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Biomedical subjects

R A Weiss

Publications and source records attributed to R A Weiss.

At least 19 recordsLinked to original sources
PubMed1992

Retroviral pseudotypes produced by rescue of a Moloney murine leukemia virus vector by C-type, but not D-type, retroviruses.

Human HOS cells containing a Moloney murine leukemia virus (Mo-MLV) recombinant genome were infected by a panel of retroviruses. The C-type viruses simian sarcoma associated virus, feline leukemia virus subgroup B, and the feline endogenous virus RD114 were able to form pseudotypes with the Mo-MLV genome, which transferred a selectable marker gene to target cells; however, Human T cell leukemia virus-1 and the D-type viruses Mason-Pfizer monkey virus and simian retrovirus-1 failed to rescue the Mo-MLV vector. Further characterization of the RD114 pseudotype demonstrated that it retained the receptor specificity of RD114 and will therefore prove useful in receptor characterization.

Animals↗
PubMed1992

CPF-DD is an inhibitor of infection by human immunodeficiency virus and other enveloped viruses in vitro.

The initial step in the infection cycle of human immunodeficiency virus type 1 (HIV-1) involves binding of its surface glycoprotein gp 120 to the T lymphocyte CD4 antigen. CPF-DD is a low molecular weight inhibitor of HIV infectivity that inhibits gp 120 binding to CD4 in vitro (Finberg et al., Science 249, 287-291, 1990). We find, however, that the actions of CPF-DD are not limited to its ability to interfere with gp 120-CD4 binding; its predominant action is to remove the viral envelope from the underlying core. Subsequently the virions disintegrate. Most enveloped viruses tested were inhibited by CPF-DD, but the infectivity of noneneloped viruses was unaffected or only slightly reduced.

Animals↗
PubMed1992

Amino acid residues of the human immunodeficiency virus type I gp120 critical for the binding of rat and human neutralizing antibodies that block the gp120-sCD4 interaction.

We have characterized the discontinuous epitopes recognized by two rat and three human neutralizing monoclonal antibodies (mAb) by examining the effect of single amino acid changes in conserved residues of gp120 on mAb recognition. A human mAb derived from an infected individual, 448D, and two rat mAbs, 39.13g and 39.3b, respectively, derived by immunization with native recombinant gp120, recognize similar epitopes. Recognition of the envelope glycoproteins by these mAbs was affected by changes in gp120 amino acid residues 88, 113, 117, 257, 368, or 370. The gp120 amino acids 257, 368, and 370 have previously been reported to be important for CD4 binding, which is consistent with the ability of these mAbs to block the gp120-CD4 interaction. Residues 88, 113, and 117 are not thought to be important for CD4 binding, suggesting that the antibody epitopes overlap, but are distinct from, the CD4 binding region. We also found that some alterations in gp120 residues 88, 117, 368, or 421 reduced the ability of polyclonal sera from HIV-1-infected individuals to inhibit the interaction of the mutant gp120 glycoproteins with soluble CD4. Thus, changes in the HIV-1 gp120 glycoprotein that minimally affect the receptor binding may allow escape from neutralizing antibodies directed against the CD4 binding region.

Amino Acids↗
PubMed1992

Variations in practice among urologists and nephrologists treating children with vesicoureteral reflux.

To analyze the current management recommendations among physicians treating children with vesicoureteral reflux, the American Urological Association Reflux Practice Guidelines Panel surveyed 100 pediatric urologists, 100 general urologists and 100 pediatric nephrologists by questionnaire, and received a 60% response. In the evaluation of a 4-year-old girl with bilateral grade 2 reflux general urologists were more likely than the other 2 groups to recommend cystoscopy and urethral dilation. At followup nuclear cystography was recommended by 76% of pediatric urologists, 48% of general urologists and 71% of pediatric nephrologists, while the latter 2 groups were less likely to recommend any subsequent upper tract evaluation. Pediatric urologists were significantly more likely to recommend antireflux surgery if the child had 1 breakthrough febrile urinary tract infection, poor compliance with medical management or persistent reflux at age 11 years. In a 6-year-old girl with unilateral grade 4 reflux and detrusor instability 44% of pediatric urologists recommended antimicrobial prophylaxis and anticholinergic therapy compared to 12% of general urologists and 6% of pediatric nephrologists. Antireflux surgery was recommended by 29% of pediatric urologists, 60% of general urologists and 59% of pediatric nephrologists. In older girls with persistent grade 2 or 3 reflux pediatric urologists were much more likely to recommend antireflux surgery. In contrast, they were less likely to recommend surgery in young girls and boys with newly diagnosed grade 4 reflux. These data demonstrate significant differences in therapeutic recommendations among pediatric urologists, general urologists and pediatric nephrologists, and suggest the need for outcomes research to determine the optimal management of children with vesicoureteral reflux.

Child↗
PubMed1992

Respirator performance rating table for mask design.

The ultimate goal for respirator mask designers is computer-aided design. Mask design, however, is a very complex operation, with many different interrelationships. Current knowledge does not allow significant incorporation of physiological information into mask design. Rather, physiological information is usually gathered during mask evaluation, after the design process has been completed. The Performance Rating Table (PRT) is a beginning step to formulating physiological knowledge in a way that can be useful for design. The PRT organizes physiological knowledge to assign performance data to various mask and level of work causes. Best estimates of tabled values were obtained from the literature.

Body Temperature Regulation↗
PubMed1992

Respirator performance rating tables for nontemperate environments.

Respirator performance rating tables have been constructed for hot, humid (29 degrees C, 95% RH); hot, dry (49 degrees C, 30% RH); and cold, dry (-32 degrees C, 70% RH) conditions. These tables convey expected wearer performance percentages compared to unmasked workers for various mask elements and work rates. The hot, humid condition was found to be the most severe overall. Many table entries approach 100%, thus leading to difficulties in correcting mask deficiencies.

Equipment Design↗
PubMed1992

Conserved structural features in the interaction between retroviral surface and transmembrane glycoproteins?

Among the retroviruses, the surface (SU) and transmembrane (TM) glycoproteins of lentiviruses are linked exclusively by noncovalent bonds. For some C-type retroviruses, however, a small proportion of the SU proteins has been shown to be linked to their TM proteins by a disulfide bond, with the remainder being noncovalently associated. A region near the carboxyl terminus of the HIV-1 SU glycoprotein has been implicated in contacting the TM glycoprotein. Computer modelling indicates that this region of divergent lentivirus and oncovirus SU glycoproteins forms a structurally conserved "pocket" which could accommodate a "knob"-like protrusion formed by an immunodominant region in the TM protein containing the CxxxxxC (lentiviruses) or CxxxxxxCC (C- and D-type viruses) motif. An anti-idiotypic monoclonal antibody, raised against a monoclonal antibody reacting with a sequence in the "pocket" of HIV-1 gp120, was found to bind to synthetic peptides close to the CxxxxxC motif. It is suggested that part of the SU-TM linkage mechanism for the lentiviruses and oncoviruses is a 'knob and socket' structure and that the interaction between SU and TM proteins is similar in one region for lentiviruses and C-type as well as D-type viruses. The conserved knob and socket linkage may be relevant to a mechanism for viral-cell membrane fusion that is broadly common to all of these retroviruses.

Amino Acid Sequence↗
PubMed1992

Investigations into the mechanism by which sulfated polysaccharides inhibit HIV infection in vitro.

Sulfated polysaccharides have been shown to inhibit human immunodeficiency virus (HIV) infection in vitro. Dextrin sulfate, fucoidan, and dextran sulfate fail to neutralize virions directly, but interact with target cells to inhibit virus entry. Ionic interactions of sulfated polyanions with oppositely charged cell surface components, including CD4, have been assumed to be the inhibitory mechanism. It is shown that the sulfated polysaccharides inhibit infection of both CD4+ and CD4- cell lines by HIV and also that they inhibit HTLV-1 and, to a lesser extent, the simian retrovirus, MPMV, which use receptors other than CD4. One binding site for radiolabeled fucoidan on the surface of human T cells is an 18 kD protein, but its significance is not yet clear.

Antiviral Agents↗
PubMed1992

Monoclonal antibodies to the C4 region of human immunodeficiency virus type 1 gp120: use in topological analysis of a CD4 binding site.

We have raised antisera and monoclonal antibodies (MAbs) to the C4 region of HIV-1 gp120, using an antigen chimaera of poliovirus as immunogen. These MAbs and sera, together with MAbs to the same region raised by other methods, fall into three groups defined by their abilities to bind to recombinant gp120 and/or the immunogenic peptide. In some cases, the amino acids recognized by the MAbs have been identified by pep-scan and by solution phase peptide inhibition of binding to recombinant gp120. Our results indicate that the amino acids WQEVGKAMYA are exposed on the surface of recombinant gp120. Antibodies to these amino acids on recombinant gp120 compete for soluble CD4 binding in vitro, but only weakly neutralize HIV.

Amino Acid Sequence↗
PubMed1992

Development of HIV-1 group-specific neutralizing antibodies after seroconversion.

OBJECTIVE: To study the induction of group-specific (gs) neutralizing antibodies to HIV-1 after seroconversion. DESIGN AND METHODS: Serum samples taken sequentially from seven Dutch homosexual men and four British haemophiliacs (anonymous sample, therefore sex not known) before and after seroconversion were tested for neutralizing antibodies effective against five diverse HIV-1 strains. Strains of HIV-1 tested included isolates from the United States, Europe and Africa. RESULTS: The gs neutralizing antibody response varied between individuals. Only five of the 11 individuals studied produced detectable neutralizing antibodies to laboratory-adapted HIV-1 strains (for example, IIIB) within 32 weeks of seroconversion. Most individuals initially produced antibodies effective against US/European isolates; the response then generally broadened to include the more diverse strains, i.e., African. CONCLUSIONS: These results suggest that the gs neutralizing target for HIV-1 is poorly immunogenic in vivo and is probably not highly conserved among diverse HIV-1 strains.

HIV Antibodies↗
PubMed1992

Physicians' negative perception of sclerotherapy for venous disorders: review of a 7-year experience with modern sclerotherapy.

Sclerotherapy is the injection of a sclerosing substance directly into a varicosity or telangiectasia to cause damage, fibrosis, and eventual obliteration of the vessel. Although sclerotherapy has been shown to be effective with a low incidence of side effects, many physicians in the United States are unaware of the technique or view it in a negative way. To better define the extent of physician unfamiliarity or prejudice toward sclerotherapy, we surveyed a local medical community of gynecologists by anonymous written questionnaire. The results indicated that 82% of the responding physicians believed that their knowledge of sclerotherapy was insufficient to advise their patients, leaving patients to learn about sclerotherapy from mass media sources. Sclerotherapy was perceived as only slightly effective therapy for varicose veins and was thought to have a relatively high incidence of side effects. With recent improvements in the technique, our collaborative experience with 3000 patients receiving 50,000 injections over the past 5 years has shown that sclerotherapy is a safe procedure achieving outstanding cosmetic results with concomitant symptomatic relief of painful varicosities and telangiectases. Sclerotherapy, as practiced today, offers an effective, simple, and less costly alternative to surgical stripping for most varicose and telangiectatic veins. The survey data demonstrate the need to educate the American medical community about the technique and merits of modern sclerotherapy so that patients may be properly guided by their physicians to the best sources of care for their aching and unsightly leg veins.

Adolescent↗
PubMed1992

A measles virus isolate from a child with Kawasaki disease: sequence comparison with contemporaneous isolates from 'classical' cases.

We examined the relationship between a measles virus isolate from a child with Kawasaki disease and two contemporaneous wild-type isolates from children with 'classical' measles and the Schwarz vaccine strain. Sequence analysis of 3118 bp from the nucleoprotein, matrix, fusion and haemagglutinin genes of each virus revealed that the isolate from the child with Kawasaki disease was not related to measles vaccine strains and did not contain any of the marked abnormalities previously found in subacute sclerosing panencephalitis isolates, but was more akin to wild-type isolates currently circulating in the U.K. A comparison of our sequences with those obtained from earlier wild-type U.K. isolates suggests significant evolution of measles virus in the U.K. over the last decade.

Amino Acid Sequence↗
PubMed1992

The Bulletin of the North American Society of Phlebology. Insurance Advisory Committee Report.

The treatment of varicose veins as taught within the specialty of phlebology consists of the best combinations of sclerotherapy and surgery after a thorough evaluation by physical examination and Doppler ultrasound, as well as other techniques. Although patients can experience some relief of symptoms by external compression hosiery, only treatment that closes up leaky valves will stop the progression of disease. Sclerotherapy is a safe, well-accepted, non-investigational, highly effective method to treat abnormally enlarged veins. Surgical procedures may be necessary to supplement sclerotherapy in certain anatomic sites. Varicose veins cause patients to experience pain, lose time from work, and can ultimately lead to permanent disability. Our healthcare system must provide the most high quality cost effective care for these patients. By keeping costs down as compared with full-scale surgical procedures, the approach of sclerotherapy or sclerotherapy with outpatient surgery, performed by properly trained physicians, provides a means to accomplish this. Medical necessity criteria allow exclusion of payments for patients seeking treatment purely for cosmetic needs.

Cardiology↗
PubMed1992

Mapping of homologous, amino-terminal neutralizing regions of human T-cell lymphotropic virus type I and II gp46 envelope glycoproteins.

Twelve synthetic peptides containing hydrophilic amino acid sequences of human T-cell lymphotropic virus type I (HTLV-I) envelope glycoprotein were coupled to tetanus toxoid and used to raise epitope-specific antisera in goats and rabbits. Low neutralizing antibody titers (1:10 to 1:20) raised in rabbits to peptides SP-2 (envelope amino acids [aa] 86 to 107), SP-3 (aa 176 to 189), and SP-4A (aa 190 to 209) as well as to combined peptide SP-3/4A (aa 176 to 209) were detected in the vesicular stomatitis virus-HTLV-I pseudotype assay. Higher-titered neutralizing antibody responses to HTLV-I (1:10 to 1:640) were detected with pseudotype and syncytium inhibition assays in four goats immunized with a combined inoculum containing peptides SP-2, SP-3, and SP-4A linked to tetanus toxoid. These neutralizing anti-HTLV-I antibodies were type specific in that they did not inhibit HTLV-II syncytium formation. Neutralizing antibodies in sera from three goats could be absorbed with peptide SP-2 (aa 86 to 107) as well as truncated peptides containing envelope aa 90 to 98, but not with equimolar amounts of peptides lacking envelope aa 90 to 98. To map critical amino acids that contributed to HTLV-I neutralization within aa 88 to 98, peptides in which each amino acid was sequentially replaced by alanine were synthesized. The resulting 11 synthetic peptides with single alanine substitutions were then used to absorb three neutralizing goat antipeptide antisera. Both asparagines at positions 93 and 95 were required for adsorption of neutralizing anti-HTLV-I antibodies from all three sera. Peptide DP-90, containing the homologous region of HTLV-II envelope glycoprotein (aa 82 to 97), elicited antipeptide neutralizing antibodies to HTLV-II in goats that were type specific. In further adsorption experiments, it was determined that amino acid differences between homologous HTLV-I and HTLV-II envelope sequences at HTLV-I aa 95 (N to Q) and 97 (G to L) determined the type specificity of these neutralizing sites. Thus, the amino-terminal regions of HTLV-I and -II gp46 contain homologous, linear, neutralizing determinants that are type specific.

Amino Acid Sequence↗
PubMed1992

Feline leukemia virus subgroup B uses the same cell surface receptor as gibbon ape leukemia virus.

Pseudotypes of gibbon ape leukemia virus/simian sarcoma-associated virus (GALV/SSAV) and feline leukemia virus subgroup B (FeLV-B) have been constructed by rescuing a Moloney murine leukemia virus vector genome with wild-type GALV/SSAV or FeLV-B. The resulting recombinant viruses utilized core and envelope proteins from the wild-type virus and conferred resistance to growth in L-histidinol upon infected cells by virtue of the HisD gene encoded by the vector genome. They displayed the host range specificity of the rescuing viruses and could be neutralized by virus-specific antisera. Receptor cross-interference was observed when the GALV/SSAV or FeLV-B pseudotypes were used to superinfect cells productively infected with either GALV/SSAV or FeLV-B. Although murine cells are resistant to FeLV-B infection, murine cells expressing the human gene for the GALV/SSAV receptor became susceptible to FeLV-B infection. Therefore GALV/SSAV and FeLV-B utilize the same cell surface receptor.

3T3 Cells↗
PubMed1992

Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4.

We describe human immunodeficiency type 2 (HIV-2) strains which induce cell-to-cell fusion and infect certain CD4- human cell lines. Soluble CD4 (sCD4) induces or enhances fusion by most HIV-2 strains tested. Soluble CD4-immunoglobulin G chimeras and conjugates of sCD4 and antibody to the third domain of CD4 block HIV-2 fusion of CD4- cells. We conclude that HIV-2 can enter CD4- cells via an alternative cell surface receptor to CD4. While some strains entered efficiently, others retained a dependency on an interaction with sCD4 to initiate changes in the virion envelope required for membrane fusion.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Retroviruses and human cancer.

Retroviruses have long been associated with cancer in many species. Human T cell leukaemia virus type I causes adult T cell leukaemia. Human immunodeficiency virus infection is associated with lymphoma and Kaposi sarcoma, but oncogenesis is largely secondary to its effect on the immune system. The incidence of Kaposi sarcoma varies greatly in different social groups with AIDS, being most frequent among male homosexuals; an unknown, sexually transmissible agent may be responsible. Human endogenous retroviral genomes are linked with myeloproliferative disease. Finally, the risk is discussed that cancer could be a side-effect of the use of retroviral vectors in human gene therapy.

Acquired Immunodeficiency Syndrome↗