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Biomedical subjects

J W Bloom

Publications and source records attributed to J W Bloom.

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

Physiologic characteristics of subjects exhibiting accelerated deterioration of ventilatory function.

From a randomly selected community population sample followed with sequential surveys since 1972, 13 subjects who exhibited a mean annual decline in FEV1 greater than 60 ml/yr were drawn for detailed studies of lung function. These subjects had developed clinically significant airway obstruction during this period of follow-up. Clinical evaluation was not successful in characterizing the nature of the disorder. None of the subjects had alpha-1-antitrypsin deficiency. In a small proportion of subjects, elevated total serum immunoglobulin E may have played a role in the obstructive airway disorder. Some subjects exhibited loss of lung elastic recoil and diminished carbon monoxide diffusing capacity suggestive of developing emphysema. Others appeared to have intrinsic airway disease involving large and/or small airways, which may be fixed in some and responsive to bronchodilator in others. Thus, neither the site nor the nature of the disorder inferred from results of physiologic tests was uniform, illustrating the heterogeneous nature of chronic obstructive lung disease.

Adult↗
PubMed1987

Coccidioidomycosis in the acquired immunodeficiency syndrome.

Of 27 patients with the acquired immunodeficiency syndrome (AIDS) in Tucson, Arizona, 7 had concurrent coccidioidomycosis. Early manifestations of infection in 6 patients included diffuse nodular pulmonary infiltrates and Coccidioides immitis in many extrathoracic sites. By comparison, a retrospective review of the cases of 300 patients hospitalized with coccidioidal infection identified only 13 patients without AIDS who had the same extent of infection, and only 3 of these patients had no immunosuppressing conditions. Antibodies for coccidioidal antigens at serum dilutions as high as 1:2048 were detected in 5 of the 7 patients with AIDS. Six had temporary responses to amphotericin B treatment, taken both alone and combined with ketoconazole, but all died within 14 months of their diagnosis of coccidioidomycosis. Because annual rates of coccidioidal infection in the Tucson area are 4% or less, the rate of 27% that we calculated, based on 7 patients having the infection during 26 years of risk for AIDS, suggests frequent reactivation of the infection or enhanced susceptibility to endemic exposure in persons with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Intravenous platelet activating factor does not affect lung epithelial permeability.

Administration of platelet activating factor has been shown to produce lung edema in several species including the rabbit. To determine if platelet activating factor increases lung alveolar epithelial permeability, we studied the effect of intravenous platelet activating factor administration on clearance of 99mTc-DTPA from the lung of the rabbit. Intravenous platelet activating factor produced marked hemodynamic and cellular responses but did not increase the clearance of 99mTc-DTPA from lung to blood. We conclude that although platelet activating factor can induce lung edema in the rabbit, it does not produce an acute increase in alveolar epithelial permeability.

Animals↗
PubMed1987

Characterization of high affinity [3H]pirenzepine and (-)-[3H] quinuclidinyl benzilate binding to muscarinic cholinergic receptors in rabbit peripheral lung.

We have characterized the binding of the selective muscarinic antagonist [3H]pirenzepine ([3H])PZ) and the classical muscarinic antagonist (-)-[3H]quinuclidinyl benzilate ((-)-[3H]QNB) to muscarinic cholinergic sites in rabbit peripheral lung membranes. For both radioligands, high affinity binding with pharmacologic specificity was demonstrated. The high affinity Kd for [3H]PZ binding determined from saturation isotherms was 4.5 nM and the Kd for (-)-[3H]QNB binding was 6.2 pM. Comparison of the total binding capacity values determined by saturation experiments with [3H] PZ and (-)-[3H]QNB demonstrates that approximately 78% of the total muscarinic binding sites in rabbit peripheral lung bind [3H]PZ with high affinity. There was no significant effect of the guanine nucleotide, guanyl-5'-yl imidodiphosphate, on the inhibition of (-)-[3H]QNB binding by the muscarinic agonist carbachol in peripheral lung membranes. If the pulmonary muscarinic receptor with high affinity for PZ proves to have an important role in bronchoconstriction, its characterization could result in the development of more selective bronchodilators.

Animals↗
PubMed1986

Monoclonal antibody binding to factor VIII:c.

The interactions of human blood clotting Factor VIII:c with 2 monoclonal antibodies, C7F7 and BD10, were examined with an enzyme-linked immunosorbent assay (ELISA) method. A Scatchard-Sips plot approach to data analysis was used to calculate an average affinity (Ko), valence (n), and heterogeneity index (a) for each interaction. Using a Factor VIII:c coating ELISA method, the following constants were determined: BD10: Ko = 5.48 X 10(8) M-1; n = 0.31; a = 0.97; C7F7: Ko = 2.3 X 10(11) M-1; n = 0.018; a = 0.77.

Antibodies, Monoclonal↗
PubMed1986

Pneumococcus-specific immunoglobulin E in cigarette smokers.

A relationship between elevated serum immunoglobulin E levels and smoking has been demonstrated in epidemiological studies. Allergy skin test data suggest that the excess immunoglobulin E of smokers is not specific for aeroallergens. It is possible that the excess immunoglobulin E is specific for microorganisms that often infect the lower respiratory tract of smokers. To investigate this possibility we utilized a radioallergosorbent test assay for detecting serum immunoglobulin E specific for Streptococcus pneumoniae, an organism commonly isolated from the respiratory tract of smokers with chronic bronchitis. We assayed sera of thirty smokers and thirty nonsmokers for immunoglobulin E specific for Streptococcus pneumoniae. Individual sera were considered positive for pneumococcus-specific immunoglobulin E if the binding was at least twice the non-specific binding at the total immunoglobulin E concentration of the particular serum. Eleven of the thirty sera of smokers and two of the thirty nonsmokers were positive for pneumococcus-specific immunoglobulin E. By chi-square analysis of these data, the prevalence of pneumococcus-specific immunoglobulin E was significantly greater in the smoking group compared with the non-smoking group (P less than 0.02). These results suggest that the excess immunoglobulin E of smokers is, at least in part, specific for microorganisms that infect the airways.

Adult↗
PubMed1986

Successful intraspinal extradural sacral nerve stimulation for bladder emptying in a victim of traumatic spinal cord transection.

This report concerns a patient with a functionally complete spinal cord transection due to trauma at T-6. Her clinical syndrome of a motor and sensory paraplegia was accompanied by hyperreflexic detrusor dysfunction. Radiofrequency-coupled bilateral stimulation of the 3rd sacral nerves in their intraspinal but extradural course achieved reliable, effective emptying of the bladder. This single case suggest that successful stimulation of the sacral neural outflow may not require intrathecal placement of stimulating electrodes, sensory rhizotomy, or pudendal neurotomy.

Adult↗
PubMed1985

Direct electrical stimulation promotes growth and enhances survival of aneurogenic muscles of the chick embryo.

Analyses of embryonic aneurogenic muscles indicate that several processes associated with early myogenesis in vivo proceed in the absence of peripheral nerves. However, aneurogenic muscles demonstrate impaired growth and limited survival. To investigate whether neurally mediated activity is responsible for these phenomena, aneurogenic muscles of the chick embryo were directly stimulated in vivo via implanted electrodes. Volumetric analyses of stimulated aneurogenic brachial (latissimus dorsi) muscles from Stage (St) 33 (7.5 to 8 days) through St 37 (11 days) demonstrated that growth was enhanced significantly beyond the level characteristic of unstimulated aneurogenic muscles. Moreover, for the majority of embryos, the stimulation regimen actually rescued the posterior latissimus dorsi muscle which characteristically does not survive beyond St 32 (7.5 days) in the aneurogenic state. Thus, our results implicate activity per se as an important factor necessary for the proper growth and survival of brachial muscles during early embryogenesis. The stimulation regimen, however, did not alter myosin ATPase profiles.

Animals↗
PubMed1984

Subclinical effects of smoking. Physiologic comparison of healthy middle-aged smokers and nonsmokers and interrelationships of lung function measurements.

Measurements of ventilatory function, distribution of ventilation, diffusing capacity, and lung mechanics were made on healthy middle-aged smokers and nonsmokers drawn from a randomly selected population in order to assess the effects of cigarette smoking and the interrelationships of the several indices of lung function. Although very few subjects had abnormal function, there were significant differences in most indices of function between smokers and nonsmokers. For the total group studied, there were significant correlations between various indices of function. A significant proportion of the variance in diffusing capacity and in diffusing capacity per liter of lung volume can be accounted for by an index of lung recoil which may, in turn, be related to size of terminal air spaces.

Adult↗
PubMed1984

Assessment of air vs helium-oxygen flow-volume curves as an epidemiologic screening test.

Air and helium-oxygen maximum expiratory flow-volume curves were employed in an epidemiologic field study to assess the utility of density dependence as a screening test. Of 1,584 subjects tested, only 54.1 percent were able to perform the test with vital capacities for the two gases that agreed to within 5 percent. Subjects unable to perform the test properly tended to be older, with a greater prevalence of ventilatory function abnormalities and respiratory problems, than those who could perform the test. There was poor concordance between density dependence, or lack thereof, and standard ventilatory function measurements or evidence of respiratory disease. Under field survey conditions, the test of density dependence did not appear to be a useful screening tool.

Adolescent↗
PubMed1979

Decarboxylation of bovine prothrombin fragment 1 and prothrombin.

Bovine prothrombin fragment 1 and prothrombin undergo decarboxylation of their gamma-carboxyglutamic acid residues when the lyophilized proteins are heated in vacuo at 110 degrees C for several hours. The fully decarboxylated fragment 1 product has lost its barium-binding ability as well as the calcium-binding function which causes fluorescence quenching in the presence of 2 mM Ca2+. There is no sign of secondary structure alteration in solution upon analysis by fluorescence emission and circular dichroic spectroscopy. A family of partially decarboxylated fragment 1 species generated by heating for shorter periods shows that the initial decrease in calcium-binding ability occurs almost twice as rapidly as the loss of gamma-carboxyglutamic acid. This is consistent with the idea that differential functions can be ascribed to the 10 gamma-carboxyglutamic acid residues in fragment 1, including both high- and low-affinity metal ion binding sites. Prothrombin itself also undergoes total decarboxylation without any apparent alteration in secondary structure. However, in this case the latent thrombin activity is progressively diminished during the heating process in terms of both clotting activity and hydrolysis of the amide substrate H-D-Phe-Pip-Arg-pNA. The present results indicate that in vitro decarboxylation of gamma-carboxyglutamic acid in dried proteins is useful for analyzing the detailed calcium-binding proteins of vitamin K dependent coagulation factors.

1-Carboxyglutamic Acid↗
PubMed1979

Phospholipid-binding properties of bovine factor V and factor Va.

Factor V and factor Va binding to single bilayer phospholipid vesicles was investigated by light-scattering intensity measurements. This technique allows the measurement of free and phospholipid-bound protein concentrations from which equilibrium constants can be obtained. As controls, the Ca2+-dependent phospholipid binding of prothrombin and factor X were also studied. The average values obtained for the dissociation constants (Kd) and lipid to protein ratio at saturation, moles/mole (n), for prothrombin (Kd = 2.3 X 10(-6) M, n = 104) and factor X (Kd = 2.5 X 10(-6) M, n = 46) binding to vesicles containing 25% Folch fraction III and 75% phosphatidylcholine in the presence of 2 mM Ca2+ were in agreement with those reported in the literature. The average factor V and factor Va values for the dissociation constants and lipid to protein ratio at saturation (moles/mole) were Kd = 7.2 X 10(-8) M and n = 270 for factor V and Kd = 4.4 X 10(-7) M and n = 76 for factor Va. In contrast to prothrombin and factor X, factor V and factor Va demonstrated Ca2+-independent lipid binding. In addition, the number of factor V and factor Va molecules bound per vesicle was found to be dependent both on the phosphatidylserine content of the vesicle and the ionic strength of the buffer.

Animals↗
PubMed1979

Prothrombin domains: circular dichroic evidence for a lack of cooperativity.

The far-ultraviolet circular dichroism spectra of bovine and human prothrombin, prothrombin fragment 1, prethrombin 1, prothrombin fragment 2, and prethrombin 2 (prethrombin 2des(1--13)) were determined and the method of Chen et al. [Chen, Y. H., Yang, J. T., & Martinez, H. M. (1972) Biochemistry 11, 4120--4131; Chen, Y. H., Yang, J. T., & Chau, K. H. (1974) Biochemistry 13, 3350--3359] was used to calculate the apparent alpha-helix, beta-sheet, and random-coil contents of each protein. Prothrombin and its activation components were found to contain a large amount of aperiodic secondary structure and there was little species difference between the spectra and, thus, secondary structures. The hypothesis that the prothrombin activation components exist as relative ly noncooperative "domains" within the prothrombin molecule was tested by comparing the circular dichroism spectrum of prothrombin with the sum of the spectra of the components. It support of the hypothesis, no gross alterations in the spectra and, hence, secondary structures of the components were found to have occurred upon activation.

Animals↗
PubMed1978

Metal ion induced conformational transitions of prothrombin and prothrombin fragment 1.

Circular dichroism experiments indicate that prothrombin fragment 1 undergoes essentially the same secondary structural change whether in the presence of Ca(2+), Mg(2+), or Mn(2+). Titration with any of these metal ions results in a sigmoidal titration curve indicative of cooperative binding. Mg(2+) and Ca(2+) have nearly identical transition midpoints, while that for Mn(2+) is an order of magnitude less. These results correlate well with the results of previous metal ion intrinsic fluorescence quenching experiments. Fragment 1 has previously been shown to undergo a second transition corresponding to dimerization at high calcium concentrations. The present circular dichroism experiments show that this transition does not result in a gross alteration of secondary structure in the fragment 1 molecule. Studies with prothrombin, similar to those with fragment 1, indicate a similar metal ion dependent conformational change but of smaller magnitude. As apparently only the fragment 1 portion of the molecule undergoes the transition, it would appear that the covalently linked fragment 1 is constrained from attaining the same conformation as the purified entity. This suggests that caution must be used in interpreting the results of metal ion binding studies using fragment 1 as an analogue for prothrombin.

Animals↗
PubMed1978

Comparison of the inhibition of thrombin by three plasma protease inhibitors.

Human alpha-thrombin is inhibited by the circulating protease inhibitors alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin. Kinetic analyses of the inhibitor thrombin interactions were carried out utilizing either fibrinogen or the synthetic substrate Bz-Phe-Val-Arg-p-nitroanilide as substrates to determine residual thrombin activity. These studies demonstrated that the inhibition of thrombin by alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin followed second-order kinetics. The rate constants for the inhibition of thrombin by alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin are 6.51 +/- 0.38 x 10(3), 3.36 +/- 0.34 x 10(5), and 2.93 +/- 0.02 x 10(4) M-1 min-1, respectively. Comparison of the second-order rate constants and the normal plasma levels of the three inhibitors demonstrates that, under the in vitro conditions utilized, antithrombin III is five times and alpha2-macroglobulin is one-third as effective as alpha1-antitrypsin in the inhibition of thrombin.

Antithrombin III↗
PubMed1978

Interactions of alpha1-antitrypsin with trypsin and chymotrypsin.

The interaction of alpha1-antitrypsin with trypsin and chymotrypsin has been investigated by protease activity assays, by electrophoretic analysis, by CD and absorption difference spectra, and by gel filtration of reaction mixtures containing excess inhibitor or excess protease. When alpha1-antitrypsin is present in excess, only one stable inhibitor - protease complex is formed. In the presence of excess protease, however, this primary complex is degraded relatively rapidly to one or more secondary complexes. These latter conversions are more pronounced in the case of the antititrypsin-chymotrypsin system. The greater lability of the antitrypsin-chymotrypsin system is evidenced by the relatively rapid release of inactive chymotrypsin from the secondary antitrypsin - chymotrypsin complex. Only minimal amounts of active protease were released from the complexes on the addition of excess protease and one protease could not displace the other from the complex, although competition experiments showed that chymotrypsin reacted more rapidly with the inhibitor than trypsin.

Amino Acids↗