HTLV-I antibodies and lymphoproliferative disease of granular lymphocytes.
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Adult↗
Biomedical subjects
D M Strong
Publications and source records attributed to D M Strong.
Molecular and immunologic analysis of a chronic lymphocytic leukemia case with antibodies against human T-cell leukemia virus.
The human T-cell leukemia virus type-I (HTLV-I) is a unique, exogenous, horizontally transmitted retrovirus which is T-cell tropic, and has been associated with a specific type of aggressive leukemia/lymphoma of mature T-cell origin. In a survey of lymphoid malignancies in Jamaica, antibodies to HTLV-I were also found in 6 of 17 patients with chronic lymphocytic leukemia (CLL), raising the possibility of an etiologic relationship. Further studies were undertaken on one of these patients to clarify the nature of the disease and possible virus relationship. Cell surface marker analysis of her peripheral blood cells documented that the majority of circulating lymphocytes were B-cells. DNA-cloned probe analysis with a complete HTLV-I proviral genome of these peripheral malignant B-cells, was negative for integrated virus. A T-cell line was established in culture from her peripheral blood. The presence of HTLV-I in the cultured T-cell line was established by the detection of expressed viral specific gag protein p-19 and proviral DNA. Thus, a B-cell lymphoid malignancy can occur in the presence of HTLV-I infected T-cells, suggesting the possibility of an indirect leukemogenic mechanism.
Aged↗
Hand-mirror variant of acute lymphoblastic leukemia. Evidence for early T-cell lineage in two cases by evaluation with monoclonal antibodies.
Lymphoid cells from two patients with hand-mirror variant of acute lymphoblastic leukemia (ALL) were studied with various monoclonal antibodies in attempts to determine their derivation and differentiation. The predominant feature of the malignant bone marrow cells was strong reactivity with antibody 3A1, which stains the majority of normal T-cells and is apparently present on all T-ALL cells. In addition, a less intense binding was observed with antibody 4F2, which reacts with activated or rapidly dividing cells, and antibody 10.2, which reacts with all thymocytes and most peripheral T-cells. Most other antibodies with a wide variety of specificities were not reactive or, in the case of a few anti-T-cell antibodies showed, by fluorescence-activated cell sorter analysis only weak staining on some cells. Sequential bone marrow studies in one patient, before and during treatment with chemotherapy, revealed a reduction of 3A1-positive cells, concordant with a decrease of malignant cells in the marrow. When involved lymph nodes, peripheral blood, or marrow were studied, similar reactivity patterns were found in all locations. The data obtained suggest that in both patients with hand-mirror variant of ALL, the malignant lymphoid cells were immature cells of early T-lymphocyte lineage. The relation of phenotype by monoclonal antibody analysis to hand-mirror morphologic type and biologic function is discussed.
Adolescent↗
Characterization of cell lines enhancing IL-2 production by human phytohemagglutinin-stimulated lymphocytes.
Certain cell lines were found to significantly enhance IL-2 production by phytohemagglutinin-stimulated T lymphocytes, and the mechanisms involved in mediating such an enhancement have been studied. All B-lymphoblastoid cell lines (B-CL) tested had an enhancing capability, even lines which were immature, surface immunoglobulin negative, or negative for EBV-associated antigens or Fc receptors. Furthermore, a B-CL lacking HLA-A, B, and C, antigens as well as a HLA-DR-deficient mutant line enhanced IL-2 production. Autologous B-CL as well as allogeneic lines were able to augment IL-2 production. Cell lines from patients with T-cell acute lymphoblastic leukemia did not stimulate, while more mature, DR-positive T-cell lines did. Although all HLA-DR positive cell lines, regardless of their derivation, provided enhancement, several lines of evidence, including blocking experiments with anti-DR antibodies, indicated that the reaction was not HLA-DR mediated. The enhancing determinant(s) appeared to be cell associated since CL supernatants were ineffective, and it may serve as an important additional signal to the preactivated IL-2-producer T-cell.
B-Lymphocytes↗
Cultured T cells from patients with T cell chronic lymphocytic leukemia demonstrate a normal phenotype.
Peripheral blood mononuclear cells from eight patients with the rare T-cell form of chronic lymphocytic leukemia were isolated and cultured with Interleukin-2 (IL-2). In all but one case, cultured T-cells (CTC) were established. Various culture conditions were tested for their effectiveness; feeder layers proved valuable for expanding the cultures to large volumes. The CTC remained IL-2 dependent. Analysis of surface determinants on these CTC showed a polyclonal proliferation of T-cells. The distribution of subset markers in the patients' CTC population had completely changed in comparison to the "fresh" peripheral blood cell population but was similar to CTC initiated from healthy donors. Our data suggest that the patients' few contaminating normal T-lymphocytes expanded in culture, while the malignant cells were unresponsive to IL-2. This conclusion is supported by growth characteristics and morphology of the CTC.
Antigens, Surface↗
Decreased helper T lymphocytes in homosexual men. I. Sexual contact in high-incidence areas for the acquired immunodeficiency syndrome.
In June 1982, sexual and other behavioral patterns were examined in 245 homosexual men in relationship to T-lymphocyte phenotypes that are characteristic of the acquired immunodeficiency syndrome (AIDS). Mean helper T-cell counts in New York City (579 +/- 32 cells/mm3) and Washington, DC, homosexual men with sexual contacts in areas at high risk (endemic) for AIDS (567 +/- 24 cells/mm3) were significantly lower than in Washington, DC, residents without such contacts (672 +/- 36 cells/mm3, p = 0.04 by analysis of variance). Helper T-cell counts in the Washington men were inversely correlated with a greater number of endemic-area homosexual contacts (p = 0.005), even after adjustment for multiple confounding variables (p = 0.02). The 31 Washington men with more than 15 endemic-area partners had a mean helper T-cell count of 517 +/- 44 cells/mm3, and 12 of those 31 men had helper T-cell counts less than 400 cells/mm3. AIDS patients are known to have a marked reduction in the number and function of helper T-lymphocytes. The data suggest that deficits of helper T lymphocytes can be acquired by homosexual contact with men in cities where AIDS is common. This supports the hypotheses that low helper T-cell counts may be caused by a sexually transmissible agent and that frequent homosexual exposure to residents of high-risk areas for AIDS may be an important means of spread of this agent.
Acquired Immunodeficiency Syndrome↗
Decreased helper T lymphocytes in homosexual men. II. Sexual practices.
In June 1982, the sexual practices of 245 homosexual male outpatients of private physicians were evaluated in relationship to decreased numbers of helper T lymphocytes, an abnormality that is characteristic of the acquired immunodeficiency syndrome (AIDS). Three risk groups were defined a priori--85 high-risk men from central Manhattan ("New York"), 96 intermediate-risk men from Washington, DC, with AIDS-area homosexual contacts ("Washington-exposed"), and 64 low-risk Washington, DC, men without such contacts ("Washington-unexposed"). An increasing number of homosexual partners was correlated with decreasing helper T-cell counts (R = -0.29, p = 0.009) and decreasing helper:suppressor T-cell ratios (R = -0.32, p = 0.005) in the entire study group combined and in New York subjects separately. Suppressor T-cell counts were unrelated to the number of partners in all three groups. Increasingly frequent receptive anal intercourse correlated with decreasing helper T-cell counts most clearly in the New York City group (R = -0.23, p = 0.04), somewhat less so in the Washington-exposed group (R = -0.18, p = 0.07), and not at all in the Washington-unexposed group (R = -0.09, p = 0.48). This association persisted in the New York and Washington-exposed groups after adjusting for seven other sexual practices, the number of homosexual partners, and five other potentially confounding variables. A transmissible agent associated with receptive anal intercourse best explains these data. The cause of these low helper T-cell counts may also be the cause of AIDS.
Acquired Immunodeficiency Syndrome↗
Interferon regulation of DR antigen expression and alloantigen-presenting capabilities of the promyelocytic cell line HL60.
Our research suggests that interferon may have an immunoregulatory role in the initiation phase of immune responses. Recent evidence has demonstrated that lymphokines regulate monocyte cell surface expression of DR antigens and, consequently, the ability of monocytes to activate T lymphocytes in an antigen-specific manner. In this report cloned interferons and a homogeneous cell line were used to demonstrate that interferon possesses these immunoregulatory functions. Cells of the promyelocytic cell line HL60, when incubated in vitro with recombinant gamma (IFN-gamma) and with alpha interferons (IFN-alpha), expressed enhanced levels of DR antigen as determined by both cytotoxicity and fluorescence-activated cell sorter analyses. Lower concentrations of IFN-gamma than IFN-alpha were needed to induce DR expression, and a higher percentage of monocytes were induced to express DR antigen by IFN-gamma than IFN-alpha. HL60 cells preincubated with lymphocyte-derived lymphokines or IFN-alpha also stimulated a significantly better in vitro allogeneic response in the mixed leukocyte reaction than untreated HL60 cells. Thus, interferon both the phenotypic expression of DR antigens of HL60 cells and their functional ability to initiate T-lymphocyte responses to an alloantigen.
Antigen-Presenting Cells↗
Refractory migraine headache controlled with alprazolam: case report.
A woman with major depressive disorder and refractory, incapacitating migraine headaches responded to alprazolam in a double-blind, placebo-controlled study. Migraine, but not depression, recurred following tapering of the drug, suggesting efficacy of alprazolam for control of refractory migraine.
Alprazolam↗
Determinants of retrovirus (HTLV-III) antibody and immunodeficiency conditions in homosexual men.
A cohort of homosexual men at high risk of the acquired immunodeficiency syndrome (AIDS) was monitored to examine the relation between lifestyle, clinical conditions, T-lymphocyte subsets, and antibody to the AIDS-associated human retrovirus, human T-cell leukaemia virus III (HTLV-III). HTLV-III antibodies were present in 35 (53%) of the 66 subjects tested in June, 1982. 4 of the seronegative subjects had HTLV-III antibodies when re-tested one year later, a seroconversion rate of 1.2% per month. In the HTLV-III seropositive subjects, AIDS developed at a rate of 6.9% per year (minimum incidence of AIDS = 4.6% per year) and other clinical signs of immunodeficiency (lesser AIDS) at 13.1% per year. All 6 of the AIDS cases and at least 8 of the 10 lesser AIDS cases had detectable HTLV-III antibodies 1 week to 21 months before diagnosis. Of 24 other subjects with stable lymphadenopathy, 19 (79%) had or acquired HTLV-III antibodies. Lower helper T-cell counts were very closely related to HTLV-III seropositivity (r = -0.53, p = 0.0001), even in the 26 healthy subjects with no clinical abnormalities (r = -0.37, p = 0.07). In both univariate and multivariate analyses, the lifestyle risk factors for HTLV-III seropositivity were large number of homosexual partners (p less than or equal to 0.03) and receptive anal intercourse (p less than or equal to 0.03), with an apparent synergistic interaction between these two activities (chi 2 = 8.71, p = 0.003). These data suggest that frequent receptive anal intercourse with many homosexual partners predisposes to HTLV-III infection with the consequent emergence of lymphadenopathy and the various manifestations of lesser and fully fledged AIDS.
Acquired Immunodeficiency Syndrome↗
Low T-lymphocyte ratios in homosexual men. Epidemiologic evidence for a transmissible agent.
To investigate risk factors for immunologic abnormalities among homosexual men, T-lymphocyte helper/suppressor (OKT4/OKT8) ratios were determined in 78 healthy Danish homosexual men. Ratios in 26 men (33%) were low (less than 1.00). Visiting the United States in 1980 to 1981 was a strong (7.7-fold) risk factor for having a ratio less than 1.00. Among nine travelers who visited only once, the risk of having a low ratio increased significantly if the visit had occurred in 1981. A risk of similar magnitude (6.9-fold) was found among the three men who had not been to the United States but who reported homosexual contact with a Danish man who became ill with Kaposi's sarcoma. Risk of low ratios did not correlate with age or years of homosexual activity. Promiscuity was not a significant risk factor, but these men generally had fewer sex partners than that which has been reported from the United States. Neither nitrite inhalant use nor cytomegalovirus antibody (prevalence or titer) was associated with low ratios. These data support the hypothesis that a transmissible biologic agent may be etiologically responsible for the low helper/suppressor ratios in homosexual men.
Adult↗
Time-varying magnetic fields: effect on DNA synthesis.
Human fibroblasts have exhibited enhanced DNA synthesis when exposed to sinusoidally varying magnetic fields for a wide range of frequencies (15 hertz to 4 kilohertz) and amplitudes (2.3 X 10(-6) to 5.6 X 10(-4) tesla). This effect, which is at maximum during the middle of the S phase of the cell cycle, appears to be independent of the time derivative of the magnetic field, suggesting an underlying mechanism other than Faraday's law. The threshold is estimated to be between 0.5 X 10(-5) and 2.5 X 10(-5) tesla per second. These results bring into question the allegedly specific magnetic wave shapes now used in therapeutic devices for bone nonunion. The range of magnetic field amplitudes tested encompass the geomagnetic field, suggesting the possibility of mutagenic interactions directly arising from short-term changes in the earth's field.
Cells, Cultured↗
Characterization of two patients with lymphomas of large granular lymphocytes.
Two patients with non cutaneous well-differentiated lymphocytic lymphoma with leukemic spread are reported. The large majority of their peripheral blood mononuclear cells (PBMC) formed rosettes with sheep erythrocytes, had receptors for the Fc portion of IgG, and an enzymatic profile of relatively mature T-cells. These cells were morphologically characterized as large granular lymphocytes. Studies with monoclonal antibodies in one of the cases showed an OKT3+, OKT10-, OKT4-, OKT8-, HNK-1-, OKM1+ phenotype, whereas PBMC from the other case were OKT3+, OKT10-, OKT4-, OKT8+, HNK-1+, OKM1-. PBMC from the first patient were able to suppress in vitro B-cell differentiation and were capable of a strong antibody dependent cellular cytotoxicity (ADCC) activity. Natural killer (NK) activity was reduced. Cells from the other patient who was hypogammaglobulinemic, exerted suppressor activity in immunoregulatory assays, and showed ADCC and NK activity. These data support the existence of LGL lymphomas consisting of the proliferation of mature appearing cells capable of functional activity.
Antibodies, Monoclonal↗
Identification of the human T cell lymphoma virus in B cell lines established from patients with adult T cell leukemia.
Cell lines were established from the peripheral blood of two patients with adult T cell leukemia. In contrast to our previous experience, where all such lines expressed T cell markers, these two cell lines expressed B cell antigens and Ig light chains (kappa on CF-2, lambda on HS). Human T cell lymphoma proviral (HTLV) sequences were demonstrated in both cell lines. Since only a portion of the cells in culture expressed Ig light chains, experiments were carried out to exclude the possibility that the cultures were not a mixture of B and T or non-B cells. Cells that expressed kappa- or lambda-light chains were separated by cell sorting from kappa- or lambda-negative cells and replaced in culture. Light chain negative cells reexpressed light chains after time in culture. After 5-azacytidine treatment of the cell lines, all cells expressed Ig light chains. These studies show that the human retrovirus HTLV, which has been demonstrated to be associated with certain T cell malignancies, can infect B cells or B cell precursors.
Adult↗
DRGs, cost containment and materials management.
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Cost Control↗
Studies on the antigenicity of bone. II. Donor-specific anti-HLA antibodies in human recipients of freeze-dried allografts.
UNLABELLED: Freeze-dried bone allografts from donors of known tissue type evoked donor-specific anti-HLA antibodies in nine of forty-three patients (forty-four procedures). Eight of the nine sensitized patients were followed roentgenographically for an average of twenty-three months and were known to have had a satisfactory resolution of the benign process for which the graft was employed. The ninth patient was doing well when lost to follow-up four months after receiving a bone allograft. CLINICAL RELEVANCE: The questions of whether immune responses to bone allografts occur in humans and, if so, adversely influence the incorporation of the graft can be answered at this time only by demonstrating the presence and frequency of such responses and how they correlate with clinical events. A large variety of techniques can be used to demonstrate immune responses. The technique that we used revealed that a small group of patients became sensitized to HLA antigens that were known to be present in the allograft donor but none of the recipients had evidence of adverse effects caused by the graft, as judged non-invasively.
Adolescent↗
Primary structure of papain-solubilized human histocompatibility antigen HLA-B40 (-Bw60). An outline of alloantigenic determinants.
The primary structure of papain-solubilized human histocompatibility antigen HLA-B40 (-Bw60) has been determined. Its comparison with that of the cross-reactive HLA-B7 antigen allows for the first time a direct sequence comparison between two HLA-B locus products and an outline of the location of their alloantigenic sites. Overall sequence homology between HLA-B40 and HLA-B7 is 93%. Of 19 detected differences, 18 are located in the two amino-terminal domains (residues 1-182). Half of them are clustered in two short segments spanning residues 63-74 and 147-156, respectively, which suggests that they may encompass major sites of their alloantigenic determinants. The first of these segments is highly polymorphic in HLA and H-2 molecules. It is proposed that it may belong to a hypervariable region of class I histocompatibility antigens. The remaining substitutions are scattered through the N-terminal portions of the two external domains. Thus, in addition to the above-mentioned segments, other positions may contribute significantly to the antigenic polymorphism of these molecules.
Amino Acid Sequence↗
Thymosin alpha 1 levels and helper:suppressor ratios in homosexual men.
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Acquired Immunodeficiency Syndrome↗