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Biomedical subjects

D J Gocke

Publications and source records attributed to D J Gocke.

11 recordsLinked to original sources

Anti-HIV-1 activity of recombinant and hybrid species of interferon-alpha.

To identify candidate interferons (IFNs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection and to investigate sequence-function relationships, the antiviral activities of nine species of recombinant IFN-alpha [IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)] were evaluated against HIV-1. MT-2 cells were exposed to various concentrations of each IFN and were then infected with HIV. Protective effect was determined by cell viability using a tetrazolium dye assay. Activity against vesicular stomatitis virus (VSV) was assessed on MDBK and WISH cells. The 50% inhibitory concentration against HIV was 37 +/- 14 pg/ml for IFN-alpha A, and ranged from 15 +/- 3 pg/ml for IFN-alpha J/C(Fnu4HI) to > 90,000 pg/ml for IFN-alpha D. In general, relative activity against HIV was similar to relative activity against VSV on WISH cells. IFN-alpha D was notable for its decreased activity on human cells. The observations suggest that it may be possible to produce IFNs-alpha with more favorable therapeutic indices than currently available IFNs. Furthermore, the anti-HIV activity of IFNs-alpha is not determined solely by their linear amino acid sequence.

Acquired Immunodeficiency Syndrome

Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine.

To investigate whether human immunodeficiency virus type 1 pol gene mutations are selected during prolonged 2',3'-dideoxycytidine (ddC) therapy, we used the polymerase chain reaction to amplify a portion of the reverse transcriptase segment of the pol gene from the peripheral blood mononuclear cell DNA of a patient with AIDS before and after an 80-week course of ddC therapy. The consensus sequence from the second sample contained a unique double mutation (ACT to GAT) in the codon for reverse transcriptase amino acid 69, causing substitution of aspartic acid (Asp) for the wild-type threonine (Thr). A mutation (ACA to ATA) also occurred in the codon for position 165, causing substitution of isoleucine (Ile) for Thr. The GAT (Asp) codon was introduced into the pol gene of a molecular clone of human immunodeficiency virus via site-directed mutagenesis. Following transfection, mutant and wild-type viruses were tested for susceptibility to ddC by a plaque reduction assay. The mutant virus was fivefold less susceptible to ddC than the wild type; cross-resistance to 3'-azido-3'-deoxythymidine or 2'3'-dideoxyinosine was not found. The Ile-165 mutation did not confer additional ddC resistance. The Asp-69 substitution may have contributed to the generation of resistant virus in this patient.

Acquired Immunodeficiency Syndrome

Incidence and significance of antibodies to delta antigen in hepatitis B virus infection.

A microtitre solid-phase blocking radioimmunoassay (RIA) for antibody to the hepatitis B virus (HBV)-associated delta antigen was specific and detected anti-delta antibody at dilutions of serum of up to 10(6). Analysis of sera from HBsAg-negative subjects and different categories of HBsAg carriers from different regions confirmed the association of anti-delta antibody with HBV infection. Anti-delta antibody was detected in persistently high titres in 19.1% and 2.6% of sera from patients with chronic hepatitis and symptomatic chronic carriers, respectively, and was not detected in the sera of HBsAg-negative controls. Anti-delta antibody appeared transiently and in low titres (less than 1:500) in 4.8% of sera from patients with acute type B hepatitis. The presence and persistence of anti-delta antibody seem to be associated with chronic HBV infection and the development of progressive liver damage.

Acute Disease

Heparin allergy accompanying acute renal failure.

A generalized cutaneous hypersensitivity reaction to a porcine heparin preparation was observed in a patient during the course of acute renal failure. Immunological studies, including gel diffusion and immunoelectrophoresis, suggested that the reaction was to a contaminant of the heparin and involved both IgG and IgE antibodies.

Acute Kidney Injury

The epidemiology of hepatitis B infection in housestaff.

Ninety-nine medical and surgical house officers were prospectively evaluated during internship and residency for the development of hepatitis B virus (HBV) infection. The overall incidence of hepatitis B was 10.2% per year. Eighty-six percent of episodes were subclinical. The greatest risk factor appeared to be frequent hand-to-mouth activity such as smoking or licking requisition labels. The presence of a hemodialysis or transplantation unit may be an additional institutional risk factor. HBV infection was not associated with a history of needle-sticks or contact with known antigen-positive patients. Educational efforts to minimize HBV infection should concentrate on handwashing techniques and discouragement of hand-to-mouth activity in patient care areas.

Habits

Viral hepatitis.

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Animals

Vasculitis with hepatitis B antigenemia: long-term observation in nine patients.

The development of generalized necrotizing vasculitis in association with hepatitis B antigenemia is the first example in man of a chronic rheumatic disease presumably caused by a viral infection. This report reviews the experience in nine biopsy-proven cases of hepatitis B-associated necrotizing vasculitis followed for up to six years. The natural history of the disease is emphasized and the manifestations of patients with vasculitis who carry hepatitis B antigen are compared with those of vasculitis patients who are antigen negative.

Adult

Hepatitis B immune globulin as a prophylactic measure for spouses exposed to acute type B hepatitis.

Because the value of usual immune globulin preparations in preventing Type B hepatitis is doubtful, we carried out a double-blind comparison of a control human immune globulin preparation with one--identified as HBIG--that had a high concentration (442 mug per milliliter) of antibodies to surface components of hepatitis B virus. Effectiveness was tested in spouses of patients with acute Type B hepatitis. Within 150 days after injection, nine of 33 spouses in the control group had symptomatic Type B hepatitis, compared with one of 25 spouses receiving HBIG. One non-B case also occurred in the HBIG group. Five control globulin recipients had evidence of subclinical hepatitis B infection, compared with one HBIG recipient. Thus, HBIG appeared effective in suppressing not only disease, but also infection itself. Prophylactic value has been demonstrated in persons who should now be recognized as being at exceptionally high risk.

Acute Disease

Viral hepatitis.

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Antigens, Viral

Extrahepatic manifestations of viral hepatitis.

Recent evidence indicates that viral hepatitis is sometimes associated with the production of extrahepatic tissue injury. Hepatitis B virus (HBV) infection is most commonly incriminated but non-type B hepatitis may also be involved. Three types of syndromes have been recognized. First, a serum sickness-like prodrome consisting of skin eruptions, urticaria and polyarthralgias or arthritis may occur from one to six weeks prior to the onset of hepatitis in 15 to 20 per cent of patients and usually disappears by the time the patient becomes jaundiced. There is extensive evidence that circulating immune complexes are responsible for these symptoms. Second, about 30 to 40 per cent of patients with typical polyarteritis nodosa have persistent hepatitis B surface antigenemia (HBs Ag). Circulating immune complexes composed of HBs Ag, antibody, and complement have been demonstrated together with deposits of immune complexes at sites of vascular injury. Third, an immune complex type of glomerulonephritis may occur following hepatitis B virus infection, usually in association with chronic active hepatitis. Thus there is impressive evidence that hepatitis viruses, especially HBV, may produce a variety of extrahepatic manifestations in which the mechanism of pathogenesis involves an immunologic process rather than direct viral invasion and cytopathogenicity.

Complement System Proteins