Loss of Arabidopsis GAUT12/IRX8 causes anther indehiscence and leads to reduced G lignin associated with altered matrix polysaccharide deposition.

GAlactUronosylTransferase12 (GAUT12)/IRregular Xylem8 (IRX8) is a putative glycosyltransferase involved in Arabidopsis secondary cell wall biosynthesis. Previous work showed that Arabidopsis irregular xylem8 (irx8) mutants have collapsed xylem due to a reduction in xylan and a lesser reduction in a subfraction of homogalacturonan (HG). We now show that male sterility in the irx8 mutant is due to indehiscent anthers caused by reduced deposition of xylan and lignin in the endothecium cell layer.

Diminished quality of life and physical function in community-dwelling elderly with anemia.

The occurrence of anemia in older adults has been associated with adverse outcomes including functional decline, disability, morbidity, and mortality. It is not clear to what extent these outcomes are the result of the anemia or concurrent illness. We performed a cross-sectional, observational study to determine whether lower hemoglobin concentrations in older adults are associated with reduced health-related quality of life, functional status, depression, disability, and physical strength, independent of chronic disease.

Hematopoiesis is not clonal in healthy elderly women.

Clonality assays, based on X-chromosome inactivation, discriminate active from inactive alleles. Skewing of X-chromosome allelic usage, based on preferential methylation of one of the HUMARA alleles, was reported as evidence of clonal hematopoiesis in approximately 30% of elderly women. Using a quantitative, transcriptionally based clonality assay, we reported X-chromosome-transcribed allelic ratio in blood cells of healthy women consistent with random X-inactivation of 8 embryonic hematopoietic stem cells.

Disordered hematopoiesis and myelodysplasia in the elderly.

Normal hematopoiesis constitutes the process of producing diverse, differentiated blood cell types in a manner related to physiological requirement. During aging, modulation of hematopoiesis becomes disordered, impairing the ability of older people to respond appropriately to the physiological demand for blood cell replacement triggered by stimuli such as blood loss or cytoreductive chemotherapy. This may contribute to the increase in the prevalence of anemia that is observed during aging.

Hematopoiesis and cytokines. Relevance to cancer and aging.

Impaired hematopoiesis and dysregulated cytokine expression have important implications for cancer in the elderly. In aged people, hematopoiesis is dysregulated and becomes paradoxically down-modulated under periods of increased hematopoietic demand. This down-modulation may explain, at least in part, the increased incidence of anemia in the elderly, although the cause of anemia can usually be identified in these patients and frequently reversed with targeted therapy.

Impaired expression of hematopoietic growth factors: a candidate mechanism for the hematopoietic defect of aging.

Aged humans and aged experimental animals exhibit a diminished ability to upregulate hematopoiesis, but the mechanism responsible for this is unknown. The purpose of the studies was to test the hypothesis that this disregulation might be attributable to altered expression of hematopoietic growth factors. We studied the in vitro ability of cells from aged humans or mice to release bioactive colony stimulating activity (CSA) and to accumulate mRNA for defined growth factors.

Diminished transcription of interleukin-8 by monocytes from preterm neonates.

Developmental delays, which impair antibacterial host defense, are present in the neutrophil system of human preterm neonates. We hypothesized that diminished production of interleukin-8 (IL-8), a neutrophil chemotactic peptide, might in part be responsible for these defects. To test this, monocytes from the blood of preterm neonates, term neonates, and adults were isolated immunologically by "negative panning" and subsequently stimulated with interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), or lipopolysaccharide (LPS), after which IL-8 levels in the supernatants were measured by ELISA.

Evaluation of the mechanism causing anemia in infants with bronchopulmonary dysplasia.

In seven patients with bronchopulmonary dysplasia and anemia, we evaluated the mechanisms causing the anemia. All had a normocytic, normochromic, hyporegenerative anemia (mean hematocrit 26%; range 21% to 30%). The low hematocrit values seemed physiologically significant because mean (+/- SD), heart rates fell after transfusion (162 +/- 7 to 149 +/- 9 beats/min; p less than 0.

Erythropoietin affects the maturation pattern of fetal G-CSF-responsive progenitors.

A transient hyporegenerative neutropenia has been reported in neonates, but not in older children or adults, undergoing treatment with recombinant erythropoietin (epo). Monocytopenia has not been reported. We postulated that epo might selectively reduce the responsiveness of neonatal progenitors to Granulocyte Colony-Stimulating Factor (G-CSF), while not similarly affecting their responsiveness to Macrophage Colony-Stimulating Factor (M-CSF).

Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies of neonates.

Several deficiencies in antibacterial defense have been described in neonates. Among those best characterized are delayed maturation of B cells into antibody producing cells, deficient T-cell maturation, and delayed cycling of hematopoietic progenitor cells after an infectious challenge. No unifying theory has been forwarded, however, to explain the concomitance of these three developmental deficiencies.

Congenital hypoplastic (Diamond-Blackfan) anemia in seven members of one kindred.

Congenital hypoplastic (Diamond-Blackfan) anemia is a rare macrocytic anemia, generally presenting during infancy or childhood. The condition usually occurs sporadically or in a pattern consistent with autosomal recessive inheritance, although autosomal dominant transmission has been proposed in some kindreds. We report the largest known kindred of congenital hypoplastic anemia, with at least 7 affected individuals over 3 generations, and propose that studies of this kindred may be useful for identifying the mechanism by which their genetic abnormality results in congenital hypoplastic anemia.

A randomized trial to develop criteria for administering erythrocyte transfusions to anemic preterm infants 1 to 3 months of age.

A randomized trial of erythrocyte transfusion vs no transfusion was performed in 16 preterm infants 1 to 3 months old with hematocrits of less than or equal to 0.29 L/L. To determine which (if any) such patients definitely benefit from transfusion, an analysis of outcome variables was performed.

Down-modulation of neutrophil production by erythropoietin in human hematopoietic clones.

In clonogenic assays of hematopoietic progenitors, high concentrations (4 U/mL) of erythropoietin (epo) reduced the formation of granulocyte-macrophage (GM) colonies and diminished the number of granulocytes formed per culture plate. Fetal progenitors were more sensitive to these effects of epo than were progenitors from adults, displaying these reductions at greater than or equal to 1 U epo/mL. The mechanism was investigated by growing fetal progenitors stimulated by recombinant GM-CSF, in the absence of epo, and when eight-cell clones first appeared, mapping their location, then adding epo, and assessing its effect on the subsequent differentiation of the clones.

Erythroid colonies derived from fetal blood display different growth patterns from those derived from adult marrow.

Fetal blood may be useful for the study of hematopoietic development in humans. However, the methods used to study blood cell colonies in adults may not be optimal for the study of colonies derived from fetal blood. Using cord blood from six healthy term pregnancies and marrow from six healthy adult volunteers, we compared the chronology of emergence, morphology, and differentiation of progenitor cell colonies from the two sources.

Stimulation of neutrophil production in CSF-1-responsive clones.

The hematopoietic growth factor CSF-1 has been considered relatively lineage specific for the production of macrophages, whereas GM-CSF elicits a predominance of neutrophils. It is likely that in vivo, individual clones are stimulated by the two CSFs, although the effect of dual stimulation on progenitors and their progeny has not been completely explored. We found that in cultures initiated with low concentrations of CSF-1 or GM-CSF, alone or in combination, production of macrophages predominated.

Responsiveness to recombinant human erythropoietin of marrow erythroid progenitors from infants with the "anemia of prematurity".

We used cells from marrow aspirations that had been performed on 10 infants with the "anemia of prematurity" and tested the responsiveness of their erythroid colony-forming units (CFU-E) to recombinant human erythropoietin. For comparison, we also tested marrow-derived CFU-E from five healthy adults, and circulating CFU-E from cord blood of five healthy neonates. CFU-E from the anemic infants had a 50% maximal response at 0.

Haematopoietic progenitor cells in an infant who developed pancytopenia following an extensive burn.

We observed a 24-month-old infant who developed anaemia, thrombocytopenia and neutropenia while recuperating from an extensive burn. In order to determine the mechanism(s) responsible for the pancytopenia, we quantified marrow-derived haematopoietic progenitor cells, assessed the relative proliferative rate of haematopoietic progenitor cells, and sought the presence of progenitor cell inhibitors. The concentration and relative proliferative rate of pluripotent progenitors (CFU-GEMM) were elevated.

Neutrophil-mediated killing, opsonization, and serum-mediated killing of Escherichia coli K1 by neonatal rats.

Neonates are particularly susceptible to infection with Escherichia coli K1. To investigate the mechanisms which lead to this susceptibility, we examined: (a) the bactericidal activity of neutrophils; (b) opsonization, and (c) the bactericidal activity of serum in developing rats. Neutrophils from adult rats killed E.

Kinetic evaluation of the pool sizes and proliferative response of neutrophils in bacterially challenged aging mice.

Clinical observations during infection suggest that in aged patients, the kinetic or proliferative responses of neutrophils to infection may be deranged. To test this hypothesis, the neutrophil responses of 6-month-old and 30-month-old mice were compared. After intrapulmonary injection of Escherichia coli, young mice exhibited neutrophilia and diminution of the neutrophil storage pool (NSP) by a mean of 6.

Immunosuppressive efficacy of vincristine in heart transplantation: a preliminary report.

Because vincristine has immunosuppressive activity in animal models, has specific cytotoxic effects on lymphocytes, and does not have overlapping toxicity with other immunosuppressive agents, we designed a prospective randomized trial to evaluate the efficacy of the addition of vincristine to standard immunosuppressive therapy in heart transplantation. Patients received equine antithymocyte globulin for the first week or murine antihuman mature T cell (OKT3) monoclonal antibody for the first 2 weeks after transplantation and were maintained on azathioprine and cyclosporine. A steroid pulse was administered 1 day after completion of antithymocyte globulin or OKT3 monoclonal antibody and tapered off over 21 days.

The effect of administration of immunoglobulin to newborn rats with Escherichia coli sepsis and meningitis.

Newborn rats 24-36 h old were injected transthoracically with various doses of Escherichia coli K1. Eighty-six of 92 rats which received 10(4) colony-forming units/g body weight were dead within 48 h. Two h after injection, E.

Effect of intravenous immunoglobulin G on neutrophil kinetics during experimental group B streptococcal infection in neonatal rats.

A modified form of serum immunoglobulin G (pH 4.25) was tested for its effect on neutrophil kinetics and survival rates in neonatal rats with type III, group B streptococcal pneumonia and sepsis. Each of 30 animals received a transthoracic inoculation of 10(5) organisms/g of body weight; all died within 48 hr.