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Biomedical subjects

K R Young

Publications and source records attributed to K R Young.

At least 37 records · Page 2Linked to original sources

Biochemical characteristics of alveolar macrophage-specific peroxidase activities in the rat.

The biochemical characteristics of endogenous macrophage peroxidases (Po), and their relationship to myeloperoxidase (MPO), have heretofore been poorly understood and were examined in the current study. Rat alveolar macrophages (AM) were homogenized and fractionated by differential centrifugation into lysosomal and microsomal fractions. The Po activities in both fractions were separated using HPLC gel-filtration and two main activities were detected. One, in the lysosomal fraction, had a relative molecular mass (Mr) of 58,000, while the other, associated with the microsomal fraction corresponded to Mr 74,000. By comparison, MPO from rat polymorphonuclear neutrophils (PMN) had Mr 140,000. The 58- and 74-kDa Po activities also differed from MPO with respect to their apparent Km for H2O2 and optimum pH of activity. Using o-dianisidine as a substrate, the Km for H2O2 of the 58- and 74-kDa Po species was 0.4 and 0.19 mM, respectively, compared to 0.011 mM for MPO. Using monochlorodimedon, the corresponding values were 0.22 and 0.195 mM for the 58- and 74-kDa activities and 0.026 mM for MPO. With either substrate, MPO exhibited optimum activity at pH 5.4, compared to 5.2 for the 58-kDa activity and 4.8 for the 74-kDa species. Thus, rat AM contain two endogenous Po activities with biochemical characteristics distinct from those of MPO. Our findings suggest that these activities represent novel peroxidases that may play an important role in the oxidative metabolism of AM.

Animals↗

Induction of proliferation by high molecular weight B cell growth factor or low molecular weight B cell growth factor is associated with increases in intracellular calcium in different subpopulations of human B lymphocytes.

The activation of resting B cells with anti-surface Ig is associated with transient increases in intracellular calcium. In the present study, we demonstrate that stimulation of B cells which have already been activated by Staphylococcus aureus Cowan I (Sac), with high molecular weight B cell growth factor (HMW-BCGF) or low molecular weight B cell growth factor (LMW-BCGF), but not IL-2, IL-4, or interferon-gamma, is associated with an increase in intracellular calcium, which is modest compared to that seen with anti-Ig (approximately 100 nM vs approximately 400 nM). The increases in intracellular calcium induced by HMW-BCGF or LMW-BCGF occur in distinct but overlapping subpopulations of B cells. Thus, increases in intracellular calcium in human B cells occur not only upon activation but also upon the induction of proliferation by certain (but not all) B cell growth factors. Presumably, the effect of increasing intracellular calcium during the induction of proliferation is to modify a different group of intracellular molecules than those induced during activation.

B-Lymphocyte Subsets↗

The management of prolonged pregnancy--an analysis of women's attitudes before and after term.

OBJECTIVE: To determine the attitude of pregnant women to a proposal of conservative management of prolonged pregnancy. DESIGN: A prospective questionnaire-based survey. SETTING-Louise Margaret Maternity Wing, Cambridge Military Hospital, Aldershot. SUBJECTS: 500 pregnant women initially at 37 weeks gestation considered suitable for the potential conservative management of prolonged pregnancy. RESULTS: Despite a stated obstetric preference for conservative management, only 45% of the women at 37 weeks gestation were agreeable to conservative management; of those undelivered by 41 weeks gestation 31% still desired conservative management. This significant decrease was unaffected by parity or certainty of gestational age. CONCLUSIONS: Most pregnant women are unwilling to accept the conservative management of prolonged pregnancy and become more reluctant to do so if undelivered by 41 weeks gestation. Women are not as favourably disposed towards the conservative management of pregnancy as has been suggested previously.

Attitude to Health↗

High school driver education using peer tutors, direct instruction, and precision teaching.

The authors investigated the combined effects of direct instruction and precision teaching by peer tutors in a high school driver education curriculum. Learners (N = 4) included students with intellectual and learning disabilities and students without disabilities. Peer tutoring was associated with immediate increases in correct responding and a simultaneous and rapid deceleration of errors. Three learners passed the written tests in the driver education classroom, obtained driver's licenses, and produced similar or better driving records than students who did not require assistance. This program is being continued and expanded by school personnel without assistance from the authors.

Adolescent↗

Pulmonary-renal syndromes.

Although they are complex, the pulmonary-renal syndromes can be readily understood and managed using a clinical approach firmly grounded in the fundamental pathophysiology of these disorders. Several important principles must be borne in mind. First, therapeutic intervention must be preceded by making as firm a diagnosis as possible. In these disorders, histologic confirmation of the diagnosis is almost always mandatory, because the therapy differs substantially from one disorder to the next and several of the therapeutic options carry significant toxicity. Open lung biopsy is frequently required to obtain sufficient tissue to warrant a specific diagnosis, and repeat open biopsy may be necessary at times to differentiate relapse of disease from supervening infection or complications of therapy. The course of the pulmonary-renal disorders may be extraordinarily fulminant, leading to irreversible organ failure and death in a matter of hours to days; this mandates an aggressive approach to therapy, with close attention paid to monitoring of the side effects of therapy. Lastly, as these illnesses are often characterized by a relapsing course, patients must be followed with vigilance.

Anti-Glomerular Basement Membrane Disease↗

Rupture of angiomyolipoma of the kidney presenting as puerperal collapse.

We report an unusual presentation of angiomyolipoma of the kidney. Whilst a conservative surgical approach is ideal, the greatly increased cardiac output in pregnancy makes haemorrhage more severe and hence more radical surgery is often required. The difficulty in reaching a correct pre-operative diagnosis can lead to an unusual approach to nephrectomy, of which the surgeon should be forewarned.

Adult↗

Neutrophil chemotactic activity produced by normal and activated human bronchoalveolar lavage cells.

Activated macrophages can secrete a number of mediators that can attract inflammatory cells and enhance secretion of phlogistic substances from these cells. The ultimate effect of activated bronchoalveolar lavage (BAL) cells may be fibrotic lung injury. Inasmuch as pulmonary sarcoidosis is a disease associated with spontaneous activation of macrophages and lymphocytes among BAL cells, cells obtained from patients with sarcoidosis were compared with normal cells. We report that adherent BAL cells in culture from patients with sarcoidosis (n = 21) release during a resting period in vitro more chemotactic activity for neutrophils (PMNs) than do BAL cells from normal individuals (n = 14). After density fractionation of the respiratory cells by albumin gradient, cells from high-density fractions in the group with sarcoidosis secrete more chemotactic activity for neutrophils than cells from less dense fractions. The PMN chemotactic activity spontaneously released in vitro by BAL cells from patients with sarcoidosis correlates with the percentage of PMNs recovered by BAL. Immunochemical bioassay and high-performance liquid chromatographic (HPLC) analysis of BAL cell supernatants revealed a complex pattern of chemotactic factors to be present. Generally, three peaks of chemotactic activity were noted on HPLC 1-60 separations at greater than 20 kd, 8 to 10 kd, and less than 1 kd apparent molecular weights. Significantly, interleukin-1 was present in these supernatants, whereas complement components and leukotriene B4 were absent. Sarcoid BAL cells, principally alveolar macrophages, are activated in vivo as manifested by spontaneous secretion of chemotactic factors for PMNs in vitro. Interleukin-1 and other less well characterized molecules were detected. The presence of PMNs among the lavage cells of some patients with sarcoidosis appears to be an in vivo biologic correlate of this activation. These data provide additional criteria of BAL cell activation in patients with pulmonary sarcoidosis and provide further evidence concerning factors that attract inflammatory cells into the lung.

Bronchoalveolar Lavage Fluid↗

Interstitial lung diseases in the elderly patient.

In this article we have attempted to review basic aspects of the respiratory immune system and some of what is known about the effects of aging on immunity. We have discussed the more common forms of interstitial lung disease as they relate to the elderly patient and have outlined a general method of approaching interstitial disease in this population. This topic is the focus of considerable ongoing research, and a wealth of information is available for the clinician who desires to delve more deeply into the subject. It is our hope that this article will serve as a background to facilitate further study by those with a particular interest in this area.

Aged↗

Pulmonary macrophage function during experimental cytomegalovirus interstitial pneumonia.

Since cytomegalovirus (CMV) infections may alter host defense against a variety of pathogens, phagocytosis, oxygen uptake, and H2O2 release by pulmonary macrophages obtained from guinea pigs with acute CMV interstitial pneumonia were evaluated. Experimental animals were inoculated subcutaneously on day zero with 10(7.5) 50% tissue culture infective doses of virulent guinea pig CMV. Control animals received an uninfected salivary gland suspension. The animals were sacrificed on day 7; the tissues were cocultivated for virus isolation, and the lungs were lavaged to obtain pulmonary macrophages. CMV was isolated from buffy coat cells (96%), bone marrow cells (71%), whole lungs (77%), pulmonary macrophages (60%), and pulmonary granulocytes (49%). There was no significant difference between groups at sacrifice in the total number of macrophages obtained by pulmonary lavage or in the phagocytic activity of the macrophages in vitro. However, in CMV-infected animals, the maximum rates of O2 consumption in response to the soluble stimulus, phorbol myristate acetate, and the particulate stimulus, Staphylococcus aureus, were 47 and 55%, respectively, of the rates in uninfected controls. Total macrophage O2 consumption in CMV-infected animals was 32 and 37%, respectively, of control values in response to the same stimuli. In CMV-infected animals, the maximum rates of H2O2 release were 22% of those in simultaneous controls for both stimuli, and total H2O2 release was 30 and 25%, respectively, of that in controls in response to these stimuli. Such alterations in macrophage oxidative function may contribute to superinfection during CMV pneumonia.

Acute Disease↗

Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. An immunologic analysis.

Several components of cellular and humoral immunity were examined in bronchoalveolar lavage fluid and blood of 15 patients with the acquired immunodeficiency syndrome, and the results were compared to data from 25 healthy controls (including 5 asymptomatic homosexual men). Compared with that of controls, bronchoalveolar lavage fluid from patients tended to have more lymphocytes and significantly more neutrophils; a lower OKT4/OKT8 ratio, due to an increase in total OKT8 cells; and normal total OKT4 cell counts, despite a significant decrease in numbers of OKT4 cells in peripheral blood. Patients also had significantly more IgG-releasing cells and higher IgG levels than controls in lavage fluid. These data show that, in the lung lining fluid of patients with the acquired immunodeficiency syndrome, significant alterations in cellular and humoral immunity exist that differ in several important respects from immunity in controls and from corresponding changes in patients' peripheral blood.

Acquired Immunodeficiency Syndrome↗

Receptors for human IgG subclasses on human alveolar macrophages.

The biology of individual heavy chain subclasses of human IgG (IgG1-4) in lung host defenses has become important now that specific deficiencies of certain subclasses (IgG2 and IgG4) can be associated with chronic sinopulmonary infections and that IgG4 can be increased in forms of hypersensitivity lung disease. Because IgG is an important opsonic antibody that promotes attachment of bacteria or particles to phagocytes, the relative binding of IgG subclasses to membrane receptors on human alveolar macrophages might predict the efficacy of specific opsonin-mediated phagocytosis. With in vitro cultured normal alveolar macrophages, various IgG complexes were assessed for receptor binding with a rosetting assay. For respiratory cells in culture for 24 h, about 25% of the macrophages bound IgG3 and about 10% bound IgG1; binding with IgG2 and IgG4 complexes was minimal. In macrophage cultures maintained for as long as 6 days, this pattern of binding persisted. However, in very short-term cultures, 30 min and 105 min after cell adherence had occurred, binding was much greater for IgG3 complexes (about 60%); likewise IgG1 and IgG4 bound to about 20% of the cells. The IgM erythrocyte complexes, usually showing no binding at later time points in culture, bound to 20% of the cells, acutely. Therefore, our studies found that IgG3 consistently bound to more alveolar macrophages than the other subclasses, including IgG1. Also, the duration in culture of adherent cells may significantly affect the pattern of binding.

Adult↗

The acquired immune deficiency syndrome (AIDS): current status and implications for respiratory care practitioners.

The acquired immune deficiency syndrome (AIDS) has affected more than 2,600 persons since 1981, with the number of reported cases rising exponentially. The disease is characterized by a deficiency in the cell-mediated immune system, which allows entrance to a host of opportunistic infections as well as tumors. The most common infection associated with AIDS is Pneumocystis carinii pneumonia, a previously uncommon infection of immunocompromised hosts. The most common neoplasm associated with AIDS is an otherwise rare skin tumor, Kaposi's sarcoma. AIDS is most often seen in homosexuals and intravenous-drug abusers, but the spectrum of the disease is widening and now includes other high-risk groups. The pulmonary manifestations of AIDS range from a nonproductive cough to acute respiratory failure. Once hospitalized, the AIDS patient may require several diagnostic and therapeutic services from respiratory care personnel. We review the epidemiology of this new syndrome, provide the basic framework for an understanding of the immunologic dysfunction in AIDS victims, review the clinical manifestations, and discuss the implications of the communicability of AIDS for the respiratory care practitioner.

Acquired Immunodeficiency Syndrome↗