Biomedical subjects

B S Bender

Publications and source records attributed to B S Bender.

At least 37 records · Page 2Linked to original sources

PubMed1995

Beta 2-microglobulin-deficient mice demonstrate class II MHC restricted anti-viral CD4+ but not CD8+ CTL against influenza-sensitized autologous splenocytes.

Mice transgenic for beta 2-microglobulin gene deletion (beta 2M-/-) can clear respiratory pathogens but at a slower rate than control mice. How these mice eliminate virus is not known, but the process is believed to involve CD4+ T cells. Recent studies from other laboratories have suggested a role for CD8+ cytotoxic T lymphocytes (CTLs) in both recognition of beta 2M deficient cells by allogeneic mice and rejection of MHC-incompatible tumor cells by beta 2M-/- mice. After influenza inoculation, we found no evidence for anti-influenza CD8 CTL activity from the lungs or spleens of beta 2M-/- mice. Anti-influenza CD4+, class-II restricted CTL activity was demonstrated from both the lungs and spleens. We next used mitogen-stimulated splenocytes from beta 2M-/- mice for targets in an in vitro CTL assay. This method for determining MHC class II CTL activity showed that the lungs and spleens of influenza-infected beta 2M-/- mice contained precursors to CD4+, but not CD8+, effector CTLs. The data indicate that CD8+ CTLs have no role in anti-viral activity in beta 2M-/- mice. Development of anti-tumor CTLs and anti-viral CTLs may arise via different mechanisms.

Animals↗

PubMed1995

Pulmonary immune response of young and aged mice after influenza challenge.

After influenza challenge, aged mice have prolonged viral shedding that correlates with lower splenic cytotoxic T lymphocyte (CTL) activity. To evaluate the age-related pulmonary cell-mediated immune response to influenza, pulmonary lymphocytes were obtained from young and aged mice at various days after respiratory tract infection with nonlethal influenza A/PC/1/73 (H3N2) virus. In young mice, pulmonary CTL activity peaked at 48% +/- 2% on day 7 after infection. Pulmonary CTL activity peaked 1 day later in aged mice and at about half the activity (24% +/- 5%). The majority of the cells recovered from the lungs in both age groups were CD3+, CD8+ T cells. Histologic examination of the lungs revealed that aged mice had significantly less inflammation than young mice. Therefore, after influenza challenge there was a large influx of lymphocytes into the lungs of both young and aged mice, but the cells from young mice were more active on a per-cell basis. In a further experiment, challenge with a more virulent strain of influenza produced higher mortality in young mice than in aged mice. Thus the higher CTL activity of young animals leads to more rapid virai clearance, but this may be at a price to the host--that is, more immunopathologic damage.

Aging↗

PubMed1994

Enteric immunization of mice against influenza with recombinant vaccinia.

Intrajejunal administration to mice of a recombinant vaccinia virus containing the influenza virus hemagglutinin gene induced IgA antibody in nasal, gut, and vaginal secretions. It also induced IgG antibody in serum and cell-mediated immunity. The immunization provided significant protection against an influenza virus challenge. This work suggests that enteric-coated recombinant vaccinia could be an orally administered, inexpensive, multivalent, temperature-stable, safe, and effective vaccine for children that could be particularly useful in developing nations, where multiple injections are not easily administered. Oral administration of vaccines should also reduce children's fear of shots at the doctor's office.

Animals↗

PubMed1994

Effects of influenza virus-specific cytotoxic T-lymphocyte responses induced by a synthetic nucleoprotein peptide on the survival of mice challenged with a lethal dose of virus.

Even though virus-induced cytotoxic T lymphocytes (CTLs) recognize antigens as peptides presented on infected cells, short synthetic peptides without any modifications are generally considered unsuitable for inducing antigen-specific CTLs in vivo. Our results demonstrate rapid induction of influenza virus-specific CTLs in Balb/c mice by an unmodified core protein peptide known to be a dominant H-2d-restricted CTL epitope. Additionally, the immunization procedure we employed in these studies produced significant influenza virus-specific CTLs in lymph nodes, spleen and lungs. When challenged with a lethal dose of influenza virus, a statistically significant delay in the day of death was observed in peptide-immunized mice. However, viral clearance was only slightly different from that in control mice. While these results are encouraging, they suggest a requirement for multiple CTL-inducing peptides, helper T cell-inducing peptides and/or virus-specific IgA responses in order to achieve protection from influenza infection.

Amino Acid Sequence↗

PubMed1994

Class I major histocompatibility complex-restricted cytotoxic T lymphocytes are not necessary for heterotypic immunity to influenza.

Mice transgenic for beta 2-microglobulin deletion (beta 2M-/-) were immunized intranasally with either a recombinant vaccinia virus that expressed both nucleoprotein and interleukin-2 or by infection with H3N2 influenza virus; 3-4 weeks later they were challenged with H1N1 influenza virus. The immunized beta 2M-/- mice had increased survival and enhanced clearance of virus relative to nonimmune controls. This protection correlated with the development of class II major histocompatibility complex-restricted pulmonary cytotoxic T lymphocyte activity and nasal IgA anti-nucleoprotein antibody. Heterotypic immunity can therefore be generated by a mechanism that does not involve class I major histocompatibility complex-restricted T cells.

Animals↗

PubMed1994

Modeling the relationship between clinical, microbiologic, and immunologic parameters and alveolar bone levels in an elderly population.

A cross-sectional periodontal study of 74 subjects aged 65 to 75 years was performed. Clinical data were collected and related to microbiological and immunological data. A statistical model (step-wise multiple regression) of factors related to bone loss was created initially using clinical data only; then by adding either the microbiologic or immunologic data; and then by using clinical, microbiologic, and immunologic data together. When only clinical data were considered, three factors were found to have significant positive correlations with bone loss. Tooth mobility accounted for 17% of the variability in the alveolar bone level measurements, probing depth for 12%(r2), and plaque index for 3%, for a total of 32% of the variability explained by these clinical factors. Tooth mobility and probing depth were clinical factors which remained significant in the model when the microbiological data were also considered. As percentages of the total cultivable microbiota, E. corrodens (r2 = 14%) and black-pigmenting Prevotella intermedia (r2 = 4%) correlated positively with alveolar bone loss. The addition of the microbiologic data only increased the r2 to 33%. When immunological data were considered with the clinical data, pocket depth and tooth mobility were the clinical parameters which remained in the model. IgG antibody levels to P. gingivalis W83 and/or 381 (r2 = 24%) A. actinomycetemcomitans 627 (r2 = 2%) were the significant immunologic measures having a positive correlation with bone loss. Anti-F. nucleatum levels had a significant negative correlation. A total of 50% of the variability in alveolar bone level was accounted for in the model by the addition of specific serum antibody levels to subgingival plaque microorganisms. When clinical, microbiological, and immunological measurements were all considered together, antibody to P. gingivalis W83 and/or 381 (r2 = 42%), percentage of B-lymphocytes (r2 = 3%), probing depth (r2 = 4%), anti-E. corrodens levels (r2 = 2%), and anti-P. gingivalis 33277 levels (r2 = 4%) all had significant positive correlation with loss of alveolar bone. The number of enteric bacteria, anti-F. nucleatum levels, and anti-P. intermedia levels each had a significant negative correlation with alveolar bone heights. The r2 for this model was 75%. These results indicated that antibody levels to subgingival plaque microorganisms and tooth mobility were the best predictors of bone loss in the elderly patients tested in this study.

Age Factors↗

PubMed1993

What to look for after you say 'open wide'. A guide to examination of the oral cavity.

Abnormal conditions of the oral cavity can have a significant impact on overall health, yet during many ostensibly complete physical examinations, the area is given only a perfunctory glance. Drs Thomas and Bender present guidelines for systematic, comprehensive evaluation of the oral cavity and provide case reports and figures to illustrate typical important findings.

Aged↗

PubMed1993

Recombinant vaccinia immunization in the presence of passively administered antibody.

Mice were injected with immune serum to vaccinia and/or influenza virus and then immunized by scarification with a recombinant vaccinia virus expressing the influenza haemagglutinin H1. The serum IgG antibody response to the foreign gene product, influenza H1, was suppressed by the passively administered anti-influenza antibody in a dose-dependent manner. Anti-vaccinia antibody alone had no effect on the anti-haemagglutinin antibody response to the recombinant vaccinia and did not suppress an anti-vaccinia antibody response. Secondary cytotoxic T-lymphocyte killing of influenza virus-infected target cells was relatively low in all animals that were immunized with the recombinant vaccinia, and showed some dose-dependent suppression by the passively administered antibody. The dose dependence of the inhibition suggests that while immunization with recombinant vaccinia viruses may not be effective at birth, they may be useful at several months of age.

Animals↗

PubMed1993

Surgical issues in the management of the HIV-infected patient.

As of 1992, approximately 1,000,000 Americans are infected with HIV. The natural history of the illness includes a relatively long latent period (about 10 years) between infection and development of AIDS. Surgeons are called on to participate in the management of these patients, usually for diagnostic biopsies, supportive measures, or intraabdominal events. Precautions and safe surgical practices will minimize the risk of HIV transmission from patient to surgeon (or surgeon to patient).

Cross Infection↗

PubMed1993

Heterotypic immune mice lose protection against influenza virus infection with senescence.

Influenza causes significant morbidity and mortality in the elderly. To determine whether this could be due to loss of heterotypic immunity, young and aged BALB/c mice were made heterotypically immune by H3N2 influenza virus infection and then challenged, while anesthetized, with H1N1 virus. Viral clearance was delayed by 2 days in the aged mice. Naive and heterotypic immune mice were next challenged with H1N1 virus while awake. Under these conditions, initial infection was restricted to the nose in all animals. The virus spread to the lungs of the young and aged naive mice but not of heterotypic immune young mice. Heterotypic immunity of aged mice did not prevent spread of the virus to the lungs. The impaired recovery of aged mice correlated with lower antiinfluenza cytotoxic T lymphocyte (CTL) activity. Thus, a possible explanation for the increased severity of influenza in elderly humans is loss of CTL-mediated heterotypic immunity.

Aging↗

PubMed1993

Tuberculosis: a growing concern for dentistry?

Dentists are increasingly treating patients who have significant medically compromising conditions, a number of which predispose individuals to tuberculosis. Three case reports describe patients with histories of tuberculosis exposure. The authors also discuss risk assessment and offer practical guidelines for dental management of these patients.

Aged↗

PubMed1993

Decreased sensitivity to cAMP in the in vitro generation of memory splenic cytotoxic T-lymphocytes from aged mice: role of phosphodiesterase.

The effects of increased intracellular concentration of cyclic AMP (cAMP) on cellular immune function of young and aged mice were examined by using an in vitro anti-influenza cytotoxic T-lymphocyte (CTL) assay. We found that increasing intracellular concentrations of cAMP with either the cAMP analog, N,6O2'-dibutyryl cAMP, or the beta adrenergic agonist, metaproterenol, significantly inhibited the in vitro development of memory CTL activity of young mice. The development of CTL activity of aged mice, however, was less sensitive to the effects of these agents. We found that the S-isomer of cAMPS, a cAMP analog resistant to the effects of PDE, caused equivalent inhibition of CTL activity in the young and aged mice. This suggested that the cause of the decreased cAMP sensitivity in aging was increased PDE activity. In subsequent experiments, we found that the PDE from T-cells of aged mice have higher KM and higher Vmax for cAMP than the PDE from T-cells of young mice. Because beta-agonists probably act as a counter-regulatory hormone at an inflammatory site, the decreased sensitivity to cAMP in aging may be a compensatory response to the age-related decline in immune function.

Aging↗

PubMed1992

Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge.

To investigate the role of CD8+ T lymphocytes in recovery from influenza pneumonia, we used transgenic mice either homozygous (-/-) or heterozygous (+/-) for beta 2-microglobulin (beta 2-M) gene disruption. These mice lack major histocompatibility complex-restricted class I (CD8+) T cells. We found that after challenge with a nonlethal influenza virus, the beta 2-M (-/-) mice had significantly delayed pulmonary viral clearance. Furthermore, after challenge with a more virulent influenza virus, the beta 2-M (-/-) mice had a significantly higher mortality rate than did control mice. Thus, CD8+ T cells are important in recovery from virulent influenza infections, but other host defense mechanisms can clear the respiratory tract of more benign infections.

Animals↗

PubMed1992

The heterogeneity of the age-related decline in immune response: impairment in delayed-type hypersensitivity and cytotoxic T-lymphocyte activity occur independently.

Aged mice are known to have a heterogeneous cytotoxic T-lymphocyte (CTL) response to an influenza challenge. We sought to determine whether delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) was also heterogeneous in aging and, if so, whether this correlated with anti-influenza CTL activity. Aged mice developed mean footpad swelling of 0.24 +/- 0.09 mm following SRBC challenge and mean CTL activity of 35 +/- 18%. Even though these values were significantly lower than those from young mice (0.54 +/- 0.10 mm and 51 +/- 2%, respectively), no correlation was found between anti-influenza CTL activity and DTH to SRBC (r = 0.01). We believe the most likely reason for this independent decline in immune response is because different activation signals are required for DTH and CTL activity. Our data thus suggest an age-related functional mosaicism in the immune system.

Aging↗

PubMed1992

The association of E. coli peritonitis with an impaired and delayed fever response in senescent rats.

Infection is one of the leading causes of death in elderly humans, and the importance of the early diagnosis of severe infection is undisputed. In the elderly a delay in diagnosis is often due to a reduced or absent fever. To understand more fully the pathogenesis of fever in senescence, we assessed the febrile response to E. coli peritonitis in 3-, 12-, and 24-month-old rats. Baseline temperatures were unchanged with age. Following infection with 1 x 10(8) CFU E. coli, a fever was evident in 2.8 h in the young, 3.9 h in the 12-month-old rats, and delayed until 5.8 h in the senescent rats. The magnitude of the fever was quantitatively less in the older rats compared with the two younger age groups throughout the time course of the fever. Because beta-adrenergic-mediated thermogenesis in brown adipose tissue has been implicated in the genesis of fever, we also assessed adenylate cyclase activity in this tissue. There was a progressive age-related decrease in both receptor- and postreceptor-stimulated adenylate cyclase activity. Our findings indicate there is both a delay in the onset of the fever and a reduced febrile response in the senescent rats following E. coli infection.

Adenylyl Cyclases↗

PubMed1992

Impaired febrile response with age: role of thermogenesis in brown adipose tissue.

We demonstrated previously that in Escherichia coli-infected rats, the heat necessary for the febrile response is a result of thermogenesis in brown adipose tissue (BAT). To investigate whether senescent rats have an impaired febrile response to infection and whether such an impairment is a result of attenuated sympathetically activated thermogenesis in BAT, we assessed body temperature and the increase in mitochondrial guanosine 5'-diphosphate (GDP) binding sites in interscapular BAT in response to E. coli administration in young and senescent male F-344 rats. There was a significant delay of 2 hr in the onset of fever in the older animals. In addition, in senescent rats, the peak fever (1.0 +/- 0.1 delta degrees C vs 2.2 +/- 0.1) and the cumulative fever (383 +/- 43 delta degrees C.min vs 775 +/- 69) were significantly less than in the young rats (P less than 0.005). Baseline levels of GDP binding were the same in young and old rats. In young rats, during the rising phase of the fever, E. coli infection resulted in a 50% increase in the density of GDP binding sites in BAT mitochondria. In contrast, there was no increase in GDP binding in the older rats following infection. The failure to increase GDP binding may be a result of a reduced ability to unmask reserve GDP binding sites. Alternatively, there may be fewer total GDP binding sites (masked and unmasked) in senescent rats and these sites may already be unmasked. Collectively, these data suggest that the impaired febrile response with age is due to reduced thermogenesis in BAT.

Adipose Tissue, Brown↗

PubMed1992

Outpatient management of patients infected with human immunodeficiency virus.

The outpatient management of patients infected with human immunodeficiency syndrome is reviewed. Patients with CD4+ cell counts of greater than 0.5 x 10(9)/L (500/mm3) require no specific intervention except vaccination against influenza, pneumococcus, and possibly hepatitis B. They should have a follow-up examination every 3 to 6 months. Because of its success in preventing the progression of the disease, zidovudine (AZT), 100 mg five times per day, is recommended for patients with CD4+ cell counts of less than 0.5 x 10(9)/L (500/mm3). During this stage of the disease, a patient should be seen every 1 to 3 months and monitored for drug toxicity and disease progression. Patients with CD4+ counts of less than 0.2 x 10(9)/L (200/mm3) are at high risk of developing Pneumocystis carinii pneumonia. Prophylaxis with oral trimethoprim-sulfamethoxazole (one double-strength tablet three times weekly) or dapsone (100 mg three times weekly) is recommended. Treatment costs for the patient with CD4+ cells less than 0.5 x 10(9)/L (500/mm3) are at least $3000 per year.

Adult↗

PubMed1992

Sepsis.

Septic shock is associated with a very high mortality in elderly patients. This is likely due to the age-related anatomic and physiologic changes and the presence of comorbid diseases. Medical management of patients with septic shock consists of antibiotics, fluids, vasopressors, and careful monitoring. Judicious use of antiendotoxin monoclonal antibodies may be a beneficial adjunctive therapy.

Aged↗