Ultrastructure de la thyroïde humaine

Summary The ultrastructural changes of the thyroid were studied in Basedow disease and nodular goitre. We observed the important and different changes concerning the ultrastructural pattern of microvillis, secretory droplets, endoplasmatic reticulum and mitochondria. This study throws some light upon human thyroid histophysiology.     

The effects of continuous chloroform and halothane anesthesia on plasma prolactin levels in ovariectomized estrogen-treated rats

Summary In ovariectomized, estrogen-treated rats bearing indwelling aortic catheters, continuous inhalation of chloroform or halothane resulted in increases in plasma prolactin levels 10 min after the exposure to the anesthetics. The plasma prolactin levels over the subsequent 2 h, however, were not significantly different from that of the control animals.Supported by NSF Research Grant BMS 74-17332.The authors wish to express their appreciation to Mrs Cynthia Van De Walle for her outstanding assistance in the performance of the prolactin RIA and the art work.     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin.

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

Amino acid incorporation by human milk fat globules membranes (author's transl)]

Human milk fat globule membranes (MFGM) can incorporate radioactive 14C amino acids in a hot trichloracetic acid-insoluble material. Aspecific adsorption and bacterial contamination are unlikely. The products of protein synthesis were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate or by action of proteolytic enzymes. Various inhibitors of protein synthesis were assayed. Fragments of rough endoplasmic reticulum or mitochondria could be involved in this incorporation.     

Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity

Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E1 analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation.     

Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity

Summary Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E₁ analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation.     

Incorporation d'acides aminés radioactifs dans les membranes des globules lipidiques du lait humain

Summary Human milk fat globule membranes (MFGM) can incorporate radioactive¹⁴C amino acids in a hot trichloracetic acid-insoluble material. Aspecific adsorption and bacterial contamination are unlikely. The products of protein synthesis were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate or by action of proteolytic enzymes. Various inhibitors of protein synthesis were assayed. Fragments of rough endoplasmic reticulum or mitochondria could be involved in this incorporation.     

Proteinzuwachs und Glukoseaufnahme isolierter Myokardzellen von Hühnchenembryo und Ratte in der Primärkultur

Summary Primary cultures of isolated myocardial cells of the chicken embryo (Ch) and of the new-born rat (R) present a characteristic behaviour of an increase of protein synthesis and glucose uptake: while in the Ch the increase of protein synthesis exceeds, in the R a high glucose uptake is shown. Both processes could be influenced by insulin.     

Eiweissvermehrung in ein- und zweikernigen systemen vonAcetabularia

Summary (1) The rate of protein synthesis was found to be different inAcetabularia crenulata andAcetabularia mediterranea the higher cytoplasmic protein synthesis inA. crenulata depending upon the diameter of the stalk.(2) In systems containing one or two nuclei, there was no difference in the rate of cytoplasmic synthesis of proteins. This corresponds to the diminution of size and efficiency of the nuclei in binucleated systems.(3) In interspecific grafts, the rate of cytoplasmic protein synthesis corresponds nearly to the rate of protein synthesis ofAcetabularia crenulata. Corresponding to morphogenetic processes, thecren-action is prevalent.     

Ultrastructural and quantitative analysis of the lipid droplet clustering induced by hepatitis C virus core protein

Hepatitis C virus (HCV) release is linked to the formation of lipid droplet (LD) clusters in the perinuclear area of infected cells, induced by the core protein. We used electron microscopy (EM) to monitor and compare the number and size of LD in cells producing the mature and immature forms of the HCV core protein, and 3D EM to reconstruct whole cells producing the mature core protein. Only the mature protein coated the LD and induced their clustering and emergence from endoplasmic reticulum membranes enriched in this protein. We found no particular association between LD clusters and the centrosome in reconstructed cells. The LD clustering induced by the mature core protein was associated with an increase in LD synthesis potentially due, at least in part, to the ability of this protein to coat the LD. These observations provide useful information for further studies of the mechanisms involved in HCV-induced steatosis.     

Signaling pathways between the plasma membrane and endoplasmic reticulum calcium stores

This review discusses multiple ways in which the endoplasmic reticulum participates in and is influenced by signal transduction pathways. The endoplasmic reticulum provides a Ca2+ store that can be mobilized either by calcium-induced calcium release or by the diffusible messenger inositol 1,4,5-trisphosphate. Depletion of endoplasmic reticulum Ca2+ stores provides a signal that activates surface membrane Ca2+ channels, a process known as capacitative calcium entry. Depletion of endoplasmic reticulum stores can also signal long-term cellular responses such as gene expression and programmed cell death or apoptosis. In addition to serving as a source of cellular signals, the endoplasmic reticulum is also functionally and structurally modified by the Ca2+ and protein kinase C pathways. Elevated cytoplasmic Ca2+ causes a rearrangement and fragmentation of endoplasmic reticulum membranes. Protein kinase C activation reduces the storage capacity of the endoplasmic reticulum Ca2+ pool. In some cell types, protein kinase C inhibits capacitative calcium entry. Protein kinase C activation also protects the endoplasmic reticulum from the structural effects of high cytoplasmic Ca2+. The emerging view is one of a complex network of pathways through which the endoplasmic reticulum and the Ca2+ and protein kinase C signaling pathways interact at various levels regulating cellular structure and function.     

Etude des modifications quantitatives des cellules somatotropes hypophysaires de rat après thymectomie. Action opothérapique de substitution à l'aide d'un extrait thymique

Summary Removal of thymus is followed by a degranulation of somatotropic cells, by an increase of the surface of the granular endoplasmic reticulum, and of the plasma level of growth hormone. An opotherapic substitution was realized with a thymic extract.

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Les auteurs remercient le NIAMD pour la fourniture des réactifs permettant le dosage radioimmunologique de la GH plasmatique de rat.     

Zum Proliferations-Stoffwechsel der Rattenleber nach Teilhepatektomie. Autoradiographische Untersuchungen mit3H-Cytidin,-Phenylalanin und -Thymidin

Summary During the first wave of parenchymal liver regeneration in adult rats after partial hepatectomy, the cellular synthesis and migration of RNA and the metabolism of protein were studied by autoradiography following an injection of³H-cytidine or³H-l-phenylalanine and double injections of 1 of these precursors +³H-thymidine. The following results were obtained: the synthesis and migration of RNA and the metabolism of protein are enhanced under these conditions of proliferation. In spite of this, the relation of metabolic activity in nucleolus, karyoplasm and cytoplasm remains constant. By double injection techniques it is proved that no differences exist in migration of RNA into the cytoplasm and cytoplasmic protein synthesis between cells with or without DNA synthesizing nuclei.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Legionella pneumophila down-regulates MHC class I expression of human monocytic host cells and thereby inhibits T cell activation

Legionella (L.) pneumophila, the causative agent of Legionnaires disease, is an intracellular pathogen of alveolar macrophages that resides in a compartment displaying features of endoplasmatic reticulum (ER). In this study, we show that intracellular multiplication of L. pneumophila results in a remarkable decrease in MHC class I expression by the infected monocytes. During intracellular multiplication, L. pneumophila absorbs ER-resident chaperons such as calnexin and BiP, molecules that are required for the correct formation of the MHC class I complex. Due to reduced MHC class I expression, stimulation of allogeneic blood mononuclear cells was severely inhibited by infected host cells but cytotoxicity of autologous natural killer cells against Legionella-infected monocytes was not enhanced. Thus, reduced expression of MHC class I in infected monocytes may resemble a new immune escape mechanism induced by L. pneumophila.Received 22 November 2004; received after revision 27 December 2004; accepted 5 January 2005     

Expression and cellular distribution of perchloric acid-soluble protein is dependent on the cell-proliferating states of NRK-52E cells

To clarify the biological role of kidney perchloric acid-soluble protein 1 (K-PSP1), its expression and intracellular distribution were examined in normal rat kidney epithelial NRK-52E cells. K-PSP1 expression was low during the proliferating phase and high in the stationary phase, and shown to have a negative relationship with the protein-synthesizing activity of the cells. Immunocytochemical studies revealed that K-PSP1 is predominantly located in the cytosol, especially in endoplasmic reticulum and Golgi apparatus of proliferating cells. In the stationary phase, K-PSP1 was not detected immunologically even though protein and mRNA expression were high. This disappearance of reactivity with anti-serum seems to be due to a conformational change in K-PSP1 induced by unknown factors. These results suggest that the role of K-PSP1 is to regulate cell proliferation, and this may be related to a previously reported ability to inhibit protein synthesis.     

Steroid-induced concentric membrane whorls in dog liver

Summary When daily doses of 10 mg/kg of the androgenic steroids fluoxymesterone, methyltestosterone, testosterone propionate, oxymetholone and mepitiostane were administered to adult male and female beagle dogs for 6 months, concentric membrane whorls were produced in the hepatocytes of all groups. The whorls frequently had a central core mainly composed of lipids or mitochondria and the membranes of the whorls, consisting of paired membranes, continued to the smooth or granular endoplasmic reticulum at the periphery of the structures.     

In vitro development ofXenopus skin glands producing 5-hydroxytryptamine and caerulein

The granular glands of amphibian skin synthesize and store a large amount of bioactive amines and peptides which are structurally similar to mammalian brain-gut peptides. To investigate the development of peptide- and amine-producing cells in the granular glands, pieces of dorsal skin taken at various stages fromXenopus laevis tadpoles were cultured, and the contents of caerulein and 5-hydroxytryptamine (5-HT) were measured. When pieces of skin from tadpoles at stages 57 to 60 (Nieuwkoop and Faber stages) were cultured in a medium containing 10% fetal calf serum (FCS medium) or one containing FCS treated with charcoal (chFCS medium), the caerulein and 5-HT levels were increased for the six days of the incubation period. The caerulein content was lower in the chFCS medium than in the FCS medium. Addition of thyroxine to the chFCS medium had no significant effect on the caerulein content. These results show that the caerulein-and 5-HT-producing cells of the granular glands can develop in a culture system with FCS- or chFCS-containing media, and suggest that FCS contains substances which are absorbed by charcoal and stimulate development of the amine- and peptideproducing cells of the glands. In a preliminary search for correlation between caerulein and 5-HT synthesis, addition of 5-hydroxytryptophan (5-HTP), a precursor to 5-HT, to the FCS medium increased 5-HT content and, conversely, caused significant decrease in caerulein content, suggesting that accumulation of caerulein in the granular glands is influenced by the amount of 5-HT synthesis. These studies indicate that this culture system is a useful model for investigating the development of peptide- and amine-producing cells.     

Influence of ventilatory and circulatory changes on the pharmacokinetics of halothane and isoflurane

In two groups of dogs, uptake and elimination of halothane and isoflurane were studied using a closed-loop anesthesia system which automatically controlled end-tidal halothane or isoflurane partial pressure at minimal alveolar concentration (MAC) equivalent levels. Hemodynamic and respiratory variables were recorded and the anesthetic partial pressure was measured in the inspired and expired air, as well as in the arterial, cerebrovenous and mixed venous blood. Data were recorded during wash-in, hyperventilation, hypercirculation, hypotension and wash-out. For halothane, the controller delivered a higher inspired partial pressure than for isoflurane to compensate for the higher blood/gas partition coefficient. This was especially pronounced during the wash-in and the hypercirculation periods. Smaller differences between halothane and isoflurane partial pressures occurred during hyperventilation, hypotension and the wash-out period and could be explained by the lower solubility of isoflurane. These results show that even under unstable ventilatory and hemodynamic conditions, the inspired concentration of isoflurane has to be adjusted less often and to a smaller degree than that of halothane if end-tidal concentrations are to be maintained constant.