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Biomedical subjects

B S Bender

Publications and source records attributed to B S Bender.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1987

Homosexual men with thrombocytopenia have impaired reticuloendothelial system Fc receptor-specific clearance.

Classic immune thrombocytopenia purpura (ITP) occurs predominantly in women and is associated with either normal or impaired Fc receptor-mediated clearance of antibody-coated cells. Recently, an increasing incidence of thrombocytopenia has been observed in homosexual men, but whether Fc receptor-mediated clearance of antibody-coated cells is normal or impaired in these men is unknown. To study this question, we measured the in vivo clearance of anti-Rho(D) IgG antibody-sensitized 51Cr-labeled autologous red cells in five homosexual men with thrombocytopenia without an evident cause. All five had antibodies to human immunodeficiency virus, and four had circulating immune complexes as determined by a Clq-binding assay. Two of the men tested also had an increase in platelet-associated IgG. In the four homosexual men with platelet counts of 20,000/microL or less, the clearance half-time of IgG-sensitized red cells was prolonged (mean, 106 minutes; range, 72 to 140 minutes) as compared with the clearance of such cells in five hematologically normal men (mean, 39 minutes; range 30 to 50 minutes; P less than .005). One homosexual man with a platelet count of 81,000/microL had a normal clearance half-time (30 minutes). Three patients whose platelet counts increased after corticosteroid therapy were restudied. In all three, the clearance of antibody-coated cells was shortened and returned to normal in the one patient who had achieved a complete remission. No correlation was observed between the presence of platelet-associated IgG or circulating immune complexes and the clearance half-time. These data indicate that severe thrombocytopenia occurring in homosexual men as in some patients with classic ITP is associated with defective in vivo Fc receptor-mediated clearance of antibody-coated cells.

Adrenal Cortex Hormones↗
PubMed1986

Is Clostridium difficile endemic in chronic-care facilities?

An apparent outbreak of Clostridium difficile diarrhoea on the chronic hospital ward of a long-term care facility prompted an investigation lasting seven months. Approximately a third of patients had stools that were positive for C difficile by either toxin or culture. Attempts to eradicate the infection by simultaneously treating all toxin-positive patients with metronidazole, limiting antibiotic use, and implementing enteric isolation were unsuccessful. New cases were both nosocomially acquired and imported into the facility. Of the C difficile toxin-positive patients, 34% had diarrhoea and 19/49 (38%) died during the study period. C difficile is not routinely sought by most clinical microbiology laboratories and may therefore be endemic in many long-term care facilities for the elderly.

Adult↗
PubMed1986

Age differences in phagocytosis by polymorphonuclear leukocytes measured by flow cytometry.

Elderly persons have increased morbidity and mortality due to bacterial infections. Since the polymorphonuclear leukocyte (PMN) is a major defense against bacterial infection, we utilized fluorescent microspheres and flow cytometry to examine phagocytosis by PMNs from 55 young and middle-aged adults (mean age 41.5 yrs) and two groups of elderly subjects: one group of 35 healthy individuals (mean age 74.1 years) living at home, and a second group of 11 residents (mean age 83.1 years) with severe mental and physical disabilities, living in a domiciliary care facility. We determined the percent phagocytic PMNs, the number of microspheres per PMN, and the number of microspheres per 100 PMNs. The mean number of microspheres per phagocytic PMN was similar for all groups. Statistically significant differences were found between the young and middle-aged group and the healthy or ill elderly groups for the percent phagocytic PMNs (75.3% vs 51.5% and 43.8%), and the number of microspheres per 100 phagocytic PMNs (197.3 vs 131.4 and 103.2). There were no significant differences in these parameters between healthy and debilitated elderly subjects. These data document that there is an age-related increase in representation of a population of PMNs which have a defect in phagocytic ability.

Adult↗
PubMed1986

New developments in infectious diarrhea.

The past decade has produced exciting advances in our knowledge of infectious diarrhea. The list of potential enteric pathogens continues to grow with both the identification of new organisms, e.g., E. coli serotype O157:H7, and the recognition that previously characterized microorganisms, e.g., M. avium-intracellulare, can also cause gastrointestinal disease in immunosuppressed patients. Multiple investigations have led to a greater understanding of the epidemiology and clinical features of these illnesses. Application of modern biological techniques has yielded a number of diagnostic assays that are just now becoming clinically relevant. New drugs and treatment modalities for enteric infections have been developed and are now being evaluated in clinical trials. Despite these advancements, however, many questions still remain unanswered. For example, the etiology of the debilitating diarrhea in AIDS patients in whom no known intestinal pathogen can be identified remains unknown. The mechanism of diarrhea due to Cryptosporidium, Isospora, and Giardia remains elusive. And last, will new intestinal vaccines be effective in preventing diarrheal disease? Certainly, the next decade of research in enteric diseases should prove to be even more interesting than the last.

Adolescent↗
PubMed1986

Absolute peripheral blood lymphocyte count and subsequent mortality of elderly men. The Baltimore Longitudinal Study of Aging.

In this 16-year longitudinal study of 105 healthy elderly men, we analyzed one aspect of immunosenescence--a decline in the absolute number of peripheral blood lymphocytes--with particular reference to its relationship with subsequent mortality. It was found that there was a significantly (P less than .01) lower absolute lymphocyte count (1432 +/- 55/mm3; mean +/- SEM) within three years of death when compared with five years (1719 +/- 89/mm3) or 10 years (1715 +/- 98/mm3) before death. There was no relationship between this decrease in lymphocytes and age at death, smoking status, or prior cardiac illness. Previous cross-sectional studies have yielded conflicting data on age-related decreases in lymphocytes which may have been the result of an unrecognized selection process that either eliminated or included subjects who were close to death.

Aged↗