained by the deformations of transition state and unstable species, following the imaginary normal modes. The transformation barrier between the transition state species and corresponding stable ones was presented. It was found that there were two types of stable clusters: (1) a low symmetry species with lower frequencies and lower geometrical change barriers and ( 2 ) a high symmetry one with higher frequencies. The former type was considered as a structural "soft" species and the latter as a "hard' species.

In spite of recent advance in understanding of the stoichiometry of 22-kDa human GH (22K-hGH) with cell surface hGH receptor (hGHR) and hGH-binding protein (hGH-BP) circulating in human plasma, that of 20-kDa hGH (20K-hGH) is poorly understood. To clarify this, mouse pro-B Ba/F3 cells stably expressing the full-length hGHR (Ba/F3-hGHR) and both recombinant and native hGH-BP were used in this study. Cell proliferation assay revealed that the two hGH isoforms increased Ba/F3-hGHR cells to the same extent in a dose-dependent manner at 0.1 pM-10 nM. However, the self-inhibition observed in 20K-hGH at 5 microM was significantly less than that in 22K-hGH. Furthermore, addition of 1 and 10 nM recombinant hGH-BP caused a slight inhibition in 20K-hGH, but a drastic inhibition in 22K-hGH. Gel filtration chromatography of mixtures of 20K-hGH with recombinant hGH-BP clearly demonstrated that 20K-hGH formed a 1:2 (hGH:hGH-BP) complex efficiently but no detectable 1:1 complex in any conditions. Supporting data were also obtained with native hGH-BP. Computer-aided homology modeling of 20K-hGH has provided speculative data that the conformational change caused by deletion of 15 residues may occur only in the loop between helix 1 and helix 2, resulting in the reduction of its site 1 affinity. In conclusion, 20K-hGH possesses a unique property for forming a 1:2 complex to the same extent as 22K-hGH but has difficulty in forming a 1:1 complex, which might be attributed to the conformational change restricted to its site 1 region.