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Biomedical subjects

J Ayub

Publications and source records attributed to J Ayub.

9 recordsLinked to original sources
PubMed1994

Subunit interaction in B19 parvovirus empty capsids.

B19 parvovirus is a small single-stranded DNA virus with a genome that encodes only two structural proteins, designated VP1 and VP2. 60 copies of the structural proteins assemble into the viral capsid, with approximately 95% VP2 and 5% VP1. Recombinant empty capsids composed of VP2 alone or of VP2 and VP1 self-assemble into particles that are morphologically indistinguishable from full virions. Empty capsids containing both VP2 and VP1 elicit a strong neutralizing antibody response when used to immunize rabbits. Capsids containing only VP2 are similarly antigenic but elicit only weak neutralizing activity. We performed fine structure epitope mapping by measuring the reactivity of antisera raised against capsids composed of VP2 and VP1 or VP2 alone against 85 overlapping peptides spanning the sequence of the two structural proteins. A profile of the antigenic difference between empty capsids with and without VP1 was produced from the resulting data. This profile divided the sequence of the structural proteins into four regions that correlated well with expected viral structures. Thus, the addition of a small number of VP1 residues altered the antigenicity of the entire capsid. The major area of enhanced antigenicity is homologous to the spike of canine parvovirus, an area known to contain both neutralizing and host-range determinants. Our data are consistent with a model in which the unique region of VP1 is necessary for the virus to assume its mature capsid conformation.

Amino Acid Sequence↗
PubMed1992

Survival after first recurrence of breast cancer. The Miami experience.

BACKGROUND: Four hundred thirty-three patients with recurrent breast cancer were treated by the authors at a large medical breast oncology facility from 1976-1982. The median survival time from first relapse (MSFR) for the 193 patients whose survival experience was not confounded by lead-time bias was 26 months. This MSFR is similar to that of most series published in the 1970s and 1980s and is approximately double that of series published in the 1960s. METHODS: In this series, regression analysis identified disease-free interval (DFI), estrogen receptor (ER) status, and dominant disease site as significant prognostic variables, similar to other published series. RESULTS: In 113 patients with known ER values, DFI, and dominant metastatic sites, a prognostic spectrum of MSFR patterns was identified among combinations of these three variables. The MSFR ranged from 15 months for poor risk patients with negative ER values, visceral dominant sites, and DFI of less than 24 months, to more than 90 months for good risk patients with positive ER values, soft tissue dominant sites, and DFI of more than 24 months. Although menopausal status alone was not a significant prognostic variable in regression analysis, 66% of premenopausal patients had a constellation of "poor" prognostic variables. CONCLUSIONS: This type of prognostic factor analysis at first relapse could help identify subsets of patients who might be considered for aggressive investigational therapies such as high-dose chemotherapy with autologous bone marrow reconstitution.

Breast Neoplasms↗
PubMed1992

Nosocomial human parvovirus B19 infection: lack of transmission from a chronically infected patient to hospital staff.

OBJECTIVE: To assess the potential for nosocomial spread of parvovirus B19 from a chronically infected patient. DESIGN: Employees exposed to the index case and control (unexposed) employees were evaluated by baseline and follow up parvovirus B19 serologies and hematologic assessments, and completed baseline and follow up epidemiologic questionnaires. SETTING: A chronically infected patient was hospitalized on a hematology ward in a research referral hospital for 3.5 weeks prior to a diagnosis of parvovirus B19 infection and the institution of isolation precautions. METHODS: Sera were screened for parvovirus B19 DNA (dot blot analysis), and IgG and IgM anti-B19 antibodies (capture immunoassay). Hematologic assessment included CBC, differential, and reticulocyte count. RESULTS: The index case had parvovirus B19 DNA at approximately 10(6) genome copies per ml of serum, elevated IgM and low levels of IgG B19 antibodies. Of the 21 exposed staff, 11 (52%) had IgG B19 antibodies and were immune; of the 8 unexposed staff, 6 (75%) had IgG B19 antibodies. No employees developed IgM B19 antibodies, B19 DNA, hematologic abnormalities, or clinical symptoms. CONCLUSIONS: In contrast to reports of documented nosocomial transmission of B19 parvovirus from patients in transient aplastic crisis, nosocomial transmission did not occur--even in the absence of isolation precautions--presumably from the lower level of B19 viremia in our chronically infected (rather than acutely infected) patient.

Antibodies, Viral↗
PubMed1988

Translational regulation of B19 parvovirus capsid protein production by multiple upstream AUG triplets.

The B19 parvovirus produces two capsid proteins in strikingly different quantities (VP1 less than 4%, VP2 greater than 96%) from overlapping RNAs that are derived from the same transcription unit. Immediately upstream from the VP1 translation initiation site is an unusual sequence containing multiple ATG triplets. During RNA processing this sequence is spliced out of VP2 RNA. To test the regulatory role on translation of this sequence containing upstream AUGs, synthetic RNAs were produced in vitro by T7 RNA polymerase from various plasmid constructions. Translation of VP1 RNA was very inefficient compared to VP2 RNA in a cell-free system, indicating that capsid protein production was regulated at the level of translation. Removal of upstream AUG sequences from VP1 RNA greatly increased the efficiency of translation. Conversely, the addition of the same AUG-rich sequence upstream of the initiation site of VP2 decreased its translation. These data indicate that an upstream AUG-rich region acts as a negative regulatory element in the translational control of B19 capsid protein production.

Capsid↗
PubMed1988

Functional mapping of the genome of the B19 (human) parvovirus by in vitro translation after negative hybrid selection.

We have analyzed the coding capacity of B19 parvovirus transcripts by in vitro translation using the negative hybrid selection technique. Five different antisense oligonucleotides (18-mers) corresponding to different portions of the B19 genome were hybridized to RNA samples extracted from human erythroid bone marrow cells infected with B19 parvovirus in vitro, and RNase H was added to cleave specific B19 RNA molecules at selected sites. B19-specific translation products of these RNA samples were determined by immunoprecipitation. We localized the B19 nonstructural protein to the left-side transcript and the two capsid proteins to overlapping transcripts from the right side of the genome.

Erythroblasts↗
PubMed1988

The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells.

The B19 parvovirus is a cause of bone marrow failure in humans. B19 is toxic to erythroid progenitor cells in vitro. Viral products possibly responsible for toxicity were explored by transfection of cloned B19 genome into HeLa cells. The nonstructural (NS) protein was detected in cells 30 h after transfection. Plasmids containing the B19 genome were transfected with selectable marker genes in stable transformation assays. Plasmids that contained the left side of the B19 genome, which encodes the NS protein of the virus, inhibited antibiotic-resistant colony formation. Transformation occurred when NS protein expression was blocked by mutation. Suppression of transformation by NS protein was not tissue specific, suggesting a role for NS protein in toxicity for nonpermissive cells without parvovirus replication or virion accumulation.

Capsid↗
PubMed1987

Novel transcription map for the B19 (human) pathogenic parvovirus.

The B19 parvovirus, a small single-stranded DNA virus of 5.4 kilobases, is pathogenic in humans. B19 has remarkable specificity for erythroid progenitor cells and has been propagated in vitro only with human erythroid bone marrow. Replication of viral DNA and the viral protein products of B19 appear similar to those of other animal parvoviruses. However, B19 transcription had unusual features in comparison with that in other animal parvoviruses. At least nine overlapping poly(A)+ transcripts were identified in infected cells; all but one contained large introns. B19 differed from other parvoviruses in the initiation of all transcripts at a strong left side promoter (p6) and the absence of a functional internal promoter; the presence of short 5' leader sequences of about 60 bases and very large introns for RNAs encoded by the right side of the genome; two separate transcription termination sites, in contrast to cotermination at the far right side of the genome for other parvoviruses; the probable utilization by three transcripts of a variant polyadenylation signal (ATTAAA or AATAAC) in the middle of the genome; and the abundance of two unique transcripts from the middle of the genome which did not code for capsid proteins. The unusual transcription map of B19 suggests that regulation of the relative abundance of transcripts occurs by splicing and termination-polyadenylation events rather than by promoter strength. In combination with the published nucleotide sequence, the novel transcription map separated the pathogenic B19 virus at a molecular level from other animal parvoviruses and human adeno-associated virus.

Bone Marrow↗
PubMed1985

Danazol therapy for autoimmune hemolytic anemia.

We evaluated the use of danazol in 15 patients with autoimmune hemolytic anemia of the warm antibody type. Danazol, 600 to 800 mg/d, was added to previous regimens or given initially in conjunction with high-dose prednisone treatment. Twelve patients with autoimmune hemolytic anemia associated with nonmalignant disorders or idiopathic autoimmune hemolytic anemia and 1 of 3 patients with underlying neoplasms showed a rise in hematocrit within 1 to 3 weeks. Thereafter, glucocorticoid doses were tapered to a minimum requirement or stopped. Once remission was sustained, the dose of danazol was reduced to 200 to 400 mg/d. Although levels of erythrocyte-bound IgG antibody and C3 decreased with therapy, only the decrease in C3 was statistically significant (p less than 0.05) in this limited study. Danazol was effective regardless of the severity of the disorder and success or failure of previous treatments. Danazol is valuable in the treatment of autoimmune hemolytic anemia and may be better suited than glucocorticoids for long-term management.

Adolescent↗