The ability of heat stress and metabolic preconditioning to protect primary rat cardiac myocytes

Primary rat cardiocytes were subjected to either thermal preconditioning for 30 min at 43°C or 20 min metabolic preconditioning (10 mM deoxyglucose, 20 mM lactate, pH 6.5). Eighteen hours later cells were analysed either for hsp 70i expression or subjected to a subsequent lethal heat stress or simulated ischaemia (10 mM deoxyglucose, 20 mM lactate, 0.75 mM sodium dithionite, 12 mM potassium chloride, pH 6.5) for 2 hours and assessed for survival by trypan blue exclusion.Hsp 70i was induced over 100 fold by thermal preconditioning and 30 fold by metabolic preconditioning (p<0.001, p<0.05), hsp 90 was induced 2.71 fold and 2.24 fold (p<0.001, p<0.001) by thermal and metabolic preconditioning respectively, while hsp 60 was not induced by either treatment. Preconditioned cultures had improved survival against subsequent lethal heat stress or simulated ischaemia: Thermal preconditioning reduced death from 69.22% to 52.46% upon subsequent lethal heat stress and from 49.13% to 36.66% upon subsequent lethal simulated ischaemia. Metabolic preconditioning reduced cell death from 51.29% to 33.8% against subsequent lethal heat stress, and from 69.09% to 55.61% upon subsequent lethal simulated ischaemia. A second marker of cell death, the release of lactate dehydrogenase activity into the culture media, was reduced to 65% and 60% of control values for thermally preconditioned cells subjected to lethal heat or lethal simulated ischaemia respectively. Metabolically preconditioned cells demonstrated lactate dehydrogenase activity of 59% and 51% that of control values, when subjected to lethal heat or lethal simulated ischaemia respectively.Abbreviations hsp heat stress protein - hsp 70i inducible 70 kDa heat stress protein - LDH lactate dehydrogenase - PBS phosphate buffered saline     

Chromosomenuntersuchung zur Charakterisierung eines Impftumors

Zusammenfassung Chromosomenzahl und marker-chromosomen eines Impftumors der Maus (Lymphoms) wurden bestimmt. Die Stammlinie mit 45 Chromosomen sowie zwei marker-chromosomen weisen eine auffallende Übereinstimmung mit Befunden an Ehrlich-Carcinomstämmen auf. Das zweischenkelige marker-chromosom tritt in zwei unterschiedlichen Varianten auf, ein weiteres weniger deutlich ausgeprägtes sehr langes telozentrisches Element wurde als drittes marker-chromosom dieses Tumors betrachtet.Unter gleichbleibenden Transplantationsbedingungen blieb der Karyotyp durch 14 Monate hindurch konstant. Auch durch hochdosierte Oestrogengaben an die tumortragenden Mäuse konnte nach 21 Passagen keine wesentliche Änderung des Karyotyps erzielt werden, sondern lediglich eine allmähliche Zunahme der Tumorzellen mit 46–49 Chromosomen, bei gleichbleibenden marker-chromosomen.

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Summary The chromosome number and marker-chromosomes of a transplantable tumor with of the mouse (lymphoma) were determined. The stemline 45 chromosomes and the two marker-chromosomes corresponded strikingly with results of studies on strains of Ehrlich carcinoma. The two-limbed marker-chromosome appeared in two different variations, and as a third marker-chromosome of this tumor a less striking but very long telocentric element was further observed. Throughout a 14 month period under constant conditions of transplantation the karyotype remained unchanged. Furthermore, no important changes of the karrotype could be obtained by high doses of estrogen in tumor-bearing mice after 21 passages. Only a gradual increase of tumor cells with 46–49 chromosomes occurred; the marker chromosomes remained constant.

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Mit 4 Textabbildungen     

Follow-up of “non-diabetic” relatives of diabetics by retesting oral glucose tolerance after 5 years

Summary Of 743 first degree relatives of diabetics in whom oral glucose tolerance tests had been performed in 1967 488 were re-tested in 1972. Among the original normals (n = 353) 17.6% had developed a subclinical and 1.3% an overt diabetes within 5 years. The original subclinical diabetics (n = 118) showed a remission to normal in 35.6% and a progression to overt diabetes in 13.6%. 3 out of the 17 formerly overt diabetics were found to be normal after 5 years and 3 were subclinical diabetics. Thus the performance of an oral glucose tolerance test is of limited prognostic value in the individual case. In both studies a higher prevalence of abnormal test results occurred in the older age groups and in overweight subjects. Remission or deterioration did not depend, however, on age or on weight changes. The frequency of abnormal tests was higher in males than in females, but the tendency towards the development of diabetes was more pronounced in females, in accordance with a previous observation of a higher age dependance of glucose tolerance in females.     

Extrarenal nephroblastomas

Summary The cases of extrarenal nephroblastoma published in the world literature have been tabulated and reviewed, and are discussed from a historical point of view.The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author     

Estimation of the malignant potential of gastrointestinal stromal tumors: the value of contrast-enhanced coded phase-inversion harmonics US

Background Recently, contrast agents for ultrasonography (US) such as Levovist have been introduced for routine clinical use. The contrast-enhanced US with Levovist permits evaluation of the intratumoral vascularity of hepatic and pancreatic tumors and is useful for their differential diagnosis. The purpose of the present study was to assess tumor vessels and the parenchymal flow of gastrointestinal stromal tumors (GISTs) by contrast-enhanced coded phase-inversion harmonic US and to evaluate whether vascularity is related to the malignant grade of the GISTs.Methods Thirteen patients with GISTs were included in the present study. Tumors were observed in a real-time fashion of contrast-enhanced coded phase-inversion harmonic US after the injection of Levovist (400mg/ml). The vascular patterns were compared with tumor size, histological diagnosis, KIT mutations, and clinical findings such as metastasis.Results The contrast-enhanced US images of the GISTs were classified into two types according to the blood flow area of the tumors as seen by real-time continuous imaging of the tumor vessels. The image pattern Poor represented vessels flowing only in the peripheral part of the tumor, and Rich represented abundant vessels flowing from the periphery to the central part of the tumor. According to the contrast-enhanced US images, five GISTs were classified as Poor and the others as Rich. Based on the final diagnosis, all tumors with Poor images were determined to be benign GISTs, and the rest tumors except one with Rich images were determined to be malignant GISTs.Conclusions Contrast-enhanced US image is more closely correlated with the final diagnosis than the histological findings.     

Gastric “pseudolymphoma” with restricted light chain expression in a patient with obscure gastrointestinal blood loss

Summary We present a case report of a gastric pseudolymphoma (GL) that exhibits restricted light chain expression and, therefore, illustrates the dilemma encountered when histologically benign lesions have phenotypic abnormalities suggesting malignancy. For many years this lesion has been considered usually benign; however, recent reports such as this one demonstrate immunologic signs of monoclonality in an otherwise histologically benign lesion. This finding challenges our assumptions as to the nature of this lesion and our definition of cancer. The lesion also displays Castleman-like features (angiofollicular hyperplasia) as well as common inflammatory germinal centers. In addition we briefly review the literature.     

Zur Rolle der enzymatischen DNA-Reparatur bei Carcinogenese und Krebschemotherapie

Ohne ZusammenfassungCancer 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. The EditorsDie Zeitschrift für Krebsforschung und Klinische Onkologie bringt in zwangloser Folge Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autos wieder. Die HerausgeberHerrn Prof. Harold P. Rusch, Madison, Wisc., in aufrichtiger Verehrung zum 70. Geburtstag gewidmet     

Interpretation of blood cultures yielding staphylococcus aureus

Summary Forty-eight patients with blood cultures positive for Staphylococcus aureus were classified according to clinical criteria in three groups: definite, possible, and doubtful septicemia. Using traditional blood culture sets with two bottles (thioglycollate and tryptic soy broths), we found that patients with definite septicemia always showed more than one positive bottle per day if more than one set was drawn, that the mean detection time was 1.7 days, and that 95% of the first positive bottles and 92% of all positive bottles grew within two days of incubation. Patients with doubtful septicemia were more often (88%) positive in one bottle only, the mean detection time for all bottles was 3.7 days, and only 35% of the first positive bottles and 33% of all positive bottles yielded growth within two days. Possible cases took a position between these two extremes but tended more towards the doubtful cases. The implications of these findings for the interpretation of blood cultures with S. aureus are discussed.

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Interpretation von Blutkulturen mit Staphylococcus aureus

Zusammenfassung 48 Patienten, aus deren Blutkulturen Staphylococcus aureus gezüchtet worden war, wurden nach klinischen Kriterien in drei Gruppen eingeteilt: unzweifelhafte, mögliche und zweifelhafte Septikämie. Bei Verwendung eines traditionellen Blutkultursystems mit zwei Flaschen pro Kultur (Thioglykolat- und Tryptic Soy-Bouillons) ergab sich, daß Patienten mit unzweifelhafter Septikämie stets mehr als eine positive Flasche pro Tag aufwiesen — sofern mehr als eine Kultur pro Tag entnommen worden war —, daß die mittlere Bebrütungsdauer bis zur Positivität 1,7 Tage betrug, und daß 95% der ersten positiven Flaschen und 92% aller positiven Flaschen innerhalb von zwei Tagen Wachstum von S. aureus zeigten. Patienten mit zweifelhafter Septikämie zeigten häufiger (in 88%) Wachstum in nur einer Flasche, die mittlere Bebrütungsdauer betrug 3,7 Tage, und nur 35% der ersten positiven Flaschen und 33% aller positiven Flaschen ergaben Wachstum innerhalb von zwei Tagen. Mögliche Septikämien nahmen eine Zwischenstellung ein, tendierten jedoch mehr nach der zweifelhaften Kategoric. Folgerungen für die Interpretation von Blutkulturen mit S. aureus werden diskutiert.

     

The efficacy of neuraminidase treatment in studies on red cell aging

Summary An in vitro system was developed to test the propensity of rat erythrocytes (RBC) toward phagocytosis by homologous peritoneal macrophages after in vivo aging or after in vitro surface modification. Old RBC obtained from erythrocyte populations separated into fractions on the basis of their density were found to be phagocytosed to a significantly greater extent than cells obtained from young cell fractions. Neuraminidase treatment of RBC resulted in extensive phagocytosis in comparison to control cells representing the whole population or old cells. Galactose oxidase treatment of neuraminidase treated RBC afforded no protection from uptake by macrophages. In contrast, treatment of RBC with neuraminidase immobilized on Sepharose 4B, leading to removal of up to 25% of the total membrane sialic acid, did not lead to phagocytosis above control values. These results indicate that extreme caution is necessary in the interpretation of experiments in which neuraminidase is utilized to produce simulated aged RBC.     

Histomorphologische und cytologische Befunde bei einem Fall von Gewebsmastzell-Retikulose mit akutem leukämieartigem Verlauf

Zusammenfassung Es wird über einen Krankheitsfall berichtet, welcher nach der bisherigen Nomenklatur als Gewebsmastzellen-Leukämie oder als maligne Mastocytose mit leukämieartigen Manifestationen (Efrati et al., 1957) bezeichnet worden ist; er muß als akute subleukämische Gewebsmastzellen-Reticulose klassifiziert werden.

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Summary The author reports a case which, according to the past nomenclature, was designated as tissue-mast-cell leukemia or as malignant mastocytosis with leukemia-like manifestations (Efrati et al., 1957). This case must be classified as an acute subleucemic tissue-mast-cell reticulosis.

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Vortrag auf dem 12. Kongreß der Deutschen Gesellschaft für Hämatologie, Berlin 1966.     

The establishment of a polyposis register

Guidelines are presented for the establishment of a regional or national register of patients with familial adenomatous polyposis. The detailed recommendations are based on the work in committees of the Leeds Castle Polyposis Group and the EuroFAP. The aims of national and regional polyposis registers are discussed, and the stages of development of a register are reviewed: Ascertainment of probands, construction of pedigrees, identification of family members at risk, and screening of members at risk. The problem of data confidentiality is discussed.

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Résumé Les consignes sont présentées pour l'établissement d'un registre Régional ou National des patients avec polypose adénomateuse familiale. Les recommandations détaillées sont basées sur les travaux des comités du Leeds Castle Polyposis Group et de EuroFAP. Les buts des registres Régionaux ou Nationaux des polyposes sont discutés et les stades de développement du registre sont passés en revu: l'assurance de probande, la construction de l'arbre généalogique, l'identification des familles des membres à risques et l'étude des membres à risques. Le problème de la confidentialité des faits est discuté.

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This paper is based on a report from committees of the Leeds Castle Polyposis Group and the EuroFAP.     

Slow metabolic deterioration towards diabetes in islet cell antibody positive patients with autoimmune polyendocrine disease

Summary We studied metabolic progression to IDDM in a cohort of adults who are ICA-positive and have associated autoimmune endocrine disease or circulating organ-specific autoantibodies (the Polyendocrine Study). Of the 186 individuals recruited 27 developed overt diabetes after a median follow-up of 4.5 years (range 0.4–12). Of these, eight patients did not require insulin treatment until at least 6 months after clinical diagnosis, with an interval of 1.8 years (1.2–5.7). An IVGTT was performed in 38 subjects and 23 had sequential studies. Of the initial 38 subjects six developed diabetes and only three showed a loss of FPIR to glucose (below the first percentile of a normal control group) before clinical onset of the disease. An additional three subjects showed a loss of the FPIR, and all still have normal glucose tolerance after median follow-up of 28 months (22–95). A whole or mixed pattern of islet cell staining was found in five of the six patients who developed diabetes and antibodies against an islet 37 k-antigen were detectable in four patients, all of whom required insulin soon after diagnosis. A beta-cell selective ICA staining pattern was seen in 14 of 17 subjects who did not develop diabetes and the mixed pattern in only three. None of this group had detectable 37k-antibodies. We conclude that metabolic deterioration is slow in polyendocrine patients, and that the IVGTT has less prognostic significance in this group than in first degree relatives of patients with IDDM. In contrast, the presence of the whole or mixed ICA staining pattern or of 37k-antibodies can identify a high risk of progression to IDDM within this polyendocrine population and may indicate the rate of metabolic deterioration.Abbreviations IDDM Insulin-dependent diabetes mellitus - ICA islet cell antibodies - IVGTT intravenous glucose tolerance test - FPIR first phase insulin response - OGTT oral glucose tolerance test - GAD glutamic acid decarboxylase - JDF Juvenile Diabetes Foundation     

Converting enzyme inhibitors (captopril,enalapril, perindopril) prevent early-post infarction ventricular fibrillation in the anaesthetized rat

Summary The angiotensin-converting enzyme inhibitors, captopril, enalapril and perindopril, exert antiarrhythmic effects on early post-infarction arrhythmias in anaesthetized rats. These studies support the hypothesis that converting enzyme inhibitors could have a cardioprotective effect, but the doses used are probably high in relation to those therapeutically applicable to man.     

Local and regional immunotherapy of cancer with interleukin 2

Conclusion The results obtained in preclinical systems as well as the first clinical trials suggest that local IL-2 immunotherapy may represent a novel approach to the treatment of some neoplasms. However, the experimental results should be confirmed and substantially extended before definitive conclusions can be drawn. We hope that the data and considerations discussed in this article will facilitate thoughts concerned with future clinical IL-2 trials and be instrumental in the optimization of IL-2 cancer immunotherapy.The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author     

The problem of thresholds in chemical carcinogenesis some views on theoretical and practical aspects

Conclusions I have tried to show that the threshold problem for carcinogens is still unsolved and that this unsatisfactory situation creates many problems for the scientific evaluation of the carcinogenesis problem as well as for its regulative aspects. In view of the extremely low acceptance of cancer risks in the general population, which is justified as well as understandable, carcinogenesis research must present new ideas to come nearer to a solution of such problems. More sound data on dose-time-effect curves in the low incidence range of 10-0.1% tumor incidences could indicated whether the established linearity in the higher incidence range might eventually by interrupted. Increase of animal numbers could also increase reliability of carcinogenicity experiments and allow the detection of low-dose effect; the disadvantages of this approach (mega-mouse experiment) however, in regard to cost and space necessary are evident. Increases of the mean life span by optimization of animal husbandry still would be another way of approach. However, no real breakthrough is to be expected here.The most promising approach seems to be the use of other indicators for carcinogenicity instead of tumor formation. Binding studies of carcinogens to biopolymers (Neumann 1980), especially DNA, as well as the determination of preneoplastic, enzyme-deficient islands (Kunz et al. 1978) have been shown to give dose-response curves parallel to the corresponding curves from carcinogenicity studies (Kunz) and extendable over 6 orders of magnitude of doses, without deviation from linearity (Neumann). Additional parameters might be found, which, altogether, might prove to be an important step toward further knowledge in this important field of carcinogenesis research.Oh König, das kann ich dir nicht sagen, und was du frägst, das wirst du nie erfahren R. Wagner, Tristan und IsoldeJournal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinicial oncology. These contributions represent exclusively the personal opinion of the author. The Editors Die Zeitschrift Journal of Cancer Research and Clinical Oncology bringt in zwangloser Folge Editorials und Guest Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autors wieder.     

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     

Untersuchungen mit Phytoagglutininen bei Inzuchthühnern

Zusammenfassung Es wurde in einem Inzuchtstamm von rebhuhnfarbigen Italienern durch drei Generationen der Hi-Faktor mit sechs selbst hergestellten Phytoagglutininen untersucht. Das Vorhandensein des Hi-Antigens konnte bestätigt werden. Seine natürliche Nachweisbarkeit beschränkte sich auf weibliche Tiere. Das vorliegende Gen HI, das dominant vererbt wird, konnte bei beiden Geschlechtern und allen Altersstufen bei Vorhandensein des weiblichen Geschlechtshormons (Östrogen) nachgewiesen werden.

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Summary The Hi-factor was studied with six self-produced phytoagglutinins in an inbred strain of partridge coloured Italiens through three generations. The presence of Hi-antigen could be confirmed. It can only be demonstrated in female animals. The HI gen, which is inherited in a dominant manner, could be demonstrated in both sexes and at all ages in the presence of female sex hormone (estrogen).

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Die Arbeiten wurden mit Mitteln der Deutschen Forschungsgemeinschaft durchgeführt.     

The Physical Conditions of Different Organs Are Reflected Specifically in the Pressure Pulse Spectrum of the Peripheral Artery

We try to solve the hemodynamic inverse problem of the internal organs in terms of the peripheral pressure pulse spectrum analysis. Side-branch organs are approximated as resonators with own natural frequencies. They are depicted not as ordinary reflection sites but as antennas that receive energy from the main artery and undergo forced oscillations with selective frequencies. Every organ also reacts back to the main artery as a secondary small heart source that generated harmonic forces with maximum amplitude near its own natural frequency. The whole arterial system is in a steady distributed oscillatory state that is the superposition result of encountering the forces generated by the heart and many internal organs. A frequency matching theory of the organ and the main artery is proposed. The Fourier components of the pressure pulse in the arterial system are related to the matching conditions of different organs. In vivo studies in kidney and spleen of rats are provided.     

The Ovarian Androgen-Producing Cells: A 2001 Perspective

The androgen-producing cells in the postnatal mammalian ovary are located in the interstitial compartment of the ovary. The most important types of androgen-producing interstitial cells are the cells in the theca interna and the cells of the secondary interstitial glands. There has been some confusion in recent years regarding the terminology used to describe the ovarian androgen-producing cells, namely that theca-interstitial cells are somehow different from theca cells. In fact, these are the same cells. The name theca-interstitial was used by Erickson et al. [1] to describe the theca cells as one of the four androgen-producing cell types in the interstitial compartment of the ovary along with primary interstitial cells which are present only during embryonic development, secondary interstitial gland cells, and steroidogenic cells located in the hilar region of the ovary. For the sake of clarity and according to current convention, the term theca cell will be used throughout this review to refer to cells in the theca interna of the ovarian follicle.     

Abnormal depolarizing patterns in three patients with filarial infection

Several authors have described a particular potential of automated depolarization analysis in detecting malaria infection as part of the routine full blood count (FBC) performed by the Cell-Dyn 4000 analyzer. In these cases, abnormal depolarizing patterns are due to the presence of leukocyte-associated malaria hemozoin, a pigment which depolarizes the laser light. In this report we describe samples from three individual patients who did not have malaria infection but showed abnormal depolarizing events. Further investigation determined that these samples were from patients infected by the nematode Mansonella perstans. The observed depolarizing pattern consisted of a normal depolarizing eosinophil population and in addition an abnormal depolarizing population that showed a close linear relationship between granularity (90° depolarization) and lobularity (90° polarization). This atypical population was smaller than normal leukocytes and thus clearly different from the patterns associated with malaria infection. Abnormal depolarization patterns of M. perstans clearly do not reflect leukocyte-associated malaria hemozoin. It is possible however that the erythrocyte-lysing agent used to facilitate leukocyte analysis by the instrument may have caused microfilaria fragmentation and thus the distinctive straight-line features of the abnormal scatter plots