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Biomedical subjects

R A Weiss

Publications and source records attributed to R A Weiss.

At least 289 records · Page 16Linked to original sources

Human T-cell leukemia virus type I: pseudotype neutralization of Japanese and American isolates with human and rabbit sera.

CCC/2M, CCC/10Y and CCC/MT-2 cat kidney cells producing Japanese isolates of human T-cell leukemia virus type I (HTLVs) and HOS/PL human osteosarcoma cells producing an American isolate of HTLV were infected with vesicular stomatitis virus (VSV) to prepare VSV pseudotypes bearing envelope antigens of HTLVs. VSV propagated in CCC/2M cells contained plaque-forming fractions that were not neutralized by treatment with anti-VSV serum alone: VSV pseudotypes bearing envelope antigens of HTLV2M and CCC cat endogenous virus were formed by infection of CCC/2M cells with VSV. Japanese HTLV2M, HTLV10Y and HTLVMT-2 and American HTLVPL pseudotypes were neutralized by sera of Japanese, American and British patients with ATL. Each serum, including the serum of the patient from whom HTLV2M or HTLV10Y had been derived, gave similar antibody titers against Japanese and American HTLV pseudotypes. The HTLV pseudotypes were also neutralized by rabbit serum raised against HTLVMT-2. A rabbit antiserum against the C-terminal half of the HTLV env protein produced in E. coli also neutralized Japanese and American HTLV pseudotypes. Thus, VSV pseudotype analyses indicated that envelope antigens of HTLVs represent a single serotype worldwide. The env protein produced in E. coli may be used to raise neutralizing antibody against HTLVs.

Acute Disease↗

Slim disease: a new disease in Uganda and its association with HTLV-III infection.

A new disease has recently been recognised in rural Uganda. Because the major symptoms are weight loss and diarrhoea, it is known locally as slim disease. It is strongly associated with HTLV-III infection (63 out of 71 patients) and affects females nearly as frequently as males. The clinical features are similar to those of enteropathic acquired immunodeficiency syndrome as seen in neighbouring Zaire. However, the syndrome is rarely associated with Kaposi's sarcoma (KS), although KS is endemic in this area of Uganda. Slim disease occurs predominantly in the heterosexually promiscuous population and there is no clear evidence to implicate other possible means of transmission, such as by insect vectors or re-used injection needles. The site and timing of the first reported cases suggest that the disease arose in Tanzania.

Acquired Immunodeficiency Syndrome↗

Human T-lymphotropic virus type III (HTLV-III) infection in seronegative haemophiliacs after transfusion of factor VIII.

Fifteen haemophiliac patients acquired antibodies to human T-lymphotropic virus type III during 1984. One batch of factor VIII concentrate given to all these patients is presumed to be the cause of the seroconversion. A further eighteen patients who received the same batch did not seroconvert and one other patient became seropositive but had not received this batch. Before transfusion of the implicated batch the patients had low T-helper-cell numbers and T-helper/suppressor ratios; neither changed in those who seroconverted. The probability of seroconversion was independently related to the pre-existing low T-helper/suppressor ratio, the number of vials of the implicated batch transfused, and the total annual factor VIII consumption. Ten other patients received a batch of factor IX concentrate from the same donor plasma; none of these patients seroconverted.

Acquired Immunodeficiency Syndrome↗

HTLV-III serology distinguishes atypical and endemic Kaposi's sarcoma in Africa.

Serum samples from African patients with Kaposi's sarcoma and acquired-immuno-deficiency-syndrome-related (AIDS-related) disorders and from normal subjects in Uganda and Zambia were tested for antibodies to the human T-lymphotropic retroviruses (HTLV) types I, II, and III. Nearly 90% of patients with AIDS-related disorders or with atypical, aggressive Kaposi's sarcoma were seropositive for HTLV-III in both countries, whereas only 17% of patients with classic endemic Kaposi's sarcoma were seropositive. Among the controls 20% were seropositive for HTLV-III in Uganda but only 2% in Zambia. None of the subjects tested had antibodies to HTLV-I or HTLV-II. These results are further evidence of the emergence of a clinically atypical form of Kaposi's sarcoma in Africans, which resembles that seen in American patients with AIDS, and which is associated with HTLV-III infection. The low frequency of antibodies to HTLV-III in the normal Zambian population together with the first appearance of HTLV-III-associated diseases during the past 2 years suggests that this virus is new to Zambia, although it may have been present in Uganda for longer.

Acquired Immunodeficiency Syndrome↗

Autosomal dominantly inherited retinitis pigmentosa. Visual acuity loss by subtype.

Sixty-eight patients with autosomal dominant retinitis pigmentosa were divided into two distinct subtypes and studied for visual function using a life-table analysis. Type 1 patients (n = 23) had diffuse pigmentation, concentric visual field loss, and no recordable electroretinogram. Type 2 patients (n = 45) as a group had regionalized pigmentation, sectorial field loss, and some recordable electroretinogram. The cumulative probability of maintaining a visual acuity of 6/12 (20/40) or better over each decade of life decreased rapidly in eyes of type 1 patients; for type 2 eyes, this probability remained above 90% through the fifth decade of life. The presence of an atrophic-appearing foveal lesion was associated with a reduction in visual acuity to 6/15 (20/50) or worse in a majority of patients. Data from this study indicate that investigators should look for subtypes within the major genetic groupings of retinitis pigmentosa for more accurate assessment of a patient's potential for maintaining good central visual acuity.

Adolescent↗

Biological properties of HTLVIII.

Since the first discovery of HTLVIII 2 years ago, there have been remarkable advances in the molecular characterization of the virus, our understanding of its replication and the development of serological tests. But a great deal remains to be elucidated about the natural history of viral transmission and of the spectrum of disease resulting from infection.

Acquired Immunodeficiency Syndrome↗

Monoclonal antikeratin antibody: production, characterization, and immunohistochemical application.

A monoclonal antikeratin antibody, EKH4, was produced from a hybridoma cell line which was established by fusing P3X63SAg8 mouse myeloma cells with spleen cells of mice immunized with human trichilemmoma cells. Immunoblot analysis showed that EKH4 antibody reacts predominantly with 50 kilodalton keratin polypeptide in normal epidermis. By indirect immunofluorescence and immunoperoxidase techniques, EKH4 antibody reacted with the lower 2-3 cell layers of the epidermis as well as most cells of pilosebaceous follicle of human and animal skin. Tumor cells of human basal cell epitheliomas and squamous cell carcinomas were also stained with this antibody. The staining was much more regular and intense compared with an available monoclonal antikeratin antibody, AE1. In the lesion of epidermal proliferative disorders, such as psoriasis and actinic keratosis, the entire epidermis instead of the lower layers was stained with EKH4 antibody. Normal skin overlying or adjacent to epithelial tumors also showed positive staining in the entire epidermis. By using indirect immunoperoxidase technique, EKH4 also stained alcohol-fixed, paraffin-embedded tissue sections.

Animals↗

The status of pulmonary host defense in the neonatal sheep: cellular and humoral aspects.

In consideration of the sheep neonate as a compromised host, we have examined the status of cellular and humoral pulmonary host defense components at selected developmental time points. The dynamic character of the early neonatal LFC population, reflected in changes in subpopulations and proliferative capacity, most probably contributed to the observed changes in in vitro cell function. While certain cell responses, e.g., blood and LFC PMN chemotaxis, appeared intact by day 1, others developed subsequently. The ability of AMs to elaborate a chemotactic factor(s) was first noted at day 21. Bacteria binding and killing presented a biphasic maturation pattern, with full competence not present until day 180. Although the in vitro binding and killing activity of day 8 LFCs was comparable to that of the adult, it may be a poor indicator of in vivo host defense capacity, given the relative paucity of endogenous opsonins at that age. In fact, the interdependence of mediators suggests that the sheep neonate may remain a compromised host during the first 3 months of life. Thereafter, cellular and humoral parameters begin to approximate those of adult sheep and by 180 days of life pulmonary defense, as assessed in this study, is fully developed.

Age Factors↗

Prevalence of antibody to human T-lymphotropic virus type III in AIDS and AIDS-risk patients in Britain.

2000 persons in the UK were examined serologically for antibodies to human T-lymphotropic virus type III (HTLV-III). Sera reacting in a membrane immunofluorescence assay (IFA) to HTLV-III were also positive when tested against cells infected with lymphadenopathy virus (LAV-1), and cross-adsorption tests indicated that these retroviruses are probably identical. A competitive radioimmunoassay (RIA), which was wholly concordant with IFA, was used to screen the sera. 30/31 patients with the acquired immunodeficiency syndrome (AIDS) were seropositive, as were 89% patients with persistent generalised lymphadenopathy (PGL), 17% symptomless homosexual men, 34% haemophiliacs receiving pooled clotting factors, and 1.5% intravenous drug abusers. None of more than 1000 unselected blood donors was seropositive. These data confirm the close association between HTLV-III and AIDS and PGL and show that infection with HTLV-III is also prevalent in the populations in whom these syndromes are most likely to develop. However, it would be unwise to presume that AIDS will necessarily develop in seropositive subjects.

Acquired Immunodeficiency Syndrome↗

Clinical findings and serological evidence of HTLV-III infection in homosexual contacts of patients with AIDS and persistent generalised lymphadenopathy in London.

Between 1980 and 1984 28 homosexual men who had had ano-genital intercourse with patients with either acquired immunodeficiency syndrome (AIDS) or persistent generalised lymphadenopathy (PGL) were followed up. The pattern of the sexual links indicated that within this group there were two clusters, one consisting of 7 men and the other of 13.17 of the 28 contacts became ill with either AIDS or PGL; among those in the clusters, 4 died of AIDS and 11 had PGL, and of the rest 2 had PGL. 16 of the 19 men in the clusters who were tested for HTLV-III antibodies were seropositive, as were 7 of those not in the clusters. 111 men attending a genitourinary medicine clinic who had not had known contact with either AIDS or PGL patients and who were being screened for syphilis served as controls. Of these, 19/86 who were homosexual and 0/25 who were heterosexual were positive for HTLV-III antibodies. None of the 4 who died of AIDS had had contact with each other. The 2 in the first cluster seemed to have been linked by a symptomless HTLV-III-negative man, who was also probably the link between the two clusters, while in the second cluster the chief "carrier" seemed to be a seropositive man in whom PGL developed. These findings are consistent with the hypothesis that HTLV-III is the sexually transmitted causative agent of AIDS and PGL.

Acquired Immunodeficiency Syndrome↗

Low prevalence in the UK of HTLV-I and HTLV-II infection in subjects with AIDS, with extended lymphadenopathy, and at risk of AIDS.

Antibodies reacting selectively with human T-cell leukaemia virus type I (HTLV-I) were detected in approximately 5% patients with extended lymphadenopathy syndrome (ELAS) and in less than 1% of unselected homosexual patients and drug abusers. None of 22 patients with acquired immunodeficiency syndrome (AIDS) had HTLV-I antibodies and neither did 85 haemophiliacs and 940 blood donors. 3 out of 113 drug addicts had high titres of antibodies to human T-cell leukaemia virus type II (HTLV-II). A T-cell line was derived from 1 of the seropositive ELAS patients. This line was found to be infected with, and releasing, HTLV-I. Infection by HTLV-I and HTLV-II retroviruses thus occurs more frequently in ELAS patients and drug addicts than in the UK population as a whole, but the low prevalence of these infections in ELAS and AIDS patients indicates that these two strains of lymphotropic retroviruses have no aetiological role in ELAS and AIDS.

Acquired Immunodeficiency Syndrome↗

Isolated hematuria in children: indications for a renal biopsy.

Previous reviews of hematuria in children and adolescents have included patients with proteinuria and other renal functional abnormalities such as hypertension and reduced GFR. We report the clinico-pathological correlations in 76 pediatric patients, aged 3 to 19 years, who underwent a renal biopsy because of isolated hematuria during the 10-year period, 1972 to 1981. All specimens were examined by light and electron microscopy and immunofluorescence techniques. The overall prevalence of abnormal renal histology was 56%. The vast majority (41 of 43) of the abnormal biopsy specimens could be classified into four distinct histological categories: (1) Alport syndrome (N = 9); (2) IgA nephropathy (N = 8); (3) thinning of the glomerular basement membrane (N = 17); (4) vascular C3 staining (N = 7). The children were divided into three clinical subgroups (1) isolated microscopic hematuria ( IMH ), N = 42; (2) IMH plus a family history of hematuria in a first degree relative, N = 15; and (3) IMH plus at least one episode of gross hematuria, N = 19. A significant graded increase in the likelihood of obtaining an abnormal renal biopsy was demonstrated (X2 = 10, P less than 0.007) from groups one to three. Sex, age at onset, or duration of hematuria were not associated with an increased proportion of histopathologic abnormalities. These findings indicate that the yield of a renal biopsy in children with isolated hematuria can be predicted accurately from specific clinical characteristics.

Adolescent↗

Pseudotypes of human T-cell leukemia virus types 1 and 2: neutralization by patients' sera.

Pseudotypes of vesicular stomatitis virus (VSV) bearing envelope antigens of human T-cell leukemia virus (HTLV) types 1 and 2 were prepared by propagating VSV in cells lines productively infected with HTLV. Plaque assays of VSV (HTLV) pseudotypes were employed to determine the presence of (i) HTLV receptors on cells and (ii) neutralizing antibodies in the serum of patients with adult T-cell leukemia-lymphoma (ATLL). Cell surface receptors for HTLV-1 and HTLV-2 were found on nonlymphoid cells of human and mammalian origin. Neutralizing antibodies specific to VSV(HTLV-1) were found in sera of ATLL patients in titers varying from 1:50 to 1:30,000 and did not correlate closely with antibody titers for internal viral antigens. Sera from ATLL patients in the United Kingdom (Caribbean immigrants), United States, and Japan completely neutralized VSV (HTLV-1), indicating that the HTLV isolates from these distinct geographic regions represent a single envelope serotype. Neutralization of VSV (HTLV-1) was more specific and more sensitive than assays of syncytium inhibition. No cross-neutralization was observed between bovine leukosis virus and HTLV, and only limited cross-reaction was found for envelope antigens of HTLV-1 and HTLV-2. These studies show that VSV (HTLV) pseudotypes can be readily used to screen for neutralizing antibodies in patients' sera and to distinguish HTLV envelope serotypes.

Antigens, Viral↗