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Biomedical subjects

B S Bender

Publications and source records attributed to B S Bender.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Influenza: pathogenesis and host defense.

Our understanding of the host defense and pathogenesis of influenza has come from parallel studies in animal models and humans. Infection is initiated by deposition of influenza particles on either the upper respiratory tract epithelium or directly into the alveoli, with the former method having a lethal dose several orders of magnitude greater than the latter. The virus attaches to its cellular receptor by its hemagglutinin (HA); if this step is blocked by specific antibody, infection does not take place. The major role of antibody is in the prevention of disease. Even though serum antibody (primarily antihemagglutinin, but also antineuraminidase) has been known for decades to prevent viral pneumonia, it has only more recently been shown that passive administration of anti-influenza serum to virgin mice prevents pneumonia, but not rhinotracheitis. Further, intravenously administered anti-influenza IgA has been shown to be specifically transported into the nasal secretions and protect the murine nasopharynx against influenza infection. Whereas antibody is clearly required for protection against influenza, cytotoxic T-lymphocyte (CTL) activity is both necessary and sufficient for recovery from influenza. This was best shown in studies using nude (athymic) mice. Influenza-infected nude mice shed virus from their lungs indefinitely. Adoptive transfer of anti-influenza CTLs to influenza-infected nude mice will clear the virus from their lungs, whereas administration of anti-influenza antibody will lead to a cessation of viral shedding only as long as antibody is present. Influenza in aging presents a serious clinical problem. Recent studies suggest that the age-related decrease in anti-influenza CTL activity causes both prolonged viral shedding and increased viral spread through the respiratory tract.

Aging↗
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

Escherichia coli peritonitis activates thermogenesis in brown adipose tissue: relationship to fever.

Fever is a complex and important nonspecific, host defense mechanism against infection. The generation of the heat necessary to increase body temperature may involve thermogenesis in brown adipose tissue. To investigate whether the febrile response to Escherichia coli peritonitis involves thermogenesis in brown adipose tissue, we assessed whole rat oxygen consumption and brown adipose tissue mitochondrial guanosine 5'-diphosphate binding. Non-lethal doses of E. coli, 1 x 10(6) to 1 x 10(8) colony forming units, induced a fever for greater than 8 h. In contrast, a dose of 1 x 10(9) colony forming units resulted in a progressive hypothermia culminating in death. A 48% increase in oxygen consumption (p less than 0.05) in E. coli-infected rats occurred almost immediately, preceded the development of the fever, and was sustained throughout the fever. There was a highly significant correlation (r = 0.736, p less than 0.01) between oxygen consumption and body temperature for both control and infected animals. Guanosine 5'-diphosphate binding assessed by multi-point Scatchard analysis of [3H]guanosine 5'-diphosphate binding to isolated mitochondria was increased by 45.4 +/- 7.3% at 1.75 h and by 31.9 +/- 9.0% at 3.5 h (p less than 0.05). The greater increase was during the rising phase of the fever. Unexpectedly, a lethal dose of 5 x 10(9) colony forming units of E. coli also increased guanosine 5'-diphosphate binding sites by 54.4 +/- 14.2% (p less than 0.05) despite a hypothermia of -1.71 +/- 0.29 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

Role of anaerobic bacteria in perimandibular space infections.

This review includes 44 patients with perimandibular space infections admitted to Johns Hopkins Hospital during a 5-year period. The most frequent spaces involved were the submandibular, peritonsillar, and parapharyngeal spaces. As expected, 1) peritonsillar abscesses were invariably associated with pharyngitis, 2) submandibular and buccal space infections generally represented complications of dental infections, and 3) parapharyngeal space infections were associated with both portals of entry. Most patients were treated with drainage procedures, and all received antimicrobial agents, the most common being penicillin. Serious complications included potential airway obstruction requiring tracheostomy in six patients with Fusobacterium bacteremia and two patients with septic emboli to the lung. All patients survived, and most had a relatively brief hospitalization with no sequelae.

Adult↗
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

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

Long-term urinary tract catheterization.

As the nursing home population expands, the number of patients exposed to the risks of chronic indwelling urinary catheters will increase. The physician must therefore be familiar with the characteristic findings in such patients and be able to recognize complications as they arise. Mechanical or local problems, such as asymptomatic bacteriuria, catheter blockage, nondeflatable balloon, and chronic cystitis, are very common. Further studies are needed to define optimum measures to control these problems. The clinician must be aware that pyuria and bacteriuria are universal and not helpful in diagnosis of infection in this population. Use of chronic antibiotics is not recommended and there is no evidence to support elaborate daily care regimens, such as antibiotic ointments or irrigations. Careful consideration of the indications for catheter use on a long-term basis may reduce the population at risk. Physician awareness of the possibility of life-threatening complications, such as squamous cell carcinoma, bacteremia, and bladder perforation, can help avoid serious consequences of the use of urinary drainage devices.

Aged↗
PubMed1989

Viral pneumonia attenuates adenylate cyclase but not beta-adrenergic receptors in murine lung.

Respiratory infections provoke increased airway reactivity in both asthmatic and otherwise healthy subjects in part through impaired beta-adrenergic relaxation of bronchial and tracheal muscle. The precise mechanism remains obscure, but some studies report a decrease in the number of beta-adrenergic receptors. The present study was designed to assess the effect of viral respiratory infection with influenza A on lung beta-adrenergic receptors and adenylate cyclase activation in mice under two separate protocols. First, to determine whether changes are due to a local or systemic effect, we compared mice with influenza infections limited to the upper respiratory tract to mice with infection of the total respiratory tract. Four days after upper respiratory tract infection there were no changes in either isoproterenol- or NaF-stimulated adenylate cyclase activity. In contrast, there was an 82% decrease in isoproterenol- and a 25% decrease in NaF-stimulated adenylate cyclase activity on the fourth day after total respiratory tract infection. There were no changes in beta-adrenergic receptors or receptor coupling to adenylate cyclase with either type of infection. Our second protocol compared acutely infected mice to postrecovery mice. Twelve days after infection the virus was no longer present in the lungs, and adenylate cyclase activity was restored to normal. These data suggest that viral respiratory infection may impair airway function through attenuation of receptor and postreceptor activation of adenylate cyclase activity.

Adenylyl Cyclases↗
PubMed1988

Depressed natural killer cell function in thermally injured adults: successful in vivo and in vitro immunomodulation and the role of endotoxin.

Natural killer (NK) cells mediate host defense against infections and are regulated by interleukin 2 (IL-2) and other factors. We studied NK cell function in burn patients using a 51Cr release assay with K562 target cells. We found that peripheral blood lymphocytes from burn patients had depressed NK activity (target cell lysis = 22.0 +/- 3.1% vs 39.8 +/- 3.2% in healthy volunteers, P less than 0.001) and also a lower response to IL-2 (28.9 +/- 3.8% vs 53.2 +/- 4.3%, P less than 0.001). Thirteen burn patients were randomly assigned to receive either standard therapy or 5 days of intravenous polymyxin B in addition to standard therapy. After 2 weeks, the patients not receiving polymyxin B had a significant decline in peripheral blood NK activity (P less than 0.01) and response to IL-2 (P less than 0.05), while no decline in NK cell activity was seen in patients who received polymyxin B. Sera from burn patients was found to suppress the NK activity of lymphocytes from healthy adults by 5-75%. After using affinity chromatography to remove endotoxin, the sera from burn patients no longer suppressed NK cell activity. Circulating endotoxin appears to be involved in the suppression of NK activity in burn patients.

Adult↗
PubMed1988

Decline in rates of clearance of IgG-sensitized erythrocytes with increasing age.

Decreased immune functions have been suggested as a cause for the increased incidence of autoimmunity, malignancy, and infection in the elderly population. To assess the possible role of changes in macrophage function in the aging process we studied the Fc receptor-mediated clearance of IgG-coated erythrocytes in 56 healthy normal volunteers by following the removal of radiolabeled autologous erythrocytes. An age-related decrease in Fc-mediated clearance rates in both female and male subjects was found, which suggests a physiological decline of this macrophage function in older individuals.

Adult↗
PubMed1987

Demonstration of defective C3-receptor-mediated clearance by the reticuloendothelial system in patients with acquired immunodeficiency syndrome.

The function of macrophage C3 receptors was assessed in vivo by measuring the clearance of C3-sensitized autologous erythrocytes in seven acquired immunodeficiency syndrome (AIDS) patients, eight healthy homosexual men, eight healthy heterosexual men, and four infected controls. Healthy heterosexual men had an initial clearance of 50.1 +/- 2.0% of the inoculum, with a release of a small portion of these cells (10.9 +/- 1.3%) into the circulation. Healthy homosexual men had a greater initial clearance of 66.0 +/- 4.2% (P less than 0.01) followed by a similar release (14.0 +/- 3.3%). AIDS patients had an initial clearance of 60.6 +/- 7.5% but had a relatively large release of cells (25.6 +/- 3.2%) (P less than 0.005 vs. heterosexuals; P less than 0.05 vs. homosexuals), suggesting a failure of macrophage phagocytosis. Infected controls had an initial clearance of 59.4 +/- 4.9%, with a release of 19.6 +/- 3.8% (P = NS vs. AIDS). These data, in addition to Fc-receptor dysfunction, demonstrate a global reticuloendothelial system dysfunction in AIDS patients. This may contribute to their frequent infections with opportunistic pathogens and inappropriate immune responses against these microorganisms.

Acquired Immunodeficiency Syndrome↗