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Biomedical subjects

R Peck

Publications and source records attributed to R Peck.

At least 19 recordsLinked to original sources
PubMed1992

[Injuries from mines].

In autumn 1991, 157 patients injured by mine explosions were taken care of by a Norwegian military medical unit attached to the United Nations mission in the demilitarized zone between Iraq and Kuwait. 146 of the patients were seen during a three week period of Iraqi mine harvesting in the desert. The detachment worked according to the principles of a second echelon surgical installation. The patients were operated upon if necessary, stabilized and evacuated to Iraqi hospitals. 20 patients in all (13%) died primarily. Four of 109 patients evacuated to the field hospital died (4%). 68 patients had major amputations, in seven of them two extremities were blown off. One patient had an open chest wound, two had tracheal puncture wounds, and one had penetrating head injury. 27 patients had eye injuries, 13 of which were penetrating. 64 major surgical procedures were performed. When evacuation times are long after mine injuries, approximately six hours, almost only patients with injuries to the extremities can be expected to reach hospital for treatment. The pattern of injury was regular, with crushed extremities, amputations and damaged eyes.

Adult↗
PubMed1992

Inhibition of proliferation by retinoids, cytokines and their combination in four human transformed epithelial cell lines.

Various combinations of retinoids and cytokines were examined for their synergistic effect on inhibition in proliferation of four human transformed epithelial cell lines, MCF7 (mammary carcinoma), SCC4, SCC15 and A431 (squamous cell carcinomas). Synergism depended on the cell line tested, to some degree on the specific retinoid but particularly on the type of cytokine used. IFN alpha had the widest spectrum of activity. IFN gamma, TNF-alpha, IL-1, EGF and TGF-beta also exerted a synergistic effect on proliferation inhibition in certain cell lines, whereas G-CSF was inactive. Association of retinoids and cytokines represents a new approach to antitumor chemotherapy.

Breast Neoplasms↗
PubMed1991

Antiproliferative activity of retinoids, interferon alpha and their combination in five human transformed cell lines.

Tretinoin, isotretinoin and acitretin were examined for their capacity to modulate the proliferation of the cell lines: HL-60 (acute promyelocytic leukemia), MCF7 (mammary carcinoma), SCC4, SCC15 and A431 (squamous cell carcinomas). Retinoids inhibited proliferation to a varying extent in all 5 cell lines. The cytokine IFN alpha had a significant antiproliferative effect only on HL-60, SCC4 and SCC15. The combination of retinoids with IFN alpha led in all 5 cell lines to a more profound reduction in proliferation than either retinoids or IFN alpha alone.

Acitretin↗
PubMed1991

The principal tumor necrosis factor receptor in monocyte cytotoxicity is on the effector cell, not on the target cell.

Several tumor target cell lines, prototypically K562 cells, are resistant to lysis by recombinant tumor necrosis factor (TNF alpha) but are killed by monocytes expressing membrane-associated TNF, suggesting that membrane TNF could account for monocyte-mediated cytotoxicity. Formaldehyde-fixed monocytes or extracted monocyte membrane fragments are cytotoxic to K562 target cells. Treatment of monocytes with interferon-gamma (IFN-gamma) increases cytotoxicity by live and fixed cells or by extracted monocyte membranes. Both TNF and TNF receptors are detectable on monocyte membranes by FACS analysis, and the levels of each are modulated by treatment with IFN-gamma. Cytotoxicity can be inhibited by either anti-TNF or anti-TNF receptor antibodies. Incubation of effector cells with exogenous soluble TNF prior to fixation or membrane preparation increases their cytotoxicity. In contrast, incubation of the target cells with exogenous TNF neither increases nor decreases killing by effector cell membrane fragments or intact effector cells. The data suggest that the TNF receptors on the effector cell, but not on the target cell, play a crucial role in TNF-mediated cytotoxicity.

Cytotoxicity, Immunologic↗
PubMed1991

Potentiation of retinoid-induced differentiation of HL-60 and U937 cell lines by cytokines.

Retinoids varied in their capacity to induce differentiation in HL-60 cells in this order: Ro 13-6307, tretinoin, isotretinoin, acitretin and Ro 13-7410 (high to low). In contrast, retinoids lacking a polar carboxylic acid, such as temarotene and Ro 14-6113, were inactive. Various cytokines had no differentiation-inducing effect by themselves. However, the addition of cytokines to retinoids increased differentiation. Combined with tretinoin, cytokines increased differentiation in this order: interferon (IFN) gamma, granulocyte colony-stimulating factor, interleukin-1 alpha (IL-1 alpha), IL-4, tumour necrosis factor alpha and IFN-alpha. Combination of cytokines with isotretinoin, acitretin, Ro 13-7410, and Ro 13-6307 showed a similar pattern of potentiation to that of tretinoin. Temarotene or Ro 14-6113 did not induce differentiation, alone or with cytokines. Combinations of cytokines were not synergistic in the presence of retinoids; antagonism was even observed. In U937 cells, lower levels of differentiation-induction were observed. Potentiation of the differentiation-inducing effect of retinoids by cytokines might indicate a clinical differentiation therapy of tumours.

Cell Differentiation↗
PubMed1991

Modulation of human immune functions in vitro by temarotene and its metabolite.

The arotinoid temarotene (Ro 15-0778) and its metabolite Ro 14-6113 were examined in a variety of in vitro assays quantitating parameters of human immune functions. Both immunosuppressive and immunostimulatory activities of these compounds were identified. These activities were compared with those of the known immunomodulatory compound ciclosporin A (CsA) at concentrations corresponding to clinically effective plasma concentrations. Like CsA, Ro 14-6113 inhibited the mitogen- or alloantigen-induced proliferation of T cells as well as their capacity to secrete interleukin-2 (IL-2), interferon-gamma and tumor necrosis factor alpha. Ro 15-0778 showed no activity in inhibiting cytokine secretion and was considerably less effective than Ro 14-6113 in inhibiting T cell proliferation. Ro 14-6113 was more effective than CsA in inhibiting IL-2 receptor expression. Ro 14-6113 modulated both positively or negatively the proliferation of B cells, depending on the concentration. Ro 14-6113 inhibited the secretion of IgM, IgG, and IgA, while stimulating IgE secretion. A different profile of activity for Ro 14-6113 and CsA was observed, suggesting differing effectiveness in immunologically mediated diseases.

B-Lymphocytes↗
PubMed1991

Pectoralis major myocutaneous flap reconstruction in head and neck surgery--experience with 60 cases.

The aim of this paper is to evaluate the results of the use of the pectoralis major myocutaneous flap for reconstruction in 60 otolaryngology--head and neck patients over a five year period. There were 52 patients with Stage III (30%) and Stage IV (70%) untreated squamous cell carcinomas. Of the eight recurrent tumours, three patients had nasopharyngeal carcinoma with extensive post-radiation neck failures requiring extended neck dissections and flap reconstruction. The oral cavity and oropharynx were the predominant sites for reconstruction accounting for 70% of the operations performed. Twenty-eight patients had composite resections, ten with pectoralis osteo-myocutaneous flap incorporating a vascularised split sternum bone graft and titanium plate fixation for immediate mandibular reconstruction. All 52 patients underwent post-operative radiation. Major necrosis did not occur but minor tip necrosis of the skin island occurred in two cases (3%). The mean hospitalisation was 19 days for all patients and 21 days for patients with composite resections. The pectoralis major myocutaneous flap in our experience is not only a versatile flap but also a very reliable and robust flap for single stage immediate head and neck reconstruction.

Adult↗
PubMed1989

Gamma interferon induces monocyte killing of Listeria monocytogenes by an oxygen-dependent pathway; alpha- or beta-interferons by oxygen-independent pathways.

Human peripheral blood monocytes purified by counterflow centrifugal elutriation were treated with recombinant interferons-gamma (IFN-gamma), alpha (IFN-alpha), or beta (IFN-beta)--and tested for their capacity to kill Listeria monocytogenes. All three IFNs increased the monocyte bactericidal activity in a dose-dependent fashion. Exogeneous catalase, an inhibitor of monocyte-generated hydrogen peroxide, did not affect bactericidal activity. However, exogenous superoxide dismutase inhibited killing by IFN-gamma-activated monocytes, but not by IFN-alpha- or IFN-beta-activated monocytes. By contrast, exogenous soybean trypsin inhibitor inhibited killing by IFN-alpha or IFN-beta-activated monocytes, but not by IFN-gamma-activated monocytes. Combinations of IFN-gamma and IFN-alpha resulted in no increase in bactericidal activity. Finally, treatment with IFN-gamma resulted in different receptiveness of the cell to subsequent oxidative burst-stimulating signals than did treatment with either IFN-alpha or IFN-beta. These results suggest that monocytes treated with IFN-gamma kill L. monocytogenes by an oxygen-dependent mechanism, but treatment with IFN-alpha or IFN-beta elicits principally oxygen-independent mechanisms.

Blood Bactericidal Activity↗
PubMed1989

Cell surface tumor necrosis factor (TNF) accounts for monocyte- and lymphocyte-mediated killing of TNF-resistant target cells.

WEHI164 cells are susceptible to cytotoxicity by soluble recombinant or monocyte-derived TNF alpha, as well as to cell-mediated cytotoxicity by monocytes or lymphocytes. In contrast, K562 cells are resistant to lysis by soluble recombinant or natural TNF alpha, but are killed by monocyte or lymphocyte effector cells. Cell-mediated cytotoxicity against both target cell lines is enhanced by treatment of monocyte effector cells with recombinant interferon gamma or lymphocyte effector cells with interleukin-2. However, treatment of monocytes with LPS, or of lymphocytes with PHA, although inducing secretion of soluble TNF alpha in the medium, does not increase cell-mediated cytotoxicity. Anti-TNF alpha neutralizing antibodies partially inhibit monocyte- as well as lymphocyte-mediated cytotoxicity against WEHI164 and K562 cells. Formaldehyde-fixed effector cells are cytotoxic to both target cell lines. Cytotoxicity by fixed effector cells can be inhibited by anti-TNF alpha antibodies. The extent of cell-mediated cytotoxicity induced by treatment of effector cells with stimulators prior to fixation corresponds to the expression of TNF on monocyte membranes, but not to the titers of secreted TNF. The data suggest that membrane-associated TNF alpha may be a mechanism of human monocyte- as well as lymphocyte-mediated cytotoxicity, regardless of whether the target cells are sensitive or insensitive to soluble TNF.

Animals↗
PubMed1989

Nerve growth factor induces growth and differentiation of human B lymphocytes.

Nerve growth factor (NGF) is known to affect peripheral sympathetic and sensory neurons as well as defined populations of neurons in the central nervous system. This paper presents evidence that NGF is also active in modulation of B-cell-mediated immune responses. NGF receptors were immunoprecipitated from highly purified human B-cell populations, and to a lesser extent, from T-cell populations, by using a monoclonal antibody recognizing NGF receptors present on neural cells. NGF receptors were also detected in significant amounts in human spleen and lymph node tissue. In addition, NGF induced a dose-dependent increase in B-cell DNA synthesis as determined by incorporation of [3H]thymidine. This B-cell growth-promoting activity was inhibited by a neutralizing anti-NGF monoclonal antibody. Immunoglobulin secretion, principally affecting IgM synthesis, was also modulated by NGF. The concentrations that affected B-cell proliferation are consistent with the presence of functional high-affinity NGF receptors. The results suggest that NGF, in addition to its neurotrophic function, also acts as an immunoregulatory cytokine.

Antibodies, Monoclonal↗
PubMed1989

Persistent high fever and gall-bladder wall thickening in a child with primary Epstein-Barr viral infection.

A 3.5 year old girl presented with a history of high fever, rigors, and mild cough for 1 week. Physical examination revealed normal chest findings but gross hepatomegaly was detected. Liver function tests were abnormal and indicated biliary obstruction. Ultrasonography revealed a distended gall-bladder with increased wall thickness up to 0.6 cm. The diagnosis of primary Epstein-Barr viral infection was eventually made by specific serological study. The patient's fever subsided 2 weeks later and her liver function tests returned to normal 1 month later. Abdominal ultrasonography at this time was normal.

Acute Disease↗
PubMed1988

Immunocytochemical studies on the basal ganglia and substantia nigra in Parkinson's disease and Huntington's chorea.

The basal ganglia and substantia nigra, taken from control human brain and from patients dying with a diagnosis of Parkinson's disease or Huntington's chorea, were analysed with histochemical and biochemical techniques. The pigmented neurons of the substantia nigra pars compacta possess tyrosine hydroxylase immunoreactivity and are disposed in three major layers, alpha, beta and gamma. This pattern became obscured in choreic brains by the severe shrinkage of the nigra, but total numbers of pigmented neurons were within the normal range. In contrast, pigmented neurons were lost from all layers of the substantia nigra in Parkinson's disease, although examination of cases with minimal cell loss suggested that an internal part of the lateral alpha sub-layer was most severely and consistently affected. A dopaminergic projection between this internal part of the alpha sub-layer and the putamen was suggested by the preferential loss of catecholamines from the putamen in Parkinson's disease. The distribution of the peptides, substance P, methionine-enkephalin and dynorphin 1-17 were mapped immunohistochemically within the substantia nigra. The different patterns of immunoreactive axons and terminals were found to be extensive, at least partially overlapping, and largely avoided the region of the pigmented perikarya of the alpha sub-layer and nucleus paranigralis. All peptides were depleted in choreic substantia nigra, reflecting the degeneration of the striatonigral pathway. However, concentrations of enkephalin-like immunoreactivity were increased within the interpeduncular nucleus. In Parkinson's disease there was a loss of enkephalin- and dynorphin-like immunoreactivity from the substantia nigra but a fall in substance P-like immunoreactivity was only detected by radioimmunoassay, not by immunocytochemistry. Peptide immunoreactivity was also reduced within choreic basal ganglia. However, no gross changes were found in peptide staining of the parkinsonian basal ganglia. In summary we have reported a number of changes in peptide-containing pathways in human degenerative disorders that may reflect the degeneration of neuronal pathways either as a primary event or secondary to initial lesion. We have also emphasized the sensitivity of the alpha sub-layer of nigral neurons to damage in Parkinson's disease. We suggest that the lower density of peptidergic fibres in the area of the perikarya may contribute to the susceptibility of these neurons to damage.

Adult↗
PubMed1987

Neuropeptides modulating macrophage function.

The immune system and the neuroendocrine system affect each other via molecules and receptors shared by both systems. Neuroendocrine hormones may act either positively or negatively in regulating the activities of a key cell of the immune system, the macrophage. For example, adenocorticotropic hormone (ACTH), somatostatin, and substance P are all capable of increasing the cytotoxicity of macrophages against tumor cells. However, ACTH and somatostatin, but not substance P, can also block the tumoricidal activity of macrophages induced by recombinant gamma interferon (IFN-gamma), a non-neuroendocrine immunomodulating hormone. In contrast, substance P increased tumoricidal activity, both independent of IFN-gamma and in addition to IFN-gamma. Neurotensin, alpha-endorphin, beta-endorphin, met-enkephalin, vasopressin, and substance K did not affect tumoricidal function, either alone or in combination with IFN-gamma. Substance P, but not the other neuropeptides, increased substantially the proportion of macrophages able to secrete superoxide ions, suggesting a possible influence on macrophage capacity to deal with microbial infection. Such positive and negative modulation of macrophage effector functions could contribute to the influence of cognitive stimuli in infection and neoplasia.

Adjuvants, Immunologic↗
PubMed1987

Recombinant interferons or interleukin-2 increase cytotoxicity by human monocytes and NK cells.

Human peripheral blood monocytes and NK cell enriched lymphocytes were purified by counterflow centrifugal elutriation. The cell populations were characterized by surface marker analysis using monoclonal antibodies. A variety of molecules were found to be capable of activating monocytes and NK cells to enhanced tumoricidal activity. Tumoricidal activity was evaluated using a colorimetric microassay. Numbers of tumor cell targets surviving exposure to monocytes or NK cells were calculated by computer analysis of colorimetric data derived by target cell-dependent dye reduction. The results indicated that monocyte effector cells were cytotoxic to the NK sensitive K562 cell line and to the monocyte sensitive TU5 line. Depletion of NK contaminants from the monocyte population by complement mediated cytolysis did not affect the capacity of the monocytes to kill either target. Monocyte mediated cytotoxicity was enhanced by treatment of the monocytes with recombinant IFN-alpha, IFN-beta, or IFN-tau; each in a dose-dependent manner. Simultaneous treatment of monocytes with IFN-alpha and IFN-tau resulted in additive but not synergistic effects. NK cell cytotoxicity was enhanced by treatment with IL-2 or IFN-tau. Enhancement of monocyte and NK cell cytotoxicity by IFN or IL-2 was dependent upon the time in culture of the effector cells, the duration of the effector phase, and the effector to target cell ratio. IFN or IL-2 treatment alone did not reduce target cell viability. The results suggest that monocytes as well as NK cells are capable of providing a natural defence against neoplasia, that monocytes can kill NK targets and NK cells can kill monocyte targets, and that these cytotoxic activities are enhanced by IFN or IL-2.

Cell Line↗
PubMed1986

An assay for macrophage activating factor based on the adherence of oil-elicited guinea pig macrophages: characterization of a lymphokine-induced release of hydrogen peroxide from elicited macrophages.

A convenient procedure is described for assaying guinea pig macrophage activating factor (MAF) in lymphokine preparations. The assay utilizes oil-elicited peritoneal macrophages from strain 2 guinea pigs and measures the capacity of macrophage cultures pretreated with lymphokine or medium to release hydrogen peroxide (H2O2) in the presence and absence of phorbol myristate acetate (PMA). The PMA-induced release measures a maintenance of macrophage adherence and activation. A novel aspect is a lymphokine-dependent release of H2O2 which occurs in the absence of PMA and which differs from the PMA triggered release. The differentiation process into lymphokine responsive cells has been studied using macrophages elicited from 2-21 days after oil injection. In addition macrophage responsiveness was examined in different strains of guinea pigs.

Animals↗
PubMed1985

A one-plate assay for macrophage bactericidal activity.

Human peripheral blood monocytes purified by counterflow centrifugal elutriation (CCE) showed an enhanced capacity to kill Listeria Monocytogenes and Staphylococcus aureus after activation with interferon-gamma (IFN gamma). Bactericidal activity was evaluated by a rapid colorimetric microassay based on the reduction of a tetrazolium dye, MTT. The amount of dye reduced was directly proportional to the number of viable bacteria present in each microwell. Comparison with a bacterial titration plate containing serial dilutions from stock of a known titer allowed calculation of bacterial numbers before and after exposure to macrophages. Results were read in a multiscan plate reader and compared closely with those obtained by serial dilution on agar plates (i.e., colony counts). The entire assay, i.e., culturing the monocytes, treatment with IFN gamma, addition of the bacteria, and quantitation of surviving viable bacteria, was performed in a single microtiter plate.

Blood Bactericidal Activity↗