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Biomedical subjects

R D deShazo

Publications and source records attributed to R D deShazo.

17 recordsLinked to original sources
PubMed1992

Mechanisms of neutrophil damage to human alveolar extracellular matrix: the role of serine and metalloproteases.

Many syndromes of lung injury are associated with accumulation of neutrophils within the pulmonary parenchyma. These neutrophils have the capacity to produce lung injury by products including proteases and reactive oxygen species (ROS). We examined the ability of activated neutrophils to solubilize human alveolar extracellular matrix (ECM), and by use of scavengers and inhibitors, evaluated the role of ROS and proteases in this process. Supernatants of phorbol myristate acetate-activated neutrophils routinely solubilized 10.2% +/- 0.8% (n = 30) of collagen in human alveolar ECM, as measured by hydroxyproline release. Scavengers of ROS had no significant effect on ECM solubilization. Inhibitors of metalloproteases partially inhibited ECM solubilization (38.5% +/- 4.6% inhibition by ethylenediaminetetraacetic acid [n = 6], and 37.0% +/- 14.7% by 1,10-phenanthroline [n = 6]; p less than 0.05). Inhibitors of the neutrophil serine proteases, elastase and cathepsin G, markedly inhibited ECM solubilization (100.9% +/- 3.7% by alpha 1-protease inhibitor [alpha 1-PI] [n = 6] and 81.9% +/- 0.1% by soybean trypsin inhibitor [n = 6]; p less than 0.01). Since alpha 1-PI completely inhibited solubilization, metalloprotease activity appeared to be related to serine protease activity. This finding was confirmed by the observation that addition of a metalloenzyme activator, p-aminophenylmercuric acetate, in the presence of alpha 1-PI, restored solubilization to the same level as that inhibited by metal chelators. We conclude that human neutrophil metalloproteases and serine proteases directly solubilize human alveolar ECM. Furthermore, neutrophil serine proteases activate latent metalloproteases. However, ROS were not demonstrated to play a major role in ECM solubilization in our system.

Basement Membrane↗
PubMed1992

Chronic fatigue syndrome: a conundrum.

Chronic fatigue syndrome (CFS) is a multi-faceted disorder for which no etiology has been determined. This paper discusses the implications of the new clinical case definition of CFS on previous and future studies of this illness. The authors' own management approach is also discussed.

Fatigue Syndrome, Chronic↗
PubMed1991

Effects of HIV infection on pregnancy. A clinical and immunologic evaluation.

To understand better the effects of HIV infection on pregnancy, a group of 16 HIV seropositive pregnant patients was evaluated prospectively. Complications and results of pregnancy in these individuals were compared with those of 1,906 births at Charity Hospital, New Orleans during the time of the study. A subgroup of five patients underwent immunologic testing prenatally and postpartum. Thirty-one percent of HIV seropositive subjects had premature labor and low birth weight infants. Only 3.1% of the controls had premature labor and low birth weight infants (p less than or equal to .05). The percentage of C-sections was lower in the study group (12.5% versus 31.3%, p less than .10). All patients remained free of HIV-related disease through the postpartum period. Mean CD4 percentages were lower postpartum (21.9 +/- 3.4) than prepartum (45.1 +/- 6.7) in all five patients studied, although proliferative responses to the mitogens phytohemagglutinin and pokeweed were unchanged during the study period. One of the five seropositive patients who underwent immunologic testing with a CD4:CD8 ratio of less than 1.0 prepartum, had a progressive fall in CD4 percentages from 30% to 11% during the course of the study. HIV-I core antigen was not detected in the serum of any of the five patients during pregnancy or postpartum. Thus, HIV-I infection influenced both the course and outcome of pregnancy in the population studied. Further studies are indicated to assess the effects of pregnancy on the progression of HIV-related immunodeficiency in this population.

Adolescent↗
PubMed1991

Total IgG and IgG subclass specific antibody responses to insulin in diabetic patients.

Abnormal antibody responses to insulin in diabetic patients have been associated with syndromes of insulin hypersensitivity and abnormal insulin pharmacokinetics. In this study, we evaluated total and IgG subclass antibody responses to insulin in 70 diabetic subjects on insulin distributed into five clinical groups, and in two control groups using ELISAs with CDC/WHO recommended monoclonal antibodies. As expected, levels of total IgG insulin antibody were greater in diabetic patients treated with insulin than in the control group of diabetic patients on oral agents or nondiabetic controls. Insulin antibody responses of the IgG2 subclass were negligible to absent in all groups. Adult diabetic patients on insulin without complications and those with insulin associated anaphylaxis had mean values of IgG1, IgG3, and IgG4 insulin antibodies no different from those of controls. Patients with local hypersensitivity had elevated IgG1 responses. Type I diabetic patients had elevated IgG3 responses. A group of Type II diabetic patients selected for high levels of total IgG insulin antibodies had elevated levels of IgG1, IgG3, and IgG4 antibody responses. Thus, the IgG subclass response to insulin primarily involves IgG subclasses 1, 3, and 4 and varies with the type of diabetes and complications of insulin therapy.

Adult↗
PubMed1990

Studies of the mechanism of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema: the effect of an ACE inhibitor on cutaneous responses to bradykinin, codeine, and histamine.

To understand better the mechanism of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema, we studied the effects of ACE-inhibitor treatment on wheal-and-flare responses to histamine, codeine, and bradykinin in 10 normal subjects. No change in the size of wheal-and-flare reactions to histamine occurred, but the size of wheal reactions to codeine and bradykinin increased in all study subjects after ingesting the ACE inhibitor, captopril. Five of 10 study subjects developed flushing reactions after ACE-inhibitor treatment. We conclude that inhibition of bradykinin metabolism by ACE inhibitors is the probable cause of ACE inhibitor-related angioedema and that substance P is not the predominant mediator in this process.

Adult↗
PubMed1979

Selective immunoglobulin A deficiency associated with modular lymphoid hyperplasia.

Nodular lymphoid hyperplasia (NLH) has been firmly associated with syndromes of hypogammaglobulinemia but not with selective absence of IgA. We report the case of a 5-yr-old girl with the triad of selective IgA deficiency, NLH of the small bowel, and giardiasis. Results of an extensive immunologic investigation, including immunohistochemical examinations of small bowel biopsies, support the hypothesis that the basic defect responsible for IgA deficiency in this patient was the failure of precursor IgM-bearing lymphocytes to differentiate into IgA-producing plasma cells. Furthermore, the abundance of IgM-bearing cells in biopsy specimens demonstrates the existence of a compensatory mechanism in the intestine to substitute IgM for the absent IgA.

Child, Preschool↗
PubMed1978

Insulin allergy and insulin resistance: two immunologic reactions.

Insulin allergy and insulin resistance can cause life-threatening problems for diabetic patients. Fortunately, allergic manifestations are usually localized, but increasingly severe local reactions can precede a systemic reaction. How use of newer and purer insulin preparations than those previously available will affect the incidence of immunologic reactions is yet to be determined.

Animals↗
PubMed1977

Severe persistent biphasic local (immediate and late) skin reactions to insulin.

A patient with adult-onset insulin-requirging diabetes mellitus had persistent severe local reactions to all available insulins of animal origin. Skin reactions were biphasic in nature with both immediate and late characteristics. An extensive immunologic investigation of this problem was undertaken, revealing evidence of reaginic antibody involvement in the reactions. Routine histologic studies suggested the possibility that Arthus-type mechanisms played a part, although this impression was not confirmed by immunofluorescent microscopy. A program of medical management provided some relief of symptoms.

Aspergillus fumigatus↗
PubMed1975

The spectrum of systemic vasculitis: a classification to aid diagnosis.

Determining the cause of systemic vasculitis can be facilitated by a clinicopathologic classification of the syndrome. The considerations in differential diagnosis include periarteritis nodosa, leukocytoclastic angiitis (hypersensitivity angiitis, Schonlein-Henoch purpura, other disease-associated vasculitis), Wegener's granulomatosis, allergic granulomatosis (granulomatous angiitis), and giant cell arteritis.

Arteritis↗