Bone Marrow Graft in Man after Conditioning by Antilymphocytic Serum

Allogeneic bone marrow grafts carried out after previous administration of antilymphocytic serum alone were attempted in 16 patients. Of these, six had acute myeloblastic leukaemia, four acute lymphoblastic leukaemia, and one a blast cell crisis in polycythaemia vera. Ten of these patients were in an overt phase of the disease and resistant to chemotherapy, while nine had complete agranulocytosis. In five of these patients erythrocyte and leucocyte antigenic markers demonstrated the establishment of the graft. One patient had thalassaemia major, and four others had aplasia of the bone marrow, in one case due to chloramphenicol poisoning and in another to virus hepatitis. The grafts were successful in the last two patients and transformed their clinical condition.No signs of early acute secondary disease were noted in any of the patients, either when the donor had been given antilymphocytic serum or when he was untreated. The grafts had no adoptive immunotherapeutic effect on the acute leukaemia. These observations have clearly shown that antilymphocytic serum has an immunosuppressive effect in man when it is used alone.     

Zur überwindung der biologischen Grenze Meer—Land durch Mollusken

Zusammenfassung Je höher marine Gastropoden ins Supralitoral vordringen, umso größer wird ihre Salinitätstoleranz. Das äußert sich im Überleben auf extremen Salinitäten, in der Waschstumsgeschwindigkeit und in der Fortpflanzungsrate.Die toleranz wird bei den drei großen Gastropodengruppen—Opisthobranchier (Limapontia depressa)—Prosobranchier (Assiminea grayana)—Pulmonaten (Ovatella myosotis)—im niedrigsalzigen Bereich durch Entwicklung einer Hypertonieregulation und bei hoher Salinität durch Poikilosmotie ermöglicht. Während adulte Schnecken des Supralitorals große Schwankungen im Salzgehalt ertragen, sind die Eier dagegen sehr empfindlich; Embryonen entwickeln sich bevorzugt bei Salinitäten, bei denen die Gelege von den Adulten produziet wurden.

---

The emigration of Gastropods from the seaII. Studies on Limatpontia capitata, L. depressa und Assiminea grayana

Summary The higher marine Gastropods live on the shore the more their salinity tolerance increases. This is expressed in the animals' survival, their growth rate, and their reproduction rate on extreme salinity concentrations. In all the three gastropod groups—Opisthobranchia (Limapontia depressa), Prosobranchia (Assiminea grayana), Pulmonata (Ovatella myosotis)—a more or less effective hyperosmotic regulation has evolved which enables the animals to live with low salinity concentrations in their surrounding. In high salinities they are poikilosmotic. Adult supralittoral Gastopods can stand considerable salinity changes. The eggs are more delicate: The embryos develop best when the eggs stay on the salinity where they were produced even if the concentrations are extremely high or low.

     

Zur Überwindung der biologischen Grenze Meer—Land durch Mollusken

Zusammenfassung Die Überwindung der biologischen Grenze zwischen Meer und Land durch Mollusken ist bisher nur wenig im Hinblick auf physiologische Umstellungen untersucht worden. Unter diesem Aspekt wurden Experimente durchgeführt an Alderia modesta, einem amphibisch lebenden Opisthobranchier des unteren Supralitorals, und an Ovatella myosotis, einer Pulmonate, die im oberen Supralitoral vorkommt. Alderia zeigt eine relativ enge Salinitätstoleranz. Zu hohe und zu niedrige Salzgehalte hemmen die Entwicklung, führen zu Mißbildungen bei der Embryonalentwicklung und lassen adulte tiere rasch eingehen. In Beziehung zu der Salinität der angrenzenden Gewässer (Brackwasser der Ostsee und der Ästuare, Meerwasser der Nordsee) existieren verschiedene Biotypen, die auf Aussüßung und hohe Salzkonzentration unterschiedlich reagieren.Die weiter ins Supralitoral vorgedrungene Ovatella myositis hat eine wesentlich breitere Salinitätstoleranz. Schädigungen der Adulten treten auf Süßwasser nicht, auf Salzwasser erst oberhalb von 55 auf. Durch schrittweise Adaptation können höhere Konzentrationen ertragen werden. Der Toleranzunterschied zwischen den untersuchten Populationen ist genetisch bedingt. Eiablage, Embryonalentwicklung und Wachstum erfolgen im Bereich zwischen 5 und mindestens 50 Substratsalinität.Physiologisch wird diese große Salinitätstoleranz durch ein fast durchgehendes poikilosmotisches Verhalten ermöglicht. Auf sehr ausgesüßtem Substrat sind die Schnecken stark hypertonisch (auf Süßwasser hat das Binnenmedium auf 7), im ganzen übrigen Bereich weniger stark (3–4 über der Substratsalinität). Im oberen Extrembereich vermögen die Tiere diese Hypertonie offenbar nur schwer aufrechtzuerhalten (vgl. S. 149).Die Veränderungen von Gastropoden auf dem Wege vom Meer über das Supralitoral zum Land werden diskutiert; im Gebiet der Salzwiesen läßt sich ein günstigeres Schema zu dieser Frage aufstellen als bei den bisher meist zitierten Littorinen.

---

On the emigration of gastropodes from the sea: Studies on Alderia modesta and Ovatella myosotis

Summary Up to now little attention has been paid to the phylogenetic emigration of gastropods from the sea: almost nothing is known about the physiological changes which enable snails to live in terrestrial habitats. To help solve this question, experiments were carried out on Alderia modesta, an opisthobranch slug of the lower supralittoral, and Ovatella myositis, a primitive pulmonate snail of the upper supralittoral. In each case two subspecies were studied.North Sea Alderias differ from their Baltic counterparts in size and salinitytolerance. The difference in size between Ovatella of the Mediterranean and of the Baltic is very slight. There is a marked difference, however, in the salinity-tolerance. Alderia modesta survives in a comparatively narrow range of different salinities. The optimum is between 10 and 20 for Baltic specimens and between 15 and 35 for those of the North Sea. The results are the same in and out of water. Ovatella can live on a freshwater substratum as well as on 55. Specimens of the Mediterranean can even become adapted to 90. Flooded with water of differrent salinities the tolerated range becomes markedly smaller. Eggs are produced between 5 and 50 (Baltic specimens) or 5 and 65 (Mediterranean specimens). All eggs develop without being damaged between 5 and 40 and 10 and 45 respectively. The optimal salinity-concentration for growth and egg-production is 10. Salinity-concentrations below and above these marks disturb the development. In one spawn-mass some eggs cleave normally, others become deformed, and again others do not cleave at all. This heterogeneous reaction points to the existence of something like a physiological polymorphism in regard to salinity-tolerance. The salinity-concentration of the blood of Ovatella was measured after a long-term acclimatisation. Ovatella is poikilosmotic and slightly hypertonic (3–4) throughout almost the whole range of salinities it tolerates. On extremely low concentrations it becomes more hypertonie; on extremely high concentrations it becomes nearly isotonic.

     

Increased free-cystine content of fibroblasts cultured from patients with cystinosis

The presence of a significantly increased content of free-cystine in skin fibroblasts from both homozygotes and heterozygotes for cystinosis emphasizes the central role of cystine in this disease, even though the primary defect responsible for cystine accumulation is yet to be determined. The studies described in this communication provide evidence that cystine is compartmentalized in a subcellular location in cystinotic cells. In fact, the very growth of cystinotic fibroblasts in the presence more than 100 times the usual content of free-cystine is evidence that the accumulated cystine is not freely dispersed throughout the cell, since would otherwise inhibit many enzymes requiring free sulfhydryl groups for activity (Patrick, 1965). We have no evidence as to whether the cystine is located in a known subcellular organelle or in a previously unrecognized location. Skin fibroblasts may provide a convenient tool to pursue these questions.     

EPITHELIAL CELL PENETRATION AS AN ESSENTIAL STEP IN THE PATHOGENESIS OF BACILLARY DYSENTERY.

LaBrec, Eugene H., Herman Schneider, Thomas J. Magnani, and Samuel B. Formal. Epithelial cell penetration as an essential step in the pathogenesis of bacillary dysentery. J. Bacteriol. 88:1503-1518. 1964.-A parent strain of Shigella flexneri 2a and a colonial mutant derived from it were studied in three animal models. Both strains were equally virulent for mice when living cells suspended in hog gastric mucin were injected by the intraperitoneal route. Feeding the parent strain to starved guinea pigs, followed by the intraperitoneal injection of opium, resulted in the formation of ulcerative lesions in the intestinal tract and in the death of these animals. When the colonial variant was fed to similarly prepared animals, the animals survived and the intestinal tract remained normal. The parent produced diarrheal symptoms and intestinal lesions after its oral administration to rhesus monkeys; the variant caused neither symptoms nor pathology in this species. Studies were carried out to define the characteristics present in the parent strain and absent in the colonial mutant, which would enable the parent to produce ulcerative lesions of the bowel and death in the guinea pig model or intestinal lesions and diarrheal symptoms in the monkey. Neither serological studies nor growth studies conducted both in vitro and in vivo offered a clue to explain this difference. The virulent parent strain was shown to penetrate the bowel epithelium and enter the lamina propria; the avirulent mutant did not do this. Entrance to the lamina propria was by way of the epithelial cell of the mucosa. The avirulent mutant did not possess the capacity to penetrate this cell. This observation was extended to show that the virulent parent possesses the ability to infect and multiply within HeLa cells; furthermore, the organisms are able to penetrate epithelial cells of the guinea pig cornea, causing ulcerative lesions. The avirulent variant possesses neither of these capacities. It is suggested that epithelial cell penetration is a major factor in determining the pathogenicity of dysentery bacilli.