Role of Central Interleukin-1β in Gastrointestinal Motor Disturbances Induced by Lipopolysaccharide in Sheep

Cytokines are involved in the symptoms of theacute phase response induced by infectious diseases inhumans as well as in animals, and interleukin-1(IL-1 ) has a pivotal role in these changes. The role of central IL-1 in the gastrointestinalhypomotility and fever evoked by intravenousadministration of lipopolysaccharide (LPS) and themechanisms involved, were investigated in sheep as anexperimental model. LPS (0.1 g/kg, intravenously)induced gastrointestinal hypomotility and fever thatwere significantly reduced by priorintracerebroventricular administration of IL-1receptor antagonist protein (IL-1ra, 2 g/kg). The effects of LPS were mimickedby intracerebroventricular IL-1 (50 ng/kg),whereas IL-1 injected intravenously at the samedose only caused a slight and transient fever withoutmodifying the gastrointestinal motility. Priorintracerebroventricular administration of thecyclooxygenase inhibitor indomethacin (100 g/kg) butnot the corticotropin-releasing factor (CRF) receptorantagonist -helical CRF_9-41 (5 g/kg) blocked alleffects evoked by both LPS and IL-1. These resultssuggest that in sheep, LPS induces digestive motordisturbances through a central release of IL-1 andprostaglandins.     

A Three-dimensional Analysis of Blood Vessels in Bronchioloalveolar Carcinoma

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 m thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08±1.10 m, 3.95±1.02 m, 5.04±1.56 m, and 6.11±2.23 m, the circumferences of those vessels seen as complete circles were 43.11±12.78 m, 43.71±12.87 m, 95.21±39.32 m, and 126.77±54.65 m; the lengths between vessel bifurcations were 13.28±3.08 m, 13.47±4.58 m, 24.91±9.66 m, and 41.82±28.08 m in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.     

Increased Expression of Transforming Growth Factor-β1 During Gastric Ulcer Healing in Rats

This study was done to investigate theexpression and localization of transforming growthfactor-₁ (TGF-₁) inthe gastric ulcerated tissues produced by acetic-acidduring the healing process, by northern blot analysis and immunohistochemicaltechnique. Ulcerated TGF-₁ mRNA levelswere significantly increased from days 3 to 18, in asimilar manner to extracellular matrix proteins, andreturned to control levels at the scarred phase.Immunoreactive TGF-₁ was localized inepithelial cells beneath proliferative zone in intacttissues. 1 In ulcerated tissues, TGF-₁was localized in macrophages in the ulcer bed and in fibroblasts ormyofibroblasts in the granulation tissues. Treatmentwith prostaglandin E₁ (PGE₁)further stimulated ulcerated TGF-₁expression, being associated with the acceleration of gastric ulcer healing, while treatment withindomethacin reduced TGF-₁ expression,being accompanied by the delayed ulcer healing. Thecombination of PGE₁ and indomethacin reversedthe indomethacin-induced decrease in ulcerated TGF-₁.Thus, TGF-₁ may be implicated in theacceleration of gastric ulcer healing.     

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n=7; E-LAVAGE, n=5) or bolus (I-BOLUS, n=8; E-BOLUS, n=5), or went untreated (CONTROL, n=4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO₂ were observed in the lavage groups compared to the bolus groups and the controls. PaO₂ (mmHg) at 240 min posttreatment: I-LAVAGE=297±54, E-LAVAGE= 280±57; I-BOLUS=139±31; E-BOLUS=152±29; C=119±73 (mean± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.     

An evaluation of gastric hypothermia

Conclusions Gastric cooling is an acceptable, sustaining procedure beneficial in the control of upper gastrointestinal bleeding of known or obscure origin. In its present mode of application, gastric freezing is not entirely satisfactory for management of intractable duodenal ulcer. This technic inconsistently alters symptoms of ulcer, causes acute gastric mucosal damage, and may so influence some factor related to ulcer diathesis as to provide adjunctive therapy. Gastric freezing is deserving of further evaluation and development under more rigidly controlled circumstances.This study was supported by grants AM-07624 and AM-07539 from the National Institute of Arthritis and Metabolic Diseases, Bethesda, Md.Presented at a postgraduate course. Current Therapy in Gastroenterology. (Nov. 16–17, 1963) sponsored by Louisiana State University School of Medicine, New Orleans. La.Trainee in gastroenterology under a grant from the National Institute of Arthritis and Metabolic Diseases.     

Prognostic significance of the heterogenous expression of IgG Fc receptors in B-cell chronic lymphocytic leukemia

Summary Receptors for the Fc part of IgG (FcR) are expressed in three forms on peripheral blood lymphocytes. The presence of the releasable form (FcR_REL.) as well as of the two nonreleasable forms with lower (FcR_LOW) and higher (FcR_HIGH) cellular avidity was correlated with survival in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL). High percentage of cells with FcR_LOW as well as high absolute number of cells carrying the two nonreleasable forms of FcR were connected to unfavorable prognosis. Combining these three parameters, an FcR constellation was defined which pointed to a favorable prognosis (in 24 patients) when all three parameters were low, but detected short survivors when all three data were high (in 14 patients). The FcR constellation was capable of identifying patients with better or worse prognosis within groups that were homogeneous regarding some other known prognostic factors. FcR constellation as a prognostic factor was shown to be independent of age, sex, and Rai and Binet stages, but it was found to be connected with the total tumor mass score (TTM). The three forms of FcR on B cells might reflect stages of B-cell activation. Differences in FcR constellations between patients with B-CLL would thus correspond to differently activated B-cell clones with variable prognosis.     

Zur Epidemiologie und Ätiologie des Oesophaguscarcinoms in China

Ohne Zusammenfassung

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The epidemiology and etiology of esophageal cancer in China

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Stipendiaten der Alexander von Humboldt-Stiftung aus der Volksrepublik China

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The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.Die Zeitschrift Journal of Cancer Research and Clinical Oncology bringt in zwangsloser Folge Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autors wieder.     

Extraction,gel filtration pattern,and receptor binding of porcine gastrointestinal glucagon-like immunoreactivity

Summary Different techniques for the extraction and initial purification of porcine gastrointestinal glucagon-like immunoreactivity (GLI) were compared with reference to yield, and preservation of number and pattern of GLI components. The conventional acid-ethanol technique combined with ethanol-ether purification gave high yields and a reproducible pattern of components. Large amounts of tissue were more easily extracted using another technique, based on extraction by boiling, extraction and precipitation with acetone, and — if necessary — salting out. — By means of the latter two techniques mucosal tissue from all of the porcine gastrointestinal tract was extracted and subjected to gel filtration. Glucagon-like peptides were searched for using: — 1. a radioimmunoassay which quantifies gut type glucagon (GTG), as well as pancreatic type glucagon (PTG), 2. a radioimmunoassay highly specific for pancreatic type glucagon (PTG), and 3. a radioreceptor assay based on binding of glucagon to porcine liver cell membranes. — The oesophageal, the fundic, and the antro-pyloric parts of the gastric mucosa contained very small amounts of GLI. The cardiac gland region contained small amounts of a peptide indistinguishable from true glucagon. The duodenal mucosa contained small amounts of true glucagon and may be a smaller, glucagon-like peptide. The mucosa of the small intestine contained large amounts of both high and low molecular weight GTG and, in addition, PTG of high molecular weight and true glucagon. The colon also contained these components with true glucagon in high concentrations. Only small GTG and true glucagon were receptor-active, the former with less than its immunometric potency.     

Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes

Summary Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration (diffuse, cluster, and large) were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was diffuse in 18, cluster in 48, and large in 40 cases. RAEB-t patients accounted for about half of the large cases, and none had a diffuse pattern (p<0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by cluster blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of large cases (p<0.001) and in none of the cluster cases with severe BM fibrosis (p<0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with cluster BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.     

Interleukin-1β Inhibits Growth Factor-Stimulated Restoration of Wounded Rat Gastric Epithelial Cell Monolayers

We examined the effect of interleukin-1(IL-1) on spontaneous and enhanced restoration(cell migration and proliferation) using an in vitrowound model comprising a confluent monolayer of ratgastric epithelial RGM1 cells. Repair of an artificialwound in a cell monolayer was found to be time- andconcentration-dependent when the cells were incubatedwith epidermal growth factor (EGF) or transforming growth factor (TGF)- alone for up to 24hr. The growth factors also stimulated DNA synthesissignificantly for 24 hr in a concentration-relatedmanner. IL-1 had no effect on wound restoration in the absence of the growth factors. However, itmarkedly inhibited the restoration enhanced by EGF andTGF-, the inhibition being about 60% and 70%,respectively. In addition, IL-1 significantly reduced the DNA synthesis stimulated by thegrowth factors. The EGF- and TGF--enhancedrestoration was reduced by about 30% by mitomycin C,which potently inhibited the stimulated DNA synthesis.Mitomycin C had no effect on the spontaneous restoration.Even when treated with mitomycin C, the inhibitoryeffect of IL-1 on the enhanced wound repair wasstill observed; however, the extent of the inhibition was decreased. These results indicate thatIL-1 inhibits the migration as well as theproliferation of gastric epithelial cells enhanced byEGF and TGF-, resulting in a failure of woundhealing.     

Comparative and combined effects of transforming growth factors α and β, interleukin-1 and interferon-γ on rheumatoid synovial cell proliferation,glycolysis and prostaglandin E production

Summary Enhanced cell proliferation, glycolysis and prostaglandin E production are all characteristic features of rheumatoid synovial tissue. The interrelationships of these three cellular parameters have been examined using rheumatoid synovial fibroblasts and their responses to specific cytokines in vitro. Transforming growth factor (TGF) caused a more than threefold increase in synovial cell proliferation whilst transforming growth factor (TGF), interleukin-1 (IL-1) and interferon- (IFN-) produced only marginal changes. The combined addition of IL-1 with TGF resulted in an enhanced proliferative response comparable with that produced by TGF. Glycolysis, estimated by glucose utilisation and measurements of the glycolytic regulatory metabolite fructose 2,6-bisphosphate was significantly stimulated by TGF, IL-1 and IFN-, but less so by TGF. Prostaglandin E production was significantly increased by IL-1 to an extent much greater than that produced by TGF or TGF, although the combined addition of IL-1 with either TGF or resulted in a synergistic increase in PGE production, a response partly diminished by the addition of IFN-. These findings suggest that the extent to which a cytokine stimulates glycolysis is not consistently related to its mitogenicity, and that cytokine combinations which stimulate high levels of PGE production (a growth inhibitor) will not necessarily be associated with a reduced rate of cellular proliferation in cultured, adherent, rheumatoid synovial fibroblasts.     

Electrolytes of the gastric juice in health and gastroduodenal diseases

The results of using a new procedure for performing gastric analysis, called gastroionogram, are described. The procedure provides measurements of hydrogen, sodium, potassium, and chloride in the gastric content. The results are expressed as concentrations and outputs of these ions. A total of 2327 studies were carried out between 1965 and 1971, using different stimulants to obtain gastric juice, and analysis of the results allows the following conclusions: a) secretory response is similar with any potent stimulus; b) collection between 15 and 75 minutes after stimulation is a reliable and valid 1-hour stimulated period; and c) the outputs of ions, perhaps those of hydrogen and sodium, are potentially useful for the diagnosis of several pathologic groups-active duodenal ulcer, Zollinger-Ellison syndrome, peptic gastric ulcer, trophic gastric ulcer, and chronic gastritis. Except for the last two, the groups also show differences among themselves.Presented in part at the XIII Pan American Congress of Gastroenterology, Buenos Aires, Argentina, 1973.     

The antigenicity of human hemoglobins

Summary The correlation of the antigenicities among native hemoglobins and their subunit chains were investigated by the absorption of antisera and the combination of urea added immunoelectrophoresis with double diffusion. Alphachain showed identity with Hb-F but partial identity with -chain and Hb-A. Beta-chain showed identity with Hb-A but -chain and Hb-F showed partial identity with this chain. Gamma-chain showed identity only with Hb-F and its antigenicity was considered as being different from those of - or -chains.The lines of -, -and -chains were reconfirmed from the facts that the appearance of them depended always on the existence of anti-Hb-A or anti-Hb-F antibodies in the absorbed antisera and the minor component lines of

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Zusammenfassung Die Zusammenhänge der Antigenität zwischen nativen Hämoglobinen und deren Unterketten wurden mit der Absorption der Antiseren und der Kombination der Harnstoff-Immunelektrophorese und Doppeldiffusion untersucht. Die -Kette zeigte Identität mit Hb-F, aber nur partielle Identität mit der -Kette und Hb-A. Die -Kette war in ihrer Antigenität mit Hb-A identisch, die -Kette und Hb-F waren teilweise identisch mit der -Kette. Die -Kette zeigte die Identität mit Hb-F; es wird angenommen, daß ihre Antigenität verschieden von der -oder -Ketten ist.Für das Auftreten der Linien der -, - und -Ketten müssen Anti-Hb-A-oder Anti-Hb-F-Antikörper in den absorbierten Antiseren vorhanden sein, außerdem fusionieren die schwächeren Linien der Doppeldiffusion nicht mit irgendwelchen Linien der Unterketten. Auch gereinigte - oder -Ketten wurden zur Feststellung ihrer Linien benutzt.

     

Gastric diversion or pylorus ligation for gastric mucosal integrity and acid secretion studies in the rat?

The advantages of gastric diversion over pylorus ligation in rat gastric mucosal integrity and acid secretion studies over 6 hr were investigated. Mucosal injury developed in 80% of pylorus-ligation controls. Atropine (5 mg/kg) or cimetidine (40 mg/kg) had no effect on this injury (2.9 mm²±0.9 and 2.8 mm²±0.7, respectively, vs 3.1 mm²±1, mean±sem, N=10; however vagotomy increased it (13.7 mm²±Pylorus-ligation H⁺ output was higher than that of gastric diversion (390.5 mol±54.8 vs 61 mol±2.5, mean±sem, N=10, P<0.001). Cimetidine (40 mg/kg) depressed H⁺ output of gastric diversion (21.3 mol±1.2 vs 61 mol±2.5, mean±sem, N=10, P<0.001), but not of pylorus ligation (424 mol±74.2 vs 390.5 mol±54.8, mean±sem, N=10). Vagotomy or atropine depressed pylorus-ligation H⁺ output (P<0.001), but each allowed an output (36.6 mol±5.5 and 120 mol±29, respectively, mean±sem, N=10) significantly (P<0.001) higher than that associated with it in gastric diversion (16 mol±1.4 and 17.1 mol±1.6, respectively, mean±sem, N=10). This study demonstrates that in the rat pylorus ligation, in contrast to gastric diversion, injures the gastric mucosa, stimulates H⁺ secretion, and overshadows the efficacy of antisecretory agents.     

Modulation of pacemaker activity in sheep cardiac Purkinje fibers by stimulation of β-adrenoceptor subtypes

The electrophysiological effects mediated by ₁- and ₂- in spontaneously active sheep cardiac Purkinje fibers were investigated using the non-selective agonist (–)-isoproterenol (IPN) and the selective agonists (–)-noradrenaline (₁) and procaterol (₂) in the absence and presence of the selective antagonists bisoprolol (₁) and ICI 118,551 (₂).IPN (0.01 mol/l) increased the spontaneous rate by 54% and the slope of diastolic depolarization by 68% of the respective control values. Further, IPN increased the action potential duration at –20 mV (APD –20 mV) from 96 to 154 ms, reduced the APD –70 mV by 17% and the duration of the diastole by 39% and slightly hyperpolarized the maximum diastolic potential. These effects were partially inhibited by ICI 118,551 (0.03 mol/l), diminished by bisoprolol (0.1 mol/l) and almost completely blocked by the combination of both antagonists. Concentration response curves of IPN were influenced by the selective antagonists as follows: ICI 118,551 (0.03 mol/l) shifted the curves to the right by 0.2–0.4 log units and increased the slope factor. Bisoprolol (0.1 mol/l) induced a greater shift to the right by 1.1–1.5 log units. Combination of bisoprolol with ICI 118,551 shifted the curves to the right by 1.5–1.7 log units.Noradrenaline (0.3 mol/l) elicited similar actions as IPN. Bisoprolol (0.1 mol/l) shifted the concentration response curves of noradrenaline to the right by 1.1–1.9 log units. Actions of procaterol (0.1 mol/l) were weak, attained only 15–35% of the maximal effects of IPN and could be blocked by ICI 118,551 (0.03 mol/l).These results show that the increase of pacemaker activity induced by catecholamines in sheep cardiac Purkinje fibers is predominantly mediated by stimulation of ₁. However, contribution of ₂ mediated effects could be demonstrated.Supported by Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen, Projekt-Nr, 40008786.     

Insulin and growth hormone responses to glucose loading in treated acromegalics

Summary The insulin and growth hormone responses to oral glucose load (100 g) in 23 acronaegalic patients, previously treated by external irradiation, are described. Based on current clinical findings, sixteen acromegalics were considered inactive and seven patients active. Two of the latter were treated diabetics. Thirteen healthy, non-obese subjects formed the control group. Five inactive acromegalics had blood glucose values exceeding the upper limits of normal after the glucose load. Both the inactive and active acromegalics had hyperinsulinemia in the fasting state and after glucose load. The observation of an exaggerated serum insulin response to glucose load in clinically inactive acromegalics suggested that chronically elevated levels of circulating growth hormone may have led to permanent changes in the responsiveness of the pancreatic islets to glucose stimulation. The mean fasting value of serum growth hormone was about the same in the controls and the inactive acromegalics; the latter did not show suppression in serum growth hormone levels after glucose load.Research Fellow, Medical Research Council of Canada     

Die β-Laktamase-Inhibitoren und ihre klinische Bedeutung

Zusammenfassung Zu den verschiedenen Möglichkeiten der Überwindung einer -Laktamase-bedingten Resistenz von Mikroorganismen gehört der Einsatz von Enzyminhibitoren, die selbst keine nennenswerte eigene antimikrobielle Aktivität aufweisen, jedoch in Kombination mit einem Breitspektrumantibiotikum vom -Laktamtyp synergistisch wirken. Auf diese Weise gelangen -Laktam-resistente Bakterien erneut in das Wirkungsspektrum von Substanzen wie Penicillin G oder Ampicillin, die aufgrund steigender Resistenzentwicklung in den letzten Jahren ihre therapeutische Effizienz zu verlieren drohen. 6--Bromopenicillansäure und die sogenannten Olivansäuren weisen eine bemerkenswerte Hemmpotenz gegenüber verschiedenen -Laktamasen auf. Die mikrobiologischen und bisher vorliegenden pharmakokinetischen Daten eines Penicillansäuresulfons, das ebenfalls signifikante Hemmeigenschaften verschiedener klinisch relevanter -Laktamasen besitzt, werden diskutiert. Von Clavulansäure, einem Stoffwechselprodukt vonStreptomyces clavuligerus mit -Laktamstruktur konnte ebenfalls gezeigt werden, daß es ein progressiver Hemmstoff der -Laktamasen vom Richmond-Typ II-V ist. Neben den bisher vorliegendenIn-vitro-Untersuchungen werden auch Ergebnisse klinischer Studien mit der Kombination Clavulansäure und Amoxicillin erwähnt.

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Inhibitors of -lactamases and their clinical significance

Summary One of the various possibilities of overcoming bacterial resistance due to -lactamase production is with enzyme inhibitors. These have no remarkable intrinsic antimicrobial activity, but act synergistically in combination with a broad spectrum antibiotic of the -lactam type. Thus -lactam resistant bacteria are once again within the antibacterial spectrum of substances like penicillin G or ampicillin, which have been in danger of losing their therapeutical effectiveness in recent years due to an ever increasing development of resistance. 6--bromopenicillanic acid and the so-called olivanic acids exhibit remarkable inhibitory properties against several -lactamases. Microbiological and pharmacokinetic data published recently on a penicillanic acid sulfone, which also shows significant inhibitory properties against several clinically relevant -lactamases, are discussed in this paper. Clavulanic acid, a recently discovered product ofStreptomyces clavuligerus with a -lactam structure, acts as a progressive inhibitor of Richmond type II-V -lactamases. In addition to microbiological and enzyme-kineticin vitro data, results of clinical studies with the combination clavulanic acid and amoxicillin are summarized.

     

Further identification of protein kinase C isozymes in mouse epidermis

In the current study, the protein kinase C (PKC) isozymes present in mouse epidermis have been identified using immunological and chromatographic methods. Six PKC isozymes, PKC, PKC, PKC, PKC, PKC, and PKC, were identified in unfractionated epidermal preparations by protein immunoblotting. The subcellular distribution and presence of these isozymes was further verified by hydroxyapatite (HA) chromatography with the exception of PKE, which could not be detected following HA chromatography. The five PKC isozymes recovered following HA chromatography were detected in both epidermal cytosol and particulate fractions, although PKC was found in a much higher proportion relative to the other PKC isozymes in the particulate fraction using histone H1 as the substrate. The biochemical properties of the epidermal PKC isozymes partially purified by HA chromatography agreed with those reported for other tissues and further supported their immunological identification in epidermal preparations. The activities of HA chromatography peaks corresponding to PKC, PKC, and PKC were found to be dependent on both Ca²⁺ and phosphatidylserine (PtdSer), whereas, the activities of HA peaks corresponding to PKC and PKC were Ca²⁺-independent but PtdSer-dependent. The HA peak corresponding to PKC also displayed a characteristic biphasic modulation by arachidonic acid (activation at low, inactivation at high concentrations) and inactivation by preincubation with PtdSer. PKC activity was also characteristic, in that it was dependent on PtdSer and was not increased by the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate. Some differences in substrate specificity were also observed between the epidermal PKC isozymes. The presence of multiple isozymes of PKC in mouse epidermis suggests that the different isozymes may play distinct roles in signal transduction and tumor promotion in this tissue.Abbreviations PKC protein kinase C - HA hydroxyapatite - PtdSer phosphatidylserine - TPA 12-O-tetradecanoylphorbol 13-acetate This work was supported by USPHS grants CA 38871 (J.D.), CA 57596 (J.D.) and core grant CA 16672     

GlutathioneS-transferase expression in malignant mesothelioma and non-neoplastic mesothelium: an immunohistochemical study

Expression of the glutathioneS-transferase (GST) subclasses , and was investigated immunohistochemically in 20 normal or hyperplastic mesothelium and in 57 malignant mesothelioma cases. These results were correlated with survival and also with P-170 glycoprotein expression. Nearly all the non-neoplastic mesothelium cases were positive for GST and . About half of the non-neoplastic cases were positive for . Twenty-nine (51%) malignant mesotheliomas were positive for at least one of the GST species; 21 (37%) showed immunoreactivity for , 18 (31.5%) for and 21 (37%) for . A total of 54 mesothelioma cases displayed immunoreactivity for the P-170 glycoprotein. For GST and GST, a statistical significance between expression and increased survival was found (respectivelyP=0.012 and 0.024) while for GST no significance was found. The results of this study demonstrate that expression of GST correlates positively with increased survival in malignant mesothelioma. It is also concluded that, in mesothelioma, GST and P-170 glycoprotein may contribute to the resistance to cytotoxic drugs frequently observed in these tumours. No correlation between GST and P-170 expression was demonstrated.Abbreviation GST glutathioneS-transferase     

Correlation between infarct-related coronary artery patency and predischarge electrocardiographic patterns in patients with first anterior myocardial infarction who received thrombolytic therapy

The aim of this study was to investigate the correlation between the ST-segment and T-wave patterns in predischarge electrocardiogram and patency of left anterior descending coronary artery in patients with a first anterior myocardial infarction (AMI). One hundred and fifty-six of 175 consecutive patients who were admitted to our clinic between January 2000 and September 2002 due to a first episode of transmural AMI and who received thrombolytic therapy were enrolled. Coronary angiography was performed by the Judkins method on the 6th–10th day after the acute infarction. The corrected TIMI frame count (CTFC) was estimated according to the previously described method. According to the combination of the ST-segment and T-wave morphology on the day (6–10) of cardiac catheterization, patients were classified into four groups: group A, ST elevation 0.1mV and negative T waves; group B, ST elevation 0.1mV and negative T waves; group C, ST elevation 0.1mV and positive T waves; and group D, ST elevation 0.1mV and positive T waves. Of the 99 patients with negative T waves, 47 (48%) had CTFC 27, 32 (32%) CTFC between 27 and 40, 15 (15%) CTFC 40–100, and 5 (5%) CTFC 100. Of the 57 patients with positive T waves, CTFC was 27 in 14 (25%), between 27 and 40 in 17 (30%), 40–100 in 11 (19%), and 100 in 15 (26%) (P 0.001). From the 76 patients with an isoelectric ST segment, 38 (50%) had CTFC 27, 29 (38%) CTFC between 27 and 40, 8 (11%) CTFC 40–100, and 1 (1%) CTFC 100. Of the 80 patients with an elevated ST segment, 23 (29%) had CTFC 27, 20 (25%) CTFC between 27 and 40, 18 (23%) CTFC 40–100, and 19 (23%) CTFC 100 (P 0.001). Use of the combination of two electrocardiographic parameters (ST segment and T waves) also indicated that there were significant differences between groups A and D, and groups B and D (P 0.001 and P 0.05, respectively). Development of an isoelectric ST segment with negative T waves may indicate a better degree of reperfusion after AMI. In contrast, patients in whom ST-segment elevation and positive T waves remain at discharge from the coronary care unit have a higher probability of a nonpatent left anterior descending artery.