Über eine neue innersekretorische Funktion des Pankreas

Zusammenfassung Im normalen Pankreas wie in den Pankreascysten finden sich große Mengen aktiven Kreislaufhormons. Der aus dem Pankreas dargestellte Stoff ist mit dem aus dem Harn gewonnenen identisch.Die Ausschaltung der Bauchspeicheldrüse führt zu charakteristischen Ausfallserscheinungen im Hormonhaushalt, die nach Wiedereinschaltung des Organs behoben werden. Diese Ausfallserscheinungen beruhen auf dem Wegfall einer innersekretorischen Tätigkeit des Pankreas, die äußere Sekretion ist daran unbeteiligt.Ein ganz kleiner Pankreasrest genügt, um den Hormonspiegel einige Zeit aufrecht zu erhalten. Nach Entfernung dieses Restchens erfolgt dann sofort derselbe Absturz wie nach der Totalexstirpation des Pankreas.Das neue innere Sekret des Pankreas, das Kallikrein, ist chemisch und pharmakologisch vom Insulin scharf getrennt. Zwischen beiden Körpern bestehen aber funktionelle Beziehungen.Die Milz hat Einfluß auf den Haushalt des Kreislaufhormons.Mit 7 Abbildungen.     

Antigenic analysis of the Epstein-Barr virus major membrane antigen (gp350/220) expressed in yeast and mammalian cells: implications for the development of a subunit vaccine

The Epstein-Barr virus (EBV) major surface membrane antigen, gp350/220, was expressed in recombinant yeast cells and in several recombinant mammalian cell lines. Each of the expressed proteins was analyzed for its ability to bind to a panel of anti-gp350/220 monoclonal antibodies and to a series of anti-EBV positive human sera. The antigens also were used as immunogens for the immunization of rabbits. Each expressed protein was found to be unique both in its pattern of reactivity to the various antibodies and in the spectrum of antibody induced following animal immunization. These results suggest that cell-specific post-translational modifications critically influence the antigenic presentation of the expressed proteins. Nonetheless, all of the mammalian cell-derived versions of the membrane antigen were found capable of inducing EBV-specific neutralizing antibodies.     

Comparison of five short-term assays that measure nonspecific cytotoxicity mediated to tumor cells by activated macrophages

Five different short term assays (less than 48 h) used to measure macrophage-mediated, nonspecific cytotoxicity were compared under similar conditions in the same laboratory using the same reagents. The purpose was to determine the extent to which results were comparable. Three of the assays were dependent on the release of a radioisotope to measure cytotoxicity, one was dependent on cell counting, and the last was dependent on flow cytometric quantification of remaining viable tumor target cells after they had been exposed to macrophages. The variables examined were the following: three different populations of macrophages; four different kinds of target cells; two types of radioisotopes; and two different agents that trigger the expression of cytolytic activity by primed macrophages. Recombinant gamma interferon was used as the priming agent in all the experiments. There was unexpectedly good agreement between the results of the various assays. No differences were found among the different macrophage populations, the isotopes or the triggering agents. Perhaps the most important finding was that differences in target cell susceptibility to killing by activated macrophages, which were apparent in assays of less than 24 h duration, disappeared when the same kinds of targets were compared in assays of greater than 40 h duration. The results of this study are an important first step toward standardizing the way in which macrophage-mediated, nonspecific cytotoxicity is measured in short-term assays, laboratory to laboratory.     

Role of primate basal ganglia and frontal cortex in the internal generation of movements

The purpose of these studies was to investigate neuronal activity in the basal ganglia and frontal cortex in relation to the internal generation of goal-directed movements. Monkeys performed goal-directed arm movements at a self-chosen moment in the absence of phasic stimuli providing external temporal reference. They were rewarded with a small morsel of food for each movement, although automatic or repetitive behavior was not reinforced. For reasons of comparison, animals were also trained in a delayed go no-go task in which visual cues instructed them to perform or refrain from an arm movement reaction to a subsequent trigger stimulus. This report describes the activity of neurons in the head of the caudate nucleus and rostral putamen preceding self-initiated arm movements and compares it with instruction-induced preparatory activity preceding movements in the delay task. A total of 497 caudate and 354 putamen neurons were tested in the delay task. Two types of preparatory activity were observed: (1) transient responses to the instruction cue, and (2) sustained activity preceding the trigger stimulus or movement onset. Transient responses were found in 48 caudate and 50 putamen neurons, occurring twice as often in movement ('go') as compared to no-movement ('no-go') trials, but rarely in both. These responses may code the information contained in the instruction relative to the forthcoming behavioral reaction. Sustained activity began after instruction onset and lasted until the trigger stimulus or the arm movement occurred, this being for periods of 2-7 s, 12-35 s, or up to 80 s, depending on the task requirements. This activity was seen in 47 caudate and 45 putamen neurons, was largely confined to go trials, and was unrelated to the preparation of saccadic eye movements. In some cases, this activity began as direct responses to the instruction stimulus, but in the majority of cases developed more gradually before the movement. Thus, both transient and sustained activations appear to be related to the preparation of movements. A total of 390 caudate and 293 putamen neurons were tested during self-initiated movements. Activity preceding earliest movement-related muscle activity was found in 32 caudate and 42 putamen neurons. This premovement activity began 0.5-5.0 s before movement onset (median 1160 ms), increased slowly, reached its peak close to movement onset, and subsided rapidly thereafter. It was unrelated to the preparation of saccadic eye movements. Comparisons between the two tasks were made on 53 neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Short-Term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system

Summary The spontaneous activity of neurons in the head of the striatum was studied in rats 3 days and more than 1 year after a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine system in comparison to unlesioned animals. Cells were detected and tracked by stimulating the excitatory corticostriatal pathway.In unlesioned animals striatal cells discharged at very low frequencies, with a median of 0.04 impulses/second. The activity was increased to 0.28 impulses/second 3 days after the lesion. This increase was related to the degree of dopamine depletion. More than 1 year after the lesion, the frequency had decreased to a level indistinguishable from that measured in unlesioned animals, with a median of 0.03 impulses/second. Cells in 3-day lesioned animals discharged a higher number of bursts at shorter intervals as compared to unlesioned animals, while in long-term denervated animals the bursting pattern was similar to that in unlesioned animals.This demonstrates that removal of the dopaminergic input results in increased activity only during an initial phase and that adaptive processes subsequently occur. The data from this Parkinsonian model suggest that symptoms of this disease cannot simply be related to an increased striatal cellular activity. The fact that the initially increased spontaneous activity adapted indicates that functional effects of a lesion can only be evaluated when studying the resulting changes throughout a time course.     

Enhancement of wound healing by topical treatment with epidermal growth factor

Experimental studies in animals have demonstrated that the topical application of epidermal growth factor accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns. We conducted a prospective, randomized, double-blind clinical trial using skin-graft-donor sites to determine whether epidermal growth factor would accelerate the rate of epidermal regeneration in humans. Paired donor sites were created in 12 patients who required skin grafting for either burns or reconstructive surgery. One donor site from each patient was treated topically with silver sulfadiazine cream, and one was treated with silver sulfadiazine cream containing epidermal growth factor (10 micrograms per milliliter). The donor sites were photographed daily, and healing was measured with the use of planimetric analysis. The donor sites treated with silver sulfadiazine containing epidermal growth factor had an accelerated rate of epidermal regeneration in all 12 patients as compared with that in the paired donor sites treated with silver sulfadiazine alone. Treatment with epidermal growth factor significantly decreased the average length of time to 25 percent and 50 percent healing by approximately one day and that to 75 percent and 100 percent healing by approximately 1.5 days (P less than 0.02). Histologic evaluation of punch-biopsy specimens taken from the centers of donor sites three days after the onset of healing supported these results. We conclude that epidermal growth factor accelerates the rate of healing of partial-thickness skin wounds. Further studies are required to determine the clinical importance of this finding.     

Effects of triton WR-1339 on the rat yolk sac placenta

The cytochemistry and ultrastructure of the lysosomal area of the rat's yolk sac placenta was studied at various stages of development. The lysosomal area, located at the apical end of the yolk sac epithelial cell between the microvillous border and the nucleus, consisted of dense bodies that persisted from day 10 of pregnancy through gestation and multivesicular bodies that are present only through day 12. Acid phosphatase activity was restricted to the dense material and to the membranes of this area. Two types of pinocytotic vesicles were present in all stages of development. One was a tubular structure containing dense material and the other, a saccular, clear structure containing a “fuzz-lining” and membrane remnants. Possible relationships between the pinocytotic vesicles and the dense and multi-vesicular bodies were considered. The injection of Triton WR-1339 on day 11 of pregnancy resulted in a vacuolation of the dense and multivesicular bodies. This vacuolation began 15 minutes after injection and maximum effect was reached within 12--24 hours. A reorganization of the lysosome area occurred on days 15--16 in those animals in which pregnancy continued to term. This reorganization consisted of an increase in the dense material within the vacuoles and a reduction in vacuole size. The vacuoles remained distended in those animals in which death and resorption of the fetus occurred. The first cellular changes associated with death occurred between 48--60 hours post-injection. The microvilli became shorter, thicker and reduced in number; the pinocytotic vesicles disappeared from the cell surface; the endoplasmic reticulum became dilated and vesiculated; and vesicles were formed from the cristae of the mitochondria. With the injection regimen used in this study, 25% of the litters were resorbed while the remainder of the pregnant rats delivered viable fetuses at term.