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Biomedical subjects

A Haas

Publications and source records attributed to A Haas.

At least 109 records · Page 6Linked to original sources

A controlled trial of intralesional recombinant interferon-gamma in the treatment of keloidal scarring. Clinical and histologic findings.

Interferon-gamma (IFN-gamma) suppresses the synthesis of collagen by fibroblasts in vitro and the synthesis of collagen in vivo in animal models. Therefore, recombinant human IFN-gamma was examined for its ability to clinically modify keloids. Subjects were treated by injection of either 0.01 or 0.1 mg of recombinant human IFN-gamma into one lesional site and diluent alone into another lesional site three times per week for 3 weeks. Keloids were measured and photographed before beginning therapy and weekly thereafter. Three days after the final injection, biopsies were performed on treated and control sites. Six of eight subjects who finished the course of treatment demonstrated reduction in size at the treated site with an average reduction in height of 30.4% vs 1.1% for control sites. Lesions treated with recombinant human IFN-gamma demonstrated alterations in both the epidermis and dermis. The epidermis showed thinning of the suprapapillary plates, compact hyperkeratosis, focal or diffuse parakeratosis, exocytosis of lymphocytes, and an increased quantity of mucin. The dermis contained a diminished quantity of thickened collagen bundles and active fibroblasts and an increased number of inflammatory cells and quantity of mucin. These results suggest the feasibility of using IFN-gamma in the treatment of abnormal fibrosis. Dose-ranging studies are required to establish whether IFN-gamma can fulfill a true clinical need in the treatment of keloidal scarring.

Adolescent↗

Production, purification and characterization of hemolysins from Listeria ivanovii and Listeria monocytogenes Sv4b.

In culture supernatants of both Listeria ivanovii and Listeria monocytogenes Sv4b, for the first time a hemolysin of molecular weight 58 kDa was identified, which had all the characteristics of an SH-activated cytolysin, and which was therefore identified as listeriolysin O (LLO). In the case of L. ivanovii a second major supernatant protein of molecular weight 24 kDa co-purified with LLO. However, the function of this protein has to be determined. In culture supernatants of L. ivanovii a sphingomyelinase and a lecithinase activity could be detected, both enzymatic activities together contributing to the pronounced hemolysis caused by L. ivanovii. The N-terminal amino acid sequences of LLO and the 24 kDa from L. ivanovii are shown.

Amino Acid Sequence↗

The distribution of normal values in automated perimetry.

From 354 visual fields of 137 normal subjects, various components of variance were calculated separately for each test location of the Octopus automated-perimetry program J0. The method of component analysis of variance was used. The following components were analyzed: interindividual variation (variation of visual-field measurements in different subjects), long-term fluctuation (variation of different visual-field measurements in the same subject), differences between the right and left eyes and fluctuation within one visual field test in one subject, i.e., short-term fluctuation. The results show increased variations at the center relative to the paracentral area and a slight increase with eccentricity.

Adolescent↗

Lymphokine-activated killer cells in primary immunodeficiencies and acquired immunodeficiency syndrome.

Cytotoxic mechanisms (e.g., natural killer (NK) lysis, antibody-dependent cellular cytotoxicity, and cytotoxic T lymphocyte lysis) play an important role in host defense against various infections and neoplasms. Lymphokine-activated killer (LAK) cytotoxicity, induced in vitro by incubating mononuclear cells with interleukin 2 (IL-2) for 2-5 days, may also represent an important component of the body's cytotoxic repertoire. In 10 patients with congenital cellular immunodeficiencies, including 5 with severe combined immunodeficiency, the mean LAK activity in a 3-hr chromium release assay against Raji target cells was 44 +/- 8.1%, which is equivalent to that observed in normal adults and neonates. In only one case, a patient with reticular dysgenesis, was there absent LAK cell generation. Haploidentical T cell-depleted bone marrow transplantation (BMT) restored LAK activity in this patient. LAK activity was first observed in this patient and two others 3-6 weeks following BMT, prior to other evidence of immunologic engraftment such as lymphocyte proliferation to mitogens, NK activity, or interferon-gamma production. One patient with adenosine deaminase deficiency showed normal levels of LAK activity despite absent NK activity. Three patients with chronic granulomatous disease also had normal LAK activity (57 +/- 14% specific lysis). In 9 patients with acquired immunodeficiency syndrome (AIDS), IL-2 activation resulted in a mean cytotoxic activity of 56 +/- 8.7% toward Raji targets. In addition, 9 patients with pre-AIDS complex also showed normal levels of cytotoxicity (37 +/- 3.3% toward Raji targets), equivalent to that of 8 normal controls, including two healthy homosexual males (mean lysis 38 +/- 3.9%). These results indicate that LAK cells appear early in immunologic ontogeny. Further, the mechanism of lysis is not oxygen dependent since LAK activity was present in the 3 patients with chronic granulomatous disease. The ability to generate LAK in a wide spectrum of immunodeficiencies may indicate that IL-2 could be used in therapy of such disorders.

Acquired Immunodeficiency Syndrome↗

Isolation and characterization of genes coding for proteins involved in the cytolysis by Listeria ivanovii.

We established a library of chromosomal DNA of Listeria ivanovii in the pTZ19R plasmid system, using Escherichia coli DH5 alpha as the host. One recombinant clone reacted strongly with a polyclonal antiserum raised against the listeriolysin O and a second exoprotein (24kDa) of L. ivanovii, which is most probably also involved in cytolytic processes. The recombinant E. coli clone may contain part of the listeriolysin O gene of L. ivanovii.

Blotting, Western↗

One free sulfhydryl group of plasma fibronectin becomes titratable upon binding of the protein to solid substrates.

The accessibility in human plasma fibronectin of the two free sulfhydryl groups per chain to sulfhydryl reagents 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and a maleimide derivative has been examined. For soluble fibronectin, the free sulfhydryl groups are not accessible to DTNB unless urea or guanidine hydrochloride is added [Smith et al. (1982) J. Biol. Chem. 257, 5831-5838]. Upon binding to polystyrene beads, 0.87 +/- 0.05 sulfhydryl group per chain becomes titratable to DTNB. Experiments using fibronectin fragments demonstrate that this newly exposed sulfhydryl group is located in a Type III homologous unit between the DNA-binding and the cell-binding domains. The results suggest that, upon adsorption to solid substrates, plasma fibronectin undergoes a conformational change, thereby exposing one buried sulfhydryl group. These findings have implications regarding the "surface activation" of adhesion activities of fibronectin.

Chromatography, High Pressure Liquid↗

Interferon-induced expression of class II major histocompatibility antigens in the major histocompatibility complex (MHC) class II deficiency syndrome.

Class II antigens encoded by genes of the major histocompatibility complex (MHC) are expressed by a variety of cell types and have a vital role in the cellular interactions required for an effective immune response. We have analyzed the regulation of HLA-DR, DP, and DQ class II antigen expression on cells of different lineage from an immunodeficient patient with the MHC class II deficiency syndrome. T and B lymphocytes, monocytes, and fibroblasts, which initially expressed no class II antigens, were treated with inductive stimuli that normally lead to enhanced expression of class II antigens. Monocytes, but not fibroblasts, cultured for 48-96 hr in the presence of recombinant gamma interferon expressed all three types of class II antigens. In contrast, T lymphocytes did not express class II antigens following their exposure to a variety of stimuli, including activation with phytohemagglutinin and culture in the presence of interleukin-2, transformation by the retrovirus HTLV-1 or HTLV-2, or exposure to the demethylating agent 5-azacytidine. Similarly, class II antigens were not induced on B cells by cross-linkage of surface immunoglobulin molecules with anti-mu, exposure to Epstein-Barr virus, or treatment with soluble factors secreted by activated T cells. These results demonstrate that the regulation of class II MHC antigen expression by monocytes and lymphocytes is dissimilar and suggest that different regulatory genes are involved in the control of class II antigen expression by cells of different lineage.

Adult↗

Abnormal differentiation of immunoregulatory T-lymphocyte subpopulations in the major histocompatibility complex (MHC) class II antigen deficiency syndrome.

The major histocompatibility complex (MHC) class II deficiency syndrome is a rare immunodeficiency disease associated with defective expression of class II MHC antigens. We have examined the consequences of this defect for the differentiation and functional capabilities of immunoregulatory T-cell subpopulations in an affected patient. Although the number of circulating T cells was normal, there was a striking reduction in the number of CD4+ T cells. Furthermore, purified CD4+ cells from the patient were unable to provide help for antibody secretion. This defect in helper function appeared to be due to the abnormal differentiation of the few CD4+ cells present, virtually all of which expressed the CD4+HB11+ phenotype characteristic of immature "virgin" T cells. Abnormal development of immunoregulatory CD8+ T cells was also observed. Although increased numbers of CD8+ T cells were present, virtually none had phenotypic properties of suppressor cells (i.e., CD3+/CD8+/9.3- granular lymphocytes that coexpress the Leu-15 or Leu-7 antigens), and purified CD8+ cells from the patient had no suppressor activity. Thus, the absence of class II MHC antigens profoundly disrupts the development of immunoregulatory T cells. We propose that these effects occur by the following mechanisms: (1) the absence of intrathymic class II antigens results in deficient production of CD4+ cells, (2) the CD4+ cells that do emerge from the thymus do not undergo postthymic maturation into CD4+HB11- cells with helper capabilities, and (3) the absence of CD4+HB11- effector cells results in abortive development of suppressor cells involved in feedback suppression.

Antigens, Differentiation, T-Lymphocyte↗

Effect of methacholine induced bronchoconstriction on the pulmonary distribution and plasma pharmacokinetics of inhaled sodium cromoglycate in subjects with normal and hyperreactive airways.

Inhalation treatment may be less effective in the presence of bronchoconstriction because of the reduced penetration of drugs into the airways. The effect of bronchoconstriction on the lung deposition and plasma pharmacokinetics of inhaled sodium cromoglycate was examined. Ten subjects attended the laboratory on three occasions. On the first occasion a bronchial provocation test was performed to determine the concentration of methacholine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20). On the two subsequent occasions subjects inhaled either saline or their PC20 methacholine, followed five minutes later by an aerosol containing sodium cromoglycate and stannous phytate labelled with technetium-99m. Twenty minutes later a gamma emission lung scan was performed to determine the intrathoracic deposition of the nebulised aerosol. The central:peripheral (C:P) ratio of lung deposition was then calculated. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for four hours. Methacholine led to a 23.4% (SEM 0.6%) lower FEV1 and a 2.8 times higher C:P ratio than those observed after saline. There was a direct correlation between log PC20 methacholine and the increase in the C:P ratio (r = 0.81). Despite these changes with methacholine, the plasma pharmacokinetics of inhaled sodium cromoglycate were not significantly different after methacholine and after saline, except that the maximum concentration achieved (Cmax) was increased. These observations suggest that the area of cromoglycate deposition and the anatomical site are less important in determining the plasma pharmacokinetics of cromoglycate than is the total dose delivered to the lung.

Administration, Inhalation↗

Changes in serum K+ in healthy and in asthmatic subjects during exercise.

Adrenergic mechanisms modulate exercise-induced changes in blood serum K+ concentration ([K+]). Impairment of these same mechanisms may be associated with bronchial hyper-reactivity. If this is accurate, asthmatic subjects should show disturbed K+ regulation during exercise. We measured [K+] and FEV1 in 13 healthy control and in 13 asthmatic subjects pre-exercise, at peak exercise (within 1 min of stopping exercise), and 10 min postexercise. This was done on 2 separate days, one with and one without bronchodilator (BD) pretreatment. Both groups were equally fit, exercising to the same O2 consumption and heart rate. Resting [K+] was normal for both groups (two-day averages were 4.00 +/- 0.07 and 4.09 +/- 0.07 mmol/L, mean +/- SEM, in control and asthmatic subjects, respectively). Without BD pretreatment, at peak exercise, [K+] in control subjects rose by 0.56 +/- 0.08 compared with 0.96 +/- 0.09 in asthmatics (p less than 0.01). After exercise, [K+] returned to baseline (4.12 +/- 0.08) in control subjects but remained elevated in asthmatics (4.60 +/- 0.12, p less than 0.01). Although FEV1 was unchanged in control subjects, in asthmatics it fell after exercise (p less than 0.01). With BD pretreatment: peak exercise [K+] increased by 0.55 +/- 0.09 in control subjects, and by 0.49 +/- 0.01 in asthmatics (p less than 0.01). By 10 min postexercise, it returned to baseline in both groups (4.15 +/- 0.11 for control subjects and 4.32 +/- 0.07 for asthmatics). The asthma group's fall in FEV1 was also abolished. These data indicate that postexercise K+ remains elevated in asthmatics, supporting the suggestion that their adrenergic function is impaired.

Adult↗

Bare lymphocyte syndrome. Consequences of absent class II major histocompatibility antigen expression for B lymphocyte differentiation and function.

The bare lymphocyte syndrome is a rare combined immunodeficiency disorder associated with the absence of class I and/or class II major histocompatibility (MHC) antigens. Although it has been inferred that the immune deficiency is a consequence of disordered MHC-restricted interactions among otherwise normal cells, the biological capabilities and differentiation of B lymphocytes deficient in class II MHC antigens have not been rigorously analyzed. We have examined the phenotypic and functional attributes of B cells with absent class II MHC antigens. Our data demonstrate that these B cells are intrinsically defective in their responses to membrane-mediated activation stimuli. In addition, virtually all the B cells had phenotypic evidence of arrested differentiation at an immature stage. Finally, these B cells also failed to express the C3d-EBV receptor normally present on all B lymphocytes. These data indicate that class II MHC molecules are vital participants in early events of the B cell activation cascade, and that other non-MHC membrane molecules may also be absent as a consequence of either arrested differentiation or as a result of the basic defect affecting the expression of MHC membrane antigens.

Antibody-Producing Cells↗

[The sagittal dimension of the sinus frontalis, its wall thickness, distance from the lamina cribrosa, the depth of the so-called olfactory groove and the ethmoidal canal].

The anterior and the posterior wall of the frontal sinus and its anterior-posterior depth on the deepest area were measured in the sagittal medial plan and 2 cm outside of the median. Also estimated were the distance between the posterior side of the anterior wall of the frontal sinus and the anterior border of the lamina cribrosa (mean value 17.4 mm). The depth of the olfactory rim was measured in the anterior, the middle, and the posterior third of the lamina cribrosa. There was measured also the lower surface of the lamina cribrosa and the level of the ethmoidal canals to the lamina cribrosa and its dehiscences.

Frontal Sinus↗

Estimation of lean body mass by bioelectrical impedance analysis compared to skinfold anthropometry.

Estimation of lean body mass (LBM) is an important procedure in nutritional assessment and the availability of a rapid, portable and reproducible method would be desirable for this purpose. At present, only bioelectrical impedance analysis (BIA) and skinfold anthropometry are applicable for clinical use. We compared the prediction of LBM by these two methods in 80 subjects stratified into four subgroups by body mass index (BMI): lean, normal, obese and super-obese. Highly significant correlation coefficients (r greater than 0.92, P less than 0.001) were seen for all subgroups with a mean difference between techniques LBManthro-LBMBIA/LBManthro X 100) of less than 1 kg or 1 per cent error. A greater s.d. and error was noted in the super-obese (BMI greater than or equal to 40.0). Fifteen subjects had measurements repeated after a mean weight loss of 10 per cent. Although mean difference between methods was not statistically significant, there was a large individual variation. It is concluded that there is an excellent agreement between the estimation of LBM by bioelectrical impedance and skinfold anthropometry in the weight-stable subject.

Adult↗

Bone marrow transplantation in DiGeorge syndrome.

A Hispanic infant girl with DiGeorge syndrome underwent successful bone marrow transplantation (BMT) at age 28 1/2 weeks. She had typical facies, a cardiac defect, hypoparathyroidism, severe T and B cell immunodeficiency, and low levels of facteur thymique serique (FTS). In vitro incubation of the peripheral blood lymphocytes with thymosin alpha 1 showed no increase in the number of T cells on two occasions. A fetal thymus for transplantation was not available, and further review of past experience with thymic cells or factors revealed inconsistent and incomplete responses. Because of the patient's worsening clinical and immunologic status, BMT was performed, with her histocompatible brother as donor. The patient has had a good clinical and immunologic response to BMT, with evidence of T cell engraftment, improved B cell function, and increased levels of serum FTS. This experience indicates that minimal thymic influence is necessary for successful BMT and that patients with DiGeorge syndrome with significant T cell deficiency may benefit from this treatment.

Adult↗

Simple bone cyst of the metacarpal.

Simple bone cyst is a benign tumor-like lesion that occurs principally in the humerus and the femur. Occurrence within the hand is rare and involvement of the metacarpals is even more uncommon. Two similar cases of a simple bone cyst affecting the metacarpals were treated by complete excision of the cyst and replacement by a cortico-medullar autogenous graft.

Bone Cysts↗

Effect of aerobic training on forced expiratory airflow in exercising asthmatic humans.

Pulmonary function after exercise was evaluated in 22 asthmatic subjects before and after a 36-session training sequence of aerobic exercise. Training did not change pulmonary function values, except for a small increase in maximal voluntary ventilation (P less than 0.02), which was attributed to respiratory muscle training. After aerobic training, both external work at a given heart rate and peak O2 consumption increased by 30 and 15%, respectively. At the same minute ventilation (VE), immediate postexercise forced expiratory airflow was higher after training (P less than 0.02), and reduction in forced expiratory airflow during the first 9 min postexercise was less after training (P less than 0.01). The posttraining airflow response to the pretraining work load was, as expected, less than the pretraining response (P less than 0.02). Although the difference in maximal-to-minimal airflow at the same VE was similar before and after training, the airflow increase accounted for 50% of the response after training compared with 16% of the pretraining response. Furthermore the strong negative correlation (P less than 0.01) between maximal and minimal airflow both pre- and posttraining indicates that exercise-induced bronchospasm (EIB) severity is, in part, determined by the degree of exercise-induced bronchodilation. We conclude that aerobic training significantly increases exercise-induced bronchodilation and diminishes EIB.

Aerobiosis↗

Intravenous immunoglobulins as therapeutic agents.

Intravenous immunoglobulins are stable monomeric pooled human IgG preparations for therapeutic use. Three intravenous immunoglobulins licensed in the United States are generally therapeutically equivalent. Intravenous immunoglobulin is the preferred agent for replacement therapy for most patients with primary or secondary antibody immunodeficiency because of the rapidity and ease of giving large quantities of IgG, even by self-administration. Disadvantages of intravenous immunoglobulins include frequent (approximately 10%) but usually not serious side effects, the need for venous access (often difficult in infants and young children), and high cost. Intravenous immunoglobulins are also beneficial in the prevention of certain viral infections, such as cytomegalovirus pneumonia and varicella; they may also have a synergistic effect with antibiotics in certain bacterial diseases. Intravenous immunoglobulin has also been used successfully in the management of idiopathic thrombocytopenia purpura, Kawasaki disease, and certain autoimmune diseases. Intravenous immunoglobulin may also be of use in certain high-risk and premature newborns.

Animals↗