Biomedical subjects

B L Evatt

Publications and source records attributed to B L Evatt.

At least 91 records · Page 5Linked to original sources

PubMed1990

Maintenance of normal platelet mass in anemic Belgrade rats and their response to iron.

The Belgrade (b/b) rat has severe hypochromic, microcytic anemia accompanied by mild thrombocytopenia and a 49% reduction in megakaryocytes (MKs). The platelet counts are decreased only 34%, but relative platelet size measured by two independent methods averages 50% greater than controls. Thus, the platelet mass of the b/b rat is within the normal range. The marrow MK progenitors (MK colony-forming units, CFU-MK) respond linearly to increased colony-stimulating activity in vitro, but they are reduced 68% and form smaller colonies than normal. Flow cytometric analysis of MK ploidy indicates that significantly more MKs are distributed into the low and high ploidy classes compared with the normal, and the mean ploidy is similar. The b/b rat maintains effective thrombocytopoiesis in spite of a severe reduction in MK progenitors, primarily by an increased rate of maturation of the endomitotic compartment. Iron treatment partially arrests the b/b anemia and is associated with a significant increase in CFU-MK, a normalized MK ploidy distribution, and a significant decrease in platelet size. The favorable response to iron therapy suggests that the megakaryocytopenia is secondary to the severe anemia and results from stem cell commitment to the erythroid lineage.

Anemia↗

PubMed1989

Transforming growth factor-beta induces hemoglobin synthesis in a human erythroleukemia cell line.

We have examined the effects of TGF beta 1 and TGF beta 2 on the HEL human erythroleukemia cell line. It was observed that TGF beta 1 and 2 induced hemoglobin synthesis in these cells without causing a significant negative effect on cell proliferation. The cell surface markers glycophorin A and transferrin receptor that are associated with erythroid differentiation were also increased. This cell line may provide a model system in which to study the regulation of globin gene expression by a physiological growth factor known to act on hemopoietic cells.

Blotting, Northern↗

PubMed1989

Absence of human T-cell lymphotropic virus type I coinfection in human immunodeficiency virus-infected hemophilic men.

Concern for transmission of human T-cell lymphotropic virus, type 1 (HTLV-1) infection to recipients of infected cellular blood products has prompted development of tests to eliminate blood units with HTLV-I antibodies. Most hemophilic men from the United States became infected with human immunodeficiency virus (HIV) before HIV donor screening and before blood products were processed to inactivate the virus. To assess whether these men might also be infected with HTLV-I, we examined the HTLV-I antibody status of 127 factor VIII (hemophilia A) recipients and 71 factor IX (hemophilia B) recipients. One HIV-seronegative and four HIV-seropositive persons were HTLV-I reactive by enzyme-linked immunosorbent assay (ELISA). Four of five ELISA-reactive serum samples were negative by HTLV-I immunoblot assay (IB); 1 reactive and 1 borderline reactive serum were indeterminate on IB (p19 reactivity), but negative by radioimmunoprecipitation assay (RIPA). Peripheral blood mononuclear cells from one patient with indeterminate HTLV-I IB were negative for HTLV-I genomic sequences by polymerase chain reaction. The other indeterminate patient's serum antibody pattern was stable over a 2-year period, suggesting this was not an instance of early HTLV-I seroconversion. These results reaffirm the safety of factor components in the United States with regard to HTLV-I but emphasize the importance and need for further testing of reactive HTLV-I ELISA results with a second more specific technique.

DNA, Viral↗

PubMed1989

Sex practice correlates of human immunodeficiency virus transmission and acquired immunodeficiency syndrome incidence in heterosexual partners and offspring of U.S. hemophilic men.

We assessed the risk of human immunodeficiency virus (HIV) transmission from heterosexual seropositive hemophilic men to their female sex partners through an HIV serosurvey and questionnaire study conducted during 1984-1987. Five percent of 21 female partners of asymptomatic men and 11% of 35 partners of HIV-symptomatic (acquired immunodeficiency syndrome [AIDS], AIDS-related complex [ARC], peripheral generalized lymphadenopathy [PGL]) hemophilic men had been infected when first tested. One of 19 seronegative women tested about 1 year later reportedly seroconverted. Only 18% of a sample of the serosurvey women responding to sex practices questions said their partners used condoms "nearly always." Over 60% engaged in oral/genital sex in addition to vaginal intercourse. Only 12% of still-seronegative women followed the preventive strategy of consistent avoidance of oral/genital sex, together with consistent condom use by the male partner. Further evidence for heterosexual transmission comes from the CDC national AIDS surveillance reports showing 25 women who acquired HIV infection through heterosexual contact with U.S. hemophilic men (September 6, 1988). Seven (28%) were diagnosed and reported in the first 6 months of 1988. Their ages range from 20 years to more than 70 years. The dates of infection for the women are unknown but must have been at least 5 years before AIDS diagnosis for at least one. Only approximately 30% of their male partners had already manifested any HIV-associated illness. Through May 18, 1988, six cases of AIDS have occurred in children whose infection was acquired through exposure of the mother to a hemophilic partner. Four were diagnosed in latter 1987. The median age at diagnosis was 4.5 months. Four had died. None of their mothers is as yet diagnosed.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Protein S and C antigen levels in proteinuric patients: dependence on type of glomerular pathology.

The cause of the thrombotic tendency in nephrotic patients is unknown. Recent reports of thrombotic complications in patients with deficiencies of protein C or protein S (natural inhibitors of coagulation) have raised the possibility that decreased levels of these proteins may play a role in the hypercoagulable state of nephrotic patients. We measured the levels of protein C, total protein S, and free protein S antigens in 42 patients (21 nephrotic and 21 non-nephrotic) with one of four types of glomerular pathology: diabetic nephropathy (DM), focal glomerular sclerosis (FGS), membranous glomerulonephritis (MGN), and chronic renal failure due to hypertension (CRF). Protein C and total protein S antigen levels were significantly higher in FGS and MGN than they were in DM or CRF. Free protein S levels were lower in DM than they were in MGN. Protein C, total protein S, and free protein S levels did not significantly correlate with either serum albumin or degree of proteinuria. The mean levels of the three proteins did not differ between nephrotic and non-nephrotic patients. Free protein S and protein C were, however, significantly correlated (P less than .005 and P less than .002, respectively) with the type of glomerular pathology, independent of differences in age, sex, serum albumin, or degree of proteinuria. These data suggest that abnormalities of free protein S and protein C are related to the nature of the underlying renal disease, rather than to the degree of proteinuria.

Glycoproteins↗

PubMed1989

Geographic variability of hemophilia-associated AIDS in the United States: effect of population characteristics. Hemophilia-Associated AIDS Study Group.

National AIDS surveillance suggests that approximately 3.5% of all hemophilic patients in the United States have developed AIDS as of February 1988; however, the cumulative incidence of AIDS among seropositive patients at individual hemophilia treatment centers (HTCs) has been reported to be as high as 12%. The purpose of this study was to examine the reported excess risk of AIDS at selected HTCs. Between July 13 and November 6, 1987, we reviewed medical charts from the 598 hemophilia A and hemophilia B patients receiving comprehensive care as of 1980 at six U.S. hemophilia treatment centers (three identified as low AIDS risk and three identified as high AIDS risk using national hemophilia-associated AIDS surveillance data). The risk of AIDS among all patients was 8% and among seropositive patients was 18%. At the individual HTCs, the risk ranged from 0% to 14% among all patients and 0% to 25% among seropositive patients. Overall incidence rates were higher than those derived from national surveillance data because national estimates include all hemophilic patients (regardless of severity) whereas this study included only patients receiving comprehensive care (who are more likely to be severely affected by their coagulation disorder and receive concentrated clotting factors). The higher incidence of AIDS in the high-risk centers was attributable to the older age of the patients in these HTCs, a factor previously associated with an increased risk of AIDS in seropositive patients. These findings do not support geographic variability in the incidence of AIDS and emphasize the importance of patient characteristics when comparing the incidence of hemophilia-associated AIDS between populations.

AIDS Serodiagnosis↗

PubMed1989

Prevalence of human immunodeficiency virus type 1 DNA in hemophilic men and their sex partners. Hemophilia-AIDS Collaborative Study Group.

Polymerase chain reaction (PCR) was used to detect human immunodeficiency virus (HIV)-1 DNA in peripheral blood mononuclear cells to assess in hemophilic men whether any were HIV-seropositive but uninfected or seronegative but infected and in seronegative sex partners of seropositive hemophilic men whether any were infected. Of 40 seropositive men, 38 (95%) were PCR-positive; one was PCR-indeterminate and one PCR-negative. None of 41 seronegative men who used only donor-screened, virus-inactivated coagulation factor products were PCR-positive. However, two of six who received noninactivated products were PCR-positive; one had low T-helper cell counts and died of unrelated causes and the other had seroconverted 11 mo later. PCR with a second primer pair also detected HIV-1 DNA in these two men. None of 25 seronegative female sex partners of seropositive men, including six men with AIDS and seven with AIDS-related symptoms, were PCR-positive. These data suggest that most seropositive hemophilic men are HIV-infected; whether some are infected with defective virus remains to be resolved as does the infection status of seropositive PCR-negative men. Identification of two seronegative PCR-positive men supports the possibility that HIV-1 DNA can be detected before seroconversion.

DNA, Viral↗

PubMed1989

HIV and hemophilic children's growth.

The acquired immune deficiency syndrome (AIDS) often has profound effects on growth; however, the effects of human immunodeficiency virus (HIV) on asymptomatic children's growth are unknown. Before heat inactivation/HIV donor screening of factor concentrates, many hemophilic children became infected with HIV. We evaluated four hemophilic groups without AIDS, using age-standardized growth parameters: group 1, 41 HIV-seropositive children (median age of 13 years); group 2, 11 HIV-seronegative children (median age of 4 years); group 3, 20 children frequently receiving concentrates, evaluated before 1979 (median age of 9 years); and group 4, 11 children rarely receiving concentrates, evaluated before 1979 (median age of 6 years). Median height for age (HA), weight for age (WA), and weight for height (WH) of groups 1 and 2 exceeded the 50th percentile of referent norms. HA, WA, WH, and weight/height did not vary significantly by group, nor did these decline over periods of 11 to 70 months. However, for those less than 11 years of age in group 1, HA declined by 25 percentile points over at least a 3 year period. Also, group 1's T helper-to-suppressor cell ratios at 12 +/- 3 months following the latest growth evaluation were positively associated with both HA and WA at the last evaluation. Eight children were evaluated before 1979 and again after they seroconverted to HIV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Acquired immune deficiency syndrome associated with hemophilia in the United States.

Persons with hemophilia and other coagulation disorders were at risk for infection with HIV as a result of receiving blood products, particularly concentrated clotting factors. Because these products are now donor-screened and heat-treated to inactivate HIV, the risk of further infection in this population has been minimized. However, before the introduction of these interventions, many persons with hemophilia had been infected. As of Jan 4, 1988, 463 cases of hemophilia-associated AIDS had been reported to the Centers for Disease Control. Most patients had severe hemophilia and received commercially produced concentrated clotting factors. These patients may constitute as many as 25% of those hemophilic men known to be infected with HIV. Through heterosexual and perinatal transmission, the partners and offspring of persons with hemophilia can become infected with HIV. The seroprevalence rate for female sex partners of men with hemophilia may be as high as 21%, and 16 AIDS cases have already been reported. Counseling and public health interventions are needed to prevent the further spread of HIV infection in sex partners and offspring of these patients and to prevent the associated morbidity and fatalities. Because HIV infection can be transmitted by exposure to infected blood or blood components, health-care workers whose activities involve contact with infected blood or body fluids are also at risk for HIV infection. Prospective studies suggest this risk is very low; nevertheless, health-care workers need to adhere rigorously to infection-control precautions to minimize the risk of exposure to blood and body fluids. These precautions include wearing gloves, masks, protective eyewear, and gowns depending on the type of exposure anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1988

Potential effect of revising the CDC surveillance case definition for AIDS.

The Centers for Disease Control (CDC) revised the surveillance case definition for acquired immunodeficiency syndrome (AIDS) in August, 1987. To determine the impact of this revision, information was extracted from the medical charts of the 630 patients receiving comprehensive medical care as of 1980 at 6 haemophilia treatment centres, and who were therefore likely to have been infected with human immunodeficiency virus (HIV). 38 (6%) and 47 (7%) met the 1985 and 1987 case definitions, respectively (22% increase). Of the cases added by use of the 1987 case definition, 3 patients had HIV dementia, 3 had Pneumocystis carinii pneumonia (2 of whom were presumptively diagnosed and 1 who had been receiving steroids and immunosuppressives), and 3 had HIV wasting syndrome. These data suggest that the revision of the AIDS case definition will have a substantial impact on future AIDS surveillance trends in persons with haemophilia and perhaps in other risk groups.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Hemophilia-associated AIDS in the United States, 1981 to September 1987.

Between January 1, 1981 and September 4, 1987, 407 cases of hemophilia-associated acquired immunodeficiency syndrome (AIDS) had been reported to the Centers for Disease Control. The number of cases diagnosed each year nearly doubled, except in 1986, when cases increased only 50 per cent. Demographic characteristics of the patients did not change over time. The majority (74 per cent) had severe hemophilia and 97 per cent received commercially produced concentrated clotting factors. The cumulative incidence of AIDS between 1981 and September 1987 for persons with severe hemophilia A was substantially greater than that for persons with severe hemophilia B (4.2 cases vs 1.9 cases per 100 persons).

Acquired Immunodeficiency Syndrome↗

PubMed1988

Human immunodeficiency virus infection in hemophilic children.

The following groups were compared: (1) children less than 18 years old who have hemophilia-associated acquired immunodeficiency syndrome (AIDS) with other children with AIDS and with adults who have hemophilia-associated AIDS and (2) asymptomatic HIV-infected hemophilic children with asymptomatic HIV-infected hemophilic adults. Children with hemophilia-associated AIDS were older than other children with AIDS (medians 13 and 1 years, respectively) and less frequently had lymphocytic interstitial pneumonitis (5% v 48%) but had similar incidences of Pneumocystis carinii pneumonia (51% v 53%) and similar case to fatality ratios (59% v 61%). Children with hemophilia-associated AIDS had P carinii pneumonia significantly less often than did adults with hemophilia-associated AIDS, but both had similar case to fatality ratios (adults 72% with P carinii pneumonia, 68% dead). Significantly more hemophilic children than adults with AIDS were nonwhite (30% v 14%) and resided in the tristate area of New York/New Jersey/Pennsylvania (43% v 25%). The immune effects of human immunodeficiency virus (HIV) to date on asymptomatic pediatric and adult hemophiliacs are similar but may be more severe in adults. It is concluded that, although some of the clinical manifestations of AIDS (eg, lymphocytic interstitial pneumonitis) occurring or not occurring in older children infected through blood factor products differ from those of other children with AIDS, disease outcome to date is equally poor. The reasons for the differences between hemophilic children and hemophilic adults with and without AIDS warrant further investigation.

Acquired Immunodeficiency Syndrome↗

PubMed1988

The effects of thrombopoietic activity of rabbit plasma fractions on megakaryocytopoiesis in agar cultures.

A plasma fraction that stimulates platelet production in vivo also stimulates megakaryocytopoiesis in vitro. The plasma activity is attributed to a humoral regulator, thrombopoietin. Addition of the thrombocytopenic plasma (TP) fraction to an agar system supporting megakaryocyte colonies increased the frequency of colony formation significantly over that stimulated by spleen cell-conditioned medium (SCM). TP had no effect on the size of the colonies and, in the absence of SCM, TP did not stimulate colony formation. In studies of single megakaryocytes, the numbers of small megakaryocytes, specifically those 5-10 microns in diameter, increased significantly after 3 days of incubation with TP alone. SCM supported not an increase in the numbers, but an increase in the proportion of larger (30- to 40-microns) megakaryocytes. A normal plasma fraction contained similar but consistently less activity than fractions containing TP. The findings indicated that TP stimulates differentiation of megakaryocyte precursors from unidentifiable to identifiable cells but does not alone support colony formation. Thus, TP appears to be a potentiator of megakaryocytopoiesis. However, the augmentation of colony frequency by TP further suggests that TP may also play a role in early colony development, either by enhancing progenitor responsiveness to a megakaryocyte colony-stimulating factor or by recruiting additional colony progenitors from a noncycling progenitor population. These studies establish a link between the stimulation of platelet production observed after TP administration in vivo and the effects of TP on early events in megakaryocytopoiesis.

Acetylcholinesterase↗

PubMed1987

Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.

Three monoclonal antibodies produced against vWF:Ag by conventional hybridoma technique did not inhibit factor VIII coagulant activity (F. VIII:C) but did inhibit VIII ristocetin cofactor activity. The antibodies were used in an indirect competitive ELISA for quantifying von Willebrand's antigen (vWF:Ag) and compared with values obtained by the Laurell technique using commercial antibody by means of a ratio: ELISA/Laurell. For one monoclonal BD2-CC9, vWF:Ag values obtained in the two assays were in good agreement for normal and hemophilia A plasmas (normal, n = 19, ratio = 1.13 +/- .17, hemophilia A, n = 10, ratio = 0.91 +/- .15). However, type II vWD patients had a disproportionately low value of vWF:Ag with the ELISA. Use of the ratio normalized the difference among individual plasma values and allowed a significant separation of type II vWD plasma (n = 9, ratio = 0.46 +/- .19) from normal plasma (p = .0001) and type I vWD plasma (n = 8, ratio = 1.52 +/- .34) from type II vWD plasma (p = .0003) using BD2-CC9. Although the sample size was small, the greater degree of discrimination among the vWD plasmas tested with BD2-CC9 (compared with the other two antibodies [CA3-AE4, CC6-BG10]) suggests that this antibody may recognize conformational epitopes that reflect the degree of multimeric polymerization of the vWF molecule rather than simply recognize a decreased number of antigenic sites in a basic subunit. BD2-CC9 may be valuable in investigating the various types of vWD and/or the process of polymerization of this complex protein.

Antibodies, Monoclonal↗

PubMed1987

Hemophiliac patient's knowledge and educational needs concerning acquired immunodeficiency syndrome.

The Patient Knowledge Assessment Study (PKAS) was conducted among 107 male hemophilic patients, aged 15 to 67 years, at 19 hemophilia treatment centers (HTC). Participants were given a 30-item questionnaire concerning the cause of acquired immunodeficiency syndrome (AIDS), the groups at risk, and modes of transmission. The questionnaire included questions on the participant's status in regard to antibody to human T-lymphotropic retrovirus, type III/lymphadenopathy-associated virus (HTLV-III/LAV), and the meaning of this test result. HTC health-care providers were asked to complete a separate questionnaire containing 17 questions about information given patients concerning their HTLV-III/LAV antibody status and its meaning. Overall, patients had a good base of knowledge about AIDS; however, there were gaps in this knowledge. Twenty-nine percent of patients did not know that spouses of AIDS patients were at risk for AIDS; 47% did not know that sexual partners of persons with hemophilia were at risk; and 32% did not know that hemophilic children were at risk. Further, only 69% understood that antibody-positive individuals had had contact with the AIDS virus. Identifying these and other areas of misunderstanding will provide the information needed to design educational strategies and psychosocial support programs appropriate for the hemophilic population, and which may serve as a model for other populations.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Prevention of occlusive coronary artery thrombosis by a murine monoclonal antibody to porcine von Willebrand factor.

A murine monoclonal antibody (mAb) against porcine von Willebrand factor (vWF) induced an antithrombotic state in normal pigs. Thrombosis was induced by a standard procedure of stenosis and mechanical injury of the artery. The mAb was an IgG1 kappa that inhibited vWF-induced platelet aggregation at a titer of 1:6250 and bound to immobilized vWF at a maximal dilution of 1:512,000. The antibody did not affect two other vWF functions, platelet adhesion and binding of coagulant factor VIII (factor VIII:C). The antithrombotic state was characterized by a prolonged bleeding time and lack of plasma vWF activity, but with near-normal levels of factor VIII:C and von Willebrand antigen. The circulating Ag.mAb complex demonstrated a multimeric distribution comparable to that of native plasma vWF. Three groups of pigs were studied: group A consisted of nine untreated animals, eight of which developed occlusive coronary thrombosis; group B, four treated animals with a long bleeding time, none of which developed occlusive thrombosis; and group C, two animals with preexisting thrombosis treated with mAb, in which stable blood flow was reestablished. Morphologically, the group B animals showed adherent platelets covering the injured intima but no thrombosis. This mAb is an antithrombotic agent that prevents platelet thrombosis without affecting intrinsic platelet function.

Animals↗

PubMed1987

Antibody to human immunodeficiency virus in factor-deficient plasma. Effect of heat treatment on lyophilized plasma.

The prevalence of antibody to human immunodeficiency virus (HIV) was determined in various commercial substrate plasmas used in clotting factor assays, and viral isolation was attempted from both seropositive and seronegative samples. Antibody to HIV was detected in 13 of 13 plasma substrates used for Factor VIII assays and in 2 of 3 plasma substrates used for Factor IX assays. Antibodies were not detected in any of the other factor-specific substrates. Virus could not be isolated from any of the seropositive samples after 28 days in culture. Heat treatment of the samples under conditions known to inactivate HIV in plasma products indicated that heating the lyophilized substrate plasmas at 60 degrees C for up to eight hours had little effect on factor substrates and factor assays. Progressive loss of Factor V in the deficient plasmas was the most serious effect produced by heat treatment.

Antibodies, Viral↗

PubMed1987

The course of the epidemic of acquired immunodeficiency syndrome in the United States hemophilia population.

The time course of the epidemic of acquired immunodeficiency syndrome (AIDS) as it has occurred in the US hemophilia population is examined using surveillance data collected by the Centers for Disease Control (CDC). These data indicate that the epidemic course in hemophiliacs is distinguishable from that in the homosexual/bisexual and intravenous drug-using populations in at least one respect--the epidemic in the hemophilia population is characterized by a lack of consistent increase in the number of new AIDS cases in successive time intervals. This difference is interpreted as being attributable to the mechanisms by which AIDS virus is spread among hemophiliacs. In addition, the short survival following diagnosis of AIDS in hemophiliacs and the magnitude of yearly incidence rates for this group in 1984 and 1985 show the hemophilia population to have been severely affected by the epidemic.

Acquired Immunodeficiency Syndrome↗