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Biomedical subjects

A L Jackson

Publications and source records attributed to A L Jackson.

At least 19 recordsLinked to original sources

Hemopneumothorax in an intravenous drug abuser.

This article reports a case of an intravenous drug abuser who presented with a hemopneumothorax, which is a rare complication of jugular vein self-injection. The patient achieved an inadvertent subclavian arterotomy, causing tingling and numbness in the hand and arm, an unusual "high," and blood filling the pleura, collapsing the lung. With an increase in pulmonary complications among intravenous drug abusers from infections in the immunocompromised state, pulmonary complaints related to trauma sustained from their activity must not be overlooked.

Adult

Serum increases and lymphoid cell surface losses of IL-2 receptor CD25 in HIV infection: distinctive parameters of HIV-induced change.

Lymphocyte activation induces production of soluble IL-2 receptor (sIL-2R) which is a large portion of the CD25 membrane molecule and which is detectable in serum. Serum sIL-2R is reported here to increase as a direct effect of the HIV infection and not to be due to secondary opportunistic infections. sIL-2R increased promptly after HIV seroconversion in 83% of 50 initially seronegative homosexual men. The sIL-2R serum levels stabilized in the third year after seroconversion and were then predictive of later CD4 T cell levels and development of AIDS. In two studies of 59 and 395 seropositive men, beta-2 microglobulin (B2M) and neopterin levels in serum correlated closely with each other but not with sIL-2R levels. Thus, increased production of sIL-2R may reflect pathological processes distinct from those determining B2M and neopterin increases. Membrane CD25 expression on peripheral blood lymphocytes, unexpectedly, was found to be decreased in HIV infection. This contrasted with the increased sIL-2R in serum. Investigations with sensitive flow cytometry technics showed that CD25 was expressed at reduced levels and averaged only 12% of lymphocytes from HIV-infected individuals in contrast to 25% in noninfected individuals. All major lymphoid populations showed reductions in CD25 positive cells. This reduction in lymphoid membrane CD25, however, was not inversely correlated with the increased serum levels of sIL-2R or with other parameters of immune deficiency or activation. Thus, surface CD25 loss and serum sIL-2R increase are separate and independent consequences of HIV infection.

CD4-Positive T-Lymphocytes

Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-1 disease.

To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T-cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of beta 2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection.

Acquired Immunodeficiency Syndrome

Restricted expression of p55 interleukin 2 receptor (CD25) on normal T cells.

Using a phycoerythrin-conjugated antibody to the p55 chain of the interleukin 2 receptor, normal blood lymphocytes were found to be on average 30% positive for this marker. Two-thirds of these cells are in the CD4 subset and most are within the CD45RA negative fraction associated with activated or memory T cells.

CD4 Antigens

Quality control in the flow cytometric measurement of T-lymphocyte subsets: the multicenter AIDS cohort study experience. The Multicenter AIDS Cohort Study Group.

Since 1984, the Multicenter AIDS Cohort Study (MACS) has utilized four flow cytometry laboratories to measure T-lymphocyte subset levels semiannually in a large cohort of homosexual men. This report summarizes the steps taken in the MACS laboratories to attain comparability of lymphocyte subset determinations across the centers and over time. Identical flow cytometers, monoclonal antibodies, and analytic procedures have been used, and over a period of time, the procedure for sample preparation was also standardized. Interlaboratory proficiency testing utilizing identical specimens analyzed in the four laboratories was performed to evaluate the comparability of the data among the laboratories. Our results verify that such testing can identify technical bias in flow cytometric evaluations performed at different laboratories. Temporal laboratory consistency in flow cytometric measurements was evaluated using data from each site's HIV-seronegative homosexual reference group. Both sequential 95% confidence intervals (mean +/- 2 x SEM) and the within-person standard deviations of the immune measurements were considered. Significant variation in CD3, CD4, and CD8 lymphocyte subset percentages over time in the seronegative reference population was observed. Our observations indicate that the lymphocyte subset values of this seronegative group should be used to adjust those obtained on the seropositive study participants during a particular time period, thereby allowing improved discrimination of the effects of HIV on T cells in infected individuals. The data presented are of use for designing epidemiologic and intervention studies in HIV-1-infected individuals, especially for calculating sample sizes. The methods we have used to assess the quality of data in the MACS have general application to quality control programs in flow cytometry laboratories. In particular, comparison of sequential confidence intervals and within-person standard deviations for lymphocyte subset determinations on control populations are essential to a comprehensive proficiency testing program because they permit assessment of consistency within a laboratory over time.

Acquired Immunodeficiency Syndrome

Normal expression of p55 interleukin 2 receptor (CD25) by lymphocytes from former blood donors seropositive for human T lymphotropic virus.

Dysregulated expression of the p55 interleukin 2 receptor (CD25) is characteristic of adult T cell leukemia (ATL) associated with human T lymphotropic virus (HTLV) infection. In order to determine if similar changes characterize HTLV infection in the apparent absence of ATL, CD25 expression by peripheral blood lymphocytes from HTLV-seropositive former blood donors was measured using a sensitive dual-color cytofluorometric assay. When comparing the HTLV-seropositive group (N = 19) and a seronegative control group (N = 20), no significant differences were observed in either the proportions of the major lymphocyte subsets (CD3, CD4, CD8, CD19, CD16/56) coexpressing CD25 or the phenotypic distribution of CD25+ cells among these lymphocyte subsets. Similarly, the total percentages of CD3, CD4, CD8, and CD19 cell subsets were unchanged; however, the percentage of CD16/56+ cells was significantly decreased in the HTLV group and reflected a decrease in the percentage of CD16/56 cells lacking CD25. These findings indicate that HTLV infection without ATL is characterized by normal CD25 expression by lymphocytes and a decreased percentage of lymphocytes with a phenotype characteristic of natural killer cells.

Antigens, CD19

In vitro activation of T lymphocytes from human immunodeficiency virus (HIV)-seropositive blood donors. I. Soluble interleukin 2 receptor (IL2R) production parallels cellular IL2R expression and DNA synthesis.

We investigated the relationship of soluble interleukin 2 receptor (sIL2R) production to cellular IL2R expression and DNA synthesis by mitogen-stimulated mononuclear cells from blood donors seropositive for human immunodeficiency virus (HIV). SIL2R was measured using an enzyme-linked immunosorbent assay which employed 2 anti-IL2R monoclonal antibodies recognizing distinct IL2R epitopes. Decreased phytohemagglutinin-induced DNA synthesis and cellular IL2R expression were accompanied by decreased levels of sIL2R in cell culture supernatants. Similar findings were observed for pokeweed mitogen-induced responses. There was no detectable spontaneous secretion of sIL2R into culture supernatants by unstimulated mononuclear cells from either HIV-seropositive or control seronegative donors. These findings indicate that the in vitro T-cell activation defects which characterize HIV infection include decreased sIL2R production, as well as decreased cellular IL2R expression and DNA synthesis. Further, they show that assessment of supernatant sIL2R levels can be used as a valid, reliable assay for T-cell activation.

Acquired Immunodeficiency Syndrome

Development of a scoring system to predict mortality from upper gastrointestinal bleeding.

Despite the widespread application of endoscopy in acute upper gastrointestinal bleeding, there is little evidence of improved survival among those who undergo the procedure. To select high-risk patients who might benefit most from diagnostic and therapeutic endoscopy, the authors developed and validated a scoring system based on prognostic indicators of increased mortality. The scoring system was developed from the best clinical predictors of mortality, determined in a prospective study of consecutive bleeding patients. The model was then tested in a prospective validation phase at three hospitals. Three main factors in the model predict mortality: bleeding, including hematochezia, drop in hematocrit of 5%, short duration of bleeding, absence of melena, and hypotension; liver disease, manifested by prolonged prothrombin time and encephalopathy; and renal disease. Patients determined to be at high risk for death using the scoring system might be candidates for aggressive management and for therapeutic endoscopy.

Adolescent

Human T-cell leukemia-associated cell surface glycoprotein GP37: studies with three monoclonal antibodies and a rabbit antiserum.

Three monoclonal antibodies (mAbs), termed SN2, SN2a and SN2b, were used in the present work to study a human T-cell leukemia-associated cell surface glycoprotein, GP37. Strong specificity of mAbs SN2, SN2a and SN2b for T leukemia cells was demonstrated by radioimmunoassay and fluorescence-activated cell sorter (FACS) analysis. GP37 was not detected on normal human peripheral blood lymphocytes, purified normal T-cells, normal thymocytes nor normal bone marrow cells. Furthermore, GP37 was barely detectable on phytohemagglutinin (PHA)- and Concanavalin A (Con A)-activated T-cells. The results indicate clinical utility of these mAbs. Competitive binding experiments show that the epitopes recognized by SN2 and SN2a are sufficiently close to each other to allow complete reciprocal inhibition of binding whereas the epitopes recognized by SN2 and SN2b are less close to allow only partial reciprocal binding inhibition. The biochemical nature of antigenic determinants defined by these mAbs was studied by treating T leukemia cells with trypsin, chymotrypsin, thermolysin, neuraminidase and mixed glycosidases. The results suggest that the antigenic determinants defined by these mAbs all consist of the protein moiety of the glycoprotein GP37. No significant antigenic modulation was observed when T leukemia cells were reacted with SN2. In a sequential immunoprecipitation experiment, a 125I-labeled leukemia antigen preparation was first treated with a rabbit anti-T leukemia antiserum. The latter had been prepared by immunizing a rabbit with a partially purified human T leukemia antigen preparation and showed a good specificity for T leukemia cells. Subsequent treatment of the labeled antigen preparation with SN2 showed that SN2 antigen had been precleared. Thus, both mouse mAb SN2 and the rabbit anti-T leukemia antiserum react with the same GP37 molecule.

Animals

A current approach to rectal bleeding.

The source of bleeding from the rectum is extremely difficult to specify in many patients with moderate to severe bleeding. Lesions may be located anywhere along the gastrointestinal tract. On the basis of the available literature and reported clinical data, we conclude that moderate to severe rectal bleeding originates from the upper gut in up to 10% of patients, from the small bowel in up to 5%, and from the colon in the remaining 85%. Diverticulosis and vascular dysplasia account for 30-50% of colonic bleeding, and inflammatory bowel disease and ischemic colitis for another 5-15%. No diagnosis is made in 20-30% of patients with moderate to severe rectal bleeding. Patients with rectal bleeding can be classified as those whose bleeding stops spontaneously, those whose bleeding stops and then recurs, and those whose bleeding continues despite conventional treatment. Based on these classifications, we present an approach to the diagnosis and therapy of rectal bleeding.

Colonic Diseases

A current approach to acute upper gastrointestinal bleeding.

The mortality in patients with upper gastrointestinal bleeding has not changed in the past quarter century in spite of the introduction of new modes of therapy and treatment. In this review we address the possible reasons for a lack of change in mortality and the implications raised for the use of new techniques. We review the factors that affect the mortality of acute upper gastrointestinal hemorrhage and the diagnostic accuracy of upper gastrointestinal endoscopy. Based on this information, we present guidelines for the therapy of the major causes of upper gastrointestinal bleeding. These guidelines should be useful until new therapies have been assessed and become generally available.

Age Factors

Complement-mediated release of histamine from human leukocytes.

Activation of either the alternative or classical pathway of complement generated a factor which induced release of histamine from both non-allergic and allergic human basophils. This factor probably is derived from the complement system since 1) its formation was associated with loss of C3 activity in human serum, 2) chemotactic factor, probably also a complement product, was generated simultaneously, 3) heat inactivation blocked its formation, 4) anti-C3 and anti-C5 blocked formation of the factor, and finally 5) anti-C5 inhibited the activity of the factor once it had been formed. It appears that both complement-mediated and allergen-mediated release of histamine from basophils are secretory, non-cytolytic pathways since both were maximal at 37 degrees C, required the presence of divalent cations, and were inhibited by theophylline. One consistent difference between these two mechanisms was noted: complement-initiated release of histamine occurred more quickly.

Animals

Cells producing low-molecular-weight antibody to Escherichia coli lipopolysaccharide.

CD-1 mice immunized with sheep red blood cells (SRBC) or Escherichia coli lipopolysaccharide (LPS), developed splenic plaque-forming cells (PFC) producing low-molecular-weight antibody; these cells were detected by means of purified rabbit antisera to mouse gamma(1), gamma(2a), and gamma(2b) immunoglobulins. In contrast to SRBC, the primary gamma(1) response to LPS was absent and gamma(2a) and gamma(2b) PFC were detected irregularly. Both immunogens elicited a secondary cellular response in all three subclasses without a corresponding increase in "direct" or gamma(M) PFC. An increase in serum bactericidal antibody following a second injection of LPS was not parallelled by an increase in splenic gamma(M) PFC; it might therefore involve the synthesis of gamma(2) complement-fixing antibody.

Animals