Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction.

Hematopoietic development is a complex process that involves a large number of growth factors and cytokines. Many cytokines are known to act on more mature, lineage-restricted cells of the hematopoietic system. However, no specific factors have yet been identified that induce the expansion of the most primitive hematopoietic cells without also inducing differentiation. To search for such factors, we isolated novel cell lines from the yolk sac in order to identify genes important in early hematopoietic and endothelial development. This approach led to the discovery of B219, a sequence that is expressed in at least four isoforms in very primitive hematopoietic cell populations and which may represent a novel hemopoietin receptor. The recently published receptor for the obesity (ob) gene product (leptin) is an isoform of B219 with a nearly identical ligand binding domain. B219/obr is expressed in the yolk sac, early fetal liver, enriched hematopoietic stem cells and in a variety of lymphohematopoietic cell lines. B219/obr is also expressed at high levels in adult reproductive organs. B219/obr maps to human chromosome 1p32, a region syntenic with the recently reported location of obr on murine chromosome 4 (ref. 5).

Metabolic and morphological observations on the effect of surface-active agents of leukocytes.

Morphological and metabolic observations have been made on the effects of endotoxin, deoxycholate, and digitonin (at less than 50 microg/ml) on polymorphonuclear leukocytes and mononuclear cells. The agents stimulate the respiration and glucose oxidation of these cells in a manner similar to that seen during phagocytosis. Electron microscopy revealed no morphological changes with the first two agents, but dramatic membrane changes were seen in the case of digitonin. Here tubular projections of characteristic size and shape formed on and split off the membrane. All the agents stimulated uptake of inulin, but efforts to demonstrate increased pinocytosis by electron microscopy have not so far succeeded, probably due to limitations in present experimental techniques.

Acute changes in oxyhemoglobin affinity. Effects on oxygen transport and utilization.

It has been postulated that 2,3-diphosphoglycerate (DPG)-mediated changes in oxyhemoglobin affinity play an important role in oxygen delivery; however, the effect of an acute increase in affinity without changing red cell mass has not been systematically evaluated. This study was designed to measure changes in oxygen transport and oxygen consumption produced by an acute increase in oxyhemoglobin affinity caused by an autologous exchange transfusion using DPG-depleted stored blood. From each of 10 5-kg rhesus monkeys, 100 ml of blood was taken on the 1st and 3rd wk of the study and each stored in 25 ml of acid-citrate-dextrose storage solution. On the 5th wk, each animal underwent an exchange transfusion with 200 ml of its stored blood. Hemodynamic data were obtained before and 30 min after transfusion. The oxyhemoglobin dissociation curve shifted to the left (P(50) changed from 33.9 to 27.2 mm Hg), as mean red cell DPG decreased from 28.6 to 12.7 mumol/g of hemoglobin. No significant change was noted in pH, P(CO2), base deficit, arterial or venous percent saturation of hemoglobin, cardiac output, or oxygen consumption. However, a fall in mixed venous P(O2) from 35.3 to 27.9 mm Hg occurred.Thus, an acute shift of the oxyhemoglobin curve to the left was accompanied by a significant decrease in the mixed venous P(O2) without evidence of acidosis, decreased oxygen consumption, or a compensatory increase in cardiac output.

Conversion of bovine growth hormone cysteine residues to serine affects secretion by cultured cells and growth rates in transgenic mice.

GHs have been found to possess two disulfide bonds. We set out to determine the importance of bovine (b) GH's disulfide bonds relative to the ability of the hormone to be secreted by cultured cells in vitro and to promote growth in transgenic mice. We have generated six mutated bGH genes that encode serine (Ser) substitutions for cysteines (Cys). These mutated genes were used to generate bGH analogs in which either one or both disulfide bonds are destroyed. When the small loop of bGH was destroyed (Cys181-Ser or Cys189-Ser), the bGH analogs were found to be secreted by mouse L-cells at levels comparable to those of wild-type bGH. However, secretion was drastically reduced when the large loop was abolished (Cys53-Ser or Cys164-Ser). An immunofluorescence study of these bGH analogs revealed two distinct patterns of subcellular localization. Bovine GH analogs with mutations in the small loop demonstrated a perinuclear distribution similar to that of wild-type bGH, but analogs containing a disrupted large loop revealed a uniform cytoplasmic distribution pattern. When these mutated bGH genes were individually introduced into transgenic mice, only those animals that expressed bGH analogs with the large loop intact demonstrated a growth-enhanced phenotype. Transgenic mice that expressed bGH analogs lacking the large loop showed growth rates similar to those of nontransgenic mice. These results suggest that the integrity of the large loop, but not that of the small loop, is essential for the growth-enhancing activity of bGH in transgenic mice.

Use of blood and blood components.

The indications for transfusions are anemia compromising delivery of oxygen, acute blood loss, cardiopulmonary bypass, exchange transfusion, maintenance of hemostasis, and sepsis associated with granulocytopenia. When transfusion therapy is indicated, only that component of whole blood which is needed for correction of the problem should be given. The options for use each component have been discussed.

Etiology of leukemia. A review.

A variety of factors probably are etiologically involved in leukemia, not only in different cases but also within individual cases. Abnormalities of chromosomes have been found in various types of leukemia. Whether these chromosomal alterations are primary or secondary is undetermined, but it is likely that they are at least contributory in the development of leukemia. There is an increasing body of evidence incriminating viruses in leukemogenesis in man, and they may be a factor in all cases. Certain chemicals may be important etiologic factors in a few cases. Many different studies have established that ionizing radiation in large doses may be leukemogenic. Whether small doses of irradiation are dangerous has not been demonstrated.

Broadening the base of a rare donor program by targeting minority populations.

Some red cell phenotypes are found exclusively in one race and may be of low frequency. Finding compatible blood for patients needing one of these rare types has been extremely difficult. A program was implemented to screen large numbers of donors for blood types found solely in their racial group. Implementation steps included obtaining broad community endorsement of the concept, educating blood service personnel, developing educational materials, enlisting the support of a knowledgeable physician from a minority group, developing a computer program to facilitate selection of donors to be tested, beginning the program and making the necessary adjustments, doing the laboratory testing to identify rare bloods, notifying the rare donors, and maintaining the enthusiasm of the entire blood service for the rare donor screening program. After 7706 black donors were typed, 1 Cr-, 5 Hy-, 24 U-, and 20 Js(b-) persons were found; one U- donor was also Js(b-).

Patterns of use of group O, Rh-negative red cells in a large metropolitan area and an action plan to control utilization.

BACKGROUND: In southeastern Michigan, the group O, Rh-negative (O-) red cell supply was below emergency levels during one-sixth of 1994, despite 43-percent overcollection of O- red cell units relative to the size of the O- patient population. O- red cell units are overutilized because of their universal ABO and Rh compatibility. This study evaluated how hospitals in a large metropolitan area utilized O- red cell units, so that strategies could be devised to reduce O- usage. STUDY DESIGN AND METHODS: Through an O- red cell utilization survey, 56 hospitals were encouraged to collect three months' worth of transfusion data, either prospectively or retrospectively. O- usage was compared to total red cell usage and categorized into transfusions to O- patients, those to non-O- patients, and the number of O- units that outdated. RESULTS: Of 40,616 units transfused in 38 hospitals, 3,535 (8.7%) were O-; 71 percent of the O- units were transfused to O- patients, 28 percent were transfused to non-O- patients, and 1 percent outdated. Hospital transfusions to O- patients appeared to correlate with the racial makeup of the patient population, while hospital transfusions to non-O- patients appeared to correlate with hospital size and the hospital's transfusion practices. CONCLUSION: O- red cell usage in a hospital is dependent on the racial and ethnic mix of the hospital's patient population, the amount of transfusion activity, and the hospital's transfusion practices. An understanding of the dynamics of O- usage allowed the development of strategies to decrease O- utilization.

The prevalence of anti-latex IgE antibodies in 1000 volunteer blood donors.

BACKGROUND: Latex allergy has been recognized as a medical problem with increasing frequency since the mid 1980s. Although certain groups of individuals, such as health care workers, have been recognized as having increased risk for latex allergy, little is known about the prevalence of latex allergy in the general population. METHODS: To estimate the prevalence of latex allergy among healthy adults, we measured anti-latex IgE antibodies in residual serum samples from 1000 volunteer Red Cross blood donors. The 1000 samples were from a sample of blood units collected from workplace mobile sites throughout Southeastern Michigan. Samples collected from mobile sites operating at health care institutions were excluded to minimize sampling of health care workers. Anti-latex IgE antibodies were measured by using the AlaSTAT assay (Diagnostic Products Corp., Los Angeles, Calif.) according to the manufacturer's directions. Samples with anti-latex IgE concentrations of 0.35 IU/ml or greater were classified as positive and samples with IgE concentrations of 1.50 IU/ml or greater were classified as strongly positive. All positive samples were assayed a second time to confirm the result. All positive samples were also measured with the CAP assay (Pharmacia Diagnostics, Dublin, Ohio). RESULTS: The samples tested were from donors with a mean age of 37.8 years, and 47% were women. Sixty-four (6.4%, 95% confidence interval = 4.9-8.1%) of the samples were confirmed as repeatedly positive for anti-latex IgE, and 23 of the 64 positive samples were strongly positive (2.3% of the 1000). Sixty-one percent of the samples positive as determined by the AlaSTAT assay were also positive as determined by the CAP assay. Samples from male donors were more likely to be positive than those from female donors (8.7% vs 4.1%, p = 0.003). Prevalence of positive samples was not related to age or race. CONCLUSIONS: We conclude that the prevalence of detectable anti-latex IgE antibodies, in a large and relatively unselected adult population, is higher than previous estimates have suggested. Although the clinical significance of these observations needs further evaluation, the data suggest that latex allergy is not confined to individuals in previously recognized high-risk groups.

Priapism during filtration leukapheresis.

Priapism has been observed during two out of 3,680 filtration leukapheresis procedures in male donors and has been reported during hemodialysis. Both procedures are associated with enhanced granulocyte adhesion and aggregation presumably due to C5a. During both procedures, heparin is administered and this drug has been shown to cause heparin-dependent anti-platelet antibodies. It is suggested that complement mediated venous leukostasis or immune-induced platelet aggregates might impair the normal blood flow from the penis and result in a state of priapism.

Direct oral questions to blood donors: the impact on screening for human immunodeficiency virus.

BACKGROUND: In December 1990, the Food and Drug Administration recommended that all United States blood centers implement a policy of asking prospective donors direct oral questions (DOQs) about human immunodeficiency virus (HIV) risk behaviors to increase the safety of the blood supply. STUDY DESIGN AND METHODS: To evaluate the impact of the DOQ policy, HIV-related deferral and HIV seroprevalence data were analyzed at four American Red Cross blood centers for the year before the policy change and the year after. An epidemiologic analysis with stratification was conducted, including the calculation of odds ratios (OR) and 95-percent CIs. RESULTS: Two of the four blood centers showed an overall significant increase in HIV-related deferral after implementation of the DOQ policy: OR = 4.04, (95% CI = 3.41, 4.76); OR = 2.93, (95% CI = 2.67, 3.21). The increase in HIV-related deferral was higher for women. HIV seroprevalence decreased at all four centers, including the two that did not see an increase in HIV-related deferrals. Seroprevalence declined by 14 percent in the two centers with increases in HIV-related deferral, which was neither significant nor attributable to DOQs. CONCLUSION: Given that HIV antibody screening cannot detect HIV-seronegative (but infectious) "window-period" donations, the deferral of at-risk donors may offer some additional protection to the blood supply. However, evidence was not found of an increase in safety of the blood supply as measured by HIV seroprevalence.

Donor attitudes about exporting and importing blood.

BACKGROUND: The movement of blood among different areas of the United States and the collection of more blood than is needed locally in some areas are increasing. Little is known of donors' attitudes about this blood resource sharing. STUDY DESIGN AND METHODS: One thousand donors from five regions of the American Red Cross Blood Services were surveyed by telephone. Demographic information about the donors and the regions was obtained, and the donors were asked to describe their attitudes about blood resource sharing as well as other blood donation-related issues. RESULTS: Donors are not very knowledgeable about whether their community is self-sufficient in its blood supply. In regions that import blood, 29 to 43 percent of donors believed that enough blood was collected to meet all local needs, and, in regions that export blood, only 22 to 24 percent of donors believed that more than enough blood was collected. About three-fourths of the donors believed it acceptable to send their blood to other communities if it is needed there. However, this attitude was based on the premise that all local needs would be met first. Only 4 percent of donors would be less willing to donate if their blood was being sent to another community. CONCLUSION: Donors are not very aware of blood resource sharing but are willing, under certain circumstances, to donate blood for use outside their local communities.

Human immunodeficiency virus infection among health care workers who donate blood.

OBJECTIVE: To estimate the prevalence of human immunodeficiency virus (HIV) infection among health care workers who donate blood. DESIGN: Point prevalence survey of blood donors. SETTING: 20 U.S. blood centers that participate in an ongoing interview study of HIV-seropositive blood donors. MEASUREMENTS: Prevalence rates for HIV in persons who reported being health care workers were measured directly for 6 of the 20 blood centers. For the other 14 centers, we derived the numerator from the interview study in the same manner used for the 6 centers; we estimated the denominator using blood collection logs at those centers and extrapolations from the survey completed at the 6 blood centers. RESULTS: Between March 1990 and August 1991, 8519 health care workers donated blood at 6 hospitals and other medical facilities. Three persons were HIV seropositive: Two reported being health care workers and having nonoccupational risk factors for HIV infection; the occupation and other possible risk factors of the third seropositive donor could not be determined. Therefore, the highest overall prevalence of HIV infection among health care worker donors at these 6 centers was 0.04% (3 of 8519; upper limit of 95% CI, 0.1%). We estimated that during the same period, approximately 36,329 health care workers were tested for HIV at all 20 centers. Twenty-seven persons infected with HIV who donated at hospitals were identified; 7 did not return for interviews, so their health care occupations could not be verified. Thus, the highest estimated overall prevalence of HIV infection among health care worker donors at the 20 centers was 0.07% (27 of 36,329; upper limit of CI, 0.1%). Of the 20 known health care worker donors, 11 reported nonoccupational risks for HIV infection; 3 of the remaining 9 health care workers described occupational blood exposures that could have resulted in transmission of HIV. CONCLUSIONS: Blood donors can serve as a sentinel cohort when evaluating the risk for occupationally acquired HIV infection. These findings suggest that among the many health care worker donors in this study, HIV infection attributable to occupational exposure was uncommon.