Magnetic resonance imaging abnormalities of the brain in Goldberg-Shprintzen syndrome (Hirschsprung disease, microcephaly, and iris coloboma)

The effects of a low-casein diet fortified with methionine and threonine on renal cortical and glomerular transforming growth factor (TGF)-beta activity were studied in rats with nephritis induced by anti-rat kidney glomerular basement membrane antiserum. Both normal and nephritic rats were fed experimental diets for 10 days. An injection of nephrotoxic serum increased urinary protein excretion and renal TGF-beta activity. A methionine-threonine-supplemented 8.5% casein diet, compared with a basal 20% casein diet, decreased these two measurements without aggravating growth retardation in nephritic rats. These results suggest that aggravation and alleviation of symptoms incident to anti-GBM nephritis are relevant to elevation and reduction of TGF-beta activity, respectively. The results also suggest that amino acid-balanced low-protein diets would have beneficial effects on glomerulonephritis without causing severe protein malnutrition.     

N-acetyl-beta-glucosaminidase, beta-glucuronidase and beta-galactosidase in the leukocytes, serum and urine of healthy subjects and patients with immunocytoma

The activity of GlcNAc-ase, GlcUA-ase and Gal-ase was determined in the leukocytes serum and urine of 23 patients with M. M., 11 patients with other neoplasms including 9 with lymphoreticular proliferative processes without associated monoclonal gammapathy. The range of normal enzyme activity was established in the investigations carried out in 45 health subjects. In the group of patients with M. M. without complications. normal activity of GlcNAc-ase, GlcUA-ase and Gal-ase was found in the leukocytes. In the group of patients with white blood cell count below 2.5 g/l and in cases after long-term treatment with Alkeran the activity of GlcNAc-ase and GlcUA-ase in the leukocytes was reduced. In the patients with M. M. the activity of GlcNAc-ase was raised in the serum and urine, and this activity was higher in cases with longer duration of the disease and more advanced pathological process. The patients with M-IgG protein showed a higher GlcNAc-ase activity in the serum and urine than those with protein M-IgA. A higher activity of GlcNAc-ase in the serum and urine than those with protein M-IgGK than in those with M-IgG gamma. In patients with M. M with renal complications the urinary activity of GlcNAc-ase was higher than in patients with M. M. without renal complications. In CLL the activity of GlcNAc-ase was found to be decreased in the leukocytes and raised in the urine. In patients with Hodgkin's disease the activity of the studied enzymes was raised in leukocytes while the results of their determinations in serum and urine were equivocal.     

Cell-mediated cytolysis of equine herpesvirus-infected cells by leukocytes from young vaccinated horses

The objective of this study was to determine whether the administration of modified-live equine herpesvirus (EHV-1) to young horses with residual maternal antibodies stimulated EHV-specific cytolytic responses, and whether these responses were crossreactive between EHV-1 and EHV-4. Eighteen clinically normal Belgian cross-foals were used in the study and were commingled in two adjacent pens. Skin biopsies were harvested from 16 foals within 24 h of birth and fibroblast cultures were established, expanded and cryopreserved. Beginning at approximately 10 weeks of age, 10 randomly chosen foals were inoculated on days 0, 21, and 43 of the study with a vaccine containing modified-live EHV-1. Blood mononuclear leukocytes were obtained on days 0, 32, and 50 for the assessment of EHV-specific cytolytic activity using 5 h and 18 h chromium release assays. EHV-1-specific antibodies were assessed by enzyme-linked immunosorbent assay using serum collected on days -21, 0, 32, and 50 of the study. Lymphocyte blastogenic tests and bioassays for interferon activity were conducted on day 50. After two vaccinations, mononuclear leukocytes from seven of ten vaccinated foals had cytolytic activity against autologous EHV-1 cells and leukocytes from six of ten lysed EHV-4-infected cells when tested in an 18 h assay. This activity was enhanced by exogenous interleukin 2 and was markedly reduced using target cells from unrelated horses. Cytotoxicity was not detected in a 5 h assay following in vitro stimulation of leukocytes. After three vaccinations, blood leukocytes from 6/6 vaccinated foals and 0/6 unvaccinated foals had proliferative responses EHV-1. There were no significant differences in interferon production by leukocytes from these foals. Twelve foals tested had low concentrations of (maternal) EHV-1-specific antibody prior to vaccination. Five of eight foals tested had increases in EHV-specific antibodies, while 4/4 commingled unvaccinated foals had a decrease or no change in EHV-specific antibodies. These results demonstrate cytotoxic cellular immune responses can be induced in young horses with maternal antibodies following administration of modified-live vaccine.     

Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis

BACKGROUND: The contribution of antibody and/or immune-complex to the pathogenesis of immunologically-mediated glomerulonephritis is not fully understood, although it has been recently clarified that Fc receptors (FcRs) play critical roles in the inflammatory cascade. We therefore re-evaluated the classical model of glomerulonephritis, anti-glomerular basement membrane antibody-induced glomerulonephritis (Anti-GBM GN), from the standpoint of FcRs and also investigated the residual FcR-independent mechanisms. METHODS: We adopted an Anti-GBM GN mouse model that has two strains deficient in the FcR gamma chain [gamma(-/-)] or Fc gammaRIIB [RII(-/-)], and analyzed functional (urinary protein, serum creatinine, BUN) and pathological changes of the glomeruli. For the analyses of FcR-independent mechanisms, several doses of nephrotoxic serum were applied, and then mice were treated either with cobra venom factor or an angiotensin II type 1 receptor antagonist in gamma(-/-) mice. RESULTS: In gamma(-/-) mice, renal injuries were dramatically attenuated with an absence of polymorphonuclear cell (PMN) influx, while RII(-/-) mice suffered accelerated glomerular injuries in spite of a normal PMN influx. In the absence of FcR-dependent effects in gamma(-/-) mice, the FcR-independent pathway lead to chronic renal damage characterized by mesangial proliferation and progressive expansion of mesangial area, with monocyte/macrophage accumulation and with the expression of alpha smooth muscle actin in the mesangial cells and interstitium. Those injuries in gamma(-/-) mice were not attenuated by the decomplementation, but completely abolished by using an angiotensin II type 1 receptor antagonist. CONCLUSIONS: Our results clearly demonstrate that FcRs play a pivotal role in Anti-GBM GN, especially in its acute phase. We further clarified the existence of FcR and complement-independent but antibody-dependent pathway. Furthermore, we found that those pathological changes were strongly related to the renin-angiotensin system.     

Antibacterial activity of the derivatives of cholic acid (author''s transl)

Serum and urinary myo-inositol and urinary glucose were estimated by means of gas-liquid chromatography in 54 patients with glomerulonephritis with and without renal failure. myo-Inositol clearance was calculated and an index was formulated which reflected changes in glomerular filtration, tubular reabsorption and catabolism of myo-inositol by the kidney. Serum and urinary myo-inositol levels were increased in glomerulonephritis with a close correlation to the degree of renal failure. In advanced forms of glomerulonephritis, glomerular filtration, tubular reabsorption and catabolism of myo-inositol were shown to be markedly deranged. Evidence obtained showed further that a derangement of tubular reabsorption and catabolism of myo-inositol also accompany milder forms of glomerulonephritis without decreased glomerular filtration. The myo-inositol index value, especially, was increased in patients with signs of disease activity as indicated by a histological examination of the kidney tissue. The index can also be regarded as a highly sensitive test of renal failure. Low grade glucosuria was shown to be frequently associated with glomerulonephritis with renal failure. Evidence was produced which suggested that the tubular reabsorption of myo-inositol was deranged earlier than glucose reabsorption in glomerulonephritis, although they may share a common step in the reabsorption process. The data suggest that the estimation of serum and urinary myo-inositol has advantages in the evaluation of kidney function.     

Acute nephrotoxic serum nephritis in complement knockout mice: relative roles of the classical and alternate pathways in neutrophil recruitment and proteinuria

BACKGROUND: The importance of complement in the pathophysiology of renal disease is still being appreciated. To further address the role of this mediator system, we evaluated the influence of absolute deficiency of C3 and C4 on acute nephrotoxic serum nephritis (NSN). METHODS: Selective 'knockout' of C3 and C4 was routinely confirmed in null mice by ELISA. NSN was induced by intravenous injection of a sheep anti-rat nephrotoxic serum that cross-reacts with murine glomerular antigens. Deposition of heterologous immunoglobulin in wild-type glomeruli was associated with rapid complement deposition and neutrophil infiltration, and followed by the development of proteinuria. RESULTS: Neutrophil infiltration was markedly inhibited in C3-deficient mice indicating a role for complement in PMN recruitment. In contrast, C3 deficiency afforded only partial protection against proteinuria. NSN was studied further in C4 null mice to probe the relative roles of the classical and alternate pathway in disease pathophysiology. C3 and C4 deficiency were associated with equivalent inhibition of PMN recruitment and proteinuria. CONCLUSIONS: In aggregate, the data support a major role for complement in PMN recruitment in this model and point to complement-independent mechanisms of proteinuria in antibody-mediated glomerulonephritis. These 'knockout' mice should prove valuable for defining the complement-activated mediator systems that regulate leukocyte recruitment and tissue injury in renal diseases.     

Resistance of Fc receptor- deficient mice to fatal glomerulonephritis

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.     

Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat

Prostacyclin (PGI2) is known to have a relaxative action on vascular smooth muscle, an inhibitory action against platelet activation and neutrophil function. Previous studies showed the preventive effects of PGI2 on lupus nephritis and Thy-1 nephritis, although the mechanism has not been clarified. Glomerular endothelial expression of intercellular adhesion molecule-1 (ICAM-1) is up-regulated in experimental and human glomerular diseases, and is known to facilitate leukocyte infiltration into the glomeruli, which ultimately induces the various glomerular injuries. In the present study, we evaluated the therapeutic effects of PGI2 on a rat model for crescentic glomerulonephritis and investigated its putative mechanism in relation to ICAM-1-mediated leukocyte recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotoxic serum and received continuous intraperitoneal infusion of PGI2. PGI2 dramatically decreased proteinuria (123.0 +/- 18.8 vs. 31.6 +/- 4.5), crescent formation and deposition of fibrinogen in the glomeruli, while the deposition of rabbit IgG, rat IgG and rat C3 along the capillary walls was not changed. Furthermore, intraglomerular expression of ICAM-1 and infiltration of macrophages were significantly suppressed by administration with PGI2. In contrast, influx of CD4 or CD8 positive cells was not altered. The present results suggest that PGI2 shows the preventive effects on experimental crescentic glomerulonephritis by inhibiting intraglomerular coagulation and ICAM-1-mediated macrophage-glomerular endothelial cell adhesive pathway.     

Improved survival and amelioration of nephrotoxic nephritis in intercellular adhesion molecule-1 knockout mice

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in nephrotoxic nephritis, a model of human rapidly progressive glomerulonephritis. To evaluate the pathogenetic relevance of ICAM-1 in this model, nephrotoxic nephritis was induced in ICAM-1 knockout mice and genetic controls. Mice were preimmunized with rabbit IgG in complete Freund's adjuvant. Seven days later they received rabbit anti-mouse glomerular basement membrane IgG. The early humoral immune responses (levels of circulating mouse anti-rabbit IgG, glomerular deposition of rabbit and mouse IgG and mouse C3c) were not altered in ICAM-1 knockout mice. During 28 d of follow-up, 3 of 19 control nephritic mice and 0 of 16 ICAM-1 knockout mice died. Proteinuria was high in nephritic control mice (means 10 to 12 mg/24 h at all time points investigated) and significantly reduced in nephritic ICAM-1 knockout mice (means <4.4 mg). Mean serum creatinine rose from 29 micromol/L at day -7 to 48 micromol/L (day 28) in nephritic control mice. This increase in serum creatinine was significantly lower in ICAM-1 knockout mice: 27 (day -7) and 36 micromol/L (day 28). Histologic analysis at day 28 revealed that ICAM-1 deficiency in nephrotoxic nephritis mice led to significantly reduced glomerular crescent formation (2+/-3% in ICAM-1 knockout mice versus 13+/-8% in nephritic controls) and tubulointerstitial injury (score 0.4+/-0.4 versus 2.0+/-1.1). By immunohistochemistry, ICAM-1 deficiency in nephritic mice led to significantly reduced (peri-)glomerular and/or interstitial macrophage influx, alpha-smooth muscle actin expression, and type IV collagen accumulation. These data indicate that ICAM-1 is a central mediator of glomerular and tubulointerstitial injury in murine nephrotoxic nephritis.     

L-arginine depletion inhibits glomerular nitric oxide synthesis and exacerbates rat nephrotoxic nephritis

Nitric oxide (NO) synthesis is induced in glomeruli in glomerulonephritis; its role in the pathogenesis of glomerular injury is unknown. Interpretation of its role using the currently available analogues of L-arginine as in vivo inhibitors of NO is complicated by their lack of specificity for inducible NO synthase (iNOS). As NO synthesis by iNOS depends on extracellular L-arginine, we have here examined effects of L-arginine depletion on glomerular NO synthesis and the course of accelerated nephrotoxic nephritis (NTN). Arginase, which converts L-arginine to urea and L-ornithine, was used to achieve L-arginine depletion. A single dose of i.v. arginase produced complete depletion of plasma arginine for four hours. Two forms of NTN were induced in preimmunised rats by nephrotoxic globulin: (1) the systemic form of the model by intravenous nephrotoxic globulin; or (2) the unilateral form of model by left kidney perfusion with nephrotoxic globulin, which avoids the complications of systemic administration of nephrotoxic globulin. Arginase reduced plasma arginine levels and the synthesis of nitrite (the stable end-product of NO) by NTN glomeruli (95% inhibition). Proteinuria was exacerbated. There was no effect on early (24 hr) leukocyte infiltration. In the systemic form of the model arginine depletion by i.v. arginase increased glomerular thrombosis at 24 hours, and the severity of histological changes at four days, accompanied by systemic hypertension. In the unilateral form of the model, where i.v. arginase did not induce hypertension, there was no increase in thrombosis or histological severity of nephritis. These results show that arginine depletion, which inhibits glomerular NO synthesis in NTN, leads to increased proteinuria. Where injury is severe, or accompanied by systemic hypertension, the disease is further exacerbated by glomerular thrombosis. These results suggest that NO has an important role in limiting acute glomerular injury.     

Negative strand of hepatitis C virus RNA in the liver of patients with chronic hepatitis C after interferon treatment

In patients receiving interferon therapy for chronic hepatitis C, serum hepatitis C virus (HCV) RNA often reverts from an undetectable to a detectable form after completion of treatment. Detection of the negative strand of HCV-RNA in liver tissue is regarded as an index of viral proliferation. Therefore, we investigated changes in the hepatic negative-strand HCV-RNA following interferon therapy to determine whether this parameter could predict the long-term response to treatment. The subjects of this study were 27 patients with chronic active hepatitis C. Serum positive-strand and hepatic tissue negative-strand HCV-RNA were detected using polymerase chain reaction. At the completion of interferon treatment, serum HCV-RNA was not detected in 21 patients. One year following treatment it remained undetectable in 14 of these patients but it had reverted to a detectable form in seven. The 14 patients in whom hepatic negative-strand RNA was not detected between 2 weeks and 12 months after treatment, had not relapsed after another year. In the 13 remaining patients, negative-strand RNA was found in liver tissue and serum RNA either reverted to a detectable form or remained detectable throughout. From these findings, we conclude that the detection of negative-strand HCV-RNA in liver tissue 2 weeks after the completion of interferon therapy is useful for predicting the long-term effect of therapy.     

Ultrastructure, immunofluorescence, western blot, and PCR analysis of eight isolates of Encephalitozoon (Septata) intestinalis established in culture from sputum and urine samples and duodenal aspirates of five patients with AIDS

ONO-5046 is a potent, specific and intravenously active inhibitor of neutrophil elastase. To examine the role of elastase in glomerulonephritis, we tested the effects of ONO-5046 on nephrotoxic serum (NTS) nephritis in a rat model of the disease in humans. Rats were administered ONO-5046 or phosphate-buffered saline (PBS) intraperitoneally 24 hours prior to injection of NTS, and they were then given equal doses of ONO-5046 or PBS three hours and 1, 2, 3, 4, 5 and 6 days later. Compared with the control groups, ONO-5046 significantly reduced proteinuria and hematuria, and suppressed the formation of crescentic glomeruli in a dose-dependent manner. Our results suggest that neutrophil elastase participates in NTS nephritis by degrading glomerular basement membrane proteins, and that the elastase inhibitor, ONO-5046, suppresses crescentic formation and glomerular injury caused by elastase.     

Effect of benzimidazole derivatives on viral infection

Dibazole and vitamin B12 reduced production of hemagglutinin by influenza A (PR8 and WSN strain) and B-1/73 (Yamagata strain) viruses in chick embryos when inoculated at various intervals after infection. The drugs stimulated interferon production in serum and by blood leukocytes, showing also some protective effect in influenza infection in mice. The necessity of further study of relationships between the chemotherapeutic activity of drugs and their capacity to stimulate nonspecific resistance to infection is emphasized.     

Impaired polymorphonuclear leukocyte anticandidal function in injured adults with elevated Candida antigen titers

Per protocol, adults with an Injury Severity Score of 18 or greater underwent Candida antigen titer measurements weekly. If titers were 1:4 or greater, neutrophil function against Candida albicans was determined with use of a tritiated glucose incorporation assay, and polymorphonuclear leukocytes obtained from healthy blood donors were studied concurrently for comparison. Polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated titers were able to inhibit C albicans growth in a dose-dependent fashion. Polymorphonuclear leukocytes from injured patients with elevated titers had a significantly depressed ability to inhibit Calbicans growth compared with those from healthy blood donors at all effector cell-to-target cell ratios tested. Cytokine-treated polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated Candida antigen titers demonstrated significantly improved anticandidal activity at all ratios of polymorphonuclear leukocytes-to-Candida. Granulocyte macrophage-colony stimulating factor was the most potent cytokine at reconstituting polymorphonuclear leukocyte function, followed by interferon gamma and interleukin 8. In conclusion, an elevated Candida antigen titer in injured adults is associated with impaired polymorphonuclear leukocyte antifungal activity. This depressed activity can be reconstituted by the addition of cytokine.     

Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group

BACKGROUND: Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy, but most subsequently relapse. We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS: We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment. A total of 173 patients were randomly assigned to receive standard-dose recombinant interferon alfa-2b concurrently with ribavirin (1000 to 1200 mg orally per day, depending on body weight) for six months, and 172 patients were assigned to receive interferon and placebo. RESULTS: At the completion of treatment, serum levels of hepatitis C virus (HCV) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone (82 percent vs. 47 percent, P<0.001). Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients (49 percent) in the combination-therapy group, but in only 8 patients (5 percent) in the interferon group (P<0.001). Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response. Base-line serum HCV RNA levels of 2 x 10(6) copies per milliliter or less were associated with higher rates of response in both treatment groups. Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group. Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone. CONCLUSIONS: In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone.     

Serum erythrocyte and leukocyte adenosine deaminase activities in patients with vivax malaria in Turkey

Adenosine deaminase (ADA) activities in serum samples, erythrocytes, leukocytes and plasma hemoglobin concentrations were investigated in 50 patients with vivax malaria and compared with control group. ADA activity was determined by Bertholet reaction. Student's t-test and correlation analyses methods were used for statistical analyses. Serum ADA activity in patients with vivax malaria 49.20 +/- 29.02 IU/I, in control 21.15 +/- 8.04 IU/I (p = 0.005), erythrocyte ADA activity in patients 2.91 +/- 1.23 U/gr Hb, in control 1.65 +/- 0.59 U/gr (p = 0.001), leukocyte specific ADA activity in patients 26.23 +/- 20.21 U/mg protein, in control 25.84 +/- 9.19 U/gr Hb were determined (P > 0.05). Plasma hemoglobin concentration in patients 29.25 +/- 28.10 ml/dl, in control 9.80 +/- 13.14 mg/dl were also determined. There is no significant correlation among mentioned parameters. Erythrocyte purine salvage pathway is accelerated by Plasmodium to provide preformed purine source which can not be synthesized by Plasmodium to provide preformed purine source which can correlation between plasma hemoglobin concentration and serum ADA activity suggests that increased serum ADA activity may develop secondarily to the disease independently from the hemolyses. No higher ADA activity level than expected value of leukocytes may reflect immunosuppression of leukocytes.     

The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen

The renal tubular epithelial antigen (Tub-Ag) of rats was solublized by Pronase and purified by gel filtration and acrylamide gel electrophoresis. Purified Tub-Ag was a glycoprotein with S20,W value of 8.4. Utilizing radiolabeled Tug-Ag, a sensitive radioimmunoassay for Tub-Ag and homologous antibody (anti-Tub-Ag) was developed. Tub-Ag activity associated with a protein of the same molecular size was demonstrated in the serum, as well as in Pronase extracts of all the organs tested, including kidney, liver, lung, spleen, intestine, stomach, and heart. The physiochemical properties of the Tub-Ag of rats and its distribution were essentially the same as the Tub-Ag of humans, which had been found in immune deposits in the kidney of some patients with idiopathic membranous glomerulonephritis. Rats were immunized with the purified Tub-Ag emulsified in Freund's complete adjuvant and followed for Tub-Ag and anti-Tub-Ag in the serum, as well as for proteinuria and immunohistological changes in the kidney. Serum Tub-Ag dropped sharply after 20 days, when anti-Tub-Ag appeared in the circulation. Persistent, massive proteinuria appeared still later, more than 30 days after injection, when anti-Tub-Ag disappeared and Tub-Ag reappeared in the serum of some of those rats. In others, anti-Tub-Ag in the serum persisted throughout the observation period of 90 days. The pathology of the kidney of the rats with proteinuria was that of a typical membranous glomerulonephritis; thickening of glomerular capillary walls with granular deposits of gamma-globulin and Tub-Ag was observed. On the basis of these results, Tub-Ag in the serum, probably released from cellular membranes of various organs as a physiological metabolite, is considered to maintain the pathological process in the kidney by providing the antigen continuously to form immune complexes.     

Effectiveness of relative low-dose interferon treatment for patients with chronic hepatitis C

To demonstrate effectiveness by relative low-dose of interferon treatment for patients with chronic hepatitis C, we investigated the histological activity index (HAI) score of liver tissue, hepatitis C virus (HCV) genotype by polymerase chain reaction (PCR) with type-specific primers, HCV RNA levels by competitive PCR, serum aminotransferase, sex, age, history of blood transfusion and history of hepatitis in patients with chronic hepatitis C prior to treatment. Twenty-two patients were treated with human lymphoblastoid interferon (3 MU daily, 2 weeks, 3 MU thrice a week, 6 weeks, 1.5 MU thrice a week, 16 weeks) for 24 weeks, of whom 10 (45.5%) were responders within a 6 month follow-up. HAI score before treatment was significantly lower in responders than in a combined group of relapse patients and nonresponders (7.5 +/- 3.4 vs. 12.0 +/- 3.1, p < 0.01). The prevalence of responders in patients with genotypes III and IV was significantly higher than in those with genotype II (85.7% vs. 21.4%, p < 0.05). HCV RNA level (logarithmic transformed copy per 50 microliter of serum) was significantly lower in responders than in a combined group of relapse patients and nonresponders (4.8 +/- 1.2 vs. 5.7 +/- 0.8, p < 0.05). In case of other pretreatment factors, there were no significant differences between responders and a combined group relapse patients and nonresponders. Thus severe histological changes in the liver, HCV genotype II and high HCV RNA levels are markers of unfavorable effects of interferon treatment for patients with chronic hepatitis C.