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Biomedical subjects

S Iwarson

Publications and source records attributed to S Iwarson.

At least 73 records · Page 4Linked to original sources

Sequential changes of the plasma-protein pattern in cases of hepatitis A.

The level of 21 plasma proteins was followed in Hepatitis A for two months after onset of icterus. The mean concentration of alpha 1-antitrypsin, orosomucoid, haptoglobin, C-reactive protein (CRP) and alpha 1-antichymotrypsin increased uniformely during the first week of hepatitis A. Thus, they differ from that of inoculation hepatitis earlier described. The mean curve for IgM was higher in hepatitis A than the corresponding results for inoculation hepatitis during the first week of illness, but because of great inter-individual differences in concentrations IgM determinations can not be used to discriminate between the two diseases in a given case. IgA levels were slightly increased early in hepatitis A but no change in IgG levels was observed. Prealbumin was the best mirror of the patients' recovery or deterioration.

Acute-Phase Proteins↗

Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis. Evidence that antibody modulation may cause protracted infection.

The nucleocapsid antigens (HBc and HBe) are present on the membranes of HBV-infected hepatocytes from HBV carriers. In autologous cytotoxicity experiments we demonstrate that cytotoxic T cells sensitised to the nucleocapsid proteins of hepatitis B are present in HBe antigen-positive HBV carriers with chronic hepatitis and can be blocked by monoclonal anti-HBc and anti-HBe. Passive immunisation of chimpanzees with monoclonal anti-HBc and anti-HBe offers no protection against HBV infection but in both cases leads to an unusually prolonged hepatitis probably by modulation of HBc and HBe antigen display on the hepatocytes. High-titre anti-HBc in the circulation of HBe antigen-positive patients probably modulates the former protein making HBe the important target antigen for cytotoxic T cells mediating liver damage in chronic carriers. These data also support the hypothesis that passive transfer of IgG anti-HBc across the placenta may be one major factor promoting development of persistent infection in neonates infected from carrier mothers.

Animals↗

Retrovirus-like particles in hepatocytes of patients with transfusion-acquired non-A, non-B hepatitis.

Retrovirus-like particles 60-85 nm in diameter were observed in the cytoplasm of hepatocytes in liver biopsies obtained during the acute and chronic phases of non-A, non-B hepatitis (NANBH) in three patients with transfusion-acquired disease. The particles appeared in dilated endoplasmic reticulum cisternae as well as in enlarged Golgi vesicles. No such particles were seen in hepatocytes in liver biopsies similarly obtained during the acute or chronic phases of NANBH from 11 additional patients with NANBH who did not acquire their disease following blood transfusion. Particle-associated reverse transcriptase activity (peak activity at a density of 1.14 gm/ml) was present in the sera of all three "particle-positive" patients and also in 42% of the "particle-negative" patients. The retrovirus-like particles described here were apparently unrelated to the previously described human T cell lymphocytotropic retroviruses (HTLV), since none of the 14 patients studied had antibodies in their serum directed against antigens of any of the three known HTLVs.

Adult↗

Neutralization of hepatitis B virus infectivity by a murine monoclonal antibody: an experimental study in the chimpanzee.

Two study chimpanzees were inoculated intravenously with approximately 1,000 chimpanzee infectious doses of hepatitis B virus (HBV), one with subtype adr and one with subtype ayw, each previously incubated with 0.1 ml of a murine monoclonal antibody (IgG 1(K) class) directed against a single epitope on hepatitis B surface antigen common to most or all HBV. Two control chimpanzees received identical doses of HBV not incubated with the murine anti-HBs. Neither study chimpanzee developed HBV infection during 12 months of follow-up as judged by normal serum aminotransferase activity, normal liver biopsies, and negative serological tests for HBV-associated antigens and antibodies. In contrast, both control chimpanzees became infected by HBV as evidenced by elevated serum aminotransferase activity, liver biopsy changes characteristic of viral hepatitis, and the appearance of hepatitis B surface antigen (HBsAg) in their sera. Both study chimpanzees were shown to be fully susceptible to infection with these same HBV inocula when challenged 15 months after the initial inoculations at a time when passively administered anti-HBs was no longer detectable. Prior to challenge with HBV, one of the two study chimpanzees received a second injection of the same volume of the murine monoclonal anti-HBs. The survival of this anti-HBs in serum was reduced from six weeks (after the initial injection) to approximately two weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Protection against hepatitis B virus infection by immunization with hepatitis B core antigen.

Although antibody to the hepatitis B surface antigen usually provides protection against hepatitis B virus (HBV) infection, recent reports indicate that this is not always the case. To study the possible role of immune responses to hepatitis B core antigen in immunity to HBV infection, chimpanzees were immunized with chimpanzee liver-derived or genetically cloned hepatitis B core antigen and later challenged with known infectious HBV. Two chimpanzees, which received liver-derived or cloned hepatitis B core antigen in Freund's adjuvant and developed hepatitis B core antibody and low-titer hepatitis B e antibody, were completely protected against HBV infection following challenge. In contrast, another chimpanzee, which received liver-derived hepatitis B core antigen without adjuvant, developed hepatitis B core antibody only in serum and had a subclinical HBV infection when challenged. These findings demonstrate that protection against HBV infection can be induced by immunization with hepatitis B core antigen in adjuvant and that protection, in this case, is not solely dependent on hepatitis B surface antibody. This fact has important implications in our understanding of the biology of HBV infection and in the design of future hepatitis B vaccines.

Animals↗

Cefadroxil once daily for three or seven days versus amoxycillin for seven days in uncomplicated urinary tract infections in women.

The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.

Amoxicillin↗

Detection of reverse transcriptase activity in association with the non-A, non-B hepatitis agent(s).

Particle-associated reverse transcriptase activity was detected in four human serum specimens and in two plasma-derived products, all of which had been shown to transmit non-A, non-B hepatitis (NANBH) to other human beings and/or chimpanzees. Reverse transcriptase activity was also detected in all twelve sera from patients with acute or chronic NANBH. In contrast, reverse transcriptase activity was found in only 2 of 49 serum specimens from healthy plasma donors and laboratory workers. Sucrose density gradient fractions of two of the infectious human sera (peak reverse transcriptase activity at 1.14 g/ml) transmitted NANBH to chimpanzees. Biochemical and enzymatic data indicate that the NANBH agent(s) is a retrovirus or is retrovirus-like.

Animals↗

The delta agent in acute and chronic hepatitis B infection in Sweden.

The occurrence of the delta (delta) agent was analyzed in 89 patients with acute hepatitis B infection during 1976-1979 in Gothenburg, Sweden, and in 46 patients (16 drug addicts) with chronic HBsAg-positive liver disease. Four of the patients with acute hepatitis B had transiently detectable anti-delta antibodies in serum. At least three of these four cases were associated with intravenous drug abuse. Eleven of the HBsAg carriers (24%) were anti-delta-positive, and all of them were drug addicts. One of the drug addicts transmitted hepatitis B infection without detectable anti-delta in serum to two other non-addicts via parenteral routes. Apparently, in Sweden today delta-infection is mostly restricted to drug addicts and seldom found in other groups of hepatitis B patients.

Acute Disease↗

Recovery and turnover rate of hepatitis B immunoglobulin in volunteers.

Hepatitis B Immunoglobulin with an antibody content of 2 300 IU was injected i.m. into five healthy female volunteers without Hepatitis B markers in serum (HBsAg, anti-HBs, anti-HBc). The uptake of anti-HBs after i.m. injection was calculated by measuring the concentration of antibody in plasma. An international standard (WHO) containing 100 IU/ml was used as reference. The serum concentration of anti-HBs was analysed on day 1, 3, 5, 7, 9, 11, 13, 28 and 56 after the single i.m. injection. The peak serum concentrations after one single injection were observed between day 5 and 11. The mean recovery rate was calculated according to a compartment model where the plasma volume was estimated to be 45 ml/kg body weight. The mean recovery rate expressed as percentage of injected dose was 19.2% with a range of 14.2-28.2%. The mean biological half life of anti-HBs was 21.7 days. The recovery rate of Hepatitis B Immunoglobulin injected i.m. seems to be somewhat lower than expected but is within the same range as i.e. Ig anti-D (Eklund et al, BMJ 1982, 284: 854-855). The peak serum concentration of anti-HBs was reached comparatively late after the injection. This finding may in part explain the discouraging protection of Hepatitis B Immunoglobulin in the post-exposure situation. Intravenous administration of anti-HBs with an immediate peak concentration followed by vaccination will possibly be a better alternative for post-exposure prophylaxis against Hepatitis B.

Adult↗

Hepatitis A in Swedish foreign travellers.

Scandinavians present antibodies to hepatitis A virus (anti-HAV) in low frequency or under 25% in ages up to 50 years. This means that Scandinavians ought to be particularly vulnerable when travelling to hyperendemic hepatitis A areas. About one million Swedes travel to the Mediterranean area each year and about 75% of these travellers receive gammaglobulin before departure. Since hepatitis A is a notifiable disease in Sweden it is possible to compare the incidence of this disease in travellers during different periods of time. In the early seventies the prevalence of hepatitis A in Mediterranean travellers was one case in about 3000 travellers, while in 1980 the calculated prevalence had declined to one case in about 6000 travellers without gammaglobulin prophylaxis. The declining prevalence of hepatitis A in Swedish travellers to the northern part of the Mediterranean area is probably due to increased socio-economic and hygienic standard in the countries concerned. The relatively low prevalence of hepatitis A infection among Swedish travellers to the northern part of the Mediterranean area is in sharp contrast to the high prevalence found in Northern Africa and the Middle East (one case in about 300 travellers) as well as in Tropical Africa and Asia (one case in about 100 travellers).

Hepatitis A↗