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Biomedical subjects

S Sutherland

Publications and source records attributed to S Sutherland.

At least 73 records · Page 4Linked to original sources

Production and characterisation of a human monoclonal antibody to cytomegalovirus and its use in an early nuclear fluorescence assay.

A human monoclonal antibody to cytomegalovirus (CMV) was produced by transforming peripheral blood mononuclear cells of a patient with recent CMV infection. It is directed against a late antigen located in the nucleus of CMV infected fibroblasts at 24-72 hours postinfection and immuneprecipitates 65K and 48K proteins from 35S-labelled CMV infected cells. Results of its use in an early nuclear fluorescence assay for rapid diagnosis are presented.

Adult↗

Typing and subtyping of herpes simplex isolates by monoclonal fluorescence.

The type specificity of 16 herpes simplex monoclonal antibodies was tested on 50 isolates previously typed by endonuclease restriction. A panel of antibodies was selected and used to type isolates from 50 primary and 50 recurrent genital infections. Sixty-four isolates from 18 patients followed up for six months were subtyped by using a larger panel of monoclonal antibodies and predominant HSV1 and HSV2 subtypes were demonstrated. In addition to confirming recurrences, four possible reinfections were identified. Type-specific differences in the location of viral antigens in infected cells were noted and a possible association of this finding with the type-specific differences in rates of recurrence of genital infections discussed.

Antibodies, Monoclonal↗

Acyclovir in first attacks of genital herpes and prevention of recurrences.

Sixty women patients experiencing a first attack of genital herpes were randomly treated with either oral acyclovir for 42 days or oral acyclovir for five days followed by placebo for 37 days. The median time to the first recurrence in patients receiving acyclovir for 42 days was 66.5 days compared with 24 days in those who received acyclovir for only five days (p less than 0.0001). This significant difference, however, was only observed for the treatment period. The frequency of recurrences was also reduced during the period of treatment in those who received prolonged treatment. During the subsequent follow up period, however, patients in both groups had a similar frequency of recurrences. Patients with infections due to herpes simplex virus type I (HSV I) had a significantly longer time to the first recurrence (p less than 0.001) and fewer recurrences (p less than 0.001) than those infected with HSV II, irrespective of treatment.

Acyclovir↗

Acute encephalopathy coincident with seroconversion for anti-HTLV-III.

Acute encephalopathy was associated with the appearance of antibodies to human T-lymphotropic virus (HTLV-III) in two patients. A third patient showed seroconversion for anti-HTLV-III, but the temporal association was not established so precisely. The illness was characterised by a prodromal period of up to 2 weeks, characterised by pyrexia, general malaise, and changes of mood. The encephalopathy culminated in epileptiform seizures in two of the patients. Electroencephalographic changes were compatible with viral encephalitis, and cerebrospinal-fluid pleocytosis was minimal. Neurological signs and symptoms resolved quickly in all patients, and no residual central-nervous-system sequelae were apparent.

Acquired Immunodeficiency Syndrome↗

Rising prevalence of human T-lymphotropic virus type III (HTLV-III) infection in homosexual men in London.

The prevalence of antibody to HTLV-III has increased from 3.7% (4/107) amongst unselected British homosexual men attending a London sexually transmitted disease (STD) clinic during one week in March, 1982, to 21% (26/124) in those attending during one week in July, 1984. Seropositive men had a significantly higher prevalence of infection with hepatitis B virus than did seronegative men. 82% (27/33) of the seropositive men in 1984 were symptomless or had only local genito-urinary symptoms referable to the STD for which they were attending. The evidence suggests that HTLV-III was initially an imported but is now an endemic sexually transmitted agent. As of July, 1984, at least 2600 homosexual men in London would probably have been infected.

Acquired Immunodeficiency Syndrome↗

Factors influencing the sensitivity of herpes simplex virus detection in clinical specimens in a simultaneous enzyme-linked immunosorbent assay using monoclonal antibodies.

A rapid simultaneous enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies was investigated for herpes simplex virus (HSV) detection. All HSV isolated (n = 127) were detected, whereas no response was obtained with HSV negative preparations. Equivalent results were obtained from 275 of 277 clinical specimens in the monoclonal ELISA and in an ELISA using polyclonal antibodies, confirming that appropriately selected monoclonal antibodies may be as efficacious as polyclonal antibodies in antibody-based assays. In clinical specimens, the rate of HSV detection (sensitivity) relative to tissue culture isolation was low for both assays, and the major factor responsible for this was the low concentration of virus present in some specimens. The sensitivity of ELISA obtained in routine use varied with different panels of unselected specimens and was related to the speed of development of the cytopathic effect. These results emphasise the need for caution in assigning a definitive sensitivity level to ELISA tests evaluated on different panels of specimens.

Antibodies↗

An enzyme-linked immunosorbent assay for detection of Brucella abortus in cattle using monoclonal antibodies.

One group of 24 cattle was vaccinated with the usual calfhood dose of B. abortus strain 19 and a further 27 cattle were similarly vaccinated but as adults. Twenty-four cattle (12 from each group) and a control group of 12 cattle were subsequently challenged with B. abortus strain 544. Two monoclonal antibodies (MA (A) and MA (B) ) conjugated to horseradish peroxidase were used independently in a competitive enzyme-linked immunosorbent assay (ELISA) to test the serums. After vaccination with B. abortus strain 19, the performance of the monoclonal antibodies was in general agreement with the CFT as fewer calfhood vaccinates were positive 12 weeks after vaccination to the ELISA with MA (A) and MA (B) than adult vaccinates. After challenge, MA (A) and MA (B) ELISA tests detected the infected cattle earlier than the CFT, but more positive reactions occurred in the cattle that proved uninfected at slaughter.

Animals↗

Early experience and difficulties with bronchoalveolar lavage and transbronchial biopsy in the diagnosis of AIDS associated pneumonia in Britain.

Bronchoalveolar lavage and transbronchial biopsy have been used as adjuncts to the management of patients with pneumonia associated with the acquired immunodeficiency syndrome (AIDS) at the Middlesex Hospital and the experience gained and difficulties encountered in the first five cases are reported. Widely varying organisms were isolated from lavage aspirates, some of which may have been nasopharyngeal contaminants, and organisms cultured from the transbronchial biopsy specimens may offer a better guide to antimicrobial treatment. Pneumocystis carinii was found in two of the patients. In view of the potentially serious toxicity of high dose co-trimoxazole, continuation of this treatment may be inadvisable if Pneumocystis carinii is not identified by all available methods unless there are strong clinical grounds to suspect its presence.

Acquired Immunodeficiency Syndrome↗

Prophylactic oral acyclovir in recurrent genital herpes.

56 patients with frequently recurring genital herpes were treated in a randomised double-blind trial with either oral acyclovir 200 mg four times a day or placebo for 12 weeks. 29 patients received the drug and 27 the placebo. The mean recurrence rate per month of treatment was 1.4 in the placebo-treated patients and 0.05 in the acyclovir group. Median time to the first recurrence after the start of therapy was 14 days in the placebo group compared with 100 days in the acyclovir group. After the end of treatment the recurrence rate was similar in the two groups. Prophylactic oral acyclovir seems to be an effective treatment for patients with frequently recurring genital herpes.

Acyclovir↗

Detection of IgM antibodies against cytomegalovirus: comparison of two radioimmunoassays, enzyme-linked immunosorbent assay and immunofluorescent antibody test.

The sensitivity and specificity of direct antibody radioimmunoassay (RIA), M-antibody capture RIA (MACRIA), enzyme-linked immunosorbent assay (ELISA), and the immunofluorescent antibody (IFA) test for the detection of CMV-specific IgM was compared using 40 sera selected from different groups of patients. RIA, MACRIA, and ELISA gave concordant results with thirty-two sera but discordant results with eight sera, of which three were cord sera from congenitally infected babies, three were from immunocompromised patients with recurrent CMV infections, and two were from patients with lymphadenopathy and Paul-Bunnell-positive mononucleosis, respectively. RIA, MACRIA, and ELISA were of similar sensitivity with sera from adult patients, but ELISA was apparently less sensitive than RIA and MACRIA for the detection of CMV IgM in cord serum. By comparison IFA was significantly less sensitive than the other three tests. Rheumatoid factor is reactive in RIA, ELISA, and IFA but can efficiently be removed by absorption with latex-IgG beads or cross-linked human IgG.

Adult↗

Homosexual men in London: lymphadenopathy, immune status, and Epstein-Barr virus infection.

By November 7, 1983, 24 cases of AIDS in the United Kingdom had been reported to the Communicable Disease Surveillance Centre. At the same time an increasing number of homosexual men with unexplained lymphadenopathy syndrome (LAS) have been seen in our department. Between December 1982 and July 1983, 14 homosexual men with LAS and 11 healthy homosexual men were studied. Patients with LAS had a high number of lifetime episodes of sexually transmitted diseases, a history of recent sexual activity in the United States (9 of 14), sexual contact with British AIDS patients or other persons with LAS (7 of 14), and hypergammaglobulinemia. Low T-helper/T-suppressor ratios (less than 0.8), due mainly to a decrease in T-helper cells, were found in both groups. Lymph node biopsies showed follicular hyperplasia and hypocellular pattern. All 25 patients studied had antibodies to Epstein-Barr virus capsid antigen (anti-VCA) and 11 had antibodies to early antigen (anti-EA); 13 of 17 were excreting the virus; and two showed no Epstein-Barr-virus-specific regression. Peripheral blood immunoglobulin-producing B-cells from six patients with hypergammaglobulinemia were negative for the Epstein-Barr virus nuclear antigen (EBNA). Five lymph node biopsies showed no EBNA-positive cells. Epstein-Barr virus reactivation is common in the patients with LAS and healthy homosexual men in London, but would not seem to be the cause of the polyclonal B-cell activation or lymphadenopathy.

Adult↗

Antibodies to cytomegalovirus in homosexual and heterosexual men attending an STD clinic.

We studied the prevalence of antibody to cytomegalovirus (CMV) in 262 men (132 homosexual, 20 bisexual, and 108 heterosexual) attending the sexually transmitted diseases (STD) clinic at this hospital. Antibody to CMV at a titre of 1/4 or more was found in 92% of the homosexuals, 80% of the bisexuals, and 56% of the heterosexuals (p less than 0.0001). Among heterosexuals, but not homosexuals, nationality and social class showed a significant association with antibody to CMV. In both heterosexuals and homosexuals a history of gonorrhoea was more common in patients with antibody to CMV than in those without it. A similar finding was seen in heterosexual men with a history of non-specific urethritis (NSU). Using a series of log linear models, sexual orientation was shown to be the most important determinant of antibody to CMV in this population.

Adolescent↗