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Biomedical subjects

C E Taylor

Publications and source records attributed to C E Taylor.

At least 73 records · Page 4Linked to original sources

Antibody production in vitamin A-depleted rats is impaired after immunization with bacterial polysaccharide or protein antigens.

Vitamin A nutritional status has been implicated as important in maintaining the integrity of immune functions. We have determined the effect of vitamin A (retinol) depletion on the ability of young animals to produce antibodies after challenge with various bacterial antigens. Male Lewis rats raised on vitamin A-free or adequate diets were immunized either near 40 days of age, before signs of vitamin A deficiency were apparent, or near 47 days of age when symptoms of deficiency were beginning to be manifest. For rats immunized with polysaccharide antigens from Streptococcus pneumoniae or Neisseria meningitidis, antibody production did not exceed 0-19% of the response of control rats. Vitamin A depletion also severely compromised the response to two T cell-dependent antigens, tetanus toxoid and sheep red blood cells. In striking contrast, retinol-depleted rats immunized with lipopolysaccharides from Pseudomonas aeruginosa and Serratia marcesens produced an antibody response indistinguishable from retinol-sufficient animals. These lipopolysaccharides could elicit antibodies in rat pups, whereas the capsular polysaccharide antigens could not. This is consistent with the characteristics of type 1 and type 2 antigens, respectively. These studies indicate that retinol status is an important determinant of the humoral immune response to certain types of antigen and suggest that antibody production to capsular polysaccharides and T cell-dependent antigens is particularly dependent on adequate retinol status.

Aging↗

Inactivation of suppressor T cell activity by the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides.

Antibody responses of mice immunized with type III pneumococcal polysaccharide were examined with and without treatment with nontoxic lipopolysaccharide from Rhodopseudomonas sphaeroides (Rs-LPS). The results obtained were similar to those described previously for mice treated with monophosphoryl lipid A (MPL) except that lower amounts of Rs-LPS were needed. Both were without effect when given at the time of immunization with type III pneumococcal polysaccharide but elicited significant enhancement when given 2 to 3 days later. Such enhancement was T cell dependent and not due to polyclonal activation of immunoglobulin M synthesis by B cells. Treatment with either Rs-LPS or MPL abolished the expression but not induction of low-dose paralysis, a form of immunological unresponsiveness known to be mediated by suppressor T cells (Ts). The in vitro treatment of cell suspensions containing Ts with extremely small amounts of Rs-LPS or MPI completely eliminated the capacity of such cells to transfer suppression to other mice. These findings indicate that the immunomodulatory effects of both MPL and Rs-LPS are mainly the result of eliminating the inhibitors effects of Ts; this permits the positive effects of amplifier T cells to be more fully expressed, thereby resulting in an increased antibody response. The significance of these and other findings to the use of Rs-LPS as a pharmacotherapeutic agent for gram-negative bacterial sepsis is discussed.

Animals↗

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.

Acyclovir↗

Swaddling and acute respiratory infections.

In Turkey and China the ancient practice of swaddling is still commonly practiced. Both countries have extremely high rates of pneumonia, especially during the neonatal period. Preliminary evidence on the possibility that swaddling may interfere with normal respiratory function and thereby predispose to pneumonia was gathered in a teaching health center in Ankara. Babies who had been swaddled for at least three months were four times more likely to have developed pneumonia (confirmed radiologically) and upper respiratory infections than babies who were unswaddled. These preliminary findings were highly significant and are being followed up by further studies.

Clothing↗

T cells regulate the IgM antibody response of BALB/c mice to dextran B1355.

The IgM antibody response of BALB/c mice to bacterial (Leuconostoc) dextran B1355 is influenced in a positive and negative manner by regulatory CD4+ and CD8+ T cells, respectively. Treatment with concanavalin A (ConA) at the time of immunization or 2 days later caused suppression and enhancement of the antibody response, respectively. Priming of mice with a sub-immunogenic dose of dextran resulted in profound suppression upon subsequent immunization 3 days later. None of these effects were demonstrable in athymic mice. Transfer of T cells from mice primed 18 h previously with a subimmunogenic dose of dextran suppressed the antibody response in immunized recipients; such suppression was abolished by the treatment of transferred cells with anti Thy 1.2 or anti Lyt 2.2 (CD8) antibody in the presence of complement. By contrast, the transfer of T cells from mice, which had been given an immunogenic dose of dextran 4 days previously, increased the antibody response in immunized recipients; such enhancement was abolished by treating transferred cells with anti Thy 1.2 or anti L3T4 (CD4) antibody in the presence of complement. These findings indicate that the immune response to dextran B1355 is regulated by CD4+ T-amplifier cells (Ta cells) and by CD8+ T-suppressor cells (Ts cells) which are activated during the course of a normal antibody response.

Animals↗

Alteration of antibody response to pneumococcal polysaccharide type III in rats by neonatal immobilization stress.

Our previous studies showed that stressing newborn animals by immobilization during the first 2 weeks of life caused significant changes in the capacity of adult rats to respond to stress as measured by the adrenal and circulating levels of catecholamines. In this report the effect of stress on the antibody response to the capsular polysaccharide of Type III Streptococcus pneumoniae (SSS-III) was investigated in two different strains of rats: Sprague-Dawley (SD) and Fischer (F) 344 rats. Animals were stressed 1 h each day for a total period of 10 days. Following this period of stress, animals were reared together along with littermate controls up to 40 days of age, when they were immunized with an optimally immunogenic dose of SSS-III. The results of experiments done with SD rats showed a substantial suppression of the antibody response when the response of the neonatally stressed animals was compared to the controls. In contrast, stressing adult SD animals for 10 days, followed by a 3-week recovery period prior to immunization with SSS-III, did not result in any significant (p greater than .05) suppression of antibody response. When F rats were used, the antibody response of the neonatally stressed rats was also significantly (p less than .05) lower than that of the controls. Thus, the effects of chronic, immobilization stress on antibody response can be long-lasting when the stressor is applied during the neonatal period.

Animals↗

Vitamin A depletion and repletion: effects on antibody response to the capsular polysaccharide of Streptococcus pneumoniae, type III (SSS-III).

To determine the ability of young rats to produce antibody against pneumococcal polysaccharide (SSS-III), weaning rats were fed a semipurified diet containing no retinol (A-) or 4 micrograms retinol/g diet (A+). Splenic antibody response specific to SSS-III was 17% (p less than or equal to 0.05) of control for A- Sprague-Dawley rats; similarly, the response of retinol-depleted Lewis rats was 22% (p less than or equal to 0.05) of pair-fed controls. No kinetic differences were observed in the antibody response between A- and control Lewis rats. Retinol depletion more markedly reduced the antibody response of male rats than female rats despite equally low tissue retinol concentrations. For both strains, retinol repletion near the time of immunization normalized antibody production. When male Lewis rats were fed the A- diet longer, the antibody response of A- rats was only 3% of pair-fed controls; repletion again normalized antibody production. Thus, retinol supplementation near the time of immunization can restore the immune response in previously compromised A- rats.

Animals↗

T-cell modulation of the antibody response to bacterial polysaccharide antigens.

Pretreatment of mice with subimmunogenic doses of meningococcal polysaccharide (MP), Pseudomonas aeruginosa lipopolysaccharide (PA), or Streptococcus mutans polysaccharide (SM) resulted in suppression of antibody response. The transfer of putative suppressor T cells (Ts cells) from donor mice primed with a subimmunogenic dose of MP to naive recipients at the time of immunization with MP substantially reduced the magnitude of the antibody response. Also, the infusion of B cells taken from animals immunized with either MP or PA suppressed the antibody response of naive recipients to MP or PA, respectively, relative to controls, suggesting that Ts cells respond to determinants on immune B cells. We observed that the injection of concanavalin A or phytohemagglutinin (two lectins known to augment the activity of amplifier T cells [Ta cells]) 2 days postimmunization enhanced the antibody response to MP and SM. In addition, Ta-cell activity was transferred to naive animals by using spleen cells. Although the administration of phytohemagglutinin at the time of immunization with MP also resulted in increased antibody response, the injection of concanavalin A simultaneous with immunization resulted in a suppression of the antibody response to MP. Although Ts cells generated in response to pneumococcal polysaccharide type III were found to respond to monoclonal antibody Ly-m22, Ta cells responded to monoclonal antibodies L3T4 and Ia but not to Ly-m22. These studies suggest that Ta and Ts cells can modulate the antibody response to MP, SM, and PA in a positive and negative manner, respectively.

Animals↗

Interferon alfa, infectious virus, and virus antigen secretion in respiratory syncytial virus infections of graded severity.

Interferon alfa was measured by an immunoradiometric assay in the nasopharyngeal secretions of a group of infants admitted to hospital with respiratory syncytial virus infection. Virus replication in the upper respiratory tract was assessed by infectivity assay and by an enzyme linked immunoadsorbent assay for the viral fusion protein on the same nasopharyngeal secretions. All infants were examined daily while in hospital and allocated a score based upon a subjective assessment of the severity of their illness. There was no significant correlation between interferon, virus, or fusion (F) protein secretion and severity of illness or age of infant. It is concluded that poor interferon alfa secretion does not underly the susceptibility of infants to severe infections with this virus.

Antigens, Viral↗

IgG and IgM antibodies to viral glycoproteins in respiratory syncytial virus infections of graded severity.

Serum antibodies to the fusion (F) and large glycoprotein (G) of respiratory syncytial virus in the serum of 57 infected infants were measured by enzyme linked immunosorbent assay (ELISA). Most serum samples taken at the time of admission to hospital contained antibodies to both glycoproteins, and overall there was no significant evidence of a selective deficiency of antibody to either viral antigen. Less than a quarter of the infants showed rising IgG antibody titres to either glycoprotein after infection, whereas over threequarters produced an IgM response. There was a significant correlation between IgG response to viral glycoproteins and the age of the infant. The correlation of age with the IgM response was less pronounced, and there was no correlation between serum IgG antibody derived transplancentally in the acute phase of infection and IgM response to either glycoprotein. Neither IgG or IgM responses correlated with a clinical assessment of the severity of infection in the infants. IgM responses, however, were weakly correlated with reduced secretion of infectious virus in the upper respiratory tract.

Antibodies, Viral↗

Control of diarrheal diseases.

The tremendous advances made in the control of diarrheal diseases in the past few years indicate what more can be achieved. Even though the lives of an estimated three quarters of a million children are being saved each year, over three million children are still dying from readily preventable diarrheal disease. The challenge is to build on the successes thus far, to learn from experience, to promote changes in health habits that will prevent diarrhea, and to make all of these activities sustainable. From this analysis, we have three specific recommendations for CDD programs in the next decade. 1. ORT programs should move strongly toward promoting home treatment, building on local traditions of giving food-based preparations, with ORS available from health workers and health facilities for those who need it. Local assessment of people's beliefs and practices in caring for diarrhea should lead to simple methods of adapting ORT preparations that are culturally acceptable. Most of these traditional preparations have adequate amounts of the proteins and starches that are now being shown to produce better clinical results than the glucose in the standard ORS formula. Usually, the main change needed is more precision in the quantity of sodium added. Education of parents can then focus simply on how to make these adapted preparations, on starting rehydration early, and on replacing fluid volume as it is lost. The use of ORS packets in health facilities should continue, but the main indicator of progress in CDD should be ORT use including home solutions. Every packet of ORS should have printed on it the locally recommended formula for home ORT. 2. Nutritional support is just as important as rehydration. Diarrhea precipitates and accelerates the progression of malnutrition, which lowers resistance and increases the duration of diarrhea. Nutritional support through continued breast feeding and improved weaning practices using high density, easily digestible, local foods is especially important during and after episodes of diarrhea. 3. For long-term prevention, breaking the transmission cycles of the many common pathogens that cause diarrhea will be necessary. The most immediate preventive impact can be achieved by promoting hand washing with soap. Priority should also continue to be given to improving water supply, sanitation, and excreta control, especially of childrens' stools. Even with the great progress of recent years, the Child Survival and Development Revolution has just begun.

Child↗

American practitioners and the global primary care movement.

In conclusion, comparative studies of primary health care in various parts of the world can lead to new solutions for underserved communities in Maryland and other parts of the US. Careful review of how similar principles work under different circumstances will open new approaches. Current international experience shows that each country must evolve its own health care system. We have much to learn from those who are poorer than we, where limited resources stimulate local innovation and less waste.

Community Health Services↗

Interferon-induced inhibition of lymphocyte circulation: lack of effect on humoral immune responses to T-dependent or T-independent antigens.

We have previously demonstrated that interferon (IFN) transiently inhibits the number of recirculating thoracic duct lymphocytes (TDL), while other researchers have demonstrated similar decreases in lymphocytes in peripheral blood. In the present study we examined whether or not this decreased lymphocyte recirculation contributes to IFN's suppressive effects on antibody formation. Immunizing at varying times during the period of maximal decrease in lymphocyte recirculation, there are no significant differences in the number of plaque-forming cells (PFC) or antibody titers generated to either a T-dependent antigen, sheep erythrocytes (SRBC) or a T-independent antigen, Type III pneumococcal polysaccharide (SSS-III). These results suggest that: (i) the suppressive effects of IFN on antibody responses are not related to changes in lymphocyte recirculation and (ii) lymphocyte circulation is not required during the early phases of the humoral immune response to antigens.

Agglutination Tests↗