With reference to the relations between proliferation activity of erythroblasts and their sensitivity to hypoxia

Riassunto Da ricerche precedenti era apparso che l'ipossia inibisce la proliferazione degli eritroblasti e che il megaloblasto è più inibito del normoblasto. Onde stabilire se il grado di sensibilità è strettamente collegato con la particolare natura del tipo di eritroblasto — normo- e megaloblasto — oppure se tale grado è in rapporto soltanto con l'intensità proliferativa cellulare, gli autori hanno studiato l'influenza dell'ipossia su normoblasti altamente proliferanti (in particolare, quelli della Talassemia major). Essi hanno potuto rilevare che questi ultimi posseggono lo stesso grado di sensibilità all'ipossia del normoblasto del midollo osseo umano normale, inferiore quindi a quello del megaloblasto dell'anemia perniciosa. Pertanto gli autori concludono che le differenze tra normoblasto e megaloblasto rispetto al fenomeno esplorato sono strettamente correlate con l'intima biologia dei due tipi cellulari.     

Defining the resistance to oxygen transfer in tissue hypoxia

Studies of O2 supply in freshly isolated adult mammalian cells provide new insight into the factors that limit mitochondrial oxygenation in vivo. Of particular importance, mitochondria are present at high densities and often in apparent clusters, both of which contribute to local O2 gradients under hypoxic conditions. Current evidence indicates that the mitochondrial distribution is a component of the differentiated phenotype of adult mammalian cells and that specific motors and anchoring mechanisms are present to allow redistribution in response to developmental, physiological and pathological challenges. To compare the importance of resistance to O2 transfer under different conditions and at different sites along the supply path in vivo, a simple mathematical expression of relative resistance to O2 supply is introduced. Under various pathophysiological conditions, this resistance increases in specific regions of the pulmonary, circulatory or cellular supply path and results in O2 deficiency in the mitochondria. Regardless of cause, the relative resistance increases dramatically in the vicinity of mitochondrial clusters during hypoxia.     

Adrenal responses to hypoxia and hypercapnia in the young calf

Summary Quantitative analysis of adrenal responses to moderate hypoxia and hypercapnia in the conscious calf shows that the sensitivity of the adrenal cortical response far exceeds that of the adrenal medulla.Acknowledgment. This work has been supported by grants from the Agricultural Research Council, the Medical Research Council and the Wellcome Trust. We are also indebted to Dr D. M. Burley (CIBA) for his continued support.     

Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia

Summary Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N₂, 12% O₂ and 4% CO₂. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p<0.01) and a decrease in cyclic GMP (p<0.05) as compared to hearts perfused for 60 min with media gassed with 96% O₂, 4% CO₂.Acknowledgment. We gratefully acknowledge the excellent technical assistance provided by Mrs Inger O. Boggs and Miss Patricia C. Hannigan. This work was supported in part by U. S. Public Health Service grant HL 14661 from the National Heart and Lung Institute, and by a grant from the Central Ohio Heart Chapter.     

Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia.

Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N2, 12%O2 and 4% CO2. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p less than 0.01) and a decrease in cyclic GMP (p less than 0.05) as compared to hearts perfused for 60 min with media gassed with 96% O2. 4% CO2.     

Abnormal sensitivity to erythropoietin in the erythroblast precursors in Vaquez disease]

Marrow specimens of patients with polycythemia vera rise to erythrocytic colonies in vitro without addition of erythropoietin to the culture. This behavior was never observed with marrow cells of normal subjects or secondary erythrocytosis. These results indicate that the sensitivity of some erythrocytic progenitor cells to erythropoietin is altered in polycythemia vera.     

Species difference in sensitivity to the diabetogenic action of triphenyltin hydroxide

The sensitivity to the diabetogenic action of triphenyltin hydroxide (TPTOH) was investigated in 5 species of experimental animals. A single oral administration of TPTOH produced marked hyperglycemia and triglyceridemia in rabbits and hamsters, but no evidence of diabetes was found in mice, rats and guinea-pigs. No morphological abnormality was observed in islet tissue from TPTOH-treated hamsters.     

Species difference in sensitivity to the diabetogenic action of triphenyltin hydroxide

Summary The sensitivity to the diabetogenic action of triphenyltin hydroxide (TPTOH) was investigated in 5 species of experimental animals. A single oral administration of TPTOH produced marked hyperglycemia and triglyccridemia in rabbits and hamsters, but no evidence of diabetes was found in mice, rats and guinea-pigs. No morphological abnormality was observed in islet tissue from TPTOH-treated hamsters.     

Change in sensitivity to lipopolysaccharide during the differentiation of human monocytes to macrophages in vitro

Mononuclear phagocytes in distinct differentiation stages and cultured under different conditions were tested for their sensitivity towards lipopolysaccharide (LPS), using procoagulant activity (PCA) expression and tumor necrosis factor (TNF) production as indices. The response of mature monocyte-derived macrophages differed from that of freshly isolated monocytes 1) by higher levels of constititive PCA, 2) by responding to approximately 1,000-fold lower concentrations of LPS with PCA and TNF production, and 3) by a faster rise in PCA and TNF production. Due to the high constitutive level of PCA expression, the PCA stimulation index for LPS was low in macrophages when compared with that in monocytes. Thus, during differentiation to macrophages, human monocytes acquire increased sensitivity to LPS (2 orders of magnitude more sensitive than a sensitive turbidimetricLimulus amoebocyte lysate assay). This exquisite sensitivity to LPS is expressed regardless of whether LPS is offered in the presence or absence of lipopolysaccharide binding protein-containing serum. This points to as yet uncharacterized pathways of high affinity interaction between LPS and macrophages.     

Effect of 6-amino-nicotinamide on the tolerance of mice to hypoxic hypoxia

Zusammenfassung Eine einmalige Injektion von 6-Aminonicotinamid (6-ANA) steigerte die Sauerstoffman-gelresistenz von Mäusen in einer Atmosphäre mit 5% O₂ und 95% N₂. Hyperglykämie und Hypothermie, systemische Wirkungen von 6-ANA, konnten als Ursachen der gesteigerten Resistenz ausgeschlossen werden. Es wird deswegen vermutet, dass 6-ANA die anaerobe Utilisation von Glucose im Gehirn fördert.     

The response of human skeletal muscle tissue to hypoxia

Hypoxia refers to environmental or clinical settings that potentially threaten tissue oxygen homeostasis. One unique aspect of skeletal muscle is that, in addition to hypoxia, oxygen balance in this tissue may be further compromised when exercise is superimposed on hypoxia. This review focuses on the cellular and molecular responses of human skeletal muscle to acute and chronic hypoxia, with emphasis on physical exercise and training. Based on published work, it is suggested that hypoxia does not appear to promote angiogenesis or to greatly alter oxidative enzymes in skeletal muscle at rest. Although the HIF-1 pathway in skeletal muscle is still poorly documented, emerging evidence suggests that muscle HIF-1 signaling is only activated to a minor degree by hypoxia. On the other hand, combining hypoxia with exercise appears to improve some aspects of muscle O₂ transport and/or metabolism.     

Acute stress reduces the sensitivity of the vasculature to sympathetic control

Vascular smooth muscle from rabbits subjected to acute severe stress exhibits decreased sensitivity to sympathetic regulation. Stimulation of the sympathetic innervation of isolated vascular segments resulted in a similar subsensitivity as did exposure to norepinephrine (NE) but not histamine. Periodic contraction of these segments caused an increase in their maximum ability to contract independent of the constrictor procedure used. These results suggest that the increase in sympathetically mediated NE release that occurs in stress and some other pathological conditions may result in a blunting of neural control and possibly resistance to certain therapeutic agents.     

Acute stress reduces the sensitivity of the vasculature to sympathetic control

Summary Vascular smooth muscle from rabbits subjected to acute severe stress exhibits decreased sensitivity to sympathetic regulation. Stimulation of the sympathetic innervation of isolated vascular segments resulted in a similar subsensitivity as did exposure to norepinephrine (NE) but not histamine. Periodic contraction of these segments caused an increase in their maximum ability to contract independent of the constrictor procedure used. These results suggest that the increase in sympathetically mediated NE release that occurs in stress and some other pathological conditions may result in a blunting of neural control and possibly resistance to certain therapeutic agents.Supported by U.S.P.H.S. HL 20581 and GM 7304.     

Diurnal fluctuation of sensitivity to noradrenaline in the rat and thyroid adrenal interaction

Summary Diurnal fluctuation of the sensitivity to noradrenaline, which disappeared after thyroidectomy, was restored after novotyrol treatment. Dexamethasone treatment did not result in the restoration of the diurnal fluctuation of noradrenaline calorigenic action in adrenalectomized animals.     

Interphase differential sensitivity to protein synthesis inhibition

Summary The effect of protein synthesis inhibition during interphase ofAllium cepa L. root meristem cells was studied. Anisomycin and cycloheximide were used in intermittent treatments during interphase of a synchronous cell subpopulation labelled as binucleate by caffeine, and the delays in reaching prophase were recorded. High sensitivity to protein synthesis inhibition was detected in G₁ and in the S/G₂ boundary, while protein synthesis in most of the S and G₂ phase was not required for the normal timing of next prophase.     

Gustatory sensitivity of an anuran to cantharidin

Summary Glossopharyngeal nerve stimulation of the bullfrog,Rana catesbiana revealed responsiveness to low levels of cantharidin (1.3×10^–6M), providing a first demonstration of neural gustatory sensitivity of an animal to this defensive chemical from blister beetles, (Meloidae).Acknowledgments. Study supported in part by grant AI 02908 from NIH.     

Gustatory sensitivity of an anuran to cantharidin

Glossopharyngeal nerve stimulation of the bullfrog, Rana catesbeiana, revealed responsiveness to low levels of cantharidin (1.3 x 10(-6) M), providing a first demonstration of neural gustatory sensitivity of an animal to this defensive chemical from blister beetles (Meloidae).