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Biomedical subjects

N Williams

Publications and source records attributed to N Williams.

At least 271 records · Page 15Linked to original sources
PubMed1993

Gastrointestinal disruption and vertebral fracture associated with the use of seat belts.

Seat belts have been shown to be beneficial in reducing the type and severity of injuries sustained in road traffic accidents. The association of vertebral and visceral injuries, although previously described, is rare. This and various other confounding factors may make diagnosis of the visceral injury difficult. We describe four cases of combined vertebral and visceral injury caused by the use of seat belts. The pathogenesis of the injury and subsequent management are discussed.

Accidents, Traffic↗
PubMed1992

Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.

We report the occurrence of Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl who was one of identical twins. Molecular studies showed nonrandom X-inactivation in both her fibroblasts and lymphocytes, while her normal twin showed equal usage of both X chromosomes. In view of previous reports of 7 pairs of identical female twins in which one had Duchenne muscular dystrophy, it seems that twinning may be strongly associated with nonrandom X-inactivation, and is not specific to the properties of the disease causing gene.

DNA Probes↗
PubMed1992

Recombinant rat stem cell factor stimulates the amplification and differentiation of fractionated mouse stem cell populations.

The role of recombinant rat stem cell factor (rrSCF) was studied on defined primitive bone marrow cell populations. In agar culture of 500 lineage-negative/Sca-1-positive (Lin-/Sca-1+) cells, rrSCF alone stimulates small colonies of predominantly granulocytic cells. The combinations of rrSCF plus interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage CSF (CSF-1) stimulated primitive progenitor cells defined as high proliferative potential colony-forming cells (HPP-CFC). Synergistic increases in total colony numbers were obtained with rrSCF plus GM-CSF, granulocyte CSF (G-CSF), CSF-1, or IL-6, but not IL-1 or IL-3. Lin-/Sca-1+ cells were incubated in liquid culture at 3,000 cells/mL for 6 days in the presence of rrSCF alone or in combination with other growth factors. The total number of cells was increased twofold in the presence of rrSCF, with the progeny primarily myeloid in nature. The greatest increase in cell number was obtained with rrSCF plus IL-3, where the cell number increased 40-fold. These factors also stimulated an increase in HPP-CFC (10-fold) and GM-CFC (500-fold). To determine if these interactions were direct, single Lin-/Sca-1+ cells were sorted into microtiter wells and the cell proliferation scored 6 days later. RrSCF synergized with IL-3, IL-6, and G-CSF to stimulate the proliferation of single cells. The cells in positive wells were subcultured into colony-forming assays and up to 400 CFC per well were obtained after 14 days incubation of the secondary cultures. These data demonstrate that rrSCF acts in combination with various growth factors to directly stimulate the amplification potential of hematopoietic primitive precursors, resulting in differentiation of these precursors.

Animals↗
PubMed1992

The role of interleukin 6 in megakaryocyte formation, megakaryocyte development and platelet production.

Megakaryocytopoiesis is the cellular amplification and differentiation of precursors into immature megakaryocytes, and the cytoplasmic maturation of these megakaryocytes, a process terminating in the release of platelets into the circulation. Interleukin 6 (IL-6) stimulates megakaryocytopoiesis in the bone marrow, increasing platelet numbers in the circulation. IL-6 alone is poorly active on the growth of stem cell populations, but acts in synergy with stem cell factor (c-kit ligand) to expand the committed myeloid progenitor compartments but not the megakaryocyte progenitors. IL-6 has a direct action on megakaryocyte progenitors but only in synergy with low doses of interleukin 3 (IL-3), increasing the number of immature megakaryocytes and enhancing the processes of development into mature megakaryocytes. IL-6 is about 10 times more active on megakaryocytes than on megakaryocyte progenitors in cell culture. It is active alone and will stimulate increases in cell size and DNA content. IL-6 does not appear to stimulate the process of platelet release. IL-6 is found in bone marrow, in both macrophage subsets and megakaryocytes, indicating that it may be an important physiological regulator of both paracrinal (microenvironmental) and autocrinal mechanisms controlling megakaryocyte development in bone marrow.

Animals↗
PubMed1992

Growth factors produced by human embryonic kidney cells that influence megakaryopoiesis include erythropoietin, interleukin 6, and transforming growth factor-beta.

Partially purified protein preparations containing megakaryocyte growth factor activity were prepared from human embryonic kidney (HEK) cell conditioned medium using ammonium sulfate precipitation, Cibicron blue affinity chromatography, and wheatgerm lectin affinity chromatography. Treatment of these preparations with neutralizing antibodies directed against erythropoietin (EPO) and interleukin 6 (IL6) resulted in a dramatic reduction in their capacity to stimulate megakaryocyte maturation in vitro. The presence of EPO in these preparations was confirmed by both immunoblotting and use of a mouse spleen erythroid progenitor cell proliferation assay routinely used to quantitate EPO activity in vitro. Northern blot analysis of HEK cell-derived mRNA with IL6 DNA probes revealed the presence of an IL6 transcript with a molecular size of 1.3 kb. Analysis of the HEK cell-derived preparation by ELISA confirmed the presence of immunologically reactive IL6. In addition, it was shown that purified recombinant human EPO and IL6 stimulated megakaryocyte maturation in the in vitro assay used in this study. These data indicate that the activity in HEK cell conditioned medium that stimulates megakaryocyte maturation in vitro is predominantly due to the presence of IL6 and EPO. Immunoneutralization studies of another HEK cell-derived preparation, which was inhibitory in the megakaryocyte maturation assay, demonstrated that it contained transforming growth factor beta (TGF beta), a potent inhibitor of megakaryocyte maturation. Taken together, these studies indicate that HEK cell conditioned medium, which has previously been reported to contain megakaryocyte growth factor activity, is comprised of a complex mixture of growth and differentiation factors, some of which promote and others that inhibit the process of megakaryopoiesis.

Biological Assay↗
PubMed1992

Traumatic pneumatocele.

Traumatic pneumatocele is a recognized but uncommon complication of blunt thoracic trauma. Its clinical relevance lies in the difficulty the attending surgeon encounters in differentiating the x-ray appearances from more serious pathology requiring urgent surgical intervention. We document this case because it is important that surgeons be aware of this condition and of its benign course so as to avoid unnecessary diagnostic or operative procedures.

Air↗
PubMed1992

Midpregnancy plasma zinc in normal and growth retarded fetuses--a preliminary study.

OBJECTIVE: To determine plasma zinc concentrations in normally and abnormally growing fetuses. DESIGN: Prospective observational study. SETTING: Fetal Medicine Unit, Queen Charlotte's Maternity Hospital. SUBJECTS: 53 pregnant women attending for fetal blood sampling at between 18 and 40 weeks gestation. 27 fetuses were normal (central group), 11 fetuses were growth retarded and 15 were malformed. MAIN OUTCOME MEASURES: Plasma zinc concentrations in maternal and fetal blood at time of fetal blood sampling. RESULTS: In normally growing fetuses, between 18 and 40 weeks gestation, there was no fall in maternal plasma zinc concentration; the fetal level fell by 36%. In 10 fetuses with symmetrical growth retardation, plasma zinc concentration tended to be low, but was not significantly different from that in the normal control fetuses. CONCLUSION: The results suggest that (i) placental transfer of zinc is an uphill secretory process and that it is a rate-limiting step in the accumulation of zinc by the fetus and (ii) in fetuses with symmetrical intrauterine growth retardation, a low plasma zinc is probably a parallel phenomenon and not necessarily an aetiological factor.

Female↗
PubMed1992

Detection of subclinical autonomic neuropathy in constipated patients using a sweat test.

Chronic idiopathic constipation may be the result of an autonomic neuropathy. This hypothesis was tested in 23 constipated patients and 17 age matched controls, using the acetylcholine sweat spot test devised to test autonomic integrity in diabetes. Acetylcholine (0.01%) was injected in the dorsum of the foot painted with a mixture of starch and iodine. Active sweat glands appeared on the surface of the skin as small black dots which were photographed and counted, using a grid with 60 subareas. Two measurements were made: the number of dots per unit subarea (sweat spot test score) and the % number of abnormal subareas (with less than six spots). These two parameters were correlated. The median sweat spot test score was 9.53 in patients and 13.92 in controls (p = 0.0001), the receiver operating characteristic curve showing that a score of 12 delimited normal and abnormal subjects. Increasing age was correlated with a low score in patients, probably because of prolonged symptoms. Seventy per cent of patients and one control had a borderline or abnormal number of subareas. These results suggest that idiopathic constipation is associated with a degree of autonomic denervation. The sweat spot test is an easy, inexpensive method to test this hypothesis and deserves a place in the clinical assessment of slow transit constipated patients.

Acetylcholine↗
PubMed1992

The nature of an accessory cell in bone marrow stimulating murine megakaryocytopoiesis.

The nature of accessory cells in unstimulated mouse bone marrow that modulates in vitro megakaryocytopoiesis by releasing megakaryocyte potentiator (Mk-potentiator) activity was investigated. An active cell class was identified by the 7/4 and Ia cellular antigens. Bone marrow macrophages were obtained by their defined outgrowth in the presence of growth factors. Bone marrow macrophages grown in the presence of interleukin 3 (IL-3) were more active in producing Mk-potentiator than were macrophages grown in the presence of colony-stimulating factor 1 (CSF-1). The data indicate that the accessory cells producing Mk-potentiator are a select population of bone marrow macrophages that may be responsible for inducing megakaryocyte maturation under steady-state conditions.

Animals↗
PubMed1992

Interleukin 3 directly stimulates both megakaryocyte progenitor cells and immature megakaryocytes.

A subset of stem cell antigen (sca-1)-positive mouse megakaryocyte progenitors was identified that correlates with other primitive precursors in bone marrow. The responsive bone marrow cells were obtained by depleting the marrow of cells bearing defined lineage markers (neutrophils, macrophages, and lymphoid cells) and enriched for primitive myeloid progenitor cells with high proliferative potential, selecting for cells expressing sca-1. The sca-1-positive megakaryocyte progenitors formed colonies in the presence of interleukin 3 (IL-3) alone. Immature megakaryocytes depleted of mature megakaryocytes and of cells expressing myeloid and lymphoid lineage markers were also responsive to IL-3. These data indicate that in the presence of high doses of IL-3, accessory cells are not obligatory for growth factor stimulation of megakaryocytopoiesis in vitro.

Animals↗