Comment on the interpretation of lymphocyte phenotyping.
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Biomedical subjects
Publications and source records attributed to R H Waldman.
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Publications produced by faculty over a three-year period are used in analyzing the relative research productivity of basic and clinical science departments in a college of medicine. The citation ratings of the journals, the number of authors, and the byline position of the faculty member are used in various publication evaluation schemes. The departments vary almost tenfold in research productivity per faculty member. Results of the analysis demonstrate that the number of authors and the byline position influence departmental productivity rankings very little. Rankings are substantially affected, however, when the journals are weighted based heavily on citation ratings.
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The adjuvant activity of avridine, a synthetic lipoidal amine, incorporated in liposomes, was studied in mice immunized orally with killed influenza virus vaccine (A/PR/8/34, H1N1). Coadministration of avridine-containing liposomes and viral antigen enhanced the remote-site IgA antibody response in the respiratory tract without a concomitant serum antibody response or side effects. The results support the possible use of mucosal adjuvants for oral immunization against respiratory pathogens.
In order to investigate the possible stimulation of antibodies in the genital tract by immunization female NMRI-mice were given orally a live influenza vaccine (A/PR/8/34, H1N1) on two occasions which were 10 days apart. Subsequently, virus specific IgA antibodies measured by an enzyme immunoassay in homogenates of urinary bladder, uterus and vagina and also in uterine washings. Specific IgA antibodies were not detectable in the sera of immunized mice. The high IgA titer in uterine washings, and in the homogenates suggests enhancement by vaccine of IgA antibody production in the genital tract.
In order to compare the antibody response in serum and secretions from healthy young subjects and the elderly (greater than 60 years), volunteers were immunized with the commercial inactivated influenza virus vaccine, by the usual (parenteral) route or orally. Also, young and old mice (mean age, 20 months) were orally immunized with live influenza virus. The older mice responded with a very slight rise in their serum and respiratory tract antibody levels compared with the young mice but showed no diminution in protection against lethal viral challenge. Elderly volunteers showed only slight serum antibody responses after parenteral immunization compared with the young. Neither group demonstrated a rise in serum antibody following oral immunization. With respect to the secretory IgA (SIgA) antibody response, certain differences were noted between the young and the elderly: the preimmunization levels of antibody to influenza virus were significantly greater in nasal secretions and saliva in the elderly as compared to the young volunteers, and the salivary antibody response was diminished in the elderly. This lack of a salivary antibody response in the elderly was explicable by the inverse relationship between the preimmunization SIgA antibody titers and the response to immunization. Oral immunization led to no more side effects than observed in the placebo control group.
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Antibodies in nasal secretions and saliva were stimulated in 10 monkeys (Macacus rhesus) which had been immunized orally with a killed influenza vaccine. Prior to immunization, monkeys had no detectable antibody to influenza virus hemagglutinin or neuraminidase in sera or secretions. Oral immunization (6 times within 12 days, total of 0.6 mg hemagglutinin (HA) and 240 neuraminidase units) using intraesophageal intubation induced secretory antibodies to both antigens, but no serum antibody. Six and 8 monkeys reacted with HA-antibodies in nasal secretions and saliva, respectively, whereas neuraminidase antibodies occurred in nasal secretions of all 10 and in the saliva of 9 animals. The results support the concept of a common mucosal immune system in monkeys.
Secretory IgA antibody may be important in protection against respiratory viral infections, and the concept of a common mucosal immune system offers the theoretical basis for the convenient stimulation of this antibody. Therefore, the oral route was compared with intramuscular injection in a double-blind, placebo-controlled study in young healthy volunteers. A killed influenza vaccine, given in enteric-coated capsules (total of 98 ug hemagglutinin of A/Bangkok) led to significant salivary and nasal IgA antibody rises in a 4-week period. The preimmunization titers in secretions were inversely correlated with the antibody rise after immunization. The orally administered vaccine was associated with no more side effects than placebo, in contradistinction to reactions following the intramuscular route. The latter route also was without significant effect in regard to a stimulation of secretory antibodies. The observed simultaneous induction of antibodies in saliva and nasal secretions following oral administration of killed vaccine gives further evidence of a common mucosal immune system and its possible clinical use.
Oral immunization of 5 volunteers with an enteric-coated inactivated influenza vaccine resulted in a significant rise of IgA-specific antibodies in tears, saliva and nasal secretion, reaching a maximum response 5-7 weeks after completion of immunization.
Groups of young adult and senescent guinea pigs were fed normal and vitamin C deficient diets for 4 weeks and tested for their peritoneal macrophage functions. Serum levels of vitamin C in deficient animals indicated a progressive state of ascorbic acid deficiency and correlated well with the clinical signs and symptoms of scurvy. Fewer macrophages were obtained from the peritoneal cavities of deficient animals and morphologically they were smaller in size. Adverse effects of vitamin C deficiency were enhanced in aged animals. Significantly greater number of aged animals died by 4 weeks of deficiency. Deficient senescent animals had greater decline in macrophage random migration and bactericidal capacity. Following phagocytic stimuli, superoxide anion generation also significantly decreased. Data suggest that vitamin C deficiency might affect macrophage functions in the aged more profoundly and could compromise parameters of host defenses effective against microbial infections.
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Approximately 14 days after exploring a limestone cave in northcentral Florida in February 1973, an 18-year-old female developed a respiratory illness with pronounced shortness of breath and cyanosis. The following day, an 18-year-old male presented to the hospital with similar complaints. The association of illness with their recent caving experience prompted further epidemiologic investigation. Twenty-nine members of a church-sponsored youth group explored the implicated cave. Twenty-three of them later became ill with complaints of cough, afternoon fever and sweats, chest discomfort, and dyspnea on exertion. Histoplasmin skin tests were positive in 18 of 24 individuals tested. Serum for complement fixation (CF) was positive in 12 of 26. Testing of area residents revealed a low incidence of skin test and CF positivity (7% and 0%, respectively). That spelunkers are at risk of acquiring pulmonary histoplasmosis has been noted previously; in Florida this has been related to the exploration of caves infested with bats. This is the largest reported outbreak of acute pulmonary histoplasmosis that has been associated with spelunking and further points out that only those individuals who enter the cave are at risk of acquiring the disease, and not those who reside in the surrounding area.