Neutrophil transmigration: modulation by pentoxifylline and nitric oxide.
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Chemotaxis, Leukocyte↗
Biomedical subjects
S C Clark
Publications and source records attributed to S C Clark.
Action of human interleukin-4 and stem cell factor on erythroid and mixed colony formation by peripheral blood-derived CD34+ c-kit(high) or CD34+ c-kit(low) cells.
We studied the interaction of interleukin (IL)-4 and other burst-promoting activity (BPA) factors, such as IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-9 and stem cell factor (SCF), on erythroid burst-forming unit (BFU-E) and erythrocyte-containing mixed (CFU-Mix) colony formation in serum-free culture. IL-4 alone did not support mixed colony formation in the presence of erythropoietin (Epo). However, IL-4 showed weak but significant BPA when peripheral blood (PB)-derived CD34+c-kit(low) cells were used as the target population. The BPA of IL-4 was much weaker than that of IL-3, which exerted the most potent activity, as previously reported. When CD34+c-kit(high) cells were used as the target, four factors known to have BPA, IL-3, GM-CSF, IL-9 and SCF, could express BPA. In contrast, IL-4, alone failed to support erythroid burst formation. Interestingly, IL-4 showed a remarkable enhancing effect with SCF in promoting the development of erythroid burst and erythrocyte-containing mixed colonies from CD34+c-kit(low) and CD34+c-kit(high) cells. Delayed addition of SCF+Epo or IL-4+Epo to the cultures initiated with either IL-4 or SCF alone clearly demonstrated that SCF was a survival factor for both BFU-E and CFU-Mix progenitors. In contrast, the survival effect of IL-4 was much weaker than that of SCF, and appeared to be more important for progenitors derived from CD34+c-kit(low) cells than for those derived from CD34+c-kit(high) cells. It was recently reported that CD34+c-kit(low) cells represent a more primitive population than CD34+c-kit(high) cells. Taken together, these results suggest that IL-4 helps to recruit primitive progenitor cells in the presence of SCF.
Antigens, CD34↗
Spiking fevers with clozapine treatment.
Clozapine often causes low-grade fever and less frequently spiking fever. We describe three cases of spiking fever that occurred in the first 3 weeks of clozapine therapy. A new set of side effects of clozapine is identified, which includes spiking fever, respiratory and gastrointestinal symptoms, and neutrophilia. Possible mechanisms are discussed.
Adult↗
Solitary fibrous tumour of the diaphragm.
Solitary fibrous tumours are uncommon neoplasms that have been described as occurring in the pleura, peritoneum, lung, mediastinum, pericardium, nose and paranasal sinuses. This report describes the first known case of a solitary fibrous tumour of the diaphragm, occurring in a 60 year old woman with a two year history of respiratory symptoms. The lesion was initially misdiagnosed as an elevated left hemidiaphragm. The operative findings and histological appearance of the tumour are described. A review of the literature examines the various types and presenting features of solitary fibrous tumours as well as their clinical behaviour and postulated origin.
Diaphragm↗
A dominant negative granulocyte-macrophage colony-stimulating factor receptor alpha chain reveals the multimeric structure of the receptor complex.
The receptor for the hemopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) is composed of two chains, both of which belong to the superfamily of cytokine receptors. The alpha chain confers low affinity binding only, whereas the beta chain (betac) confers high affinity binding when associated with alpha. Ectopic expression of both chains of the receptor in murine NIH-3T3 fibroblasts results in signal transduction, mitogenesis, and morphologic transformation. The cytoplasmic domain of the GM-CSF receptor alpha subunit (GMR-alpha) comprises 54 amino acids that have been shown to be important for signal transduction through the beta chain. The present study was designed to address the possibility of receptor oligomerization and its functional implication. Cross-linking studies with 125I-GM-CSF on NIH-3T3 transfectants is consistent with the presence of alpha and betac dimers and of receptor oligomers. We have, therefore, generated an inert alpha chain through polymerase chain reaction-mediated truncation of 47 amino acids of the COOH-terminal domain of alpha (alphat), and coexpressed alphat, alpha, and betac in NIH-3T3. In cells in which alphat and alpha are present in stoichiometric proportion within the GM-CSF-binding complex, we provide evidence that alphat is dominant negative over wild type alpha on the basis of two different functional assays: cell proliferation and foci formation. Hence, our results suggest the requirement for at least two functional alpha chains for signal transduction. Together with the cross-linking studies, our data indicate that the functional GMR is an oligomer that contains at least two alpha chains.
3T3 Cells↗
Cellular and molecular mechanisms underlying IL-12-induced tumor regression.
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Animals↗
Does affective blunting in schizophrenia reflect affective deficit or neuromotor dysfunction?
Schizophrenia inpatients withdrawn from all neuroleptic medication were administered measures of affective blunting, diminished affective experience, and neuromotor dysfunction. The correlations among the measures provided support for the hypothesis that measures of affective blunting reflect both neuromotor and affective deficits. Because the interpretation of such measures is therefore ambiguous, measures of diminished affective experience may have greater validity in research on affective deficits in schizophrenia than measures of blunted affective expression.
Adult↗
Thrombopoiesis and thrombopoietin: the significance of "non-Tpo" cytokines.
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Blood Platelets↗
Vascular complications of lung transplantation.
BACKGROUND: The data on vascular anastomotic complications after single-lung and bilateral lung transplantation are scant. METHODS: We reviewed the data on our patients having single and bilateral lung transplantation to examine our experience and management of vascular anastomotic complications. RESULTS: We retrospectively identified 5 of 109 consecutive patients undergoing lung transplantation who had postoperative pulmonary arterial or venous obstruction. There were 4 women and 1 man (age range, 32 to 53 years). Three patients had left single-lung transplantation, 1 patient had right single-lung transplantation, and 1 patient underwent bilateral sequential lung transplantation. Complications comprised two right-sided and two left-sided pulmonary artery stenoses and one combined left pulmonary arterial and venous obstruction. Isotope perfusion scanning was used in 3 patients and suggested a vascular stenosis in all of them. Pulmonary angiography was used in each as a confirmatory test and to demonstrate anatomic details. Transesophageal echocardiography was used in 1 patient and did not detect a right pulmonary artery stenosis. One patient underwent revision of a pulmonary artery stenosis with a period of warm ischemia and subsequent fatal lung injury. Two revisions were undertaken on cardiopulmonary bypass with a cold blood flush to the transplanted lung. One venous anastomotic angioplasty with stent insertion was performed. Two patients died before treatment. All 5 patients died between 5 and 630 days postoperatively. CONCLUSIONS: Vascular complications carry a high mortality. Reoperation, preferably using cardiopulmonary bypass and a cold blood flush technique to avoid further lung injury, is recommended. In high-risk patients, dilation or stent insertion can be considered.
Adult↗
Medicolegal death investigator preemployment test development.
The medicolegal death investigator (MDI) represents an essential component in the multidisciplinary investigation of sudden and unexpected deaths. Presently there exists no specific program for the job training evaluation procedure for new (MDI) employees. We discuss the development of a medicolegal death investigator preemployment training tool, which consists of a training and evaluation program containing a list of tasks and task steps. After the investigator demonstrates the ability to perform individual tasks independently, the trainee will be objectively evaluated by the completion of a written test specifically designed to cover the task items. The preemployment test has been developed by those professionals best able to determine the job requirements, the death investigators. The specific outcomes of the process also include further definition of the profession, preemployment testing, policy and procedure development, posttraining evaluation, identification of training needs, curriculum design and further professional development, and identification of the profession of death investigator.
Aptitude Tests↗
The flt3 ligand supports proliferation of lymphohematopoietic progenitors and early B-lymphoid progenitors.
We have examined the effects of the murine ligand (FL) for the flt3/flk2 tyrosine kinase receptor on the proliferation of murine lymphohematopoietic progenitors as well as committed myeloid and B-cell progenitors. In the presence of erythropoietin, FL alone supported scant colony formation from enriched marrow cells of normal mice. However, when it was combined with interleukin-3 (IL-3), steel factor (SF), or IL-11, FL significantly enhanced colony formation. When tested on enriched marrow cells from 5-fluorouracil (5-FU)-treated mice, FL neither enhanced IL-3-dependent colony formation nor synergized with SF in support of colony formation. However, FL synergized with IL-6, IL-11, or granulocyte-colony stimulating factor (G-CSF) in support of formation of various types of colonies, including multilineage colonies. Approximately 30% of these colonies yielded pre-B-cell colonies when replated in secondary cultures containing SF and IL-7, indicating that 2-cytokine combinations, including FL and IL-6, IL-11, or G-CSF can support the proliferation of primitive lymphohematopoietic progenitors. FL, by itself and in synergy with IL-7 or SF, supported the proliferation of B-cell progenitors. These results show that FL has a wide range of activities in early hematopoiesis and B lymphopoiesis.
Animals↗
Effects of lethal irradiation and cyclosporin A treatment on the growth and tumoricidal activity of a T cell clone potentially useful in cancer therapy.
The TALL-104 cell line, originally derived from a patient with T cell leukemia, can be maintained indefinitely in culture in the presence of interleukin-2 (IL-2) and is endowed with a highly potent major-histocompatibility-complex (MHC)-non-restricted tumoricidal activity both in vitro and in animal models. The present study analyzes in detail the short- and long-term effects of irradiation and cyclosporin A (CsA) treatment on the growth and tumoricidal function of this T cell clone as compared to polyclonal lymphokine-activated killer (LAK) cell preparations from healthy donors. DNA and RNA syntheses by both TALL-104 and LAK cells were irreversibly arrested a few hours after irradiation with 40 Gy. However, 4-h 51Cr-release assays, performed on different days (day 1 to day 7) after irradiation, showed that the cytotoxic efficiency of TALL-104 cells against hematopoietic and solid tumor targets was only modestly reduced, whereas that of LAK cells was severely inhibited. Moreover, the cytotoxic responses to recombinant human IL-2 and IL-12, measured 18 h after irradiation and cytokine addition, were normal in the case of TALL-104 cells but were abolished in the case of LAK cells. Co-culture of IL-2- or IL-12-preactivated TALL-104 cells with a tumor target for 5 days in the absence of cytokines resulted in a lower efficiency of lysis, as compared to the non-irradiated effectors, especially if the initial stimulus was IL-12. These findings suggest the requirement of multiple cytokine stimulation for optimal expression of tumoricidal activity by lethally irradiated TALL-104 cells. CsA, while abrogating TALL-104 cell proliferation at the low dose of 0.5 microgram/ml, inhibited their cytotoxic function marginally only at high doses (100 micrograms/ml). By contrast, CsA reduced dose-dependently the cytotoxicity of LAK cells starting at very low doses (0.5 microgram/ml). CsA did not impair the ability of TALL-104 and LAK cells to produce interferon (IFN) gamma, tumor necrosis factor (TNF) alpha, and granulocyte/macrophage-colony-stimulatory factor (GM-CSF) in response to IL-2, IL-12, or tumor targets. Irradiation reduced drastically IFN gamma production by LAK, but not TALL-104 cells; release of TNF alpha and GM-CSF by either type of effector was inhibited by 10%-50%, depending on the stimulus. The high resistance and immunosuppressive drugs renders tis immortal T cell clone a potentially safe and effective reagent for new adoptive-transfer approaches to cancer in MHC-incompatible recipients.
Animals↗
Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-gamma and tumour necrosis factor-alpha in patients with myelodysplastic syndromes.
The effects of interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL-12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL-12 and/or IL-2 (type C response). All patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3- CD56+ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-gamma and TNF-alpha production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL-12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients.
Adult↗
Bilateral patellar tendon rupture secondary to repeated local steroid injections.
A case is reported of bilateral patellar tendon rupture in a fit man after a fall. He had a history of repeated local steroid injections into both tendons and histology confirmed steroid-induced changes. The history of repeated local steroid administration has to be implicated as the cause of this extremely rare injury in this patient, which can also be associated with hyperparathyroidism, systemic lupus erythematosus, diabetes and rheumatoid arthritis. All doctors performing repeated local steroid injections into the patellar tendon should be aware of the possible dangers of inducing tendon rupture and should ensure that the steroids are not delivered into its substance.
Adult↗
Oesophageal epiphrenic diverticulum: an unusual presentation and review.
Epiphrenic pulsion diverticula are rare and often asymptomatic. We describe a case presenting in an unusual fashion, and review the controversy over the management of this condition with regard to the requirement for myotomy and antireflux surgery. We believe that both procedures are necessary, but believe that both procedures are necessary, but optimal management strategies are unlikely to be resolved as the rarity of the condition precludes largescale prospective studies.
Diverticulum, Esophageal↗
Synergistic actions of stem cell factor and other burst-promoting activities on proliferation of CD34+ highly purified blood progenitors expressing HLA-DR or different levels of c-kit protein.
We studied the synergistic effects of stem cell factor (SCF) and other burst-promoting activities (BPAs) such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-9 on proliferation of human peripheral blood-derived highly purified progenitors. SCF, IL-3, GM-CSF, and IL-9 showed significant BPA when CD34+HLA-DR+ cells were used as the target population. IL-3 exerted the most potent BPA, and GM-CSF supported approximately 40% to 70% of the erythroid burst-forming units that are responsive to IL-3. SCF and IL-9 showed much weaker BPA than that of IL-3 or GM-CSF. Combinations of IL-3 with other BPAs did not show synergistic actions supporting erythroid-burst formation. However, GM-CSF showed a significant additive effect with IL-9 or SCF. When CD34+c-kithigh cells were used as the target, SCF showed a much stronger BPA. Also, a distinct additive effect between SCF and IL-3 or GM-CSF on erythrocyte-containing mixed colony formation was observed. On the other hand, when CD34+c-kitlow cells were used as the target, SCF, IL-3, and GM-CSF could express BPA. In contrast, IL-9 alone failed to support erythroid-burst formation. Because CD34+c-kithigh cells weakly expressed CD34 antigen, these cells appeared to be more mature progenitors than CD34+c-kitlow cells. These results suggest that IL-9 acts on more mature progenitors than those of SCF, IL-3, or GM-CSF and that the primary target of SCF is multipotential progenitors at the very early stage of development.
Animals↗
Negative regulation of early B lymphopoiesis by interleukin 3 and interleukin 1 alpha.
We recently developed a two-step methyl cellulose culture system for murine lymphohemopoietic progenitors that are capable of differentiation along the myeloid and B-lymphoid lineages. In this system, two-factor combinations, which include steel factor plus interleukin (IL) 6, IL-11, or granulocyte colony-stimulating factor effectively supported the lymphomyeloid potential of primary colonies. Interestingly, IL-3 could neither replace nor act synergistically with steel factor in maintaining the B-lymphoid potential of the primary colonies although the frequency of colony formation was the same with IL-3 and steel factor. We now report that addition of IL-3 or IL-1 alpha to a permissive system suppresses the B-lymphoid potential of primitive progenitor cells in primary culture in dose-dependent fashion. In vivo transfer of the primary colonies to scid mice confirmed the suppressive effects of IL-3 and IL-1 alpha. In addition, IL-1 alpha inhibited pre-B-cell colony formation in the secondary culture. Once pre-B-cell colonies had formed in secondary culture, neither factor affected the proliferation of the pre-B cells. These results suggest negative regulatory roles for IL-3 and IL-1 alpha in early stages of B lymphopoiesis.
Animals↗
Combinations of stem cell factor with other hematopoietic growth factors enhance growth and sensitivity to cytosine arabinoside of blast progenitors in acute myelogenous leukemia.
The blast progenitors in acute myelogenous leukemia grow in response to hematopoietic growth factors (HGFs), and their sensitivity to antileukemic drugs is influenced by HGFs. We report the effects of stem cell factor (SCF) on the growth and sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) of blast progenitors in acute myelogenous leukemia. SCF stimulated both colony formation and self-renewal of blast progenitors and, when used in combination with other HGFs, synergistic enhancement of colony formation was noted in 8 of the 15 patients examined. Cell fractionation studies demonstrated no unique growth dependency on SCF in either CD34+ or CD34- populations. Blast cells of patients that displayed synergistic growth enhancement with SCF displayed the highest Ara-C sensitivity when HGFs were used in combination with SCF. The tritiated thymidine suicide test (20-min exposure) revealed that the proportion of blast progenitors in the S phase of the cell cycle was highest when SCF and another HGF were simultaneously present, although 24-h exposure killed most or all of the blast progenitors. These data indicate that SCF enhances growth and sensitivity to Ara-C of acute myelogenous leukemia blast progenitors in a closely correlated fashion and that the cell cycle changes as well as other mechanisms are involved in the Ara-C sensitivity modulation by SCF.
Adolescent↗