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Biomedical subjects

M J Phillips

Publications and source records attributed to M J Phillips.

At least 127 records · Page 7Linked to original sources
PubMed1989

Effect of nedocromil sodium on neutrophil and eosinophil-induced epithelial cell desquamation in a human in vitro epithelial model.

A human amniotic epithelial membrane preparation was used as a model to study epithelial responses to neutrophils and eosinophils, obtained from normal subjects using Percoll density gradient methods, and activated by phorbyl myristate acetate (PMA). Incubation of activated neutrophils with the epithelial membrane resulted in epithelial cell desquamation, probably due to release of proteases. Activated eosinophils resulted in epithelial cell damage but no desquamation, an action that appeared to be mimicked by major basic protein (MBP). The addition of nedocromil sodium did not significantly inhibit neutrophil-induced epithelial cell desquamation. In one preliminary experiment, nedocromil sodium (10(-4) to 10(-5) mol/L) inhibited epithelial cell desquamation induced by a mixed population of eosinophils and neutrophils.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Phenotypic and molecular characterization of inducible human neuroblastoma cell lines.

Two new neuroblastoma (NB) cell lines, NUB-6 and NUB-7, were established from recurrent and primary NB tumours respectively and identified conclusively as NB by their phenotypic characteristics, catecholamine production and N-myc amplification. The cell lines could be distinguished on the bases of distinctive growth patterns in monolayer culture and semi-solid media (collagen gel and agarose), neurite formation and their response to four classes of growth and differentiation modulators. The NUB-6 cell line consisted of two distinct cell subtypes, small typical neuroblasts and larger spheroid-forming cells, while NUB-7 was homogeneously neuroblastic. Class-I agents (dibutyrl cyclic AMP [dbcAMP], butyrate, and papaverine) inhibited growth of both cell lines, while only dbcAMP stimulated the formation of short neurites by NUB-6 neuroblast cells in monolayer culture and collagen. Of the class-II agents (vitamins), retinoic acid inhibited growth of both cell lines and stimulated formation of long neurites by NUB-6 cells and NUB-7 cells in later passages. In contrast, vitamin E inhibited growth of NUB-6 and late-passage NUB-7, but stimulated early passage NUB-7. The class III agent (nerve growth factor) resembled vitamin E. The class-IV agents (interferons; rIFN-alpha 2a and rIFN-gamma 1) inhibited growth of both cell lines in monolayer culture and agarose, but stimulated NUB-6 neuroblasts and early passage NUB-7 cells to form long neurites. Thus phenotypically distinct NB cell lines were established in vitro and shown to be differentially influenced by various growth and differentiation modulators. The potent effect of IFN suggests a role for these modulators in NB behaviour in vivo.

Cell Aggregation↗
PubMed1988

Treatment of acute myeloid leukaemia with early intensive induction therapy.

Patients with primary acute myeloid leukaemia were treated with induction therapy consisting of daunorubicin 50 mg/m2 (days 1 and 2) and continuous cytosine arabinoside 400 mg/m2 (days 1-5) with a 7-10-day gap between courses. Consolidation therapy consisted of one further similar course and a final course of cytosine 1 g/m2 infusion (days 1-5). Patients were randomised to receive no further treatment or monthly maintenance therapy consisting of thioguanine 100 mg/m2 twice daily and etoposide 100 mg/m2 twice daily (days 1-5) alternating with CCNU 50 mg/m2 once to a total of 6 courses. 64 patients entered the study; median age was 54 years (range 18-74 years) and 51 patients entered complete remission (79.7%). Thirty-two patients completed consolidation and were randomised between maintenance therapy (n = 16) and no treatment (n = 16). 21 patients have relapsed with neither remission duration nor relapse rate being affected by maintenance therapy.

Adult↗
PubMed1988

Sinusoidal lining cell damage: the critical injury in cold preservation of liver allografts in the rat.

We have previously defined viability limits in a rat transplantation model. All liver allografts stored in a simple preservation solution (NaCl 0.9%, CaCl2 2 mM) at 4 degrees C for 4 hr or at 37 degrees C for 1 hr were viable upon transplantation, but all those stored at 4 degrees C for 8 hr or at 37 degrees C for 2 hr were nonviable. Only cold-preserved, nonviable livers showed increased vascular resistance, platelet trapping and an initially low, but then high, rise in aspartate transaminase (AST) upon reperfusion, all suggesting injury to the microcirculation, with secondary injury to the hepatocyte. In the present study, we investigated the morphological changes that occur in livers stored for the defined critical times, using light and electron microscopy after perfusion-fixation. Accurate and reproducible identification of specimens as belonging to viable or nonviable and warm- or cold-preserved could be made in this way. Preservation in the cold first resulted in reversible changes consisting of cellular swelling, alterations of intracellular organelles, and partial denudation of the sinusoidal lining (cold-preserved viable group). Later, under conditions of nonviable cold preservation, detachment of cell bodies of sinusoidal lining cells with nuclear changes and almost complete denudation of the sinusoidal lining was observed. Endothelial cells of larger vessels were only injured mildly. In contrast, under conditions of warm preservation, changes involving mitochondria and later nuclei were found in hepatocytes, and blebbing was more extensive. Endothelial cells were spared relatively. We also examined livers stored in isotonic citrate solution at 4 degrees C for 8 hr and 16 hr, the critical times determined for this solution in another model of rat liver transplantation. The findings were very similar to storage in saline with respect to the changes in the sinusoidal lining cells after cold preservation for the two critical times. The results provide convincing evidence of a qualitative difference between warm and cold preservation injury, with relatively selective damage to hepatocytes or sinusoidal lining cells, respectively. Endothelial damage represents the primary event, resulting in the loss of organ viability following hypothermic storage. Thus morphology may serve as a useful viability marker after preservation.

Animals↗
PubMed1988

Effect of RBCs on the activation of human complement by heparin-protamine complexes.

Complement activation on red cells by heparin-protamine complexes was studied by using whole human serum. C3 bound to red cells was measured by radiolabeled monoclonal antibody to C3, and fluid-phase C5a was determined by radioimmunoassay. Heparin and protamine in clinically relevant concentrations caused the binding of C3 to red cell membranes, and the measurement of C3 binding provided a sensitive indicator of complement activation produced by these complexes. Complement activation by these reagents occurred at concentration ratios of protamine and heparin at which protamine neutralized the anticoagulant effect of heparin. Heparin-protamine complexes appeared to bind to red cells and produce complement activation by the classic pathway. C5a generation with heparin-protamine complexes in serum was greatly enhanced in the presence of red cells and increased with increasing red cell concentration. This enhancement of complement activation in the presence of red cells was also seen as measured by depletion of available C3 hemolytic complement units in the fluid phase. Thus red cells seem to play an important role in activation of complement by heparin-protamine complexes.

Complement Activation↗
PubMed1987

Lectin histochemistry of Wilms' tumor. Comparison with normal adult and fetal kidney.

The lectin histochemical staining patterns of nine surgically resected Wilms' tumors (WIT) (five classical, one rhabdomyomatous, one monomorphic tubular, and two blastematous) and four WIT heterotransplants in nude mice were compared with those of six normal adult and fetal kidneys using 11 biotinylated and fluorochrome-labeled lectins representing a spectrum of sugar specificities. Tubular epithelial cells of fetal and adult kidney demonstrated a complex pattern of glycosubstances, as detected by staining with most of the lectins. The dysplastic tubules of WIT and WIT heterotransplants resembled distal convoluted tubules and collecting ducts of adult kidney, as detected by staining with lectins that reacted exclusively with these portions of the nephron. A simpler lectin affinity profile was observed with blastema of normal fetal kidney and blastema of WIT and WIT heterotransplants. Thus, fetal, adult, and tumor tubules and fetal and tumor blastema resemble each other in terms of lectin binding patterns.

Adult↗
PubMed1987

Histamine and allergen induced changes in nasal airways resistance measured by anterior rhinomanometry: reproducibility of the technique and the effect of topically administered antihistaminic and anti-allergic drugs.

1. Changes in nasal airways resistance (NAR) following the topical application of histamine and allergen solutions were measured by passive anterior rhinomanometry. 2. The repeatability of five consecutive measurements of resting NAR prior to provocation with histamine or allergen (expressed as the coefficient of variation) was 32.8% and following instillation of saline control solution 37.2%. 3. The repeatability of five consecutive measurements of NAR during the nasal obstruction produced by histamine and allergen was similar to that recorded prior to provocation; the coefficients of variation (median values) being 39.6% and 33.1% respectively. The degree of variability was not related to the dose of agonist or the degree of nasal obstruction. 4. The reproducibility of histamine or allergen induced changes in NAR on four separate weekly occasions showed no significant intra-subject differences. 5. The effects of sodium cromoglycate (SCG), clemastine and ketotifen administered to the nasal mucosa 30 min before provocation with histamine and allergen were compared in a random order, double-blind, placebo controlled study. 6. Clemastine and SCG, but not ketotifen, significantly inhibited the nasal response to increasing concentrations of histamine. None of the drugs administered in the concentrations used in this study significantly inhibited the nasal response to allergen.

Administration, Topical↗
PubMed1987

Perinatal hemochromatosis. Clinical, morphologic, and quantitative iron studies.

Three sibling and two isolated-case perinates (4 newborn, 1 stillborn) died with siderotic cirrhosis and widespread parenchymal siderosis, the latter similar to that seen in both hereditary and secondary hemochromatosis. Reticuloendothelial siderosis was absent, as occurs in primary hemochromatosis. Studies of iron metabolism were performed antemortem in two of the siblings and ante-, post- and internatally in their mother, who showed hyperferremia antenatally. The only finding in the affected family suggestive of hereditary hemochromatosis was the commonly associated HLA haplotype (A3, B7) in the mother and an infant. Liver morphology, including immunocytochemistry and ultrastructure, was similar in the 5 infants and suggested that liver disease commenced as massive necrosis in midfetal life. Histologic grading and chemical assays for iron and copper on liver and spleen of the 5 index cases were compared with 26 controls; placentas were compared with 12 control placentas. Hepatic iron concentration, but not hepatic copper concentration, was significantly increased in index cases, compared with controls. Hepatic iron to copper ratio was significantly increased in index cases, compared with controls, but this ratio was unaltered in spleen and placenta. Total hepatic iron, but not total hepatic copper, was significantly increased in index cases, compared with a subgroup of 11 controls of low gestational age, similar to the fetal stage when liver disease commenced in utero. The results suggest that, irrespective of the fetal liver disease being genetic or acquired, hepatic iron overload was directly involved in pathogenesis.

Copper↗
PubMed1987

Cholestasis: surgical pathology, mechanisms, and new concepts.

This report has attempted to describe concisely the main diagnostic morphological features seen in cholestasis and to explain them mechanistically. The number of clinical conditions in which cholestasis can be found is extremely large and varied, so that no single mechanism explains all cases; in fact, multiple factors are operative in frequent instances. Currently used terminology and concepts are explained. The report is not intended to be comprehensive but is intended to deal with the most common types of cholestasis and with those in which recent advances in new knowledge have been made. The first step, in all cases, is to try to localize the site of obstruction, so an anatomic classification of cholestasis is offered as being most helpful, both in diagnostic work and in consideration of the mechanisms involved. In selecting the cases for special consideration, a personal bias is introduced but is unavoidable. The discussion of canalicular cholestasis is particularly abridged because many of the mechanisms proposed, including the two that are briefly discussed, are still the subject of ongoing investigation but are included because they are illustrative of current concepts in the field.

Abnormalities, Multiple↗
PubMed1986

Three-dimensional observation of the intrahepatic lymphatics by scanning electron microscopy of corrosion casts.

The three-dimensional arrangement of intrahepatic lymphatics was demonstrated in the rabbit liver by scanning electron microscopy of corrosion casts. These casts were prepared by injecting resin into the common bile duct at a pressure that caused resin to leak from the bile ducts in the small portal tracts and drain into the lymphatics. The lymphatic channels were composed of straight vessels and anastomosing short side branches. The anastomoses were especially rich at the bifurcation of the portal tracts and formed a network. The terminal branches were blind-ended. Constrictions suggesting valves were occasionally observed.

Animals↗
PubMed1986

Ultrastructural and cytophotometric studies of lectin binding by human pulmonary macrophages from asthmatic and normal subjects.

Pulmonary macrophages from normal subjects and asthmatic patients were examined for the presence of sugar residues on their surface. The technique of bronchoalveolar lavage was employed to obtain cell samples. Ultrastructural and cytophotometric methods were used for studying the patterns of lectin binding by these two groups of macrophages. Three lectins, Concanavalin A (Con A), Wheat germ agglutinin (WGA) and Ricinus communis agglutinin (RCA), were used in this investigation. Pulmonary macrophages from both normal and asthmatic persons revealed a high level of Con A, WGA and RCA binding. The distribution of the electron dense reaction product on the macrophage surfaces was relatively uniform. Quantitative cytophotometric studies showed that the level of binding of Con A by macrophages from both groups was approximately the same. Similar results were obtained with WGA--the difference between macrophages from normal and asthmatic persons was not statistically significant. In the case of RCA, macrophages from asthmatic patients showed a higher level of lectin binding than macrophages from normal persons. The conclusion is made that macrophages from asthmatic persons have more D-galactose residues on their surface.

Adolescent↗
PubMed1986

Spindle and histiocytoid (epithelioid) hemangioendothelioma. Primary in lymph node.

A 52-year-old woman presented with a solid spindle cell primary tumor of the lymph node. On light microscopic examination, mitoses and cellular atypia were absent. Electron-microscopic studies showed endothelial cell differentiation. Intracytoplasmic localization of Factor VIII-related antigen was demonstrated by the immunoperoxidase method, which confirmed the endothelial origin of the tumor. Seven-and-a-half years after the resection of this tumor, the patient is alive with no evidence of disease.

Female↗