Professionalism in medicine: the department chair's perspective on medical students and residents.
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Education, Medical↗
Biomedical subjects
M A Mufson
Publications and source records attributed to M A Mufson.
Phosphoprotein profile analysis of ruminant respiratory syncytial virus isolates.
OBJECTIVE: To determine the apparent molecular weight for 24 ruminant respiratory syncytial viruses (RSV) on the basis of differences in the electrophoretic mobility of the phosphoprotein (P protein). PROCEDURE: 29 bovine RSV (BRSV), 20 of which were not previously tested, 3 ovine RSV, and 1 caprine RSV isolates were selected for determination of electrophoretic mobility of the P protein. Virus radiolabeled with [35S]methionine was immunoprecipitated with polyclonal antiserum to BRSV and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: On the basis of apparent molecular size of the P protein, all isolates could be categorized into 2 electropherotypes, low molecular size of 36 kd and high molecular size of 38 kd. Twenty-three BRSV, the 3 ovine RSV, and 1 caprine RSV isolates had a high molecular size P protein; 6 BRSV isolates had a low molecular size P protein. CONCLUSIONS: The apparent molecular size of the P protein of the ruminant RSV strains is greater than that of the human RSV subgroups, providing further evidence of their distinctiveness. Whether categorization of electrophoretic mobility of the P protein of BRSV underlies distinct antigenic subgroups, as it does in human RSV, requires further antigenic and genetic analysis. CLINICAL RELEVANCE: Antigenic subgroups of ruminant RSV may have relevance in the development of new vaccines for control of the disease.
Animals↗
Identification of a variant subgroup A strain of respiratory syncytial virus.
During epidemiologic surveillance of children with respiratory syncytial virus (RSV) disease in Huntington, W.Va., we identified seven strains of a new variant subgroup A RSV (subgroup A-Var) by their reactions in an enzyme immunoassay with two anti-F monoclonal antibodies (MAbs) specific for two epitopes, F1 and F4, generated against the subgroup B RSV. The prototype strain of subgroup A and all other subgroup A field strains from that epidemiologic year failed to react with these two subgroup B MAbs. Additional enzyme immunoassays with 18 subgroup B anti-F MAbs specific for 14 epitopes showed that subgroup A-Var strains also reacted with a MAb specific for the subgroup B F2 epitope. In a radioimmune precipitation assay, the molecular size of the subgroup A-Var F2 subunit of the fusion (F) protein clearly differed from those of both prototype strains of subgroup A and subgroup B RSV. The molecular size of the F2 subunit of subgroup A-Var (24 kDa) was intermediate between the size of the F2 subunit of subgroup A (25 kDa) and that of subgroup B (23 kDa). However, the molecular sizes of the F1 subunits of both subgroup A and subgroup A-Var were identical (54 kDa) and slightly larger than those of the F1 subunits of both subgroups B1 and B2 (53 kDa). These data suggest that subgroup A-Var may represent a distinct RSV A subgroup, analogous to subgroup B1 and B2 RSV, and it is the first-identified naturally occurring subgroup A RSV with an F protein different from that of the prototype A RSV.
Antibodies, Monoclonal↗
Evaluation of subgroup-specific peptides of the G protein of respiratory syncytial virus for characterization of the immune response.
Two synthetic peptides, designated peptides 12G(A) and 12G(B), representing amino acids 174-188 of the G glycoprotein of respiratory syncytial virus (RSV) subgroup A (strain A2) and subgroup B (strain CH18537) were evaluated for their properties as subgroup-specific antigens for enzyme immunoassay (ELISA). These peptides were used to characterize the immune response of children with naturally occurring RSV infection during six annual epidemics in the Huntington area, West Virginia, USA; viz. 1978-1979, 1979-1980, 1980-1981, 1983-1984, 1989-1990, and 1990-1991. The study group comprised 43 paired sera from 42 infants and children, who ranged in age between 1 month and 5.5 years of age (median age 16 months). The inclusion criteria were subgroup identification of RSV, respiratory tract illness requiring admission to hospital, and the availability of paired sera. Five of 30 children with subgroup A and 3 of 13 children with subgroup B infections developed homologous or dual fourfold or greater antibody responses to peptides 12G(A) and 12G(B) during convalescence; six of these eight children also developed antibody rises to whole virus antigens. Twenty children (14 subgroup A and 6 subgroup B) developed such responses in antibody only to whole virus (not to the peptides), and 15 children (11 subgroup A and 4 subgroup B) failed to develop a rise in antibody. Children who developed rises in antibody to the peptides were usually less than 9 months of age, suggesting that a response to peptides was more likely to occur during primary infection. Peptides 12G(A) and 12G(B) of RSV G protein lacked sufficient sensitivity and specificity to serve as antigens for ELISA for characterizing the subgroup-specific immune responses to RSV infection in infants and children.
Aging↗
Production and characterization of monoclonal antibodies to bovine respiratory syncytial virus.
Monoclonal antibodies to the SmithKline Beecham Animal Health BRSVR vaccine strain (375 isolate of Bovine Respiratory Syncytial Virus) were produced and then characterized by radioimmunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, virus neutralization, inhibition of viral-induced fusion and isotype. Nineteen hybridomas produced antibodies that were reactive with the F0, F1, N or P viral proteins of bovine respiratory syncytial virus. One hybridoma (1E72C4) produced antibodies that immunoprecipitated the F0 glycoprotein, neutralized virus (1:8) in the presence of complement, but did not inhibit fusion. Another hybridoma (8B21E7) produced antibodies that immunoprecipitated the F0, F1 and F2 glycoproteins, neutralized virus (1:4) with and without complement and inhibited fusion. Antibodies from 11 hybridomas immunoprecipitated N and F1 proteins, one hybridoma immunoprecipitated the N and P protein, and 5 hybridomas immunoprecipitated the N protein. All monoclonal antibodies were of the IgG2b subtype with either kappa or lambda light chains.
Animals↗
Emergence of penicillin-resistant invasive pneumococci in a single American community.
Three decades ago, penicillin-resistant strains of Streptococcus pneumoniae were first reported. Since then, myriad penicillin resistant strains of S. pneumoniae have been identified worldwide and in the United States. No resistant or intermediate resistant strains have been reported in West Virginia because testing has not been done. Between 1983 and 1994, the authors' surveillance of invasive pneumococcal disease in metropolitan Huntington, West Virginia, identified 356 pneumococcal strains from blood and other usually sterile sites, including 110 strains belonging to serotypes 6, 9, 14, 19, and 23, the main serotypes exhibiting penicillin resistance. The authors tested these serotypes for penicillin susceptibility by the E-test. Sixteen (14.5%) strains of types 6, 9, 14, 19, and 23 exhibited intermediate resistance to penicillin. No highly resistant strains were identified. Most of the intermediate resistant strains of types 9, 14, and 23 were detected in epidemiologic years 1992-1994. The increasing number of intermediate resistant penicillin strains signals the need for routine testing of invasive pneumococcal strains for penicillin susceptibility and necessitates appropriate antibiotic usage.
Adult↗
Pneumococcal vaccine after 15 years of use. Another view.
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Age Factors↗
Antibody responses of children to the C-terminal peptide of the SH protein of respiratory syncytial virus and the immunological characterization of this protein.
The SH protein of RSV, a small integrated hydrophobic membrane protein, consists of 64 amino acid residues in the polypeptide of subgroup A and 65 amino acid residues in the polypeptide of subgroup B. We synthesized five peptides, representing the SH protein of each RSV subgroup comprised of the following amino acid residues: 2-16, 12-26, 35-49, 45-60, and for subgroup A, 51-64 and for subgroup B, 51-65. Peptides 2-16 and 51-64/65 represented the N-terminal and C-terminal ends of the protein, respectively. In RIPA, under reducing conditions with mercaptoethanol, hyperimmune guinea pig (GP) serum against C-terminal peptide of the two subgroups precipitated the homologous 7.5 kDa and 21-30 kDa SH proteins. Under nonreducing conditions, the GP antipeptide sera precipitated all three SH proteins, suggesting that the 13-15 kDa protein exists as a dimer. The subgroup A 7.5 and 13-15 kDa proteins had apparent molecular weights about 1-2 kDa higher than the corresponding subgroup B proteins. The C-terminal peptides of subgroups A and B were used to characterize the immune response of 11 children, age 1 month to 1 year, with presumed primary RSV infection. Three of 4 children with subgroup A infection and 4 of 7 children with subgroup B infection developed homologous 4-fold rises in antibody to C-terminal peptide (aa 51-64/65) during convalescence. Except for one child with subgroup A and one child with subgroup B infection, the other 5 children developed heterologous rises also.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Antibody to capsular polysaccharides of Streptococcus pneumoniae: prevalence, persistence, and response to revaccination.
The prevalence of immunity to Streptococcus pneumoniae in the adult population of the United States is unknown. In the study described herein, military recruits had anticapsular IgG antibody to only 15% of common pneumococcal serotypes, whereas working men and elderly men had IgG antibody to 33% and 34% of the common serotypes, respectively (P < .001). Among eight elderly subjects, the prevalence of IgG antibody to capsular polysaccharides increased from 30% to 78% after pneumococcal vaccination; 6 years thereafter, the rate of positive reactions had declined to 58% and IgG levels had declined substantially. With revaccination, IgG levels returned to within (+/-) 40% of the original postvaccination levels. IgM and IgG antibody appeared or began to increase in titer 6 days after vaccination; the rate and degree of response were the same after the first and second exposures. Since most individuals rapidly develop IgG antibody after colonization by S. pneumoniae and since IgG confers immunity, these data suggest that pneumonia is infrequent among healthy adults not because preexisting immunity is widespread but because--with colonization--an immune response develops rapidly, preceding specific events that might lead to infection. Our findings support recommended vaccination procedures and suggest that wider application in subsets of healthy younger adults should be considered.
Adolescent↗
Deaths in bacteremic pneumococcal pneumonia. A comparison of two populations--Huntington, WVa, and Stockholm, Sweden.
The case fatality rate in bacteremic pneumococcal pneumonia (Pnb) has been reported to be lower in Sweden than in the United States. We retrospectively compared 231 adult Pnb patients in Stockholm (STO), Sweden, with 107 patients infected with the same serotypes or groups in Huntington, WVa (HWV). The total case fatality rate was 11/231 (5 percent) in STO versus 28/107 (26 percent) in HWV (p < 0.001), being significantly lower in STO for all age groups. Patients from HWV more often had preexisting chronic diseases, while alcoholism was more prevalent in STO. The case fatality rate was similar among alcoholics in STO and HWV, while it was much higher in nonalcoholic patients with chronic diseases in HWV (22/73;30 percent) than in STO (2/88;2 percent) (p < 0.001). No bias was found that could account for more than a small part of the higher case fatality rate in HWV. Thus, underlying chronic diseases in HWV accounted for some of the increased risk of death in this patient group. However, the major part of the difference in death rates between HWV and STO remains unexplained.
Adolescent↗
Shedding of infectious virus and virus antigen during acute infection with respiratory syncytial virus.
Shedding of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) of hospitalized children with acute respiratory infection was studied using direct antigen detection by time-resolved fluoroimmunoassay, rapid identification of infectious virus in centrifugally inoculated cell cultures by immunoperoxidase staining and conventional virus culture. Sequential NPAs, in which also local RSV-specific IgA response was measured, were collected from children with proven RSV infection. The shedding pattern was similar for both infectious virus and viral antigen. The overall agreement of the three methods was good (81%) in diagnostic specimens collected on admission, but markedly reduced (46%) in follow-up specimens. Secretory IgA was abundant in specimens giving discrepant or negative results only. The proportion of patients who shed RSV was high (> or = 87%) in the first week after onset of symptoms, and decreased sharply in the second week. An opposite temporal pattern was found in the proportion of patients with detectable RSV-IgA in their secretions. Sequentially isolated strains were antigenically stable as determined by their reactivity with a large panel of monoclonal antibodies. The findings suggest that RSV shedding should be monitored by using more than one method for virus detection.
Acute Disease↗
Distinguishing between respiratory syncytial virus subgroups by protein profile analysis.
We subgrouped 75 strains of respiratory syncytial virus by a protein profile method (PPM) which relies on different mobilities of the phosphoprotein in one-dimensional polyacrylamide gel electrophoresis and does not require monoclonal antibodies. When compared with enzyme immunoassay, PPM correctly subgrouped 54 of 56 subgroup A and all 19 subgroup B strains.
Antigens, Viral↗
Identification of subgroups of bovine respiratory syncytial virus.
The occurrence of antigenic variation among nine isolates of bovine respiratory syncytial virus (BRSV) was determined by examining their reaction patterns to human respiratory syncytial virus (HRSV) subgroup A and B monoclonal antibodies (MAbs) by enzyme immunoassay and radioimmunoprecipitation with fractionation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis by using MAbs and polyclonal antisera to HRSV and BRSV. Shared epitopes were demonstrated on four of five structural proteins between BRSV and both subgroups A and B of HRSV. The nine isolates of BRSV showed different patterns of reactivity in enzyme immunoassays with panels of MAbs to HRSV subgroups A and B. Major variations in the molecular weights of the P (phosphoprotein) and F (fusion protein) proteins were demonstrated among the BRSV isolates tested. These results suggest that BRSV belongs to a different antigenic grouping than HRSV and that BRSV is composed of two distinct subgroups.
Animals↗
Characteristics and outcome variables of HIV cases at a university-based medical practice.
An increasing number of AIDS cases occur each year in West Virginia despite its small urban population. From January 1984 to March 1991 at the Marshall University based multispecialty internal medicine group (the University Physicians in Internal Medicine), 66 HIV-infected persons were treated, most of whom are native West Virginians and always resided in the state. The study group consisted of 61 men and 5 women; four-fifths of the men are homosexual/bisexual and one-seventh used intravenous illicit drugs. Four women acquired infection heterosexually and one from transfusion. Twenty-eight patients never had any opportunistic infection (OI) and 38 experienced at least one OI, usually Pneumocystis carinii Pneumonia. About two-fifths of patients had CD4 counts less than 200 cells/cmm at their initial examination. Three-fourths of patients received AZT, six ddI, and most aerosolized pentamidine. Nineteen patients have died, all of whom suffered at least one OI. The mean interval until death from HIV infection and from AIDS was about 27 and 11.5 months, respectively.
Adult↗
Revaccination with pneumococcal vaccine of elderly persons 6 years after primary vaccination.
We vaccinated 15 persons, age 56 to 79 years, with 14-valent pneumococcal polysaccharide vaccine and revaccinated them with 23-valent vaccine 6 years later to assess adverse reactions and booster responses of anticapsular antibodies. No systemic reactions occurred after administration of either vaccine. After booster vaccination, five vaccinees developed only mild soreness or tenderness at the site of injection. The (arithmetic) mean antibody level to 12 capsular types measured by radioimmunoassay increased 3.1-fold 1 month after the first vaccine; the range was 1427-5124 ng antibody nitrogen per ml (N ml-1). Six years later, mean antibody levels waned to about half these levels. One month after administration of the second dose of vaccine, the mean antibody level increased 1.5-fold; the range was 1011-3954 ng antibody N ml-1. Revaccination with pneumococcal vaccine of elderly persons can be carried out safely; the levels of anticapsular antibody achieved after revaccination are about half the levels after primary vaccination.
Aged↗
A single-season epidemic with respiratory syncytial virus subgroup B2 during 10 epidemic years, 1978 to 1988.
Respiratory syncytial virus strains isolated from infants and children hospitalized with acute respiratory tract disease in Huntington, W. Va., from July 1979 through June 1988 were categorized by subgroup by using two panels of monoclonal antibodies specific for subgroup A and subgroup B. Of 405 strains tested, 319 (78.8%) were subgroup A, 73 (18.0%) were subgroup B1, and 13 (3.2%) were subgroup B2. The subgroup B2 strains occurred as a single-season epidemic during the epidemiologic year July 1980 to June 1981, except for one strain isolated in the epidemiologic year 1978 to 1979. Subgroup B strains were associated with significantly fewer bronchiolitis illnesses than subgroup A strains. The severity of illnesses caused by subgroup B1 and B2 strains was the same.
Age Factors↗
Genetic diversity of the attachment protein of subgroup B respiratory syncytial viruses.
Respiratory syncytial (RS) virus causes repeated infections throughout life. Between the two main antigenic subgroups of RS virus, there is antigenic variation in the attachment protein G. The antigenic differences between the subgroups appear to play a role in allowing repeated infections to occur. Antigenic differences also occur within subgroups; however, neither the extent of these differences nor their contributions to repeat infections are known. We report a molecular analysis of the extent of diversity within the subgroup B RS virus attachment protein genes of viruses isolated from children over a 30-year period. Amino acid sequence differences as high as 12% were observed in the ectodomains of the G proteins among the isolates, whereas the cytoplasmic and transmembrane domains were highly conserved. The changes in the G-protein ectodomain were localized to two areas on either side of a highly conserved region surrounding four cysteine residues. Strikingly, single-amino-acid coding changes generated by substitution mutations were not the only means by which change occurred. Changes also occurred by (i) substitutions that changed the available termination codons, resulting in proteins of various lengths, and (ii) a mutation introduced by a single nucleotide deletion and subsequent nucleotide insertion, which caused a shift in the open reading frame of the protein in comparison to the other G genes analyzed. Fifty-one percent of the G-gene nucleotide changes observed among the isolates resulted in amino acid coding changes in the G protein, indicating a selective pressure for change. Maximum-parsimony analysis demonstrated that distinct evolutionary lineages existed. These data show that sequence diversity exists among the G proteins within the subgroup B RS viruses, and this diversity may be important in the immunobiology of the RS viruses.
Amino Acid Sequence↗