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Biomedical subjects

R A Weiss

Publications and source records attributed to R A Weiss.

At least 217 records · Page 12Linked to original sources
PubMed1991

The aetiology of Kaposi's sarcoma.

The aetiology of KS remains unknown, but recent evidence suggests that the disease is caused by the presence of an infectious agent in an immunosuppressed host. Although there are a variety of clinical presentations, the putative infectious agent is likely to be the same in all cases. The pathophysiology of the lesions, the types of immunosuppression that facilitate disease expression, the response to therapy and the distribution of disease within immunosuppressed populations provide important clues to the nature of the unidentified infectious agent.

Humans↗
PubMed1990

Dissociation of gp120 from HIV-1 virions induced by soluble CD4.

The CD4 antigen is the high affinity cellular receptor for the human immunodeficiency virus type-1 (HIV-1). Binding of recombinant soluble CD4 (sCD4) or the purified V1 domain of sCD4 to the surface glycoprotein gp120 on virions resulted in rapid dissociation of gp120 from its complex with the transmembrane glycoprotein gp41. This may represent the initial stage in virus-cell and cell-cell fusion. Shedding of gp120 from virions induced by sCD4 may also contribute to the mechanism by which these soluble receptor molecules neutralize HIV-1.

Animals↗
PubMed1990

Adult T-cell leukaemia/lymphoma in Brazil and its relation to HTLV-I.

In a series of fourteen patients with adult T-cell lymphoma-leukaemia (ATLL) in Brazil the main features were lymphadenopathy, hepatosplenomegaly, hypercalcaemia, and high leucocyte counts, with abnormal lymphoid cells which had irregular nuclei. The series included the youngest patient with ATLL so far (18 months). Analysis with monoclonal antibodies showed a mature T-cell phenotype (CD4+, CD8-). Antibodies to HTLV-I and/or integration of HTLV-I proviral DNA were found in eleven patients. In the other three HTLV-I DNA could not be demonstrated even by means of the polymerase chain reaction; they therefore had HTLV-I-negative ATLL. This report of ATLL in Brazil corroborates serological reports that HTLV-I may be endemic in some parts of that country. Follow-up studies are required to identify precisely the main route of transmission of HTLV-I in South America and the risk factors for the development of ATLL in carriers.

Adult↗
PubMed1990

Duesberg, HIV and AIDS.

Last century there was a sharp difference of opinion between those, such as Koch and Pasteur, who proposed that disease could be caused by invisible microbes, and others who held that epidemics are the result of evil vapours (mal'aria). Arguments that AIDS does not have an infectious basis are as quaint as those of the miasmalists.

Acquired Immunodeficiency Syndrome↗
PubMed1990

HIV susceptibility conferred to human fibroblasts by cytomegalovirus-induced Fc receptor.

The main receptor for the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) on T and B lymphocytes, monocytes and macrophages is the CD4 antigen 1-3. Infection of these cells is blocked by monoclonal antibodies to CD4(1,2) and by recombinant soluble CD4(4-9). Expression of transfected CD4 on the surface of HeLa and other human cells renders them susceptible to HIV infection 10. HIV-antibody complexes can also infect monocytes and macrophages by means of receptors for the Fc portion of immunoglobulins (FcR)11-13), or complement receptors 14,15. The expression of IgG FcRs can be induced in cells infected with human herpes viruses such as herpes simplex virus type 1 (HSV-1)16,17 and human cytomegalovirus (CMV)18-21. Here we demonstrate that FcRs induced by CMV allow immune complexes of HIV to infect fibroblasts otherwise not permissive to HIV infection. Infection was inhibited by prior incubation with human IgG, but not by anti-CD4 antibody or by recombinant soluble CD4. Once HIV had entered CMV-infected cells by means of the FcR, its replication could be enhanced by CMV transactivating factors. Synergism between HIV and herpes viruses could also operate in vivo, enhancing immunosuppression and permitting the spread of HIV to cells not expressing CD4.

Base Sequence↗
PubMed1990

Receptor interference groups of 20 retroviruses plating on human cells.

The types of receptors on the surfaces of human and other mammalian cells for 13 C-type and 7 D-type retrovirus strains were determined by interference to the formation of syncytia and the plating of viral pseudotypes. All the D-type simian retroviruses (SRV-1-5, SMRV, PO-1-Lu) share a common receptor which is also utilized by the baboon and cat endogenous C-type viruses (BaEV, RD114). Syncytial cross-interference was also observed in human cells between the gibbon ape leukemia/simian sarcoma associated viruses (GALV/SSAV) and feline leukemia virus subgroup B (FeLV-B). Amphotropic and xenotropic murine leukemia viruses (MLV-A, MLV-X), bovine leukemia virus (BLV), and FeLV-C infect human cells via unique cell surface receptors. Human T-cell leukemia viruses types 1 and 2 (HTLV-1, HTLV-2) share a common receptor with related chimpanzee and simian viruses (STLV). Thus seven distinct receptor groups were delineated on human cells for C-type and D-type retroviruses.

Animals↗
PubMed1990

Descriptions of the participating centers and patient population in the Growth Failure in Children with Renal Diseases Study.

The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.

Child↗
PubMed1990

Characterization of recombinant gp120 and gp160 from HIV-1: binding to monoclonal antibodies and soluble CD4.

We compared four preparations of recombinant HIV-1 envelope glycoprotein: mammalian (Chinese hamster ovary cells) gp120 (Celltech); baculovirus gp120 from American Biotechnologies Inc. (ABT) and from MicroGeneSys (MGS); and baculovirus gp160 (Institute of Virology, Oxford, UK). Each envelope glycoprotein binds to a neutralizing monoclonal antibody (MAb) directed against the V3 loop, confirming the integrity of this type-specific neutralization epitope. MGS gp120 binds abnormally well to a MAb which recognizes an epitope preferentially exposed on denatured gp120. Consistent with this finding, MGS gp120 binds to soluble CD4 (sCD4) with an affinity 50-100-fold lower than that of Celltech gp120. The affinity of Celltech gp120 from sCD4 is 2.3 nM, indistinguishable from that of gp120 extracted from HIV-1 virions. Baculovirus gp120 (ABT) and gp160 also have a high affinity for sCD4. A significant proportion of anti-gp120 antibodies in HIV-positive human sera recognize epitopes that are dependent on the mammalian glycosylation pattern, and a human HIV-positive serum inhibits the binding of mammalian gp120 to sCD4 five- to 10-fold more potently than it inhibits baculovirus gp120 binding to sCD4.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The pH independence of mammalian retrovirus infection.

The pH dependence of early steps in the infection of human and other cells by mammalian retroviruses and retroviral pseudotype particles of vesicular stomatitis virus (VSV) was investigated for 10 strains of retrovirus, including C-type and D-type oncoviruses and human lentiviruses. When cells were treated with weak bases (NH4Cl and amantadine) to raise the pH of endocytic vesicles, only ecotropic murine leukaemia virus (MLV-E) and VSV showed pH-dependent entry. Pretreatment of retrovirus stocks in media below pH 5.0 did not reduce their titres but inactivated VSV to less than 10(-8) of the initial titre. VSV (MLV-E) pseudotype infection in five out of six mouse and rat cell lines was inhibited by NH4Cl, indicating that infection proceeds via receptor-mediated endocytosis. In contrast, NH4Cl treatment has no effect on the infection of XC cells in which MLV-E induces syncytia. It is postulated that the pH-independent entry and cell fusion of XC cells by MLV-E may result from the activity of a cell surface proteinase that cleaves viral gp70 at neutral pH.

Amantadine↗
PubMed1990

Resolution of pain associated with varicose and telangiectatic leg veins after compression sclerotherapy.

Many patients presenting for treatment of superficial varicosities and telangiectasias on the legs are seeking relief of pain or discomfort in addition to cosmetic improvement. Of 215 sclerotherapy patients, 114 (53%) complained of various painful symptoms involving areas of telangiectasias (vessels 0.1-1 mm in diameter) and varicosities (vessels greater than 1 mm in diameter). In order to determine whether sclerotherapy is effective in reducing leg pain and discomfort, hundreds of patients receiving two or more treatment sessions of compression sclerotherapy with hypertonic saline were surveyed for the pretreatment and post-treatment presence of numerous symptoms associated with telangiectasias and varicosities of the leg. For all symptoms combined, the overall reported relief of pain was 85% (p less than 0.001). Side effects from the treatment were minimal. These results indicate that sclerotherapy for telangiectasias and varicosities is not only a cosmetic procedure but a safe and valuable medical therapeutic modality, highly effective in relieving leg pain and discomfort.

Adolescent↗
PubMed1990

Incidence of side effects in the treatment of telangiectasias by compression sclerotherapy: hypertonic saline vs. polidocanol.

Two of the most common side effects of sclerotherapy of leg veins are telangiectatic matting (TM), and postsclerosis hyperpigmentation. A random sample of 113 female patients with similar treatment sites of telangiectasias (less than 1 mm in diameter) and venulectasias of 1-2 mm diameter on the legs were treated by sclerotherapy and assessed at 1 and 6 months later for the presence of TM and hyperpigmentation. Patients received treatment with either 23.4% hypertonic saline (HS) alone (N = 74), 1% polidocanol (POL) alone (N = 21), or a comparison treatment with both HS and 1% POL (N = 18). A subgroup of patients received both 1% POL and 0.5% POL (N = 10). The incidence of hyperpigmentation was related both to vessel size and to sclerosing solution; only one patient showed hyperpigmentation in a vessel less than 1 mm, while in 1-2 mm vessels the incidence was 10.9% for HS and 30.7% for 1% POL (p less than .004) at 1 month. At 6 months postsclerotherapy, the incidence of pigmentation was 2% for HS and 7.5% for 1% POL. Both the type and concentration of sclerosing solution affected the incidence of TM; the incidence of TM was 33% for 1% POL, compared to only 13% for HS (p less than .004). At 6 months follow-up, the incidence of TM decreased to 2% for HS and 9% for 1% POL. Ten patients who developed TM with 1% POL were treated subsequently with 0.5% POL and demonstrated no matting. These data indicate that the incidence of side effects was affected by both the concentration and type of sclerosant.

Female↗
PubMed1990

Biological and molecular variability of human immunodeficiency virus type 2 isolates from The Gambia.

Seven new human immunodeficiency virus type 2 (HIV-2) isolates (CBL-20 to CBL-26) from The Gambia were characterized. Their cytopathogenicity and growth in vitro correlated with the severity of clinical disease. CBL-22 was highly sensitive to neutralization by HIV-2 sera and was cross-neutralized by some HIV-1 sera. These findings, the differing sizes of envelope glycoproteins of individual isolates, and the sequence analysis of amplified regions of the viral DNAs show that these HIV-2 isolates from one geographical region in West Africa exhibit biological and genome variability comparable to that observed for HIV-1.

Adult↗
PubMed1990

Localization of the receptor gene for type D simian retroviruses on human chromosome 19.

Simian retrovirus (SRV) serotypes 1 to 5 are exogenous type D viruses causing immune suppression in macaque monkeys. These viruses exhibit receptor interference with each other, with two endogenous type D viruses of the langur (PO-1-Lu) and squirrel monkey, and with two type C retroviruses, feline endogenous virus (RD114/CCC) and baboon endogenous virus (BaEV), indicating that each utilizes the same cell surface receptor (M. A. Sommerfelt and R. A. Weiss, Virology 176:58-69, 1990). Vesicular stomatitis virus pseudotype particles bearing envelope glycoproteins of RD114, BaEV, and the seven SRV strains were employed to detect receptors expressed in human-rodent somatic cell hybrids segregating human chromosomes. The only human chromosome common to all the susceptible hybrids was chromosome 19. By using hybrids retaining different fragments of chromosome 19, a provisional subchromosomal localization of the receptor gene was made to 19q13.1-13.2. Antibodies previously reported to be specific to a BaEV receptor (L. Thiry, J. Cogniaux-Leclerc, R. Olislager, S. Sprecher-Goldberger, and P. Burkens, J. Virol. 48:697-708, 1983) did not block BaEV, RD114, or SRV pseudotypes or syncytia. Antibodies to known surface markers determined by genes mapped to chromosome 19 did not block virus-receptor interaction. The identity of the receptor remains to be determined.

Animals↗
PubMed1990

Activation of rat pulmonary lavage cells by intratracheal administration of polyinosinic-polycytidilic acid.

Systemic administration of biologic response modifiers (BRMs) is often limited by serious adverse effects. Local delivery of a BRM may provide a means to avoid systemic side effects while enhancing host defense. To test this hypothesis, the effects of intratracheal administration of the interferon inducer polyinosinic-polycytidilic acid (Poly-I:C) were examined. We demonstrated that intratracheal administration of Poly-I:C in rats results in alterations in pulmonary lavage cell number, population distribution, and function, suggestive of cellular activation. Following intratracheal instillation of 15, 75, or 150 mg of Poly-I:C, we observed a dose-dependent increase in Fc receptor-mediated phagocytosis, a dose-independent tumoricidal activity directed against xenogeneic P815 murine mastocytoma target cells, and a dose-independent decrease in superoxide anion (O2-) generation. With the exception of O2- generation, these functions returned to normal control levels by 7 days after a single dose of Poly-I:C. Thus, localized administration of Poly-I:C enhanced the host defense capability of pulmonary lavage cells, providing a rationale for compartmentalized immunoprophylaxis in the lung.

Analysis of Variance↗
PubMed1990

Ophthalmic neoplasms in infancy and childhood.

The most common ocular and orbital tumors presenting in infancy, childhood and adolescence are presented and discussed in this review. It has been prepared specifically for the clinical pediatrician and focuses on the clinical recognition of ophthalmic neoplasms, their diagnostic evaluation employing the use of advanced imaging techniques, biopsy when indicated and extent of disease workup. In addition, current treatment modalities are discussed. Ocular tumors addressed include: retinoblastoma, capillary hemangioma, lymphangioma, dermoid and epidermoid cysts, teratoma, glioma, astrocytic hamartoma, neurofibroma, rhabdomyosarcoma and fibrous tumors. Two aggressive and potentially fatal tumors, rhabdomyosarcoma and retinoblastoma, are presented in detail. In addition, the ocular tumors associated with the phakomatoses (von Hippel-Lindau, tuberous sclerosis and neurofibromatosis) are reviewed.

Adolescent↗
PubMed1990

Reconstruction of the anophthalmic socket: lower eyelid malposition and canthal tendon laxity.

There are a number of etiologies underlying the development of socket deformity with associated lower eyelid malposition, lateral canthal tendon laxity, and/or contraction of the inferior fornix. In addition to cosmetic considerations, each of these anatomic problems can interfere with comfortable wear and retention of a prosthesis. This chapter gives an overview of these problems and details our preferred surgical approaches to repair of these anatomic deformities. Specifically discussed are techniques for: mucous membrane and ear cartilage grafting to repair lower lid inner lamellar tissue shortage, reconstruction of the inferior fornix/cul-de-sac, direct lower eyelid lateral canthal resuspension, and resuspension using a periosteal flap or autogenous fascia lata from the iliotibial tract.

Ear Cartilage↗