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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 289 records · Page 16Linked to original sources
PubMed1988

Interleukin 1 binds to specific receptors on human keratinocytes and induces granulocyte macrophage colony-stimulating factor mRNA and protein. A potential autocrine role for interleukin 1 in epidermis.

Cultured human keratinocytes have been shown to produce IL-1 alpha and beta mRNA and protein. IL-1 biological activity has been identified in normal human epidermis; in vitro, most biologically active IL-1 resides in a cell-associated compartment. The potential for autocrine effects of IL-1 on human keratinocytes was assessed by measurement of keratinocyte IL-1 receptors. Both high- and low-affinity cell surface receptors that bound recombinant (r) IL-1 alpha and beta with comparable affinities could be identified on cultured human keratinocytes, using 125I-labeled rIL-1. Chemical crosslinking experiments identified a cell surface molecule of roughly 72,500 Mr that bound 125I-labeled IL-1, similar to the molecular weight of previously described IL-1 receptors on fibroblasts, B cells, and T cells. To assess the biological consequences of keratinocyte IL-1 binding, granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression was measured. The addition of exogenous rIL-1 alpha led to a dose-dependent increase in the accumulation of GM-CSF mRNA, as measured by a sensitive and specific S1 nuclease assay. This increase in mRNA was reflected in a marked increase in GM-CSF biological activity as measured by proliferation of blast cells from chronic myelogenous leukemia patients. The biological activity was completely inhibitable by an antibody to human rGM-CSF. GM-CSF activates mature neutrophils and macrophages and appears to enhance the efficiency of Langerhans cell antigen presentation to T cells. Release of IL-1 from injured or activated keratinocytes may lead to enhanced epidermal GM-CSF gene expression via an autocrine mechanism, thus enhancing local host defense.

Cells, Cultured↗
PubMed1988

Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system.

The response of human acute myeloid leukemia (AML) cells to the distinct hematopoietic growth factors (HGFs), ie, recombinant interleukin-3 (IL-3), granulocyte-macrophage-CSF (GM-CSF), granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), and erythropoietin (Epo) was investigated under well-defined serum-free conditions. Proliferative responses to these factors, when added separately as well as in combinations, were analyzed in 25 cases of human AML using 3H-thymidine incorporation and colony assays. The 3H-thymidine uptake data revealed that IL-3, GM-CSF, G-CSF, and M-CSF were stimulators of AML proliferation in 19, 15, 13, and 4 cases, respectively. Epo only stimulated DNA synthesis in the cells of the single erythroleukemia case. GM-CSF stimulation was seen only in IL-3 reactive cases and GM-CSF, when combined with IL-3, could not further elevate the DNA synthesis evoked by IL-3 alone. On the other hand, in six cases, G-CSF enhanced the IL-3- or GM-CSF-stimulated thymidine uptake. These results suggest that subpopulations of AML cells that are activated by distinct CSFs (eg, IL-3/GM-CSF-responsive cells and G-CSF-responsive cells) coexist. The 3H-thymidine incorporation assay was more sensitive for measuring CSF responses than methylcellulose colony cultures, since activation of DNA synthesis was more frequently seen than induction of colony formation. DNA synthesis experiments revealed eight different CSF response patterns among these 25 cases. CSF phenotyping may be a useful addition to the morphologic classification of AML, since these patterns directly reflect the ability of the proliferating subsets of AML cells to respond to the CSFs.

Cell Division↗
PubMed1987

Recombinant human macrophage colony-stimulating factor (M-CSF) requires subliminal concentrations of granulocyte/macrophage (GM)-CSF for optimal stimulation of human macrophage colony formation in vitro.

Human macrophage colony-stimulating factor (M-CSF or CSF-1), either in purified or in recombinant form, is able to generate macrophagic colonies in a murine bone marrow colony assay, but only stimulates small macrophagic colonies of 40-50 cells in a human bone marrow colony assay. We report here that recombinant human granulocytic/macrophage colony stimulating factor (rhGM-CSF) at concentrations in the range of picograms enhances the responsiveness of bone marrow progenitors to M-CSF activity, resulting in an increased number of macrophagic colonies of up to 300 cells. Polyclonal antiserum against M-CSF did not alter colony formation of bone marrow progenitors incubated with GM-CSF at optimal concentration (1-10 ng/ml) for these in vitro assays. Thus, GM-CSF at higher concentrations (nanogram range) can by itself, elicit macrophagic colonies, and at lower concentrations (picogram range) acts to enhance the responsiveness of these progenitors to M-CSF.

Animals↗
PubMed1987

Hemolytic uremic-like syndrome in two horses.

A syndrome characterized clinically by oliguria, progressive severe azotemia, and edema of the abdomen and groin was seen in 2 horses. Treatment with fluids, diuretics, and corticosteroids administered intravenously was ineffective, and the horses were euthanatized. Microscopically, there was severe necrotizing angiopathy with profuse fibrin deposition in renal glomeruli and sinusoids of peripheral lymph nodes. The signs observed in the horses resembled hemolytic-uremic syndrome in human beings.

Animals↗
PubMed1987

Isolation and characterization of the Escherichia coli mutH gene product.

The Escherichia coli mutH gene product has been isolated in near homogeneous form using an in vitro complementation assay for DNA mismatch correction (Lu, A.-L., Clark, S., and Modrich, P. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 4639-4643) which is dependent on mutH function. The protein has a subunit Mr of 25,000, and purified preparations contain a Mg2+-dependent endonuclease activity which cleaves 5' to the dG of d(GATC) sequences to generate 5'-phosphoryl and 3'-hydroxyl termini. Symmetrically methylated d(GATC) sites are resistant to the endonuclease, hemimethylated sequences are cleaved on the unmethylated strand, and unmethylated d(GATC) sites are usually subject to scission on only one DNA strand. Although this endonuclease activity is extremely weak (less than 1 scission/h/mutH monomer equivalent) and cleavage at a d(GATC) site does not depend on the presence of a mismatched base pair within the DNA substrate, the activity does not appear to be a contaminant of mutH preparations. d(GATC) endonuclease activity and mutH complementing activity co-purify through multiple column steps without change in relative specific activities, and both activities co-electrophorese under native conditions. These findings suggest that the mutH product functions at the strand discrimination stage of mismatch correction and that this stage of the reaction involves scission of the unmethylated DNA strand.

Bacterial Proteins↗
PubMed1987

Comparison of potential cytoprotective action of sucralfate and cimetidine. Studies with experimental feline esophagitis.

The potential mucosal protective effects of a liquid sucralfate preparation and the histamine (H2)-antagonist cimetidine on acid-induced esophagitis were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N hydrochloric acid at 1 ml/minute for 20 minutes. Mucosal lesions were evaluated by blinded investigators using both fiber-optic endoscopy and light microscopy. Histology was scored for basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions, demonstrated by quantitative histologic scoring. Although cimetidine did not show the same degree of protection as sucralfate, the results did show a trend towards a cytoprotective effect.

Animals↗
PubMed1987

Refining the criteria for pulsed Doppler diagnosis of mitral regurgitation by comparison with left ventricular angiography.

Doppler echocardiography is established as a useful method for detecting mitral regurgitation (MR). However, studies also show that Doppler echocardiography may be too sensitive for diagnosing pathologic MR. To determine whether the false-positive or clinically insignificant diagnosis of MR can be eliminated by defining more specific diagnostic criteria, pulsed Doppler findings were compared with left ventricular angiographic findings in 81 patients. Using the conventional Doppler criterion of any systolic increased spectral dispersion detected in the left atrium, sensitivity was 100% and specificity was 76%. Using holosystolic increased spectral dispersion as the criterion, sensitivity was 100% and specificity was 92%. Using the combined criteria of holosystolic increased spectral dispersion plus peak regurgitant blood flow velocity of greater than 150 cm/s, sensitivity was 100% and specificity was 97%. Doppler studies in 20 clinically normal persons showed that the combined Doppler criteria were 100% specific. In conclusion, the presence of holosystolic increased spectral dispersion within the left atrium with a peak regurgitant flow velocity greater than 150 cm/s appears to be as sensitive as and more specific than the presence of any systolic Doppler increased spectral dispersion in identifying patients with MR.

Angiography↗
PubMed1987

Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3.

Cloned gibbon interleukin 3 (gIL-3) was found to stimulate the proliferation and differentiation of human bone marrow cells to produce day-14 granulocyte, macrophage, granulocyte-macrophage, and eosinophil colonies in semisolid agar. In the presence of normal human plasma, gIL-3 stimulated megakaryocytes. In methylcellulose cultures, it stimulated erythroid colonies in the presence, but not in the absence, of erythropoietin. When mature human leukocytes were used, gIL-3 stimulated the function of purified mature eosinophils as measured by the capacity to kill antibody-coated target cells, to produce superoxide anions, and to phagocytize opsonized yeast particles in a manner similar to recombinant human granulocyte-macrophage colony-stimulating factor. In contrast, gIL-3 did not significantly stimulate any of the neutrophil functions tested, whereas human recombinant granulocyte-macrophage colony-stimulating factor was active in these assays. Among cytokines that are active on human hematopoietic cells, gIL-3 thus has a distinct set of functions and may predict the range of actions of the human molecule.

Animals↗
PubMed1987

Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia.

The genes for the hemopoietic growth factors, GM colony-stimulating factor (CSF) and G-CSF have been cloned, and recombinant material is available for both. We tested these recombinant factors for their effects on the blast cells of acute myeloblastic leukemia (AML). Culture methods are available that support both colony formation by AML blasts and the growth of blast stem cells in suspension. Recombinant GM-CSF is active in both culture systems, although to a varying degree. We found that recombinant G-CSF was also effective; however, the two recombinant factors showed striking synergism for the stimulation of blast growth of cells from five of eight AML patients. In these cases, the combination was equivalent to the stimulating activity of supernatants from the continuous cell line 5637. This conditioned medium (HTB9-CM) is considered the standard for blast growth. Blasts from one of the patients grew without added factor. In another instance, recombinant GM-CSF alone was almost as effective as HTB9-CM. In the third case, both recombinant factors were active, but synergism was not observed and their combined effect was not equivalent to that of HTB9-CM. Both GM-CSF and G-CSF were active on normal bone marrow granulopoietic progenitors, but synergism was not observed. We conclude that the marked heterogeneity observed when AML blasts are examined by other criteria is also observed when their response to growth factors is evaluated.

Acute Disease↗
PubMed1987

Nursing diagnosis: ineffective coping. II. Planning care.

It has been the intent of this discussion to provide nurses with a model for understanding the coping process and a framework for planning interventions that can affect the stress-coping cycle in a variety of ways. The model also provides a framework for research that identifies effective nursing activities.

Adaptation, Psychological↗
PubMed1986

Pulsed Doppler echocardiographic study of left ventricular filling in dilated cardiomyopathy.

Patients with dilated cardiomyopathy (DC) have been reported to have abnormal left ventricular (LV) diastolic properties. To evaluate LV diastolic filling characteristics in patients with DC, pulsed Doppler echocardiography was used to study mitral flow velocity in 21 patients with DC and mitral regurgitation (MR), 12 patients with DC but no MR and 19 age-matched normal subjects. Diagnosis of MR was based on the Doppler echocardiographic finding of holosystolic turbulent flow in the left atrium. Peak mitral flow velocity in early diastole (PFVE) and during atrial systole (PFVA), PFVA/PFVE and deceleration half-time of early diastolic flow were measured from Doppler mitral flow velocity recordings. In 21 patients with DC and MR, PFVE (61 +/- 13 cm/s), PFVA (37 +/- 19 cm/s) and PFVA/PFVE (0.6 +/- 0.4) were not significantly different from PFVE (53 +/- 10 cm/s), PFVA (47 +/- 12 cm/s) and PFVA/PFVE (1.0 +/- 0.4) in normal subjects (p greater than 0.05). Deceleration half-time in DC patients with MR (62 +/- 32 ms) was shorter than normal (87 +/- 25 ms) (p less than 0.05). In contrast, PFVE (31 +/- 11 cm/s) was lower and PFVA/PFVE (1.7 +/- 0.8) was higher in the 12 DC patients without MR than in normal subjects and DC patients with MR (p less than 0.005). PFVA (46 +/- 8 cm/s) and deceleration half-time (88 +/- 33 ms) in patients without MR were not significantly different from normal mean values. Thus, abnormalities of peak diastolic mitral flow velocity were detected in DC patients without MR but not in DC patients with MR, suggesting that MR masks LV filling abnormalities in patients with DC.

Adult↗
PubMed1986

A simple Doppler echocardiographic method for estimating severity of aortic regurgitation.

Doppler echocardiography is useful for detecting aortic regurgitation (AR). To determine if the presence of retrograde holodiastolic flow in the abdominal aorta can be used to assess the severity of AR, abdominal aortic flow velocity was examined by pulsed Doppler echocardiography in 33 patients with AR and 10 patients without AR confirmed by aortography, and in 15 normal subjects. Among the 33 patients with AR, 15 had mitral regurgitation, 11 had mitral stenosis, 8 had aortic stenosis, 5 had prosthetic mitral valves, 4 had prosthetic aortic valves and 2 had aorticopulmonary shunts. No retrograde holodiastolic flow was found in the abdominal aorta of 15 normal subjects or 10 patients without AR. Of the 22 patients with 1+ or 2+ AR independently determined by injection of iodinated contrast into the aortic root, 21 did not have retrograde holodiastolic abdominal aortic flow, whereas all 11 patients with 3+ or 4+ AR had retrograde holodiastolic flow in the abdominal aorta. One patient with 1+ AR and a left-to-right aorticopulmonary shunt had retrograde holodiastolic flow in the abdominal aorta. The finding of holodiastolic retrograde flow in the abdominal aorta is useful for distinguishing patients with severe AR from those with mild or absent AR. Moreover, the method is easy to perform and results appear to be independent of the presence of other cardiac diseases except significant aorticopulmonary shunt.

Adolescent↗
PubMed1986

Triton X-114 phase separation of platelet membrane glycoproteins from normal subjects and a patient with type I thrombasthenia.

Surface-labelled normal and thrombasthenic platelets have been subjected to phase separation in Triton X-114. Triton-rich and Triton-poor fractions have been analysed by SDS-PAGE and IEF-SDS-PAGE. Partitioning characteristics of the major glycoproteins have been defined. The Triton-rich fraction contained GPIIb, III, IV, VI, VII, VIII, GP38 and the IIb beta subunit. In contrast, the Triton-poor fraction contained the HMWGP, GPIa, Ib, IIb, III, V and GPIX. Analysis of the platelet membrane glycoproteins of a patient with Type 1 thrombasthenia has been carried out using Triton X-114. The value of the method in diagnosis of this condition and differences between our findings and those published previously are discussed.

Blood Platelet Disorders↗
PubMed1986

Health effects of organic dusts in the farm environment. Report on prevention and control.

Means for reduction of dust control were summarized and priorities assigned to education and engineering control of farm equipment in the work on prevention. Personal protection equipment was reviewed and positive pressure respiratory helmets suggested for more extended use. A fuller characterization of exposure agents, such as peak levels and measurement of different particle sizes was recommended. For medical prevention, priorities should be given to establishment of health care delivery organizations, particularly for farmers, and to specific prevention measures which were discussed in connection with each disease entity. Recommendations for further research include development of new measuring techniques, assessments of new equipment and work practices, and establishment of additional information on dose-response relationships and etiologic agents causing lung disease.

Agricultural Workers' Diseases↗
PubMed1986

Effects of human recombinant CSF-GM and highly purified CSF-1 on the formation of multinucleated cells with osteoclast characteristics in long-term bone marrow cultures.

Several studies have suggested that the osteoclast is derived from a mononuclear precursor which is found in bone marrow. We have developed a system for studying the formation of osteoclast-like multinucleated cells in long-term bone marrow culture of baboon cells. Recombinant human CSF-GM and highly purified CSF-1, both of which stimulate the proliferation of monocyte/macrophage precursors, were found to increase the number of osteoclast-like cells formed in long-term bone marrow culture. CSF-GM stimulated multinucleated cell formation more consistently than CSF-1. The subsequent addition of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to cultures initially treated with CSF-GM or CSF-1 further increased multinucleated cell formation. Autoradiographic studies indicate that CSF stimulated multinucleated cell formation by increasing the proliferation of the precursor cell, and that the potentiating effect of 1,25-(OH)2D3 was caused by fusion of the increased numbers of precursors. These studies suggest that the interaction of locally produced colony-stimulating factors with circulating calcium regulating hormones may be important in the control of osteoclast formation and bone resorption.

Animals↗