Assessment of local cellular immunity in lung cancer by bronchoalveolar lavage

Summary Small cell lung cancer (SCLC) is the most malignant of the pulmonary neoplasms and is associated with a poor local cellular immune response. 16 patients with non small cell lung cancer (NSCLC) and 11 patients with SCLC underwent bronchoalveolar lavage (BAL) in the lung which harbored the tumor in order to investigate the lymphocyte surface antigens utilizing the immunoperoxidase technique. Analysis of blood lymphocytes was performed in parallel. 8 patients with previous sarcoidosis in complete remission who underwent BAL and 10 normal blood donors served as controls.Among blood lymphocytes the CD3⁺, CD4⁺ and CD16⁺ cell populations were elevated significantly and the T4/T8 ratio was elevated in NSCLC patients, but only CD16⁺ were augmented in SCLC. Cell populations expressing the activation markers transferrin (TF) receptor, interleukin-2 (IL-2) receptor and the very late antigen VAL-1 were also increased in NSCLC, while SCLC was associated with antigen distributions similar to controls. No differences between the cohorts were seen in the expression of human leukocyte antigen (HLA)-DR. In BAL the population of CD3⁺ and CD4⁺ cells were reduced in SCLC and the T4/T8 ratio was diminished in contrast to controls and NSCLC patients, whereas these two latter groups did not differ from each other. The distribution pattern of CD16, TF receptor and IL-2 receptor in the study groups resembled that of cells of the blood stream, but CD16⁺ natural killer cells were additionally down regulated to control values in SCLC. No differences were seen in the distribution of VLA-1. HLA-DR⁺ cells were clearly elevated in both cancer groups.In general NSCLC was associated with a shift to higher relative numbers of immunocompetent and activated cells. This was most probably attributable to an immune response to neoplastic growth. This shift was largely lacking in SCLC. The analysis of lymphocytes from the periphery of the target organ emerged as a sensitive tool for the study of cellular immunity in lung cancer and showed many similarities to circulating blood cells. However, the analysis of natural killer cells and HLA-DR suggested a dissection of cellular immune response between blood and lung in pulmonary cancer. A depressive interaction between the tumor and the cellular host immune response may contribute to the exceptional malignancy of SCLC.Abbreviations BAL bronchoalveolar lavage - HLA-DR human leukocyte antigen-DR - IL-2 interleukin-2 - NSCLC non small cell lung cancer - SCLC small cell lung cancer - TF transferrin - VLA-1 very late antigen-1     

Vagal mediation of the cholecystokinin satiety effect in rats

Central (intracerebroventricular) and peripheral (intraperitoneal) injections of the octapeptide of cholecystokinin (CCK-8) were compared to determine the most effective route of administration to elicit satiety for food intake in the rat. Subdiaphragmatic bilateral vagotomy and spinal cordotomy (T2-T3) were also performed to investigate the importance of visceral nerves for the satiety effect. CCK-8 suppressed feeding and elicited satiety resting behavior when injected peripherally but it was less effective when injected centrally. The satiety effect of CCK-8 or CCK-33 following peripheral injections was blocked by vagotomy whereas spinal cordotomy had no effect. The results indicate that some component of the vagus is required to mediate the peripherally induced cholecystokinin satiety effect, but the splanchnic nerves are not necessary. The weak effect of CCK-8 following ventricular administration is additional evidence suggesting that cholecystokinin of intestinal origin acts in the periphery rather than directly on the brain to elicit its typically rapid satiety effect in rats.     

Cytological demonstration of chloroplast DNA behavior during gametogenesis and zygote formation in Chlamydomonas reinhardtii

Summary We used the flourescent dye DAPI to visualize nucleoids of chloroplast DNA and follow their behavior through sexual reproduction by counting nucleoids in fixed cells at various stages. Nucleoid number varied greatly among cells at each stage. The mean number of nucleoids per cell was similar in mt ⁺ and mt ^– vegetative cells, and declined similarly during gametogenesis. Longer periods of nitrogen starvation reduced the mean nucleoid number further. Mean nucleoid number declined again in mating pairs, and continued to drop in zygotes up to the latest stage that can be examined (24-h zygotes). The oldest zygotes had means of about 2 to 3 nucleoids in different experiments, significantly fewer than in the mt ⁺ gametes (usually 4 to 5). The quantitative data on nucleoid number, mating efficiency, and germination efficiency allowed us to show that the decrease in nucleoid number is not limited to gametes that do not mate, or to zygotes that do not germinate. These data are consistant with earlier biochemical studies showing loss of chloroplast DNA during gametogenesis in both mating types, and with the degradation of paternal chloroplast DNA detected biochemically and (in non-quantitative studies) by DAPI staining. There may also be some fusion of nucleoids, although if it occurs it is not complete by 24 h of zygote maturation.     

Hämostase und Hämatokrit

Zusammenfassung In einer prospektiven Studie wurden bei 500 Patienten mit angeborenen Herzfehlern, davon 55% mit azyanotischen und 45% mit zyanotischen Vitien, die Thrombozytenzahl, einige Globaltests der plasmatischen Gerinnung (Quick-Wert, partielle Thromboplastinzeit, Thrombinzeit) und des Vollblutes (Thrombelastogramm) sowie der Proaktivator-Plasminogen-Komplex als Parameter der Fibrinolyse-Aktivität im Vollblut untersucht. Die Ergebnisse wurden nach Herzfehlertyp (azyanotisch/zyanotisch), Lebensalter (Neugeborene/Säuglinge/Kinder) und Hämatokrit-Bereichen (bis 40%/41–50%/51–60%/über 60%) gruppiert. Die Signifikanz zwischen den einzelnen Gruppen wurde mit Hilfe der Varianz-Analyse, die Korrelation der Parameter zum Hämatokrit-Wert mit Hilfe der linearen Regression berechnet.Bei azyanotischen Herzfehlern lagen die untersuchten Hämostase-Parameter im Normbereich, während bei zyanotischen Herzfehlern die Mittelwerte der Thrombozytenzahl, der plasmatischen und der Vollblut-Gerinnung sowie des Proaktivator-Plasminogen-Komplexes mit zunehmendem Lebensalter zum pathologischen Bereich tendierten; die niedrigsten Werte fanden sich im Neugeborenenalter, und zwar ohne Abhängigkeit vom Herzfehlertyp, wobei ursächlich die altersphysiologische Unreife des Gerinnungssystems anzuschuldigen ist. Bei Patienten mit zyanotischen Herzfehlern nahm die Gerinnbarkeit des Vollblutes mit zunehmender Polyglobulie kontinuierlich ab, während die Parameter der plasmatischen Gerinnung bis zu Hämatokrit-Werten von 60% durchaus im Normbereich blieben; eine ausreichende Korrelation der Hämostase-Parameter zum Schweregrad der Polyglobulie war nur für Patienten mit Hämatokrit-Werten über 60% nachzuweisen. Auch die Fibrinolyse-Aktivität im Vollblut war bei zyanotischen Patienten generell und ohne gesetzmäßige Abhängigkeit vom Lebensalter vermindert und nahm entgegen dem Anstieg des Hämatokrit-Wertes deutlich ab; dieses Verhalten spricht genen die in der Literatur vielfach diskutierte Steigerung der Fibrinolyse-Aktivität bei zyanotischen Patienten, welche allerdings von anderen Autoren nur im Plasma und nicht im Vollblut bestimmt wurde.Es empfiehlt sich daher, bei höhergradiger Polyglobulie Gerinnung und Fibrinolyse vorzugsweise im Vollblut zu untersuchen und nach den hier gefundenen, hämatokrit-bezogenen Richtwerten zu beurteilen, insbesondere vor diagnostischen und chirurgischen Eingriffen. Eine Behandlung mit gerinnungsaktiven Medikamenten ist streng zu indizieren; bei extremer Polyglobulie mit Hämatokrit-Werten über 70% können therapeutische Erythropheresen im Rahmen der präoperativen Vorbereitung Rheologie und Hämostase-Parameter kurzfristig verbessern.Mit Unterstützung der Deutschen Forschungsgemeinschaft, Bad Godesberg. Für die Durchführung der Laborarbeiten und die Dokumentation der Ergebnisse danken wir Frau Gudrun Godec herzlich. Die Studie wurde auszugsweise auf der Jahrestagung der Deutschen Gesellschaft für Pädiatrische Kardiologie am 25.9.79 in Berlin vorgetragen     

New real-time strain imaging concepts using diagnostic ultrasound

Two real-time strain imaging concepts and systems are presented. Both systems are based on a conventional ultrasound scanner that is connected to a PC with an A/D converter card for real-time data acquisition of rf data. Differential strain between successively acquired rf frames are estimated using phase root seeking. The first concept uses a special real-time implementation of manual elastography. In the second concept, denoted 'vibrography', the static compression is replaced by low-frequency axial vibration of the probe, still operating in quasistatic acquisition mode. The properties of both concepts are discussed with regard to noise and motion artefacts, and it is shown, using simulations and phantom experiments, that both imaging concepts yield the same kind of strain images. Vibrography has the advantage that no manual compression has to be applied, total compression can be very low and some motion artefacts are better suppressed.     

The influence of carcinoma growth on diamine oxidase activity in human gastrointestinal tract

The distribution of diamine oxidase (DAO) activity was studied in patients having no carcinoma disease. Besides in gut DAO occurred in high activity only in kidney and mesenteric lymph nodes.In patients with adenocarcinoma of the large bowel or of the stomach the enzymic activity was reduced in the tumour tissue itself as compared with the adjacent mucosa in which part the highest activities were observed. In stomach it seemed most important that the enzymic activity was enhanced in the whole mucosa, also in a 10 cm distance from tumour where no histological alterations were found. This fact should be checked for significance in early tumour diagnosis.Supported by A. v. Humboldt Stiftung.Supported by a grant from Deutsche Forschungsgemeinschaft (Lo 199/7).     

Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two de novo mutations in sporadic optic atrophy

The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy.     

Tackling the scaling-up problem of digital health applications

Journal of Public Health - The purpose of this editorial is to provide guidance for the readers concerning the broad realm of approaches towards successful implementation of digital health...