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Biomedical subjects

D L Mann

Publications and source records attributed to D L Mann.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effects of chronic mitral regurgitation on diastolic function in isolated cardiocytes.

We have previously shown that chronic mitral regurgitation (MR) increases the rate of left ventricular early diastolic filling. These changes in chamber diastolic function were felt to be secondary to alterations in left ventricular loading conditions. Therefore, cellular diastolic function measured in cardiac muscle cells (cardiocytes) isolated from animals with chronic MR (absent alterations in loading conditions) was expected to be normal. However, chronic MR caused a decrease in sarcomere lengthening rate. The purpose of the current study was to define the mechanisms causing this decreased sarcomere lengthening rate in chronic MR cardiocytes and to explain the apparent dichotomy between chamber and cellular diastolic properties. Accordingly, sarcomere motion was measured using laser diffraction techniques in enzymatically isolated cardiocytes from seven control dogs and 11 dogs with chronic MR (produced by closed-chest transection of the mitral chordae). In the MR cardiocytes, there were abnormalities in cellular systolic function (decreased extent and velocity of shortening) and in cellular diastolic function (decreased velocity of sarcomere lengthening). Because studies in papillary muscles have shown that there is a direct relation between abnormal diastolic function (decreased velocity of muscle lengthening) and abnormal systolic function (decreased extent of muscle shortening), it was unclear whether the changes in cellular relaxation rate observed in chronic MR merely reflected a concomitant decrease in the extent of shortening or instead reflected an impairment in intrinsic relaxation properties. To make this distinction, the relation between relaxation velocity (measured as peak sarcomere lengthening rate) and sarcomere shortening extent was examined in MR cardiocytes and compared with that in control cardiocytes. There was a direct relation between sarcomere relaxation velocity and sarcomere shortening extent in both control and MR cardiocytes. Over a wide range of shortening extent, the slopes and y intercepts of this relation were similar in control and MR cardiocytes (slope, 27.7 sec-1 in control cells versus 28.1 sec-1 in MR cells; y intercept, -1.1 microns/sec in control cells versus -1.7 microns/sec in MR cells; p = NS). At any common shortening extent, relaxation velocity was the same in control and MR cardiocytes. To prove that this relation could detect abnormalities in the intrinsic myocardial relaxation process, interventions known to produce primary alterations in the intrinsic myocardial relaxation process were examined: the effects of hypothermia (30 degrees C) and isoproterenol (10(-6) M) on the relaxation velocity-shortening extent relation were studied in normal and MR cardiocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart.

To define the mechanism(s) responsible for the negative inotropic effects of tumor necrosis factor-alpha (TNF alpha) in the adult heart, we examined the functional effects of TNF alpha in the intact left ventricle and the isolated adult cardiac myocyte. Studies in both the ventricle and the isolated adult cardiac myocyte showed that TNF alpha exerted a concentration- and time-dependent negative inotropic effect that was fully reversible upon removal of this cytokine. Further, treatment with a neutralizing anti-TNF alpha antibody prevented the negative inotropic effects of TNF alpha in isolated myocytes. A cellular basis for the above findings was provided by studies which showed that treatment with TNF alpha resulted in decreased levels of peak intracellular calcium during the systolic contraction sequence; moreover, these findings did not appear to be secondary to alterations in the electrophysiological properties of the cardiac myocyte. Further studies showed that increased levels of nitric oxide, de novo protein synthesis, and metabolites of the arachidonic acid pathway were unlikely to be responsible for the TNF alpha-induced abnormalities in contractile function. Thus, these studies constitute the initial demonstration that the negative inotropic effects of TNF alpha are the direct result of alterations in intracellular calcium homeostasis in the adult cardiac myocyte.

Animals↗
PubMed1992

Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines.

Cellular proteins associated with immunodeficiency viruses were identified by determination of the amino acid sequence of the proteins and peptides present in sucrose density gradient-purified human immunodeficiency virus (HIV)-1, HIV-2, and simian immunodeficiency virus (SIV). beta 2 microglobulin (beta 2m) and the alpha and beta chains of human lymphocyte antigen (HLA) DR were present in virus preparations at one-fifth the concentration of Gag on a molar basis. Antisera to HLA DR, beta 2 m, as well as HLA class I precipitated intact viral particles, suggesting that these cellular proteins were physically associated with the surface of the virus. Antisera to class I, beta 2m, and HLA DR also inhibited infection of cultured cells by both HIV-1 and SIV. The specific, selective association of these cellular proteins in a physiologically relevant manner has major implications for our understanding of the infection process and the pathogenesis of immunodeficiency viruses and should be considered in the design of vaccines.

AIDS Vaccines↗
PubMed1992

HLA phenotype is a factor in determining rate of disease progression and outcome in HIV-1-infected individuals.

HLA allele frequencies were examined for possible association(s) with the rate of disease progression and with the disease outcome (AIDS diagnosis) in a population of HIV-1-infected individuals. Certain alleles were associated with the relative rate of CD4+ T-cell decline. Association of particular alleles with several disease outcomes associated with infection was also observed. It is important to keep these two aspects (disease progression, AIDS diagnosis) separate when studying HLA in the HIV-1-infected population. Alleles that may play a role in the rate of virus speed by effecting the immune response may be different from those found to be associated with a particular disease. We feel that the only truly informative data, in this regard, can be generated from a relative precise determination of the time of infection (to study disease progression) and adequate numbers of individuals with specific diseases to study specific disease association. If such data can be generated we will have a much better understanding of the pathogenetic process(es) of HIV-1 infection.

Alleles↗
PubMed1992

Adrenergic effects on the biology of the adult mammalian cardiocyte.

BACKGROUND: To delineate the mechanism(s) of catecholamine-mediated cardiac toxicity, we exposed cultures of adult cardiac muscle cells, or cardiocytes, to a broad range of norepinephrine concentrations. METHODS AND RESULTS: Norepinephrine stimulation resulted in a concentration-dependent decrease in cardiocyte viability, as demonstrated by a significant decrease in viable rod-shaped cells and a significant release of creatine kinase from cells in norepinephrine-treated cultures. Norepinephrine-mediated cell toxicity was attenuated significantly by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, whereas the effects mediated by the alpha-adrenoceptor were relatively less apparent. When norepinephrine stimulation was examined in terms of cardiocyte anabolic activity, there was a concentration-dependent decrease in the incorporation of [3H]phenylalanine and [3H]uridine into cytoplasmic protein and nuclear RNA, respectively. The decrease in cytoplasmic labeling was largely attenuated by beta-adrenoceptor blockade and mimicked by selective stimulation of the beta-adrenoceptor, but alpha-adrenoceptor stimulation resulted in relatively minor decreases in cytoplasmic labeling. The norepinephrine-induced toxic effect appeared to be the result of cyclic AMP-mediated calcium overload of the cell, as suggested by studies in which pharmacological strategies that increased intracellular cyclic AMP led to decreased cell viability, as well as studies that showed that influx of extracellular calcium through the verapamil-sensitive calcium channel was necessary for the induction of cell lethality. Additional time-course studies showed that norepinephrine caused a rapid, fourfold increase in intracellular cyclic AMP, followed by a 3.2-fold increase in intracellular calcium [( Ca2+]i). CONCLUSIONS: These results constitute the initial demonstration at the cellular level that adrenergic stimulation leads to cyclic AMP-mediated calcium overload of the cell, with a resultant decrease in synthetic activity and/or viability.

Animals↗
PubMed1992

Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.

This study was designed to answer two questions. First, does the left ventricular contractile dysfunction resulting from mitral regurgitation (MR) reflect a primary defect in the cardiac muscle cell? Second, what is the basis for any change in cellular contractile function that might be observed? Left ventricular volume overload was produced in 10 dogs by catheter transection of mitral chordae tendineae. Three months later in these and in seven control dogs, left ventricular contractile function was characterized by the end-ejection stress-volume relation (EESVR). Investigators who were blinded to these results then characterized the contractile performance of cardiac muscle cells, or cardiocytes, from these same left ventricles in terms of the viscosity (graded external load)-velocity relation. Finally, the tissue and cellular components of these same left ventricles were analyzed morphometrically. Both the left ventricles from the MR group and their constituent cardiocytes showed marked contractile abnormalities. By matching ventricles with cells from the same MR dogs, ventricular EESVR was correlated with cardiocyte peak sarcomere shortening velocity (SSV). The correlation coefficient between EESVR and SSV was 0.63, but between a size-independent measure of active ventricular stiffness and SSV, it was 0.88. No change in left ventricular interstitial volume fraction was found in MR dogs, but both ventricular and cellular contractile dysfunction strongly correlated with a decreased volume fraction of cardiocyte myofibrils. Last, in an attempt to relate the degree of contractile dysfunction to the hypertrophic response, left ventricular mass in the MR dogs was correlated with both cellular and ventricular contractile indexes; no significant correlation was found. Three conclusions are warranted by these studies. First, chronic left ventricular volume overload from mitral regurgitation leads to contractile defects at both the ventricular and cellular levels, the extent of which correlates well in individual animals. Second, no quantitative interstitial change resulted from MR. Taken together, these two findings strongly suggest that the contractile defect is intrinsic to the cardiocyte. Third, while the contractile abnormality in MR remains undefined, the most basic defects appear to be a combination of myofibrillar loss with the failure of compensatory hypertrophy to occur in response to progressive decrements in cellular and ventricular function.

Animals↗
PubMed1991

Molecular definition of a polymorphic antigen (LA45) of free HLA-A and -B heavy chains found on the surfaces of activated B and T cells.

A monomoprhic monoclonal antibody (LA45 antibody) reactive with "a new activation-induced surface structure on human T lymphocytes" (LA45 antigen) that resembled free class I heavy chains has recently been described (Schnabl, E., H. Stockinger, O. Majdic, H. Gaugitsch, I.J.D. Lindley, D. Maurer, A. Hajek-Rosenmayr, and W. Knapp. 1990. J. Exp. Med. 171:1431). This antibody was used to clone a class I-like heavy chain (LA45 gene) from the HUT 102 tumor cell, which paradoxically did not give rise to the LA45 antigen on transfection into monkey COS cells. We show here that the LA45 gene is HLA-Aw66.2, a previously uncharacterized allele of the HLA-A locus. The previously determined LA45 sequence differs from that of HLA-Aw66.2, from HUT 102, and the CR-B B cell line derived from the same individual as HUT 102 by substitution of tryptophan for serine at position 4 in the alpha 1 domain. Transfection of HLA-Aw66.2, and of a mutant of this gene with serine 4 substituted for tryptophan, into a human B cell line (C1R) both resulted in expression of the LA45 epitope. Furthermore, we find expression of the LA45 epitope on Epstein Barr virus-transformed B cell lines as well as lectin-activated T cells, but not on long-term T cell lines or unstimulated peripheral blood T cells. The specificity of the LA45 antibody is polymorphic and the presence of the LA45 epitope is precisely correlated with the sequence arginine, asparagine (RN) at residues 62 and 63 of the helix of the alpha 1 domain. The LA45 epitope is broadly distributed, being associated with half the alleles of both HLA-A and -B loci but none of the HLA-C locus. All the results are consistent with the presence of pools of free HLA-A and -B heavy chains at the surfaces of certain cell types but not others. Such molecules are probably responsible for the HLA-associated class I alloantigens of lectin-activated T cells. We hypothesize the free heavy chains result from dissociation of beta 2-microglobulin from subpopulations of empty HLA-A,B molecules, or molecules with weakly bound peptides, that vary in size depending on cellular activation and peptide supply.

Alleles↗
PubMed1991

Cryopreservation and long-term liquid nitrogen storage of peripheral blood mononuclear cells for flow cytometry analysis: effects on cell subset proportions and fluorescence intensity.

The effect of cryopreservation and long-term liquid nitrogen storage on peripheral blood mononuclear cell (PBMC) subsets was prospectively analyzed using monoclonal antibodies and flow cytometry. Brief cryopreservation did not significantly alter the proportion of positively stained cells for CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells. A small but statistically significant increase in the proportion of positive cells was observed for HLA-DR+ and HLe-1+ cells. Brief cryopreservation was associated with a decrease in the mean fluorescence intensity (MFI) values for CD3+, CD4+, and CD8+ cells; an increase in MFI values for CD14+ and HLA-DR+ cells; and no change for CD16+, CD19+, and HLe-1+ cells. There was no significant change in the proportion of CD3+, CD4+, or CD16+ cells during 20 months of storage in liquid nitrogen. Small but statistically significant decreases in the proportion of CD8+ and CD19+ cells were observed over the same interval, and the proportion of CD14+ cells (monocytes) was highly variable. Chronologic changes in fluorescence intensity during long-term storage were observed for all cell subsets except CD16+ and CD19+ cells. Cryopreservation is a valuable technique for long-term storage of viable cells. For many laboratory applications, the small changes noted in the present study will have no practical importance. However, for clinical and epidemiological investigations encompassing large numbers of samples, statistical techniques to adjust for small changes during storage should be considered.

Antigens, CD↗
PubMed1991

Single- versus dual-chamber sensor-driven pacing: comparison of cardiac outputs.

Previous studies have shown that single-chamber sensor-driven pacing improves exercise tolerance for patients with chronotropic incompetence. However, long-term single-chamber pacing has a number of inherent problems that limit its usefulness. Although sensor-driven dual-chamber pacing largely obviates the problems inherent with single-chamber sensor-driven pacing, the physiologic benefit of dual-chamber sensor-driven pacing has not yet been demonstrated. Accordingly, the purpose of this study was to compare exercise-induced cardiac output for patients with chronotropic incompetence, after programming their pacemakers to either a simulated sensor-driven single or simulated dual-chamber mode. Cardiac output was measured noninvasively at rest and peak exercise using standard Doppler-derived measurements, obtained in a blinded fashion. At rest the Doppler-derived resting VVI and DDD cardiac outputs were 4.49 +/- 0.3 L/min and 4.68 +/- 0.3 L/min, respectively. At peak exercise, the DDD cardiac output was 5.07 +/- 0.5 L/min, whereas the simulated activity VVI and DDD cardiac outputs were 6.33 +/- 0.6 L/min and 7.41 +/- 0.70 L/min, respectively. Analysis of variance showed that there was an overall significant difference in cardiac output from rest to peak exercise (p less than 0.001). However, only the simulated activity DDD cardiac output was significantly different from its respective control value (p less than 0.05). Thus this study shows for the first time that the addition of rate responsiveness to dual-chamber pacing results in a significant improvement in cardiac output for patients with chronotropic incompetence.

Aged↗
PubMed1991

Dialysis-induced alterations in left ventricular filling: mechanisms and clinical significance.

Quantitative two-dimensional (2-D) and Doppler echocardiography were used to determine whether hemodialysis results in alterations in left ventricular (LV) diastolic filling that might contribute to dialysis-induced hypotension, as well as to assess whether any hemodynamic variables or indices of diastolic filling might be used to identify which patients were at the greatest risk of becoming hemodynamically unstable during dialysis. Sixteen male patients undergoing routine maintenance hemodialysis for end-stage renal disease were prospectively studied before and after hemodialysis. Following hemodialysis there was a significant prolongation (P less than 0.05) in LV isovolumetric relaxation time (IVRT), as well as a significant reduction in the rate and extent of early rapid ventricular filling (P less than 0.005); in contrast, late atrial-assisted filling did not change significantly. A multiple stepwise linear regression analysis of predialysis hemodynamic parameters and noninvasive indices of LV filling showed that there was a significant independent inverse relationship between the frequency of dialysis-related hypotensive episodes and the duration of early LV filling (r = -0.81; P less than 0.001). These results suggest that hemodialysis results in discrete alterations in early LV filling, with no significant compensatory increase in late atrial-assisted ventricular filling. Further, patients with the shortest early LV filling times appeared to have the greatest predilection for becoming hemodynamically unstable during dialysis.

Aged↗
PubMed1991

Signals for cardiac muscle hypertrophy in hypertension.

Hypertension is associated with a rise in arterial pressure and a compensatory increase in cardiac mass, which if not treated effectively, progresses to decompensated congestive heart failure. This decompensation of an initially compensatory hypertrophy has intensified interest in the factors that initiate and maintain the development of cardiac hypertrophy. The potential signals that induce the development of cardiac hypertrophy are grouped as hemodynamic, growth-promoting hormonal, vasoconstriction-promoting hormonal, and genetic factors. Growth-promoting hormones such as insulin and thyroxine appear to play a permissive, but essential, role in the development and maintenance of cardiac hypertrophy. However, changes in cardiac load, both above and below normal, result in parallel changes in cardiac mass, which will return to normal when a normal load is restored. This adaptive response of the myocardium in direct response to elevated and depressed loads demonstrates that cardiac structure, composition, and function are not fixed postneonatal cardiac properties, but instead are regulated dynamically by the cardiocyte loading environment. This adaptive response is subject to modulation by vasoconstriction-promoting hormones and genetic factors. The current thrust in this research area is to elucidate the cellular signals that transduce the physical stimulus for hypertrophy into biochemical events underlying hypertrophic cardiac growth. To remove complex systemic interactions in vivo from the experimental paradigm, several in vitro models have been used to examine three general, but distinct, cellular pathways involving protein kinase C activation, cyclic AMP formation, and increased ion fluxes. Each pathway demonstrated a stimulatory effect on general protein synthesis, which is necessary for growth in all cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cellular versus myocardial basis for the contractile dysfunction of hypertrophied myocardium.

Contractile dysfunction has been demonstrated in many previous studies of experimental right ventricular pressure-overload hypertrophy; however, given the complex changes that occur both in the cardiac muscle cell and in the multiple components of the cardiac interstitium, it is not clear whether the contractile dysfunction observed is an intrinsic property of the cardiac muscle cell or whether it is the result of a mechanically normal cardiac muscle cell contracting within an abnormal interstitial environment. The purpose of the present study was to examine the contractile behavior of cardiac muscle cells, or cardiocytes, isolated from seven cat right ventricles that were pressure-overloaded by banding the pulmonary artery; right ventricular cardiocytes from seven sham-operated cats served as controls. Cardiocytes were obtained from these cats via standard cell isolation procedures; contractile function of the cardiocytes in response to graded viscous external loads was defined by laser diffraction. The cells were stimulated to contract at a frequency of 0.25 Hz, using 100-microA direct current pulses of alternating polarity. Hypertrophied right ventricular cardiocytes obtained from banded cats showed marked systolic contractile abnormalities in comparison with right ventricular cardiocytes from sham-operated cats. The peak velocity of sarcomere shortening for the control and hypertrophied cardiocytes in 1-cp superfusate was 3.6 +/- 0.2 and 2.1 +/- 0.1 microns/sec, respectively (p less than 0.001); the maximum extent of sarcomere shortening for the control and hypertrophied cardiocytes was 0.21 +/- 0.01 and 0.14 +/- 0.01 microns, respectively (p less than 0.001). Further, the time to peak shortening in the 1-cp superfusate was significantly longer for the hypertrophied cardiocytes (150.1 +/- 3.3 versus 160.4 +/- 3.7 msec; p less than 0.04). When the relengthening properties of the cells were examined in the 1-cp superfusate, there were significant differences between cardiocyte groups. The peak rate of sarcomere relengthening was 3.5 +/- 0.2 microns/sec in the control cardiocytes and 2.2 +/- 0.17 microns/sec in the hypertrophied cardiocytes (p less than 0.001). Similarly, the time to peak velocity of sarcomere relengthening (48.8 +/- 1.8 versus 57.9 +/- 2.9 msec) and the time to 50% maximal sarcomere relengthening (57.1 +/- 3.1 versus 67.1 +/- 3.1 msec) were both significantly prolonged for the hypertrophied cardiocytes (p less than 0.02). This study shows for the first time that the contractile defect in this model of right ventricular pressure-overload hypertrophy is intrinsic to the cardiac muscle cell itself. This finding provides a basis for further, more focused investigations designed to determine the mechanisms responsible for the contractile dysfunction observed in this form of experimental cardiac hypertrophy.

Animals↗
PubMed1991

T cell subsets in healthy black smokers and nonsmokers. Evidence for ethnic group as an important response modifier.

The influence of cigarette smoking on T cell subsets has been studied in white subjects, but comparable data are not available for blacks. We analyzed peripheral blood mononuclear cell subsets in a population-based, stratified, random sample of healthy black adults using monoclonal antibodies and flow cytometry. The study population consisted of 94 men and 79 women, including 73 smokers (CS) and 100 nonsmokers (NS). Cigarette smoking was associated with a significant elevation in leukocyte (WBC) count (CS 7,270 +/- 230 cells/mm3 versus NS 6,260 +/- 160 cells/mm3; p = 0.001), although WBC counts for both groups were substantially lower than those reported for white smokers and nonsmokers. Smokers had a significantly lower proportion of CD4+ cells than nonsmokers (CS 55.4 +/- 0.9% versus NS 58.7 +/- 0.9; p = 0.01), adjusting for age and gender. No significant smoking-related changes were observed for CD8+ cells, the CD4/CD8 ratio, or total T cells (CD3+), monocytes (CD14+), or natural killer cells (CD16+). Among black smokers, a significant dose-related decrease in CD4+ cells was observed as the number of cigarettes smoked per day increased. Among black exsmokers, the level of WBC and CD4+ cells returned to the level observed in never smokers within 2 to 5 yr after smoking cessation. These results contrast sharply with the previously reported increase in CD4+ cells and decrease in natural killer cells associated with cigarette smoking in whites. The data suggest that the immunologic effects of cigarette smoking may be significantly modified by ethnic characteristics.

Adult↗
PubMed1991

Catheter-induced tricuspid regurgitation. Incidence and clinical significance.

The incidence and severity of catheter-induced tricuspid regurgitation has not been studied extensively. Given the frequency with which right heart catheters are employed to measure cardiac output, it is important to know whether the severity of catheter-induced tricuspid regurgitation is sufficient to invalidate the measurement of thermodilution cardiac output. Accordingly, the purpose of the present prospective study was to determine the incidence and severity of catheter-induced tricuspid regurgitation in 25 men (mean age, 58.1 +/- 1.4 years) using Doppler ultrasound. The tricuspid valve was interrogated from two orthogonal views using pulsed-wave and color flow Doppler, either in the presence or absence of a 7-French catheter across the tricuspid valve. The severity of catheter-induced tricuspid regurgitation was graded semiquantitatively using a validated scoring system. Pulsed-wave Doppler studies showed that the incidence of catheter-induced tricuspid regurgitation was 48 percent, and that the average tricuspid regurgitation score increased from 0.41 +/- 0.16 to 0.61 +/- 0.17 (p less than 0.01). Color flow Doppler studies showed similar findings. Further, the incidence of catheter-induced tricuspid regurgitation was not related to the patient's underlying hemodynamic status or right ventricular geometry. In conclusion, this study shows for the first time that the quantitative extent of catheter-induced tricuspid regurgitation is small, and is therefore unlikely to be important clinically, particularly with regard to the assessment of thermodilution cardiac output.

Cardiac Catheterization↗
PubMed1990

HIV-1 transmission and function of virus-infected monocytes/macrophages.

Monocyte/macrophages (MM) were isolated from HIV-1 seronegative individuals, infected with HIV-1 and examined for their ability to infect autologous T lymphocytes with and without concomitant presentation of exogenous Ag. HIV-1-infected MM presented tetanus toxin (TT) and streptokinase to T cells (as measured by [3H]thymidine incorporation) comparable to presentation by uninfected MM. In these studies, it was observed that HIV-1-infected MM without additional exogenous Ag stimulated autologous T lymphocytes, however, to a lesser degree than with TT and streptokinase. Virus production in T cells appeared to be relative to the degree of stimulation with the highest levels of stimulation and infection observed when T cells were exposed to HIV-1-infected TT-presenting MM. Studies were carried out to examine some of the restricting elements in MM-mediated infection of T lymphocytes with and without TT presentation. Antibodies to CD4, as well as soluble immunopurified gp120, blocked cell-mediated infection indicating that infection of T cells was through the CD4 molecule as has been demonstrated with cell-free virus. In addition, soluble gp120 inhibited Ag presentation by HIV-1-infected and uninfected MM. mAb to MHC class II Ag HLA-DR and -DP blocked T cell infection by HIV-1-infected MM with and without presentation of TT. No effect was observed with mAb to MHC class I Ag. These results indicate that virus transmission to T lymphocytes can be mediated by HIV-1-infected MM and that these cells maintain their function as APC. Activation of T cells appears to be important in the process of T cell infection in this system inasmuch as antibodies that block Ag presentation and thus a T cell proliferative signal inhibit infection.

Antigen-Presenting Cells↗
PubMed1990

Association of rare alleles of the Harvey ras protooncogene locus with lung cancer.

The hypothesis that rare variable nucleotide tandem repeat alleles of the Ha-ras-1 polymorphism are an inherited predisposing factor in human lung carcinogenesis has been evaluated in an age, race, and smoking matched case-control study. Twenty-three different alleles were identified by their restriction fragment length in DNA isolated from peripheral blood lymphocytes and were categorized into three groups: common; intermediate; and rare. The frequencies of rare alleles in blacks with either squamous cell carcinoma, large cell carcinoma, or small cell carcinoma were found to be significantly higher than those among groups of control subjects that were comprised of chronic obstructive pulmonary disease patients and patients with cancer at sites other than the lung. A similar trend which did not reach statistical significance was observed in whites. These data are consistent with the hypothesis that inheritance of Ha-ras-1 rare restriction fragment length alleles represents a genetic risk factor for some human lung cancers. The biological basis of this observation remains to be clarified, and it is possible that ethnic variations in rare allele frequencies are responsible for the differences noted. However, the data suggest that further evaluation of the Ha-ras-1 polymorphism as a marker of individual lung cancer susceptibility is warranted.

Adenocarcinoma↗
PubMed1990

Cell surface antigens and function of monocytes and a monocyte-like cell line before and after infection with HIV.

The human immunodeficiency virus (HIV-1) preferentially infects cells that express the CD4 molecule, including monocytes and cells of the monocyte lineage. The monocyte-like cell line U937 and monocytes isolated from peripheral blood lymphocytes (PBL) were infected with HIV-1. Cell surface antigen expression was determined in infected and noninfected cells as was the ability to stimulate in mixed lymphocyte reaction. The CD4 antigen decreased in infected cells U937 and PBL monocytes. MHC class II antigens HLA-DR, HLA-DQ, and HLA-DP increased in HIV-1 infected U937 cells. In infected PBL-derived monocytes, HLA-DR increased, HLA-DQ decreased, and HLA-DP was unchanged. Infected U937 and PBL monocytes were capable of stimulating allogeneic lymphocytes, thus demonstrating retention of the alloantigen presentation function of HIV-1-infected monocytes.

Antigens, Surface↗