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R C Holman

Publications and source records attributed to R C Holman.

At least 73 records · Page 4Linked to original sources
PubMed1993

Cross-reactivity of 75 monoclonal antibodies to human immunoglobulin with sera of non-human primates.

We systematically analyzed a panel of 75 murine monoclonal antibodies (mAbs) reactive with human immunoglobulins IgG, IgA, IgM, IgD, and kappa and lambda light chains for reactivity with serum immunoglobulins of higher primates. In the great apes, and to a lesser extent in other primates, epitopes related to human light chains, IgM, IgA, IgD, and all 4 IgG subclasses were identified with many of the mAbs. Those mAbs identified as reactive with a given species may be useful for immunologic studies of these species. Cladistic analysis of antigenic relatedness generated a phylogenetic tree consistent with current anatomic or molecular taxonomies.

Animals↗
PubMed1993

Response of human immunodeficiency virus-infected adults to measles-rubella vaccination.

Measles-mumps-rubella vaccine (MMR) is recommended for human immunodeficiency virus-infected (HIV+) adults. Data concerning MMR vaccination of HIV+ patients are limited to children. We evaluated 39 HIV+ (97% with > 200 CD4+ lymphocytes) and 17 non-HIV+ control adults receiving measles-rubella vaccine (MR). Clinical adverse events did not differ between groups. Prevaccination, three HIV+ and two control vaccinees were measles seronegative; no HIV+ and one control vaccinee seroconverted. No initially measles-seropositive vaccinee had a significant antibody elevation. Four HIV+ and three control vaccinees were rubella seronegative prevaccination; three HIV+ and two control vaccinees seroconverted. Among those initially rubella seropositive, two HIV+ and one control vaccinee had significant antibody elevations. There were no significant percentage CD4+ or CD8+ lymphocyte changes between groups. Three HIV+ vaccinees were p24 antigen positive pre- and postvaccination. Although MR vaccination appears safe in HIV+ adults, questions remain about the response of measles and rubella antibody-negative HIV+ adults and those with < 200 CD4+ lymphocytes.

Adult↗
PubMed1992

Rabies surveillance in the United States during 1991.

In 1991, 49 states, the District of Columbia, and Puerto Rico reported 6,972 cases of rabies in nonhuman animals and 3 cases in human beings to the Centers for Disease Control. Ninety-one percent (6,354 cases) were wild animals, whereas 8.9% (618 cases) were domestic species. The total number of reported cases of rabies increased 42.9% over that of 1990 (4,881 cases), with most of the increase resulting from continued spread of the epizootic of rabies in raccoons in the mid-Atlantic and northeastern states. Large increases in cases of rabies in animals were reported from Connecticut (200 cases in 1991, compared with 3 in 1990, an increase of 6,567%), Delaware (197 cases in 1991, compared with 44 in 1990, an increase of 348%), New York (1,303 cases in 1991, compared with 242 in 1990, an increase of 326%), and New Jersey (994 cases in 1991, compared with 469 in 1990, an increase of 112%). Other noteworthy increases were reported by Wyoming (96.4%), Texas (69.7%), California (41.3%), Oklahoma (33.1%), Minnesota (31.4%), Georgia (26.7%), and Maryland (23.7%). Hawaii reported 1 imported case of rabies in a bat. Only 16 states reported decreases in rabies in animals in 1991, compared with 30 in 1990. Pennsylvania and Iowa reported decreases of 40.6% and 27.4%, respectively. Rhode Island was the only state that did not report a case of rabies in 1991.

Adult↗
PubMed1992

Differential effects of sequential, simultaneous, and single agent interleukin-3 and granulocyte-macrophage colony-stimulating factor on megakaryocyte maturation and platelet response in primates.

Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) following interleukin-3 (IL-3) priming has been shown to increase thrombopoiesis. To elucidate the comparative abilities of IL-3 and GM-CSF in influencing megakaryocyte development in vivo, serial bone marrow analyses were performed on rhesus monkeys treated with 5 micrograms/kg/d of IL-3 and 5 micrograms/kg/d of GM-CSF sequentially for 4 days each, simultaneously for 8 days, and as single agents for 8 days. Platelet counts maximally increased to a mean of 7.5 x 10(5)/microL (n = 3) on days 11 through 12 in monkeys treated with sequential IL-3/GM-CSF. In contrast, neither IL-3 alone nor simultaneously administered IL-3/GM-CSF elicited increases in thrombopoiesis between days 3 and 15. GM-CSF elicited a variable platelet response. Megakaryocyte ploidy distributions were significantly (P < .001) shifted between days 7 and 10 in monkeys treated sequentially and between days 3 and 15 in monkeys treated with combined IL-3/GM-CSF and with GM-CSF alone but not in monkeys treated with IL-3 alone. The changes in mean DNA content and megakaryocyte size, as determined by digital image analysis, were larger in monkeys treated with sequential IL-3/GM-CSF and with GM-CSF alone than in simultaneously treated monkeys. In addition, sequentially but not simultaneously treated monkeys showed increased numbers of megakaryocytes on bone marrow biopsy. We conclude that administration of IL-3 followed by GM-CSF treatment increases thrombopoiesis by sequentially increasing megakaryocyte numbers and maturation and that these effects are diminished by simultaneous administration of the two cytokines.

Animals↗
PubMed1992

Hodgkin disease mortality in the United States: 1979-1988.

Mortality trends for Hodgkin disease in the United States were examined from 1979 to 1988 with the use of mortality data for multiple causes of death, which were obtained from the National Center for Health Statistics. A progressive decrease in the death rate from Hodgkin disease was observed over this period. The decrease in death rate was greatest among white patients. Patients who were 55 years or older had the highest death rate. Analysis by geographic region showed decreases in each of the regions, with no significant difference among groups of states with high and low incidences of acquired immune deficiency syndrome. However, the decrease in the South was approximately 35% greater than that in the North-east. In 1988 the most significant difference in death rates between male and female patients was in the 35-54-year age group, whereas a significant difference in death rates between white and black patients was seen only in patients who were 55 years of age or older. In summary, although there has been a significant reduction in deaths resulting from Hodgkin disease between 1979 and 1988, the decreases observed have varied between sexes and among age groups, racial groups, and geographic regions.

Adolescent↗
PubMed1992

Survival of hemophilic males with acquired immunodeficiency syndrome with and without risk factors for AIDS other than hemophilia.

Between January 1, 1981, and June 30, 1990, 1,514 hemophilia-associated acquired immunodeficiency syndrome (AIDS) cases in males were diagnosed in the United States. In 1,394, hemophilia was reported as the sole risk factor. For an additional 120, other risk factors were reported: of 101 of these, 40 had homosexual/bisexual activity, 53 had a history of intravenous drug use, and 8 had both of these risk factors. We examined the demographic data and the survival data of two principal groups: males for whom hemophilia was the sole reported risk factor for human immunodeficiency virus (HIV) exposure, and hemophilic males for whom homosexual/bisexual activity, intravenous drug use, or both of these additional risk factors were reported. The survival curves showed marginal differences between the hemophilia-only and the multiple risk groups; the median survival times were 13.1 and 14.6 months, with the cumulative probability of survival at 1 year as 52.7% and 54.0%, respectively. Kaposi's sarcoma was among AIDS indicator diseases more commonly found in the multiple risk factor group. Pneumocystis carinii pneumonia was the sole reported diagnosis indicative of AIDS for 34.4% of those in the hemophilia-only group, compared with 20.8% of those with multiple risk factors. The principal demographic difference between the two groups was the age distribution; those in the multiple risk factor group were primarily between 20 and 44 years of age. Restricting the analysis to those between 20 and 44 years resulted in a slightly longer survival time in the hemophilia-only group and no appreciable difference between the disease distributions and survival curves of the two groups.

Acquired Immunodeficiency Syndrome↗
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↗
PubMed1991

Enumeration of antigen sites on cells by flow cytometry.

We evaluated a cytofluorometric method for determining the number of antigens expressed on the cell surface of human lymphocytes. Using beads that have a known number of binding sites for mouse immunoglobulin and monoclonal antibodies specific for various antigens on human lymphocytes, we found that this system is quite reproducible, reliable and technically easy to perform. The greatest source of variation in expression of cell surface antigens is interdonor variability.

Antibodies, Monoclonal↗
PubMed1991

Epidemiology of progressive multifocal leukoencephalopathy in the United States: analysis of national mortality and AIDS surveillance data.

We analyzed progressive multifocal leukoencephalopathy (PML) mortality data from 1979 to 1987 and data on persons with acquired immunodeficiency syndrome (AIDS) reported to the Centers for Disease Control (CDC). Based on analyses of multiple-cause-of-death vital statistics, deaths related to PML have increased fourfold from 1.5/10,000,000 persons in 1979 to 6.1/10,000,000 persons in 1987. The increase in the PML annual death rate began in 1984, occurred primarily in men 20 to 49 years of age, and was greatest in states known to have a high incidence of AIDS. In 1987, 56% of death certificates that listed PML as a cause of death also listed human immunodeficiency virus (HIV) infection. Analysis of AIDS case reports to the CDC from 1981 through June 1990 demonstrated that 0.72% of persons with AIDS were reported as having PML. Although most persons with AIDS who had PML were 20 to 49 years of age (84.6%), PML was reported more frequently among persons with AIDS greater than or equal to 50 years old than less than 50 years old. In addition, PML was reported more frequently among persons with AIDS who were exposed to HIV by blood transfusion than those in all other exposure categories. These data demonstrate that the increase in PML mortality from 1979 to 1987 was associated with the large increase in immunosuppressed persons with AIDS.

Acquired Immunodeficiency Syndrome↗
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↗
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

Lack of correlation between human herpesvirus-6 infection and the course of human immunodeficiency virus infection.

Human herpesvirus-6 (HHV-6) and human immunodeficiency virus (HIV) are both tropic for CD4+ lymphocytes. To determine whether HHV-6 infection affects the susceptibility to or the course of HIV infection, HHV-6 titers were measured by an anticomplement immunofluorescence assay in serum of three groups of homosexual or bisexual men: (1) those with AIDS (n = 78), (2) those with HIV-associated lymphadenopathy (LAS; n = 81), and (3) those who were HIV-seronegative (n = 55). Early and late serum samples were available for 45 men with LAS (median interval 49 months). Men with early LAS did not differ from HIV-seronegative men in either the percentage that were HHV-6-seropositive or in the distribution of titers. There was a significantly lower percentage of seropositives in AIDS patients than in the other two groups (P less than .01). LAS patients who progressed to AIDS did not differ in percentage seropositivity or distribution of titers from nonprogressors. HHV-6 titers tended to decrease over time. HHV-6 titers late in LAS were similar to those in AIDS patients. These findings suggest that it is unlikely that previous exposure to HHV-6 either predisposes to or affects the course of HIV infection.

AIDS-Related Complex↗
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↗
PubMed1989

Comparison of monocyte separation methods using flow cytometric analysis.

We isolated normal, nonactivated human monocytes from peripheral blood by four different methods: (1) rosetting with sheep erythrocytes pretreated with 2-aminoethylisothiouronium bromide hydrobromide (AET) followed by monoclonal antibody (OKT3 (CD3), B1 (CD19), Leu7, Leu11 (CD16] and complement treatment; (2) adherence to gelatin/plasma-coated flasks; (3) adherence to plastic dishes; and (4) separation by the Sepracell technique. We monitored these monocyte separations by determining cell recoveries, OKT4A+ lymphocyte contamination, monocyte binding to human immunodeficiency virus (HIV), number of non-specific esterase-positive cells, and proportion of mononuclear cells reactive with a battery of monoclonal antibodies specific for monocytes. Our results indicate that of the four methods compared, adherence to gelatin/plasma-coated flasks produced the highest purity, recovery, and satisfactory binding to HIV with the fewest contaminating CD4+ T cells.

Antibodies, Monoclonal↗
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

Deterioration in immunologic status of human immunodeficiency virus (HIV)-infected homosexual men with lymphadenopathy: prognostic implications.

Changes in immunologic parameters were followed in members of a cohort of human immunodeficiency virus (HIV)-positive homosexual or bisexual men with lymphadenopathy and were analyzed for differences between those who have and those who have not progressed to the acquired immunodeficiency syndrome (AIDS) (progressors, nonprogressors). T helpers and the Th/Ts ratio were lower in progressors than in nonprogressors both at entry into the study and at the latest visit. T suppressors were not different in the two groups at entry but were higher in nonprogressors at the latest visit. Evaluation of the patterns of change over time showed that T helpers and Th/Ts ratios tended to decrease over time in both nonprogressors and progressors, while T suppressors increased in nonprogressors and decreased in progressors. Although progressors had a greater deterioration in immunologic parameters over time, nonprogressors also had significant deterioration when compared with controls. Based on the respective percentages of men with abnormal or normal T helpers or Th/Ts ratio at entry who have already progressed to AIDS, we would conservatively estimate, considering their latest T helpers and Th/Ts ratio, that at least an additional 16 (32%) of our nonprogressors will develop AIDS in the next 5 years.

AIDS-Related Complex↗
PubMed1989

Serial determinations of HIV-1 titers in HIV-infected homosexual men: association of rising titers with CD4 T cell depletion and progression to AIDS.

Lymphocyte subset enumerations, antibody titers to specific proteins of human immunodeficiency virus (HIV), and measurement of infectious HIV titers in peripheral blood mononuclear cells were performed on serial blood specimens from 15 HIV-infected homosexual men with chronic lymphadenopathy syndrome (LAS); 6 of these men have subsequently progressed to AIDS (progressors), and 9 have remained clinically stable (nonprogressors). For the earliest samples studied, no test distinguished those who would progress to AIDS from those who have not. The two groups diverged significantly about 1 year before AIDS diagnosis in the progressor group. Virus titers rose in progressors but remained relatively stable in nonprogressors. CD4 T cells and the CD4 T cell subset, 4B4, declined more rapidly in progressors than in nonprogressors. HIV antibody titers tended to decline in progressors, but the differences were significant only for antibody and to the pol-encoded proteins, p51/65, and the gag-encoded polyprotein, p55. Before the onset of clinical AIDS, progressors are distinguished from nonprogressors by markedly different rates of CD4 cell depletion and virus replication, but the elements that control these dynamics remain to be defined.

AIDS-Related Complex↗