Biomedical subjects

B L Evatt

Publications and source records attributed to B L Evatt.

At least 73 records · Page 4Linked to original sources

PubMed1992

Epidemiology of AIDS in females with hemophilia and other chronic bleeding disorders in the United States: comparisons with males with chronic bleeding disorders and AIDS and with nonhemophilic female blood-transfusion recipients with AIDS.

From January 1, 1981 through June 30, 1990, 32 females with chronic bleeding disorders were diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States. Most (81.3%) were white and greater than or equal to 30 years of age, with a median age of 37.5 years. Eighteen (56.3%) had von Willebrand's disease. Pneumocystis carinii pneumonia was reported for 16 (50%). None had Kaposi sarcoma. The median survival time was 10.8 months, with a cumulative probability of survival at 1 year of 47.3% and at 2 years of 27.6%. We compared the demographic data and survival times of these females with those of males with a chronic bleeding disorder and AIDS, and with those of nonhemophilic females with AIDS whose exposure to the human immunodeficiency virus (HIV) was through receipt of blood transfusions, blood components, or tissue. The principal demographic difference was age distribution. The females with chronic bleeding disorders tended to be younger than the transfused, nonhemophilic females, but older than the males. The survival time from AIDS diagnosis to death for the females with chronic bleeding disorders did not differ statistically from that of the other two groups, although older nonhemophilic females whose exposure was transfusion may progress more rapidly to AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Use of the polymerase chain reaction to detect hypermethylation in the calcitonin gene. A new, sensitive approach to monitor tumor cells in acute myelogenous leukemia.

Based on the recent observations that, in a majority of patients with acute leukemia, the 5' end of the calcitonin gene was hypermethylated and abnormal DNA fragments were observed following HpaII restriction digestion, we have developed a PCR-based method to sensitively detect this abnormal methylation of the calcitonin gene in AML. Applying the concept of competitive PCR, a semi-quantitative correlation was obtained between the amount of hypermethylation and the amount of leukemic cells present. These results suggest that this method will be useful to monitor the amount of tumor cells in bone marrow from patients with AML.

Base Sequence↗

PubMed1992

Human papillomavirus infection and anal carcinoma. Retrospective analysis by in situ hybridization and the polymerase chain reaction.

To examine the association of human papillomavirus (HPV) infection with anal squamous cell carcinoma, the authors applied the highly sensitive polymerase chain reaction (PCR) and in situ hybridization (ISH) techniques to detect HPV DNA in formalin-fixed, paraffin-embedded tissues from 18 patients. The presence of HPV types 16/18 in 3 (16.7%) of 18 patients with anal carcinoma was found, using a colorimetric ISH technique for HPV types 6, 11, 16, 18, 31, 35, and 51. Results from one of these three patients were also positive for HPV 31, 35, 51 by ISH techniques. When the same series was analyzed using the PCR and consensus primers to the L1 open reading frame of the HPV genomes, the frequency of positive patients rose to 14 (77.8%) of 18. PCR analysis of the 14 lesions containing HPV DNA, using type-specific primers and probes for HPV 6, 11, 16, 18, and 33, showed that 1 contained HPV 6, 1 contained HPV 11, 4 contained HPV 16, 1 contained HPV 18, 1 contained HPV 33, 5 contained HPV of unclassified type(s), and 1 contained a mixture of three HPV types. There was concordance between typing of cases that were positive by ISH and PCR methods. These data agree with the concept that HPV, in particular type 16, is implicated in the pathogenesis of anal cancer.

Anus Neoplasms↗

PubMed1991

Effects of human interleukin-6 on megakaryocyte development and thrombocytopoiesis in primates.

Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in mice and primates. To elucidate the mechanisms underlying this phenomenon, serial analyses were performed on megakaryocytes obtained from rhesus monkeys treated for 8 days with 30 micrograms/kg/d of recombinant human IL-6. Platelet counts increased to a maximum of 7.8 x 10(5)/microL with biphasic peaks on days 7 and 12 without significant changes in platelet volumes. Large increases in DNA content were seen by two-color flow cytometry and digital image analysis. Ploidy distribution underwent a significant shift between study days 3 and 11 (P less than .0001) with large increases in the frequency of 64N and 128N megakaryocytes. The modal ploidy increased from the normal 16N to 64N. Megakaryocyte size, as measured by area, was increased 2- to 2.7-fold. On day 3, multiple megakaryocytes were seen in endomitosis, along with an abundance of young cells with wide, organelle-free peripheral zones. The giant megakaryocytes seen on days 5 to 7 exhibited marked membrane hyperplasia that occupied much of the cell. Emperipolesis occurred frequently, as did megakaryocyte cell death. No giant platelets were seen. We conclude that IL-6 significantly alters the process of megakaryocyte maturation and thrombocytopoiesis, and that these effects, at least in the doses of IL-6 administered, should not be equated with the physiologic mechanisms operative during accelerated platelet production.

Animals↗

PubMed1991

Sinonasal papillomas and human papillomavirus: human papillomavirus 11 detected in fungiform Schneiderian papillomas by in situ hybridization and the polymerase chain reaction.

A series of 19 paraffin-embedded sinonasal papillomas (four squamous papillomas, three fungiform papillomas, nine inverted papillomas, and three cylindrical cell papillomas) were investigated for evidence of human papillomavirus (HPV) infection using immunohistochemistry (polyclonal antibody to HPV capsid antigen), in situ hybridization (DNA probes for HPV 6/11, 16/18, and 31/33/35), and the polymerase chain reaction (primers and probes for HPV 6, 11, 16, 18, and 33). All three fungiform papillomas were positive by all three techniques: immunohistochemistry, in situ hybridization for HPV 6/11, and the polymerase chain reaction for HPV 11. None of the other lesions contained detectable HPV using the specific probes included in this study. These results support the continued classification of fungiform papilloma as a distinctive variant of schneiderian papilloma characterized by a predominantly exophytic growth pattern and an association with HPV 11.

Adult↗

PubMed1991

Cellular kinetics of transforming growth factor-beta induced hemoglobin accumulation in the HEL erythroleukemia cell line.

Transforming growth factor-beta 1 (TGF beta 1) can induce hemoglobin accumulation in a clone of the human HEL erythroleukemia cell line. This clone has previously been designated as HEL-T. The effect of TGF beta 1 was reversible and it had to be continuously present for the maximal number of cells to become positive for hemoglobin. The TGF beta 1 effect was blocked by phorbol ester and partially blocked by the calmodulin antagonist W-7, but not by dexamethasone. Simultaneous exposure to gamma-interferon, IL-1, IL-6, IL-3 and GM-CSF had no significant effect on TGF beta induced hemoglobin accumulation. However, when TGF beta was combined with TNF alpha, it was observed that there was approximately a 10-15% reduction in benzidine-positive cells. Cell-cycle analysis revealed no significant long-term alterations in any of the compartments. Analysis of the TGF beta 1 effect on 10 different HEL-T-derived clones revealed that the number of benzidine-positive cells ranged from 12 to 70% after 5 days of continuous exposure. Cell proliferation was similarly differentially affected. Another HEL cell line, designated as W-HEL, did not accumulate hemoglobin in the presence of TGF beta 1, but did have an increase in alpha-globin RNA expression.

Cell Cycle↗

PubMed1991

The synergistic effect of hemin and transforming growth factor-beta on hemoglobin accumulation in HEL erythroleukemia cells.

Transforming growth factor-beta (TGF beta) and hemin can both independently induce hemoglobin accumulation in the human HEL erythroleukemia cell line. The combination of these two agents resulted in a synergistic effect in the production of hemoglobin. On day 1, following exposure to both hemin and TGF beta, approximately 35% of the cells had accumulated hemoglobin, as evidenced, by benzidine staining. Whereas, when treated alone with either agent, the percentage of benzidine-positive cells was less than 10%. By day 5, approximately 70-80% on the cells treated with the combination were benzidine-positive. Cell surface analysis showed that the combination of TGF beta and hemin increased the expression of CD34, CD64, glycophorin A, and GPIIb-IIIa(CDW41). Cell proliferation was decreased by the combination.

Antigens, Surface↗

PubMed1991

Immunoglobulin G subclass values in healthy black and white children.

To determine whether IgG subclass concentrations differed between healthy black and white children, we measured IgG1, IgG2, IgG3, and IgG4 immunoglobulins by enzyme-linked immunosorbent assay in sera from 246 black children aged 6 to 42 months. We then compared these values with the normal values established for 664 white children aged 6 to 60 months. The IgG1, IgG2, and IgG4 subclass concentrations of the black children were lower than those for white children; many of the values were below the 95% confidence limits established for white children: 46 (19%) of 246 IgG2 values and 19 (8%) of 246 IgG4 values for black children were below the normal limits. We compared the geometric mean values for black and white children, as determined for each 6-month age grouping between 6 and 42 months of age; 367 of the 664 white children were less than 42 months of age and were included in this analysis. The geometric mean values for IgG1, IgG2, and IgG4 levels were consistently lower for black children than for white children. The differences were significant for IgG1 subclass values of those children older than 24 months and for IgG2 and IgG4 values of those children older than 18 months. No consistent differences were noted for IgG3 subclass values. We conclude that young black children have lower IgG1, IgG2, and IgG4 serum concentrations than are found in white children. If normal IgG values for white children are used, healthy black children may be erroneously classified as IgG subclass deficient. The mechanism and biologic relevance of these population differences need to be evaluated.

Black People↗

PubMed1991

Human papillomavirus type 6 detected by the polymerase chain reaction in invasive sinonasal papillary squamous cell carcinoma.

Eight sinonasal carcinomas (one adenocarcinoma, two undifferentiated nasopharyngeal carcinomas, and five squamous cell carcinomas) were investigated for evidence of human papillomavirus (HPV) infection using in situ hybridization and the polymerase chain reaction for HPV types 6, 11, 16, 18, and 33. All eight cases were negative for HPV infection by in situ hybridization, while a single HPV-6-positive case was identified by the polymerase chain reaction. The HPV-positive case was an invasive papillary squamous cell carcinoma of the maxillary sinus. Although HPV-6 is usually associated with benign anogenital condylomata, it has been identified in malignant lesions of the upper respiratory tract. This may reflect exposure of the upper aerodigestive tract to additional carcinogens, such as smoke and alcohol, superimposed on the background proliferative stimulus of the HPV infection.

Adult↗

PubMed1991

Recombinant human granulocyte-macrophage colony-stimulating factor promotes megakaryocyte maturation in nonhuman primates.

Megakaryocytes are responsive to several nonlineage-specific cytokines in vitro. In this study, we examined the in vivo effects of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) on late stages of megakaryocytopoiesis in the rhesus monkey. Four rhesus monkeys were given 10 micrograms/kg body weight/day of rh GM-CSF s.c. in two divided doses daily for 8 days. Megakaryocyte maturation was evaluated serially by measuring nuclear ploidy and cytoplasmic size. GM-CSF-treated monkeys developed significant shifts in ploidy distribution from days 3 through 15 (p less than or equal to 0.001), with increased frequencies of 64N and 128N megakaryocytes. Mean megakaryocyte size increased 92.5% on day 9, paralleling the increase in DNA content, although megakaryocyte size within ploidy groups did not increase. Megakaryocyte number remained unchanged following rh GM-CSF treatment. The platelet count responses were variable, and mean platelet volume did not change. The present study demonstrates that therapeutic doses of rh GM-CSF stimulate megakaryocyte endomitosis and increase mean size. The data indicate that GM-CSF is effective in promoting the maturation stage of megakaryocyte development but does not result in a consistent thrombopoietic response.

Animals↗

PubMed1991

Human markers for IgG2 and IgG4 appear to be on the same molecule in the chimpanzee.

It has been reported that all four immunoglobulin G (IgG) subclasses present in human serum are also present in chimpanzee serum, as detected with antibodies specific for the human IgG subclasses. We used monoclonal antibodies (mAb) specific for human IgG subclasses to measure concentrations of the four subclasses in the chimpanzee sera. Initial ELISA studies indicated that epitopes for all four human subclasses are present in chimpanzee sera. The concentrations of IgG1, IgG2 and IgG3 were similar in human and chimpanzee sera, but the registered concentrations of IgG4 were different. Absorption of IgG2-reactive material from chimpanzee serum with IgG2 mAb resulted in removal of IgG4-reactive material as well. Conversely, absorption of IgG4-reactive material removed IgG2-reactive material. IgG2-reactive material, isolated from chimpanzee serum using solid-phase anti-IgG2 mAb, reacted with anti-IgG4 mAb, and isolated IgG4-reactive material reacted with anti-IgG2 mAb. Three anti-IgG2 mAb and five anti-IgG4 mAb, each of which react with separate epitopes on their respective human isotype, were used in these studies. We conclude that chimpanzee serum contains only three IgG isotypes related to those of humans, one of which contains determinants related to both human IgG2 and IgG4.

Adult↗

PubMed1990

Relationship of partially purified factor concentrates to immune tests and AIDS. The Hemophilia-AIDS. Collaborative Study Group.

We evaluated those members of a cohort of 203 hemophilic men providing all necessary information at their 1984 and 1985 evaluations, to determine whether non-heated or less than 80 degrees C dry heat-treated partially purified factor products were associated with 1) the development of AIDS in human immunodeficiency virus (HIV)-infected persons or 2) abnormal immune test results in participants seroconverting or remaining HIV seronegative. We found no relationship between type of factor (VIII vs. IX) (n = 162), frequency of usage (greater than or equal to once a week vs. less than once a week) (n = 141) or yearly doses of non-heated or dry heat-treated partially purified factor (n = 118) and the development of AIDS. Seroconverting participants using partially purified factor products greater than or equal to once a week in 1984 had lower T-helper cell numbers in 1985 than those receiving factor less frequently (median 515 vs. 772/mm3, n = 9), as did those using factor greater than or equal to once a week in 1985 (median 515 vs. 726/mm3, n = 10). A similar relation was seen between 1984 frequency and 1985 T-helper cell numbers of seronegative participants (median 741 vs. 1037/mm3, n = 31). The yearly dose of heat-treated products was not associated with any immune test result or changes in results between years. These findings suggested that frequency of administration of partially purified factor materials may have had an effect upon the immune system, but that total yearly dose did not. Previously used partly purified, dry heat-treated factor concentrates were not associated with the development of AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Free protein S deficiency in a family with venous thrombosis.

Inherited deficiencies of protein S, an inhibitor of the coagulation system, are now recognized as occurring at least twice as frequently as antithrombin III deficiency in patients with venous thrombosis. Protein S is present in plasma in a complexed form, which is inactive, and in a free or functional form. Free protein S combines with activated protein C to inhibit factors V and VIII. This report describes the evaluation of a family with recurrent deep venous thrombosis and superficial thrombophlebitis. Levels of antithrombin III and protein C as well as plasminogen were normal. The levels of total protein S, which includes the value for the free and complexed forms of protein S, were also normal. However, the free protein S levels were greatly reduced in all symptomatic members who were studied. This report illustrates the importance of obtaining measurement of free protein S levels in patients who are suspected of having inherited venous thrombotic disorders.

Adult↗

PubMed1990

Concordance of polymerase chain reaction with human immunodeficiency virus antibody detection.

To evaluate the correlation of detection of human immunodeficiency virus (HIV) by polymerase chain reaction (PCR) with detection of HIV antibody, 271 simultaneous serum and peripheral blood mononuclear cell samples were examined from 242 persons whose activities placed them at increased risk for HIV infection: 142 from homosexual men, 86 from hemophilic men, and 43 from heterosexual partners of HIV-infected persons. PCR was performed using the gag region primer pair SK38/39 and the env region primer pairs SK68/69 and CO71/72. Amplified HIV DNA was detected using specific oligomer probes. Of 63 HIV antibody-positive samples, 58 (92%) had HIV DNA by PCR. Of 208 HIV antibody-negative samples, 7 (3.4%) had HIV DNA by PCR. On follow-up, 4 of the latter persons were seropositive when next tested; 2 were well and antibody- and PCR-negative; 1 had died of a stroke before retesting. Thus, PCR detects HIV in most antibody-positive persons; detection is increased by use of multiple primer pairs. PCR-positive antibody-negative specimens may indicate HIV infection in which antibody has not yet developed or may be false-positive PCR results. When PCR is discordant with HIV antibody, testing of additional specimens and clinical follow-up are necessary to assess HIV infection status.

Bisexuality↗

PubMed1990

Phorbol ester induces morphological changes and acidic fibroblast growth factor RNA expression in the RD/TE 671 cell line.

The TE 671 medulloblastoma cell line was induced by phorbol-12-myristate-13-acetate (PMA) to resemble neuronal cells by both morphological and immunohistochemical criteria. Five days following PMA treatment at a concentration of 10 ng/ml, the cells acquired long cellular processes and cell growth was markedly inhibited. Immunohistochemically, PMA-treated cells stained intensely for neuron-specific enolase and were positive for neurofilaments. Northern blot analysis revealed that PMA induced the transcript for acidic fibroblast growth factor. Our data suggest that the TE 671 cell may be useful not only in the study of acidic fibroblast growth factor regulation but also as a model for embryonic tumor cell differentiation.

Cell Differentiation↗

PubMed1990

Age and human immunodeficiency virus infection in persons with hemophilia in California.

Thirteen hemophilia centers provide comprehensive care to approximately 90 percent of persons with hemophilia in California. For 1987, these centers reported patient human immunodeficiency virus (HIV) antibody status, age group, level of clotting factor deficiency, and hemophilia type on 1,438 persons with hemophilia A and B; HIV serologic status was known for 860 persons (59.8 percent) of whom 537 (62.4 percent) were HIV-antibody-positive. The HIV positivity rate increased with age after taking into account hemophilia type, clotting factor level and treatment center type. The three-year cumulative incidence of reported AIDS (acquired immunodeficiency syndrome) cases based on the number of HIV positive patients, was 11.6 percent. The cumulative incidence rate was 14.6 percent (54 of 370) for those patients over 20 years of age and 4.8 percent (8 of 167) for those under 21 years of age. Although a comparable distribution of the date of diagnoses of AIDS was seen by age group, there appeared to be a bimodal distribution in the rate of AIDS among the age groups, with the 6-12-year-olds and the 21 and older age groups showing higher incidence rates.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Studies of myeloperoxidase gene expression at the cellular level by in situ hybridization.

Recent studies have demonstrated myeloperoxidase (MPO) gene expression during granulocytic differentiation. Since these studies have been done exclusively by Northern and dot blot analysis and frequently with mixed populations of cells, quantitative changes in gene expression for particular populations of cells are difficult to assess. We therefore examined MPO expression at the cellular level in various normal and malignant hematopoietic cells by the in situ hybridization (ISH) technique. Using this approach, we demonstrated that inducing the promyelocytic HL-60 cell line to differentiate along either monocytic or granulocytic pathways decreases MPO mRNA expression. Similarly, when ISH was performed on normal bone marrow, relatively high levels of MPO mRNA were detected in myeloblasts, promyelocytes, and early eosinophilic precursors, whereas the expression was markedly decreased in more advanced stages of myeloid differentiation. These findings agree with the known decrease in MPO protein synthesis observed during granulocytic differentiation and suggest that regulation of MPO protein synthesis occurs at the level of MPO mRNA expression. We conclude by showing that ISH can detect MPO mRNA in myeloblasts of patients with acute leukemia and can be a potentially useful technique in the study of myeloid differentiation in acute leukemias.

Adolescent↗

PubMed1990

Pregnancies in human immunodeficiency virus-infected sex partners of hemophilic men. The Hemophilia-AIDS Collaborative Study Group.

We investigated 24 completed pregnancies of 20 healthy, human immunodeficiency virus (HIV)-seropositive sex partners of 20 seropositive hemophilic men. One woman had recurrent herpes simplex type 2 infection; no woman was known to use illicit drugs or to have other purported cofactors for vertical HIV transmission. For 8 offspring, the mothers learned of their partners' serostatus and received counseling against pregnancy prior to the fifth month of gestation; for 9 offspring (37.5%), the mothers learned of their own seropositivity and received counseling prior to the fifth month. Acquired immunodeficiency syndrome developed in 7 (35%) of 20 fathers, 4 of whom died; HIV-related symptoms developed in 4; severe liver disease developed in 2; and 7 (35%) were in good health. In four mothers (20%) HIV-related symptoms developed. Five offspring were breast-fed for 2 days to more than 3 years, two while the mother was known to be seropositive; four of these were seronegative and healthy, and one was seropositive at 30 months of age and had persistent cervical lymphadenopathy at 48 months of age. Infants were born at term; median birth weight was 2.86 kg. Solely on the basis of serologic studies and symptoms for those with more than 15 months of follow-up, the minimum perinatal transmission rate for this group of women without putative transmission cofactors (drug usage, promiscuity, malnutrition, HIV symptoms) was at least 25%, a rate comparable to that reported for women in other risk groups.

Acquired Immunodeficiency Syndrome↗