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Biomedical subjects

P A Small

Publications and source records attributed to P A Small.

At least 37 records · Page 2Linked to original sources
PubMed1991

Influenza immunization: intranasal live vaccinia recombinant contrasted with parenteral inactivated vaccine.

To compare the efficacy and duration of the immune response to local and systemic vaccination, Balb/c mice were vaccinated either intraperitoneally (i.p.) with an inactivated A/PR/8/34 (H1N1) vaccine or intranasally (i.n.) with a vaccinia recombinant containing the H1 gene of influenza. The i.p. inactivated vaccine stimulated high serum IgG anti-influenza titres and protected the lungs against viral challenge for the duration of the experiment (17 months). Little nasal wash IgA was induced and the noses were susceptible to challenge. Animals vaccinated i.n. with the recombinant had lower serum IgG titres and the lungs showed poor protection against challenge. Nasal wash IgA titres were higher, however, and the noses were largely protected from viral challenge for 17 months.

Administration, Intranasal↗
PubMed1991

Immunoglobulin A mediation of murine nasal anti-influenza virus immunity.

Most mice which have recovered from influenza virus infection are immune to reinfection with the same influenza virus. This immunity could be abrogated by the intranasal instillation of anti-immunoglobulin A (anti-IgA) but not of anti-IgG or anti-IgM antiserum. Thus, IgA is the major, if not the sole, mediator of nasal immunity to influenza virus in immunocompetent mice.

Animals↗
PubMed1991

Influenza in senescent mice: impaired cytotoxic T-lymphocyte activity is correlated with prolonged infection.

Influenza and pneumonia are leading causes of death in the elderly. Cytotoxic T-lymphocyte activity is responsible for viral clearance after infection and declines with age. We hypothesized that following intranasal infection with influenza virus, aged mice would have decreased anti-influenza cytotoxic T-lymphocyte activity that would correlate with prolonged pulmonary viral shedding. To test this, young (1.5-4.0 month) and aged (22-25 month) BALB/c mice were infected intranasally with influenza A/Port Chalmers/1/73(H3N2). Mice were killed at 3-19 days following infection. Their splenic cytotoxic T-lymphocyte activity was measured by a secondary in vitro chromium release assay. Pulmonary viral titres were quantified by growth of titrated lung specimens in fertilized hens' eggs. Serum antibody titres were measured by an ELISA. Young mice responded in a relatively homogeneous fashion. They developed maximal cytotoxic T-lymphocyte activity of 60.9 +/- 2.0% by Days 11-13, and all except one cleared virus from the lung by Day 7. In contrast, old mice were heterogeneous. Their cytotoxic T-lymphocyte activity peaked at 46.9 +/- 5.0% and was delayed by 5-7 days. Forty-five per cent were still shedding virus at Days 7 and 8, and shedding persisted for at least 13 days in some mice. There was a strong correlation in both young and aged mice between the presence of virus in the lungs and decreased splenic cytotoxic T-lymphocyte activity (chi 2 = 30.2, P much less than 0.001). No significant difference was found between young and aged animals in serum IgG1 anti-H3 antibody titres. We conclude that following influenza infection in aged mice, impaired cytotoxic T-lymphocyte activity leads to prolonged duration of infection. These observations may lead to a better understanding of the excess morbidity and mortality in elderly persons that occur with influenza.

Aging↗
PubMed1990

Influenza: pathogenesis and host defense.

Why does influenza virus variously eventuate in mild upper respiratory tract infection, bacterial pneumonia, or rapidly fatal viral pneumonia? The depth of infection is important. So is competence of immunologic effectors--local antibody (secretory IgA) for preventing URI, systemic antibody for preventing pneumonia, and cellular immunity for recovery from either.

Adult↗
PubMed1990

Enhancement of anti-influenza cytotoxic T-lymphocyte activity in senescent mice by vaccination early in life.

The elderly suffer significantly from influenza and respond poorly to influenza vaccines. This may be due to the fact that cytotoxic T-lymphocyte (CTL) activity is responsible for recovery from viral infections and is decreased in the elderly. We hypothesized that vaccination early in life might increase activity in senescence. To test this, groups of BALB/c mice were infected with influenza virus and/or vaccinated with an inactivated vaccine. CTL activity was measured by 51Cr release from H1N1-infected P815 cells. We found that aged mice have low CTL activity when initially vaccinated at 22 months (4 +/- 4% vs. 23 +/- 6% for vaccinated young mice). However, CTL activity was significantly increased when animals were initially vaccinated when young and then re-vaccinated when old (28 +/- 10% vs. 13 +/- 17% for mice vaccinated twice in old age). We next measured CTL activity in response to infection. We found a very high level of activity (57 +/- 11%) in animals vaccinated at 1.5 months and then infected at 23 months. This was indistinguishable from young controls (56 +/- 7%). These data suggest that primary inoculation at an early age induces a relatively larger number of precursor CTLs than does inoculation in senescence.

Aging↗
PubMed1989

Virus infection as a stressor: influenza virus elevates plasma concentrations of corticosterone, and brain concentrations of MHPG and tryptophan.

Balb/c mice were infected with influenza virus PR8 (H1N1) by the intranasal route. At various subsequent times, brain samples were examined for their content of catecholamine and indoleamine metabolites, and plasma corticosterone was measured. Virus infection was associated with a progressive loss of body and thymus weights, and an increase in plasma corticosterone. Spleen weight initially increased then decreased. There were also increases in the cerebral content of free tryptophan throughout the brain, and of MHPG, a major catabolite of norepinephrine, especially prominent in the hypothalamus. Thus influenza virus can be regarded as a stressor because, like behavioral stressors, it activates the hypothalamic-pituitary-adrenal axis, and increases cerebral concentrations of tryptophan and norepinephrine catabolites. These changes resemble those observed following administration of sheep red blood cells and Newcastle disease virus, noninfectious activators of the immune system, suggesting that noradrenergic and HPA activation are common concomitants of antigenic stimulation. The mediator of these effects may be interleukin-1 released by activated macrophages. It should be noted that animals infected with viruses can be expected to exhibit stress-like endocrine and neurochemical changes.

Animals↗
PubMed1989

Intranasal immunization with proteoliposomes protects against influenza.

Worldwide, influenza virus remains a serious disease which has successfully eluded numerous attempts to design a consistently effective vaccine. In part, these attempts have been thwarted because of a lack of basic understanding of the mechanisms which mediate protection and recovery from influenza infection. A better understanding of the roles of secretory antibody, serum antibody and cell mediated immunity vis-à-vis protection and recovery from influenza infection has allowed us more rationally to approach the design and administration of a vaccine for influenza. We have constructed a vaccine composed of glycoproteins from the envelopes of either influenza of Sendai virus embedded in a lipid bilayer (immunosomes) mimicking the presentation of the virus to the cells during natural infection. Intranasal immunization with these immunosomes induces an adequate systemic Ir compared with intramuscular immunization and a superior local IgA response. These animals were specifically protected from virus challenge.

Administration, Intranasal↗
PubMed1988

Consequences for medical education of problem-solving in science and medicine.

The problem-solving process used by scientists and by clinicians is compared and contrasted. The most creative step for both groups is the ability to make an association between some external stimulus or situation and concepts stored in memory. Medical education must put more emphasis on teaching that improves students' abilities to make these associations. Two teaching methods that can promote development of the necessary association skills in clinical contexts--"wait time" and "concept mapping"--are briefly reviewed. Concept mapping consists of connecting words that represent concepts with lines that represent relationships and then labeling the lines. Wait time is waiting three to five seconds between asking a group of students a question and calling on a student to answer or waiting three to five seconds before responding to the student's answer.

Association↗
PubMed1988

Passive serum antibody causes temporary recovery from influenza virus infection of the nose, trachea and lung of nude mice.

BALB/c normal and nude mice were infected with a non-lethal mouse-passaged A/PC/1/73 (H3N2) influenza virus in order to assess the role of T cells on the course of disease of the nose, trachea and lung. The tracheal epithelium of both mouse strains was desquamated by 3 days after infection. Although normal regeneration began, nude mice never completed that regeneration whereas normal mice had fully regenerated tracheas by Day 14. This failure to complete the recovery was also evident from the continued virus shedding by the nude mouse. In order to assess the role of serum antibody on recovery from infection, ferret, goat or mouse antibody to H3N2 influenza virus was passively administered to nude mice after infection. It resulted in a transient decrease in virus shedding from the nose, trachea and lung, and complete but temporary regeneration of the tracheal epithelium. However, later in the course of the infection, when serum antibody levels were no longer detectable, the tracheal epithelium of these animals redesquamated and large amounts of virus were again shed from nose, trachea and lungs. We conclude that: (i) desquamation of the ciliated epithelium of the trachea is not T-cell dependent; and (ii) serum antibody can contribute to temporary recovery from infection, but by itself is insufficient for permanent recovery of the nose, trachea or lung.

Animals↗
PubMed1988

Maternal-infant transfer of influenza-specific immunity not detectable by haemagglutination inhibition.

Evidence was sought for the transfer from mother to infant mouse of influenza-specific immunity other than that associated with haemagglutination inhibition (HI) specific antibody. Data were analysed for infant mice born to three groups of mothers: influenza immunized mothers with high levels of HI antibody. influenza immunized mothers in whom influenza-specific HI antibody was suppressed to undetectable levels by passive administration of antibody prior to influenza immunization, and non-immunized control mothers. At 4 weeks of age, infants were given either a lethal or a non-lethal influenza challenge. After a lethal influenza challenge, infants of immunized mothers with HI antibody showed no mortality. Infants of immunized mothers in whom HI antibody was suppressed showed a mortality of 8 to 33%, which was significantly lower than the 71% mortality found in infants of non-immunized control mothers (P less than 0.001). The lower mortality in infants of immunized mothers without HI antibody appeared to be associated with breast feeding, but could not be attributed to the transfer from mother to infant of a local immune response, an influenza specific cytotoxic response, or a secondary antibody response after non-lethal influenza infection. When sera were additionally tested for anti-influenza IgG by ELISA, this lower mortality was found to correlate with anti-influenza serum IgG measurable by ELISA but not detectable by HI. Protective immunity in infants undetectable by HI could be attributable to very low levels of antibody detected by more sensitive ELISA.

Animals↗
PubMed1987

Effect of passive maternal antibody on influenza illness in children: a prospective study of influenza A in mother-infant pairs.

To determine the effect of passive antibody on the incidence of influenza in infants, infants born to mothers with serum antibody to influenza A (immune) and those born to mothers without evidence for this serum antibody (non-immune) were followed during the influenza H1N1 epidemic of 1979. Immune mothers had higher H1-specific antibody titers before the epidemic (P less than 0.001), were less frequently culture positive, showed fewer titer rises (P less than 0.001) and were less symptomatic than were nonimmune mothers. Infants of immune mothers had higher H1-specific passive antibody titers that correlated with their mother's antibody titers. Although infants of both groups showed no difference in incidence of influenza infection, infants of immune mothers had influenza symptoms that were delayed in onset (P = 0.02) and were of shorter mean duration compared with infants of nonimmune mothers. These findings suggest that passive maternal antibody delays the onset and decreases the severity of influenza disease in young infants.

Antibodies, Viral↗
PubMed1985

Protection and recovery in influenza virus-infected mice immunosuppressed with anti-IgM.

BALB/c mice, immunosuppressed from birth with goat anti-mouse IgM, were able to recover from influenza virus infection in the absence of detectable serum and nasal antibody. Recovery was delayed a few days when compared with control animals. Antibody-deficient mice, that had recovered from an initial influenza virus infection, i.e., convalescent mice, were subsequently rechallenged with homologous influenza virus in order to study the importance of nasal and serum antibody in prevention of infection. Convalescent mice were susceptible to reinfection when nasal and serum antibody were not detectable. The mice were resistant to reinfection when serum and/or nasal antibody was detectable by radioimmunoassay. Normal mice that were passively immunized with high titer mouse anti-influenza virus serum were susceptible to challenge with homologous influenza virus. The serum antibody levels in these mice were higher than most of those found in the immune convalescent mice suppressed with anti-IgM, thereby suggesting that the serum antibody, found in convalescent suppressed mice, is not protective. We conclude that 1) mice can recover from influenza virus infection in the absence of detectable levels of nasal and serum antibody, thus indirectly confirming the role of cell-mediated immunity in recovery; 2) serum IgM, IgG2A, IgG2B, IgG3, and probably IgG1 antibody levels are not responsible for protection against influenza virus infection of the upper respiratory tract; and 3) nasal IgA antibody correlates best with protection against reinfection of the upper respiratory tract, but some other locally protective agent cannot be excluded.

Animals↗
PubMed1984

A case report of the successful treatment of recurrent aphthous stomatitis with some preparations of orally administered transfer factor.

A patient with severe disabling recurrent aphthous stomatitis (RAS) was treated with four different preparations of oral human transfer factor (TF), as well as placebo, following a double-blind protocol. Two of the TF preparations had a significant effect upon the course of the patient's illness by prolonging the interval between attacks and decreasing the severity of attacks. No side effects attributable to any of the preparations were noted by the patient. Thus, some but not all preparations of human transfer factor given orally are an effective therapy for RAS.

Administration, Oral↗
PubMed1983

Influenza infection in the infant mouse.

A nonlethal influenza infection [A/PC/1/73 (H3N2)] was given to infant mice to determine (1) the pathology of tracheal epithelium and lung, (2) the time course of viral shedding from the nose and lung, and (3) the subsequent development of protective immunity during adulthood. Both desquamation of the tracheal epithelium and lung pathology similar to that described in adults after influenza infection were observed in the infant. Animals infected at 3 days of age show virus shedding in 12 of 13 infant mice that persists for at least 2 days longer than in the adult. This longer duration of influenza infection did not result from either malnutrition or from intralitter transmission of virus. Recovery from virus shedding in both the upper and lower airway occurred in the absence of detectable serum antibody in six of seven mice. Infants that recover from infection, when rechallenged during adulthood, manifest complete protection in 11 of 13 mice after nonlethal challenge and no mortality after lethal challenge.

Animals↗
PubMed1983

Maternal-infant transfer of influenza-specific immunity in the mouse.

The effects of maternal-infant transfer of influenza-specific antibody on influenza infection in the infant mouse were studied by following mortality, hemagglutination inhibition antibody, virus shedding from the nose and lung, and pathology of the upper and lower airway. By cross-fostering infants, influenza-specific antibody was shown to be acquired mainly by breast-feeding. Mice acquiring specific antibody survived lethal influenza infection (p less than 0.001) and had no evidence of influenza pneumonitis. There was variable suppression of nasal virus shedding and tracheal desquamation. Infected infants that initially acquired high levels of serum antibody also showed no evidence for serum antibody 10 wk later. Infant mice surviving initial influenza infection were lethally rechallenged 10 wk later. Rechallenged mice had a higher survival rate when compared to control mice (p less than 0.001) in spite of the absence of anti-influenza antibody and the presence of high lung virus titers in both groups 1 day after rechallenge. Rechallenged mice showed evidence for both significantly lower nasal virus titers (p less than 0.001) and a secondary serum antibody response with associated decline in lung virus titer. These results suggest maternal influenza-specific antibody a) is transferred to the infant mouse; b) is transferred mainly by breast-feeding; c) is life saving and lowers lung virus titers in the infant; and d) suppresses the infant's serum antibody production after challenge without affecting local immunity or the ability to mount a secondary antibody response.

Animals↗
PubMed1980

Autopsies on two native American Mummies.

An interdisciplinary team performed autopsies on an adult male and an infant male mummy from the American Southwest. Cause of death has not been determined for the infant. The presence of an unhealed skull fracture associated with an apparent hematoma in the adult male is suggestive of trauma as the cause of death in the adult. Evidence of disease is minimal. Analysis of powder thought to be dried blood from the thoracic cavity of the adult suggests the presence of human IgG. The instability of this protein may indicate the presence of proteolytic activity by enzymes that degrade immunoglobulins upon rehydration. The possibility of enzymatic degradation of proteins will be an important factor in future studies of such immunoglobulins in mummy remains and also indicates the importance of maintaining the desiccated condition of mummy tissues.

Adult↗