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Biomedical subjects

P Henson

Publications and source records attributed to P Henson.

At least 19 recordsLinked to original sources
PubMed2000

MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.

MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in addition to regulating the c-Jun NH(2)-terminal kinase (JNK) pathway, is involved in the control of cell motility. MEKK1(-/-) mice are defective in eyelid closure, a TGFalpha-directed process involving the migration of epithelial cells. MEKK1 expression in epithelial cells stimulates lamellipodia formation, a process required for cell movement. In addition, mouse embryo fibroblasts derived from MEKK1(-/-) mice are inhibited in their migration relative to MEKK1(+/+) fibroblasts. MEKK1 is required for JNK but not NF-kappaB activation in response to virus infection, microtubule disruption, and stimulation of embryonic stem cells with lysophosphatidic acid. MEKK1 is not required for TNFalpha or IL-1 regulation of JNK or NF-kappaB activation in macrophages or fibroblasts. Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli.

Animals↗
PubMed1999

Reactive oxygen species regulate activation-induced T cell apoptosis.

Reactive oxygen species (ROS) mediate apoptosis in a number of cell types. We studied the role that ROS play in activated T cell apoptosis by activating T cells in vivo and then culturing them for a short time. Activated T cells died independently of Fas and TNF alpha. Their death was characterized by rapid loss of mitochondrial transmembrane potential (delta psi(m)), caspase-dependent DNA fragmentation, and superoxide generation. A superoxide dismutase mimetic, Mn (III) tetrakis (5, 10, 15, 20-benzoic acid) porphyrin (MnTBAP), protected T cells from superoxide generation, caspase-dependent DNA loss, loss of delta psi(m), and cell death. These results indicate that ROS can regulate signals involved in caspase activation and apoptosis and may contribute to peripheral T cell deletion.

Animals↗
PubMed1994

Iodine-131 in breast milk following therapy for thyroid carcinoma.

UNLABELLED: This study evaluates breast milk secretion of 131I following therapeutic administration of 4000 MBq of 131I-iodide during lactation. METHODS: Breast milk 131I activity concentration was measured over a 32-day period. Dosimetry calculations were undertaken to estimate the period for discontinuation of breast feeding and the equivalent dose to the breasts. RESULTS: To achieve an infant effective dose < 1 mSv and an infant thyroid dose < 10 mSv, breast feeding would need to be discontinued for at least 52 days. The estimated equivalent dose to the breasts was 1.6 Gy. CONCLUSION: It is suggested that 131I-iodide administration is not undertaken during lactation and that breast feeding is discontinued several days prior to administration.

Adenocarcinoma, Follicular↗
PubMed1993

Phagocyte recognition of cells undergoing apoptosis.

A key feature of apoptosis is that cells undergoing this programmed form of death are recognized by phagocytes and ingested while still intact, protecting tissues from the potentially harmful consequences of exposure to the contents of the dying cells. This article reviews recent data which indicate that phagocyte recognition of apoptotic cells as 'senescent-self' involves at least three classes of receptors on the phagocyte surface, while apoptotic cells may display their 'edible' status in a number of different ways.

Amino Acid Sequence↗
PubMed1991

Fetal pulmonary vasodilation after exogenous platelet-activating factor.

To determine the fetal pulmonary vascular response to platelet-activating factor (PAF), we studied the hemodynamic effects of the infusion of PAF directly into the left pulmonary artery in 21 chronically catheterized fetal lambs. Left pulmonary arterial blood flow (Q) was measured with electromagnetic flow transducers. Ten-minute infusions of low-dose PAF (10-100 ng/min) produced increases in Q from a baseline of 71 +/- 5 to 207 +/- 20 ml/min (P less than 0.001) without changes in pulmonary arterial pressure. Pulmonary vasodilation with PAF was further confirmed through increases in Q with brief (15-s) infusions and increases in the slope of the pressure-flow relationship as assessed by rapid incremental compressions of the ductus arteriosus during PAF infusion. Infusion of Lyso-PAF had no effect on Q or pulmonary arterial pressure. Treatment with CV-3988, a selective PAF receptor antagonist, but not with meclofenamate, atropine, or diphenhydramine and cimetidine blocked the response to PAF infusion and did not affect baseline tone. Systemic infusion of high-dose PAF (300 ng/min) through the fetal inferior vena cava increased pulmonary arterial pressure (46.5 +/- 1.0 to 54.8 +/- 1.9 mmHg, P less than 0.01) and aorta pressure (44.3 +/- 1.0 to 52.7 +/- 2.2 mmHg, P less than 0.01) while also increasing Q. Neither PAF nor CV-3988 changed the gradient between pulmonary arterial and aorta pressures, suggesting that PAF does not affect ductal tone. We conclude that PAF is a potent fetal pulmonary vasodilator and that the effects are not mediated through cyclooxygenase products or by cholinergic or histaminergic effects.

Animals↗
PubMed1990

Binding of platelet activating factor to albumin.

Binding of platelet activating factor (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine) to albumin is an important facet of the biological activity of this phospholipid. Measurement of that binding has been hampered by the physical nature of the lipid, which made estimation of the free and bound concentrations difficult. With the use of ultracentrifugation to generate an albumin gradient and to produce a region free of protein, the successful measurement of free PAF and PAF bound to albumin was accomplished. This study has demonstrated that PAF binds to albumin at four binding sites and that the average equilibrium dissociation constant for this binding is 1.10(-7) M. Consideration of these data has led to the hypothesis that the receptor active form of PAF is the albumin-PAF complex, rather than free PAF.

Humans↗
PubMed1987

Association of an abnormality of neutrophil chemotaxis in human periodontal disease with a cell surface protein.

Localized juvenile periodontitis (LJP) is characterized by severe, early-onset, molar and incisor bone loss; neutrophil chemotaxis disorders; and a high prevalence of Actinobacillus actinomycetemcomitans infection. LJP is further characterized by significant familial aggregation of the disease. Recent work in our laboratory has demonstrated the selective depletion of a surface glycoprotein of 110,000 Mr (GP110) from LJP neutrophils by using surface labeling with [14C]formaldehyde and autofluorography. The function of GP110 is unknown; however, it does not appear to be a chemotactic factor receptor. Rather, it is bound by a monoclonal antibody (NCD-1) that recognizes a neutrophil differentiation antigen and which itself alters neutrophil chemotactic and secreting functions. To quantify GP110 on LJP and normal neutrophils, fluorescein-labeled NCD-1 was bound to neutrophils and the amount of fluorescence was evaluated by using cytofluorography. Our results indicate that there is a quantifiable reduction (40%) of GP110 on the surface of LJP and GJP neutrophils, compared with controls. Other patients with neutrophil defects express normal quantities of GP110, suggesting disease specificity. Our data suggest that GP110 may be a useful disease marker for LJP and may provide a useful probe for the study of neutrophil chemotactic function and dysfunction.

Aggressive Periodontitis↗
PubMed1986

Acetylcholine-induced pulmonary vasodilation in lung vascular injury.

Recent work with isolated blood vessels has emphasized the importance of intact endothelium when the relaxation of vascular smooth muscle is induced by acetylcholine (ACh). However, the physiologic significance of this endothelial-dependent ACh response in a complete organ circulation is unclear. We questioned whether diminished ACh vasodilation would result from damage of lung vascular endothelium and whether this response could be used as an indication of endothelial injury. We therefore induced pulmonary endothelial cell injury in one rat model by repeated injections of alpha-naphthyl thiourea (ANTU) and in a second rat model by exposing rats for 52 h to 100% oxygen at a barometric pressure of 760 torr (hyperoxia). Rats injected with Tween 80, the solvent for ANTU, or exposed to ambient Denver air served as the respective control animals. The isolated lungs of these rats were perfused with a recirculating cell- and plasma-free, physiological salt solution to study the effect of ACh or NaCl infusion on pulmonary perfusion pressure and vascular responsiveness. ANTU-treated rats demonstrated an intact vasodilatory response after ACh infusion when compared with the solvent control animals. The immediate pulmonary vasodilation after ACh infusion was slightly enhanced in the hyperoxic rat lung when compared with the rats exposed to ambient air, but there was no difference between these groups in the prolonged depression of vascular responsiveness to hypoxia or angiotensin II. Thus, in both models of lung endothelial cell injury, the pulmonary vascular responses to ACh were intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1983

Normal repair of ultraviolet-induced DNA damage in a hypersensitive strain of fibroblasts from a patient with Gardner's syndrome.

Gardner's syndrome is an autosomal dominant disorder that predisposes to cancer of the large intestine and to other tumors. We have previously demonstrated that fibroblasts from a patient with this disease are hypersensitive to the cytotoxic effects of ultraviolet light. In this report we have measured several parameters of the repair of ultraviolet light-induced DNA damage in an attempt to identify a defect responsible for the hypersensitivity. We have found the excision rate of pyrimidine dimers, the host cell reactivation of UV-irradiated herpes simplex virus, the induction and rejoining of DNA single strand breaks and the response of semi-conservative DNA replication to UV-irradiation to be in all cases indistinguishable from such phenomena in a variety of normal cells.

Cells, Cultured↗
PubMed1983

Coordinate production by a T cell hybridoma of gamma interferon and three other lymphokine activities: multiple activities of a single lymphokine?

The T cell hybridoma FS7-20, produced by the fusion of normal B10.BR T cells to the AKR thymoma BW5147, was found when stimulated with concanavalin A (Con A) to produce the lymphokines: interleukin 2 (IL 2), interferon-gamma (IFN gamma), macrophage-activating factor (MAF), Ia induction factor IaIF), and the B cell helper factor interleukin X (IL X). The clones and subclones of FS7-20 varied dramatically in their ability to produce these lymphokines, presumably because of karyotypic variations. The ability to produce IL 2 segregated independently from the ability to produce the four other lymphokine activities; however, production of the latter activities showed a strong correlation. This coordinate production of IFN gamma, MAF, IaIF, and IL X was also observed with a cloned normal cytotoxic T cell line, cr15. These results suggest either that IFN gamma, MAF, IaIF, and IL X are all manifestations of a single molecular species or that, although these activities are different structurally, their production is controlled by a common genetic mechanism. In support of the first possibility, the IFN gamma, MAF, IaIF, and IL X activity produced by FS7-20 were all found to be equally sensitive to inactivation at pH 2. These results illustrate the usefulness of using T cell hybridomas for the study of lymphokines.

Animals↗
PubMed1981

Excision of ultraviolet damage and the effect of irradiation on DNA synthesis in a strain of Bloom's syndrome fibroblasts.

We have studied repair of ultraviolet light (UV)-induced damage in a strain of Bloom's syndrome cells which we have shown to be defective in host cell reactivation of UV-irradiated herpes simplex virus. Excision repair was monitored by following loss of sensitivity of DNA in permeabilized cells to digestion by the Micrococcus luteus UV endonuclease preparation. The Bloom's syndrome fibroblasts apparently removed endonuclease-sensitive sites from the DNA slightly less efficiently than did normal strains. After 24 hr, 38% of the sites remained in the Bloom's syndrome cells in comparison with 16% in normal fibroblasts. DNA newly synthesized in UV-irradiated Bloom's syndrome cells sedimented less far into alkaline sucrose gradients than did DNA from similarly treated normal cells. In other respects, including the effect of caffeine exposure, DNA synthesis in Bloom's syndrome cells was indistinguishable from that in normal cells. We were therefore able to detect only minor defects in the repair of UV-induced damage in Bloom's syndrome fibroblasts. This is consistent with the normal survival exhibited by these cells. The defect in excision repair may, however, be sufficient to allow the cellular repair capacity to become saturated at high infecting multiplicities of UV-irradiated herpes simplex virus.

Caffeine↗
PubMed1979

Defective reactivation of ultraviolet light-irradiated herpesvirus by a Bloom's syndrome fibroblast strain.

We have used the technique of host cell reactivation of UV-irradiated herpes simplex virus type 1 as a measure of the repair capacity of three Bloom's syndrome skin fibroblast strains. At low multiplicity of infection (less than 6 x 10(-4) plaque-forming unit/cell), reactivation of the virus by the Bloom's syndrome strains was indistinguishable from that by normal strains. Reactivation at higher multiplicities was measured using an infectious centers assay. At 3 plaque-forming units/cell, survival of UV-irradiated herpes simplex virus was higher in all cell strains as a result of the multiplicity reactivation effect. This effect was, however, much smaller in one Bloom's syndrome strain, GM1492, than in either the normal strains or the other Bloom's syndrome fibroblasts. The defect in GM1492 was manifest only at relatively high multiplicates of infection. Thus, at 0.01 plaque-forming unit/cell, the GM1492 strain appeared normal, using the infectious centers assay. Clonal survival of the UV-irradiated GM1492 fibroblasts was also normal. Caffeine at 4 mM had little effect on either virus or cell survival following UV irradiation. The results indicate that the Bloom's syndrome strain GM1492 may be deficient in one of the cellular functions responsible for the multiplicity reactivation effect. These effects include complementation and recombinational events. Alternatively, the GM1492 strain may have a defective UV repair system which becomes saturated at high levels of damage.

Caffeine↗
PubMed1979

Mechanisms of platelet response to monosodium urate crystals.

The mechanisms of urate-crystal-induced release of platelet constituents has been studied morphologically and biochemically. Urate crystals provoked an early energy-dependent release of the dense-body constituents serotonin, ADP, and ATP from washed platelets. Concurrently, platelet ultrastructure showed evidence of shape change, contractile wave, and aggregation. These are typical morphologic concomitants of platelet secretion. By 30 minutes' incubation, urate-induced platelet lysis occurred, as shown by loss of the cytoplasmic enzyme lactic dehydrogenase (LDH) and ultrastructurally by disruption of platelet membrane integrity. Cytochalasin B inhibited the urate-crystal-induced shape change, aggregation, and disruption of cell membranes. Platelet degranulation was not inhibited and the initial component of serotonin release was not affected. Cytochalasin B also abrogated crystal-induced LDH loss. Thus, the initial crystal-induced serotonin release does not depend on platelet lysis. It is concluded that urate-crystal--induced release of serotonin, ATP, and ADP represents an example of platelet secretion.

Adenosine Diphosphate↗