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Biomedical subjects

H H Newball

Publications and source records attributed to H H Newball.

At least 19 recordsLinked to original sources
PubMed1992

Uptake, distribution and fate of bacterial lipopolysaccharides in monocytes and macrophages: an ultrastructural and functional correlation.

Bacterial lipopolysaccharides (LPS), which are important components of the cell wall of gram-negative bacteria, induce a number of host responses both beneficial and harmful. The present review elucidates the uptake, distribution and functions of LPS in mononuclear phagocytes in an attempt to gain an insight into the mechanisms which control the pathogenesis of LPS mediated septic shock. The unique feature of LPS bilayer structure, the tagged LPS and antibodies to LPS provide means for studying binding, uptake, fate and subcellular distribution of LPS in tissues and cells. LPS bind to monocytes and macrophages by specific interaction via receptors such as scavenger receptors, CD14 and CD18 and by non-specific interactions, and enter the cells via receptor-mediated endocytosis, absorptive pinocytosis, phagocytosis, and diffusion. The ingested LPS are localized in pinocytic vesicles, phagocytic vacuoles, cytoplasm, mitochondria, rough endoplasmic reticulum, Golgi apparatus, and nucleus. The interactions of LPS with monocytes and macrophages trigger a broad spectrum of cellular responses, including production of important bioactive factors or mediators, such as IL-1, TNF, interferons, prostaglandins, and macrophage-derived growth factor, which are implicated in the pathogenesis of septic shock and wound healing. However, there is no conclusive evidence indicating that production of the mediators can only be induced through specific interactions.

Animals↗
PubMed1979

Anaphylactic release of a basophil kallikrein-like activity. I. Purification and characterization.

These studies describe the IgE-mediated relase of a basophil kallikrein-like enzyme that is an arginine esterase and is inhibited by plasma, diisopropylphosphofluoridate, and Trasylol. The substrate specificity for the synthetic amino acid ester substrates p-toluenesulfonyl-L-arginien methyl ester, benzoyl-arginine methyl ester, and acetyl-tyrosine methyl ester is similar for the basophil enzyme and plasma kallikrein. The interaction of arginine esterase-active fractions from ion-exchange (DEAE-Sephacel) and gel filtration (Sepharose 6B) chromatography, with human plasma kininogen, generates immunoreactive kinin. The basophil arginine esterase and kinin-generating activities co-chromatograph on Sepharose 6B and the quantity of kinin generated is, in general, proportional to the arginine esterase activity of the column fractions, suggesting that these two activities are subserved by the same protease. The ability of this protease to generate kinin equally well from heat- and acid-treated plasma, as from fresh human plasma, suggests that this protease has kallikrein-like activity. These data suggest that kallikrein-like activity can be generated from human basophils as a direct result of a primary IgE-mediated immune reaction, thus providing a potential link between reactions of immediate hypersensitivity and the plasma and(or) tissue kinin-generating systems.

Anaphylaxis↗
PubMed1979

Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions.

This report describes the immune release of a new mediator from human peripheral leukocytes, a basophil kallikrein-like activity (BK-A). The release process is initiated by the interaction of antigen on anti-IgE with cell-bound IgE, and appears to be similar in mechanism to the relase of histamine and other mediators of the immediate hypersensitivity reaction. The dose-response relationships and kinetics of histamine and BK-A release from antigen-challenged peripheral leukocytes are similar. The relase of the BK-A is calcium and temperature dependent, requires metabolic energy, and is controlled by hormone-receptor interactions that influence the cellular level of cyclic AMP, as has been described for other mediators of immediate hypersensitivity reactions. The data indicate that the interaction of BK-A with human plasma kininogen, generates immunoreactive kinin. We conclude that the antigen-IgE interation leads to the release from human basophils of a new mediator, a basophil kallikrein-like activity which may well be a link between reactions of immediate hypersenstivitity and the plasma and/or tissue kinin-generating systems.

Anaphylaxis↗
PubMed1979

Activation of human Hageman factor by a leukocytic protease.

We earlier reported the IgE-mediated release of a basophil kallikrein of anaphylaxis (BK-A) which, like plasma kallikrein, is an arginine esterase and cleaves human plasma kininogen generating immunoreactive kinin. We herein report that, like plasma kallikrein, preparations rich in this basophil protease also activate human Hageman Factor by proteolytic cleavage of the zymogen molecule into light and heavy chains. These fragments of 28,000 and 52,000 daltons are similar in size to those produced during activation of Hageman Factor by plasma kallikrein. Exposure of Hageman Factor (bound to a negatively charged surface) to BK-A led to the proteolytic cleavage of Hageman Factor producing a 28,000 molecular weight fragment (HFa) which is functionally active and capable of activating prekallikrein to kallikrein. We conclude that, during anaphylaxis, basophils may release a protease that is capable of cleaving and activating Hageman Factor, thus providing a mechanism for initiating the in vivo activation of the Hageman Factor dependent systems.

Anaphylaxis↗
PubMed1979

Basophil kallikrein of anaphylaxis (BK-A)--purification and characterization.

These studies describe the IgE-mediated release of a basophil kallikrein of anaphylaxis (BK-A) that has arginine esterase activity and is inhibited by plasma, DFP, and Trasylol. The interaction of BK-A active fractions from ion exchange (DEAE-Sephacel) and gel filtration (Sepharose 6B) chromatography, with human plasma kininogen generates immunoreactive kinin. The BK-A and kinin-generating activities co-chromatograph on DEAE-Sephacel and Sepharose 6B columns, and the quantity of kinin generated is, in general, proportional to the BK-A activity of the column fractions, suggesting that these two activities are subserved by the same protease. These data suggest that kallikrein-like activity can be generated from human basophils as a direct result of a primary IgE-mediated immune reaction, thus providing a potential link between reactions of immediate hypersensitivity and the plasma and/or tissue kinin-generating systems.

Anaphylaxis↗
PubMed1978

Collateral ventilation in man.

To determine whether collateral ventilation (defined as the ventilation of alveolar structures through passages or channels that bypass the normal airways) changes with age or emphysema, we compared the mechanics of collateral ventilation in seven young normal subjects, three old normal subjects and five patients with emphysema. In supine normal subjects at the end of a quiet expiration, resistance to airflow was greater through collateral channels than through bronchi and bronchioles. In emphysema, airways resistance could exceed collateral resistance, causing air to flow preferentially through collateral pathways. We conclude that high collateral resistance minimizes collateral airflow in supine normal subjects. When peripheral airways become obstructed or obliterated in emphysema, collateral channels may provide for more even distribution of ventilation.

Adult↗
PubMed1977

The influence of atropine and cromolyn on human bronchial hyperreactivity to aerosolized prostaglandin F2 alpha.

The mechanism of prostaglandin F2 alpha(PGF2alpha)-induced airway constriction was explored by determining the influence of atropine and cromolyn on the bronchoconstrictive properties of PGF2alpha. Increasing doses of aerosolized PGF2alpha were given (150, 300, 600, 1200 microgram) and the response of subjects was determined by measurements of spirometry, specific airway conductance (SGaw), and closing volumes. In normal subjects, PGF2alpha induced small but significant decreases of SGaw and spirometric parameters (FVC, FEV1), whereas there was no effect on the closing volumes. In contrast, in asthmatics, PGF2 alpha induced large decreases of SGaw and spirometric parameters. Asthmatics experienced severe and prolonged shortness of breath and wheezing, whereas normal controls experienced neither. Neither atropine nor atropine plus cromolyn was capable of preventing or substantially reversing the PGF2alpha-induced symptoms and airway constriction. The data suggest that reflex bronchoconstriction via irritant receptors is not a major mechanism of PGF2alpha-induced airway constriction. Although a minor vagally mediated reflex component may participate in the PGF2alpha-induced bronchoconstriction, it is masked by an overwhelming non-reflex mechanism that is probably a direct constricting effect of airways smooth muscle that is exquisitely sensitive to PGF2alpha.

Adolescent↗
PubMed1977

Chronic obstructive airway disease in patients with Sjögren's syndrome.

To determine the incidence of airway disease in Sjögren's syndrome, respiratory function was evaluated in 13 patients with this disorder. Six patients had clear evidence of airway disease without overt evidence of loss of elastic recoil, and 7 patients had normal pulmonary function studies. Five of the 6 patients with abnormal pulmonary function studies had never smoked cigarettes. Of the patients with severe airway disease, all had exertional dyspnea but none had chronic cough with sputum production or recurrent bronchospasm. The 3 patients with the most severely impaired pulmonary function studies showed abnormal single-breath nitrogen curves, increased residual volumes, and hypoxemia, whereas static pressure-volume curves and maximal static elastic recoil at total lung capacity were within predicted norms. Lung biopsy of 2 patients showed mononuclear cell infiltration aroung narrowed small airways. We concluded that certain patients with Sjögren's syndrome develop an unusual type of chronic obstructive airway disease, which is probably a result of a chronic mononuclear cell inflammatory process similar to that seen in their salivary and lacrimal glands. The data suggest that human airways should be considered another target organ of Sjögren's syndrome. Earlier reports have stressed the association of a restrictive pulmonary defect with Sjögren's syndrome. Our data suggest that the restrictive pulmonary defect seen in patients with the complete variation of Sjögren's syndrome is probably the result of the associated connective tissue disorder, rather than the result in the sicca complex.

Adult↗
PubMed1976

Effects of alternate-day prednisone therapy on respiratory function in myasthenia gravis.

To determine the effects of alternate-day prednisone therapy on respiratory function in myasthenia gravis, eight patients were evaluated during "days on" and "days off" prednisone. The patients were treated with long-term (up to three years), high-single-dose, alternate-day oral prednisone. After patients had been controlled with alternate-day prednisone they had no episodes of acute respiratory insufficiency or myasthenic crises. Although a small reduction in respiratory function during the day off prednisone was seen in some patients, the change was not statistically significant for the group and was probably physiologically unimportant in most patients. The data indicate that in myasthenic patients who have no underlying lung disease respiratory function is not significantly compromised by administering the prednisone on alternate days.

Adolescent↗
PubMed1976

Lung volumes and compliance in myasthenia gravis and reversible airway obstruction.

A patient with myasthenia gravis, reversible airway obstruction, and a vertical chest wall pressure-volume curve was shown to inflate his lungs to 12 liter during the night. During the day, either spontaneously or after isoproterenol, his functional residual capacity decreased by more than 2 liter. The large lung volume changes occurred without a change in slope of the static pressure-volume curve of the lung above functional residual capacity. The changes in the position of this curve might be due to the the very slow filling and emptying of bullae or to unexplained alterations in the length-tension characteristics of the alveoli. The vertical pressure-volume curve of the chest wall suggested that, unlike other patients who have normal or decreased chest wall compliance, this patient's chest wal was not a factor that limited ventilation at high lung volumes.

Airway Obstruction↗
PubMed1976

Separation of slow reacting substance of anaphylaxis (SRS-A) from human lung into four biologically active fractions.

Slow reacting substance of anaphylaxis (SRS-A) was released from human lung passively sensitized with ragweed antibody and challenged with specific antigen E. After purification by ethanol extraction, incubation with alkali (0.1 M NaOH for 30 min at 37 degrees C) and chromatography on silicic acid and DEAE-cellulose, human SRS-A was separated into four biologically active fractions (Fractions I to IV). Arylsulfatase (Type H-1) in 0.1 M sodium acetate buffer, pH 4.5, destroyed the biologic activity of only Fraction I. All four fractions, like SO4=, inhibited the arylsulfatase activity at pH 4.5 but not at pH 6.0 when p-nitrocatechol sulfate was used as substrate. These results suggest that SRS-A contain a sulfur group and that human STS-A, like the prostaglandins, may be a family of compounds. The instability of the purified SRS-A to storage remains a major barrier to their further purification and chemical identification.

Arylsulfatases↗
PubMed1975

Bradykinin and human airways.

This work explored the effects of bradykinin (BK) on human airways. Bradykinin (1 mug/kg body weight) was rapidly injected intravenously and respiratory system resistance (Rrs), closing volume (CV), forced vital capacity (FVC), expiratory volume in the first second (FEV1) maximal midexpiratory flow (MMF), and peak flow (PF) were measured. Bradykinin in normals produced no changes in Rrs or CV, but reduced the FVC. This suggests alveolar duct constriction, since no constriction of either large or small airways occurred with the decreased FVC. Bradykinin in asthmatics decreased the Rrs and CV, and increased the FEV1, MMF and PF, while the FVC did not change significantly. The absence of a significant increase in the FVC in the presence of concomitant bronchodilation, suggests that asthmatics also had alveolar duct construction. These data are consistent with animal studies which show that BK may release adrenalin (or other agents) with secondary effects, such as bronchodilation. The secondary bronchodilation seen in asthmatics but not in normals, is probably a result of the initial higher intrinsic bronchial tone of the asthmatics.

Adolescent↗
PubMed1975

Effect of elevated triglycerides on the diffusing capacity of man.

In view of the decreased diffusing capacity recently reported in man during lipid infusion, studies have now been made on the effects of hyperlipidemia on the diffusing capacity for carbon monoxide (DLco). In normal volunteers and patients with hyperlipidemias, DLco and plasma triglyceride concentrations were determined during fat tolerance tests and while the patients were on diets that increased or decreased triglyceride concentrations. During the fat tolerance tests, the largest triglyceride and DLco changes were from 346 mg per 100 ml with a DLco of 18.8 ml per min per mm Hg to 1,545 mg per 100 ml with a DLco of 23.4 ml per min per mm Hg. While patients were on speical diets, the largest triglyceride and DLco changes were from 5,102 mg per 100 ml and 29.0 ml per min per mm Hg to 492 mg per 100 ml and 26.4 ml per min per mm Hg, respectively. Sta tistical tests showed no significant change of DLco with change in triglyceride concentration. The data suggest that there is normally no association between change in triglyceride concentration and change in DLco, and that triglycerides normally transported in plasma, even when present in extreme amounts as chylomicrons or very-low-density lipoprotein, do not affect the DLco.

Adult↗
PubMed1975

Follow-up respiratory function of a patient treated with a membrane lung.

A patient in remission from acute lymphoblastic leukemia developed the adult respiratory distress syndrome. Despite "optimal respiratory therapy" and ventilatory assistance with 100 per cent inspired O2 (fraction of inspired O2 = 1) and 15 cm of positive end-expiratory pressure, the patient's arterial PO2 remained at 33 mm Hg. Prepulmonary venovenous respiratory support was given for 10 days with a spiral coil membrane lung. The data document the sequential improvement in respiratory function and suggest that despite the severe lung damage that may occur during the adult respiratory distress syndrome treated with prolonged high inspired concentration of O2, if the patient's lungs recover from the acute process, the respiratory system can recover so that there is little, if any, permanent restriction of the subject's activities as a result of respiratory impairment.

Child↗
PubMed1975

Specificity of opsonic antibodies to enhance phagocytosis of Pseudomonas aeruginosa by human alveolar macrophages.

These studies compared the ability of specific secretory IgA (sIgA) and IgG antibodies to promote phagocytosis of viable pseudomonas aeruginosa by human alveolar macrophages. Macrophages were obtained by lung lavage of normal adult smoker and nonsmoker volunteers and were maintained as in vitro cell monolayers. Both immune sIgA and IgG agglutinating antibodies were demonstrated to coat and opsonize viable bacteria, whereas similar nonimmune immunoglobulin preparations did not. When alveolar macrophages were challenged with viable opsonized 14C-labeled Pseudomonas IgG-reacted bacteria were ingested better and killed more readily than sIgA-opsonized organisms. Phagocytic responses were not significantly different between macrophages obtained from smokers and nonsmokers. Although sIgA and IgG antibodies can be found in respiratory secretions and both are undoubtedly important in pulmonary host defense, IgG opsonic antibody was superior in enhancing the uptake of Pseudomonas by in vitro-cultured alveolar macrophages. It may be the more important respiratory antibody for certain bacterial infections.

Adult↗
PubMed1975

The unreliability of the maximal midexpiratory flow as an index of acute airway changes.

This study evaluates the reliability of the maximal midexpiratory flow (MMF) as an index of acute airway changes. In a group of asthmatics, intravenous histamine induced a significant decrease in the forced vital capacity, expiratory volume in the first second, and peak flow, while increasing the respiratory system resistance and the closing volume. The studies showed narrowing of the airways, while the MMF significantly increased in all subjects, implying dilation of the airways. The increased closing volume suggested narrowing of the small airways. The data, however, suggest that the paradoxic increase of the MMF is a result of histamine-induced early small airway closure, eliminating the lung units with longer time constants. Unless the MMF is related to absolute lung volumes (as presently measured the MMF is not related to absolute lung volumes) it may be misleading, and is thus an unreliable index of acute airway changes.

Adolescent↗