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Biomedical subjects

M A Fletcher

Publications and source records attributed to M A Fletcher.

At least 109 records · Page 6Linked to original sources

Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations.

OBJECTIVE: To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS: We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS: Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS: Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.

Acquired Immunodeficiency Syndrome↗

HTLV-I/II seropositivity and death from AIDS among HIV-1 seropositive intravenous drug users.

In a prospective study of street-recruited intravenous drug users (IVDUs) in Miami, Florida, USA, 107 (46.5%) of 230 IVDUs were infected with HIV-1. Of these HIV-1 seropositive individuals, 23 were also infected with human T-lymphotropic virus type I or II (HTLV-I/II). To test the hypothesis that HTLV-I/II infection has an effect on the survival of HIV-1 seropositive IVDUs, various baseline clinical and laboratory HIV-1 related indices in HTLV-I/II positive and negative groups were compared. Life table analysis and Cox's proportional hazards model were used to estimate the potential effect of HTLV-I/II infection on the survival patterns of people infected with HIV-1. IVDUs infected with both viruses were three times more likely to die from AIDS during follow-up than were those infected with HIV-1 only. This finding suggests that HTLV-I/II seropositivity may adversely affect the clinical outcome of HIV-1 seropositive patients.

Acquired Immunodeficiency Syndrome↗

Exercise intervention attenuates emotional distress and natural killer cell decrements following notification of positive serologic status for HIV-1.

The impact of aerobic exercise training as a buffer of the affective distress and immune decrements which accompany the notification of HIV-1 antibody status in an AIDS risk group was studied. Fifty asymptomatic gay males with a pretraining fitness level of average or below (determined by predicted VO2 max) were randomly assigned to either an aerobic exercise training program or a no-contact control condition. After five weeks of training, at a point 72 hours before serostatus notification, psychometric, fitness and immunologic data were collected on all subjects. Psychometric and immunologic measures were again collected one-week postnotification. Seropositive controls showed significant increases in anxiety and depression, as well as decrements in natural killer cell number following notification whereas, seropositive exercisers showed no similar changes and in fact, resembled both seronegative groups. These findings suggest that concurrent changes in some affective and immunologic measures in response to an acute stressor might be attenuated by an experimentally manipulated aerobic exercise training intervention.

Adult↗

Leukocyte immunophenotyping by flow cytometry in a multisite study: standardization, quality control, and normal values in the Transfusion Safety Study. The Transfusion Safety Study Group.

The Transfusion Safety Study (TSS) is a multicenter, cooperative investigation of factors that may determine the occurrence and modify the expression of transfusion-transmitted infections. A flow cytometry laboratory was established in each of the six participating centers in order to avoid alterations in cell phenotypes which may be caused by shipping delays, temperature changes, and handling. As a consequence, in order to assure compatibility of results, stringent standardization, quality control, and proficiency testing procedures were developed. This paper documents (i) the effect of time from phlebotomy to specimen staining and then to analysis for the antibodies used in the study; (ii) the effects of variations in light scatter cursor location for certain antibodies; (iii) a quality control program and data management and analysis system, each specifically designed for the study; and (iv) presents extensive data on age- and sex-related reference (normal) ranges for the several individual and paired monoclonal antibodies used in the study. Problems encountered, including obtaining reliable absolute lymphocyte counts, interference by nucleated erythrocytes, and sources of variability in results, are discussed. This study is meant to serve as a reference for future TSS publications.

Blood Transfusion↗

Epstein-Barr virus infection and immunologic dysfunction in patients with aqueous tear deficiency.

The authors tested their hypothesis that Epstein-Barr virus (EBV) infection is a risk factor for aqueous tear deficiency (ATD) by evaluating 38 ATD patients and 17 controls for serologic evidence of EBV infection. Aqueous tear deficiency was graded clinically as mild or severe. A linear trend toward elevated EBV capsid (P less than 0.05) and early antigen (P less than 0.001) titers was noted from control to severe ATD patients. Rubella and cytomegalovirus antibody titers were poorly correlated with EBV titers, suggesting that the elevated EBV antibodies in ATD patients were not due to nonspecific polyclonal B-cell activation. Epstein-Barr virus antigens were detected in two of six lacrimal gland biopsies from severe ATD patients with Sjögren's syndrome, but in none of the control glands. Aqueous tear deficiency patients were evaluated for immunologic dysfunction associated with EBV infection. Linear trends of elevated serum IgG (P less than 0.05), autoantibody and immune complex positivity (P less than 0.05), and reduced natural killer cell cytotoxicity (P less than 0.05) were found from controls to severe ATD patients. Furthermore, reduced T-helper lymphocyte counts (P less than 0.06) and an increased percentage of HLA-DR+ CD8 lymphocytes (P less than 0.05) were observed in severe ATD patients compared with the mild and control groups. A multivariate analysis of the data showed a significant correlation between severe ATD and elevated EBV early antigen titers, Sjögren's syndrome, and an increased percentage of HLA-DR+ CD8 lymphocytes. The authors' findings suggest that EBV infection may be a risk factor for development of ATD in a subset of ATD patients with greater disease severity, Sjögren's syndrome, and immunologic dysfunction.

Adult↗

Psychoneuroimmunology and HIV-1.

Recent psychoneuroimmunologic findings have suggested that it may be useful to evaluate the influence of behavioral factors on immune functioning and disease progression among human immunodeficiency virus-Type 1 (HIV-1) infected individuals. Behavioral interventions with immunomodulatory capabilities may help restore competence and thereby arrest HIV-1 disease promotion at the earliest stages of the infectious continuum. Evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high-risk HIV-1 seronegative and very early stage seropositive gay men is presented. The HIV-1 infection is cast as a chronic disease for which early immunomodulatory behavioral interventions may have important physical and psychological impact.

Acquired Immunodeficiency Syndrome↗

Immunologic abnormalities in chronic fatigue syndrome.

The chronic fatigue syndrome (CFS), formerly known as chronic Epstein-Barr virus syndrome, is a clinical state of some complexity and uncertain etiology. In order to characterize in a comprehensive manner the status of laboratory markers associated with cellular immune function in patients with this syndrome, 30 patients with clinically defined CFS were studied. All of the subjects were found to have multiple abnormalities in these markers. The most consistent immunological abnormality detected among these patients, when compared with normal controls, was low natural killer (NK) cell cytotoxicity. The number of NK cells, as defined by reactivity with monoclonal antibody NKH.1 (CD56), was elevated, but the killing of K562 tumor cells per CD56 cell was significantly diminished. Lymphoproliferative responses after stimulation with phytohemagglutinin and pokeweed mitogen were decreased in most patients when compared with those in normal controls, as was the production of gamma interferon following mitogen stimulation. Lymphocyte phenotypic marker analysis of peripheral blood lymphocytes showed that there were significant differences between patients with CFS and controls. There was an increase in the percentage of suppressor-cytotoxic T lymphocytes, CD8, and a proportionally larger increase in the number of CD8 cells expressing the class II activation marker. Most patients had an elevated number of CD2 cells which expressed the activation marker CDw26. The numbers of CD4 cells and the helper subset of CD4+CD29+ cells in patients with CFS were not different from those in controls. There was, however, a significant decrease in the suppressor inducer subset of CD4+ CD45RA+ cells. The number of B cells, CD20 and CD21, were elevated, as were the numbers of a subset of B cells which coexpressed CD20 and CD5. The patterns of immune marker abnormalities observed was compatible with a chronic viral reactivation syndrome.

Adult↗

HIV seropositivity of needles from shooting galleries in south Florida.

Needle/syringe combinations were collected from three shooting galleries in South Florida and tested for the presence of antibodies to HIV-1. Fifteen of 148 needles (10.1 percent) tested positive for HIV-1 antibody. Seropositivity rates did not vary by the day of the week of collection, nor by shooting gallery from which they were collected. When the needle appeared to contain blood residue, 20.0 percent were positive versus 5.1 percent with no blood residue. These findings suggest that needles/syringes used in shooting galleries are likely to serve as reservoirs and/or vectors of transmission of the HIV-1 virus, and that although visual inspection of the needle/syringe may be useful in lessening the chance for transmission, even the visually "clean" needles may result in transmission of infection.

Acquired Immunodeficiency Syndrome↗

Immunophenotyping in a multicenter study: the Transfusion Safety Study experience.

The Transfusion Safety Study (TSS) is a cooperative investigation of factors that determine the occurrence of and modify the expression of transfusion-transmitted infections. A major component of its data is derived from lymphocyte immunophenotyping using a large panel of monoclonal antibodies and two-color flow cytometric analysis. The multicenter longitudinal character of TSS necessitates a uniformity of instrumentation, reagents, and protocols, as well as an intensive quality control program. The baseline assessment of a cohort of males 10 years of age and over with congenital clotting disorders (CCD) exemplifies the approach and some of the flow cytometry results. A comparison of anti-HIV-1 positive and negative subjects shows that more of the loss of T4+ cells was attributable to a decrease in the T4+4B4+ subset than the T4+2H4+ subset. There was an overall increase in CD8 cells, with a significant increase in the I2+T8+ and Leu7+T8+ cells, but a fall in NKH.1+T8+ cells. Monocytes, MO2+I2+ cells, increased. In CCD patients under the age of 10, both anti-HIV-1 positive and negative, there were absolute elevations in immunocytes, including CD4. There was also a distinctly different distribution of CD4 subsets. The suppressor inducer subset, 2H4+T4+, was increased relative to the helper inducer subset, 4B4+T4+, in the younger subjects.

Acquired Immunodeficiency Syndrome↗

Multiple sclerosis-like illness occurring with human immunodeficiency virus infection.

We describe seven men with a neurologic disease clinically indistinguishable from multiple sclerosis occurring in association with seropositivity for the human immunodeficiency virus, type 1 (HIV-1). Histopathology of the CNS obtained in three patients (2 by brain biopsy, 1 at autopsy) was consistent with MS. The neurologic symptoms preceded the onset of clinically evident immunosuppression in all patients. In three men, HIV-1 seropositivity was demonstrated concomitantly or within 3 months of the onset of their neurologic disease. In the others, features of MS preceded the demonstration of HIV-1 seropositivity by 41 months, 59 months, 11 years, and 18 years, respectively. Despite the superimposition of varying degrees of cellular immunodeficiency associated with HIV-1 infection, six of these men continued to experience relapsing neurologic symptoms.

Acquired Immunodeficiency Syndrome↗

Seroepidemiologic studies of cytomegalovirus and Epstein-Barr virus infections in relation to human immunodeficiency virus type 1 infection in selected recipient populations. Transfusion Safety Study Group.

Antibodies to human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were evaluated among 1,171 persons with and without antibodies to human immunodeficiency virus type 1 (anti-HIV-1). These included 97 blood donors, 577 persons given blood components or products, and 497 controls. A significantly higher proportion of anti-HIV-1 positive than -negative donors were anti-CMV-positive, a finding associated with homosexual contact among some of the former. Among subjects with treated clotting disorders, there was no difference in prevalence of anti-CMV or anti-EBV between anti-HIV-1-positive and -negative persons. The prevalence of antibodies to EBV early antigens showed no relationship to anti-HIV-1 status. Anti-CMV positivity in anti-HIV-1-negative donors was associated with an increase in mean CD8 counts and lower mean CD4/CD8 ratio. Anti-CMV and anti-EBV positivity in anti-HIV-1-positive subjects with treated clotting disorders was not associated with a lower CD4 or higher CD8 count than HIV-1 infection alone. Subjects who developed AIDS after enrollment had no significant difference in median time from entry to diagnosis when analyzed by serologic evidence of CMV and EBV antibody status at entry, and a few subjects had AIDS at entry without serologic evidence of prior CMV or EBV infection. The overall results are consistent with acquisition and progression of HIV-1 independently of coincident CMV or EBV infection.

Acquired Immunodeficiency Syndrome↗

Segregation of lymphocyte low-molecular-weight DNA and antinuclear-antibodies in a family with systemic lupus erythematosus in first cousins.

All patients with systemic lupus erythematosus (SLE) demonstrated two classes of newly synthesized DNA in sucrose density gradients of PHA (phytohemagglutinin)-stimulated lymphocytes: a large-molecular-weight fraction that comigrates with control DNA and an excess low-molecular-weight DNA (LMW-DNA) fraction not found in control lymphocytes. Excess LMW-DNA was independent of disease activity or drug therapy. LMW-DNA and serologic abnormalities were studied in a four-generation family in which two first cousins had SLE. Excess LMW-DNA was found in the cousins with SLE, sibling parents of the SLE patients, a common grandparent, four of nine siblings of one patient, and five of seven at risk children. Both males and females had excess LMW-DNA. Male-male transmission was observed. The expression of excess LMW-DNA in stimulated lymphocytes is inherited as an autosomal dominant genetic trait in this family. All unaffected adult family members with the marker had positive antinuclear antibodies (ANAs) except the grandmother. However, none of the five children with excess LMW-DNA showed positive ANAs. Excess LMW-DNA precedes the appearance of ANAs when found in children of adults with excess LMW-DNA, and may be a predisposing factor in the development of the immunologic responses of systemic lupus erythematosus.

Antibodies, Antinuclear↗

Evaluation of heterosexual partners, children, and household contacts of adults with AIDS.

Forty-five adults with the acquired immunodeficiency syndrome (AIDS) and their 45 spouses, 109 children, and 29 household contacts were studied for evidence of heterosexual, perinatal, and household spread of human T-cell lymphotropic virus type III (HTLV-III) infection. Of the 45 spouses enrolled, 26 (58%) had antibody to HTLV-III, including 12 (71%) of 17 male spouses and 14 (50%) of 28 female spouses. Of the 12 seropositive male spouses, nine were seropositive at enrollment and three had seroconversion. Of the 14 seropositive female spouses, four were seropositive at enrollment and ten seroconverted. Lack of barrier contraceptive use and oral sex were associated with seroconversion. Of the 109 children enrolled, 15 had AIDS or an AIDS-related illness, two had evidence of passive transfer of maternal antibodies, and two had HTLV-III infection acquired outside the household. None of the 90 seronegative children seroconverted. Of 29 household contacts studied, none developed antibody to HTLV-III.

Acquired Immunodeficiency Syndrome↗

Suppression of peripheral blood natural killer cell activity by excess thyroid hormone.

Natural killer (NK) cells were assessed in patients with hyperthyroxinemia due to Graves' disease or treatment with thyroxine (T4). Cytolytic activity was measured with 51Cr-labeled K562 tumor cells and NK enumeration was by flow cytometry using NKH-1 monoclonal antibody to identify the relevant surface marker. Activity was uniformly decreased in association with hyperthyroxinemia, regardless of the underlying pathology; however, there was no reduction in the number of NKH-1+ cells. NK activity was enhanced by addition of interleukin 2 (IL-2) in both control and patients' cells although the value in the latter instance failed to reach the basal control level. Production of IL-2 by lymphocytes from hyperthyroxinemic subjects, in response to phytohemagglutinin, was also reduced. Since NK cells are thought to act as a defense against viral infections and some malignancies and may play a role in autoregulation of the immune system, this effect of T4 may have significant biological implications.

Cell Line↗

Use of whole blood methods in assessment of immune parameters in immunodeficiency states.

Whole blood (WB) methods requiring less than 4 ml heparinized peripheral blood were used to define mononuclear cell phenotype, lymphocyte proliferation, and natural cell-mediated cytotoxicity (CYT) in samples from normal controls and patients with immunodeficiency states of acquired immunodeficiency syndrome (AIDS) and AIDS-related complexes (ARC). Results from two-color direct immunofluorescence staining of blood samples with monoclonal antibodies (Mabs) conjugated to phycoerythrin (PE) or to fluorescein isothiocyanate (FITC) and flow cytometry for the determination of mononuclear cells reactive with T11, T4, T8, B1, and NKH.1 surface markers were compared to one-color indirect immunofluorescence analysis with unlabeled Mabs and FITC-labeled goat anti-mouse IgG and flow cytometry. We found that two-color analysis was as sensitive as one-color analysis in detecting abnormal subset distribution in the patient groups. Functional properties of mononuclear cells (MNC) in WB samples and after density gradient separation were studied by mitogen-induced lymphocyte proliferation and CYT. Although the means of the groups studied varied depending on method used, results using WB methods clearly delineated the expected differences between the immunodepressed patients and normal subjects. The effects of sample storage on results obtained with WB methods for surface marker analysis, lymphocyte proliferation, and natural killer activity were also examined.

AIDS-Related Complex↗

Reducing complications of perinatal care.

There can be no easy formula for preventing complications in neonatal care. Everyone involved either directly or indirectly in the care of neonates has to be aware and concerned about known or potential complications. Likewise, we each need to commit to accumulating experience and disseminating information through supervision and communication, while assuming our share of responsibility in following our patients. Effort needs to be individual and collaborative with a primary goal such as that of the SGCPC: the prevention of complications of perinatal care. Recognition, communication, supervision, documentation, follow-up, and research are suggested areas for attention where we all can impact on the outcome of our patients.

Female↗