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Biomedical subjects

G W Fernald

Publications and source records attributed to G W Fernald.

30 records · Page 2Linked to original sources

Protective Effect of Vaccines in Experimental Mycoplasma pneumoniae Disease.

The mechanisms of immunity to Mycoplasma pneumoniae were investigated by evaluating different vaccination procedures in an experimental animal model. Hamsters were immunized by intranasal inoculation of broth cultures or by parenteral injections of saline-suspended organisms. All vaccinees received a standardized intranasal challenge which produced pneumonia in 94% of controls. Intranasal immunization with virulent organisms produced a 71% reduction in pneumonia. Subcutaneous and intraperitoneal inoculation of the same organisms yielded 56 and 61% reductions, respectively. Animals similarly immunized with an attenuated strain developed resistance to pneumonia only after intranasal infection. Serum antibody levels did not correlate with protection. Growth-inhibiting activity was demonstrated in bronchial washings of challenged animals, suggesting the development of local antibody in response to infection with M. pneumoniae. Crosschallenge studies were performed in animals vaccinated intranasally with virulent and avirulent variants of the same strain. The avirulent vaccine prevented pneumonia in animals challenged with homologous virulent organisms but not in those receiving an unrelated strain; the virulent vaccine provided protection to both homologous and heterologous challenge. These studies indicate that organism strain variation as well as vaccination technique are important determinants of the immune response to M. pneumoniae.

Journal Article↗

Chronic lung disease in children referred to a teaching hospital.

Etiology, symptomatology, and host factors were studied in 184 children referred to a teaching hospital for evaluation in an attempt to classify chronic or potentially chronic lung disease. A standardized historical questionnaire, physical findings, chest radiographs, and a laboratory panel identified a diagnosis that could be related directly or indirectly to chronic lung disease in 22% of the subjects. Among the remaining 78%, bronchiectasis was found in 9%, chronic pneumonia in 9%, chronic diseases with wheezing in 56%, and no significant lower respiratory disease in 4%. Analysis of cases with no apparent etiology revealed that the majority of patients had historical evidence of wheezing; often this previously had not been appreciated. Laboratory tests, such as eosinophil count and immunoglobulin E (IgE) testing, did not differentiate between wheezing and nonwheezing patients. Spirometric evaluation was limited because most subjects were younger than 5 years old. For the same reason, testing for bronchial hyperreactivity was not done. This study reemphasizes that wheezing is a major symptom of chronic lung disease in childhood and provides an outline for its evaluation. Although clinical airways reactivity, as exemplified by wheezing, proved to be the most prominent host defect found in this study, its nature, genetic or otherwise, remains to be defined.

Child, Hospitalized↗

The longitudinal approach to the pathogenesis of respiratory disease.

Longitudinal observations were made of a well-defined population of children at a day care center in an investigation of the pathogenesis of infections due to respiratory syncytial virus (RSV) and Mycoplasma pneumoniae. A single RSV infection induced a modest but significant degree of resistance to further RSV infection in these children. Age and immunity seemed to interact to decrease the intensity of the clinical expression of illness associated with RSV infection. Infants and young children had asymptomatic or mild infections with M. pneumoniae; some of these children also became reinfected. A rise in titer of antibody to M. pneumoniae was demonstrated frequently in children of all ages. However, stimulation of peripheral lymphocytes by M. pneumoniae antigen was demonstrated infrequently in children younger than four years of age but frequently in children older than four years of age. It is speculated that the clinical expression of disease due to M. pneumoniae is modulated by immune responses; this hypothesis would explain the greater severity of illness in older children and young adults than in younger children. It is also speculated that RSV vaccines will not prevent RSV infection but may be expected to lessen the severity of clinical disease that follows such infections. M. pneumoniae vaccines probably should not be used in children because these vaccines may enhance immunity and increase the sevrity of illness.

Child↗

Immunological interactions between host cells and mycoplasmas: an introduction.

In addition to eliciting host immune responses, many mycoplasmas interact nonspecifically with host cells. Early reports revealed peculiar inhibitory and stimulatory effects of mycoplasmas on the immune response in vivo; several investigators have now clearly defined nonspecific stimulation of B and T lymphocytes and also a nonspecific immunosuppressive effect on experimental animals and humans. These interactions relate to attachment of mycoplasmas to host cell membranes and perhaps involve sharing of membrane components. The implications of these peculiar effects of mycoplasmas on host cells suggest that much of the disease seen in the infected host is due to a nonspecific, inflammatory response to the mitogenic properties of the organism. Since the organism becomes intimately involved with the host cell membrane, this could enable the organism to evade the immunologic surveillance system and thus achieve the prolonged surface colonization characteristic of many mycoplasmas.

Animals↗

Microtubular discontinuities as acquired ciliary defects in airway epithelium of patients with chronic respiratory diseases.

A critical relationship exists between ordered ciliary ultrastructure and optimal mucociliary clearance in the respiratory airways. Structurally defective cilia derived from heritable syndromes or from epithelial cell injury may promote or exacerbate chronic disease processes. A lesion of airway epithelial cilia characterized by microtubular discontinuities and previously associated with primary ciliary dyskinesia (PCD) has been documented in other forms of chronic airways diseases, including cystic fibrosis (CF). Nasal cilia obtained by curettage of the inferior nasal turbinate from 89 patients without CF but exhibiting symptoms favoring PCD were evaluated by transmission electron microscopy. Of the 89 patients in the study group, 19 (21.4%) were diagnosed with PCD. Among the PCD patients, 16 (84.2%) exhibited microtubular discontinuities. Nine patients from this group without ultrastructural evidence of PCD also exhibited these defects, however. Furthermore, seven of eight nasal biopsy specimens from patients with CF in a separate disease control group exhibited microtubular discontinuities. Microtubular discontinuities were quantitatively negligible among control groups of healthy human subjects and individuals experimentally and naturally subjected to acute airway injury. These data provide evidence that ciliary microtubular discontinuities represent acquired ciliary defects reflective of chronic airway disease injury and are not components of a primary structural abnormality in PCD.

Adult↗

Cystic fibrosis: a current review.

Cystic fibrosis (CF) is the most common severe genetic disorder seen in Caucasians. Defective exocrine gland secretions result in chronic diseases of the respiratory and gastrointestinal systems. However, the CF gene recently has been located and cloned. Currently, genetic technology allows identification of sibling carriers and antenatal diagnosis within families. Oral implications associated with CF include enamel hypoplasia and tooth discoloration, salivary gland involvement, reduced incidence of dental caries, reservoir for potentially pathogenic respiratory bacteria, mouth breathing, and anterior open bite associated with nasal and sinus obstruction. Continued efforts to improve early diagnosis and treatment of CF should increase life expectancy. Affected patients are expected to seek regular dental care more frequently as they learn to view the disease as manageable.

Cystic Fibrosis↗

Immunologic mechanisms suggested in the association of M. pneumoniae infection and extrapulmonary disease: a review.

Numerous case reports and retrospective studies suggest an association between M. pneumoniae respiratory infection and extrapulmonary complications, the most common of which involve the central nervous system. There is insufficient evidence based on prospective, carefully controlled observations to confirm this association at the present time. A variety of mechanisms has been suggested to explain the involvement of distant organ systems. These include metastatic infection, autoimmunity, toxin generation, and altered host immunity. While none of these is based on evidence to prove an association, the state of anergy which accompanies M. pneumoniae pneumonia deserves consideration and further study as the most plausible link between infecting organisms and extrapulmonary manifestations.

Animals↗