Effects of confinement (110 and 240 days) on neuroendocrine stress response and changes of immune cells in men.

The aim of the study was to evaluate the effects of long-term confinement on stress-permissive neuroendocrine and immune responses in humans. Two groups of four male subjects were confined 240 days (group 240) or 110 days (group 110) in two space modules of 100 or 200 m3, respectively. During confinement, none of the volunteers developed psychic stress as could be examined and verified by a current stress test. However, in group 240 but not in group 110, the diurnal rhythm of cortisol secretion was slightly depressed and the urine excretion of norepinephrine significantly increased. The innate part of the immune system became activated as seen by a rise in the number of circulating granulocytes and the enhanced expression of beta2-integrins. In contrast, the ratio of T-helper to T-suppressor cells decreased. All these effects, observed during confinement, were even more pronounced in both groups when values of endocrinological and immunological parameters were compared between before and 1 wk after the end of the confinement period. Hence, return to normal life exerts pronounced effects to a much higher degree, irrespective of how long or under which conditions individuals were confined. Because the delayed-type hypersensitivity skin reaction against recall antigens remained unaffected, it is to be presumed that confinement appears to induce distinct sympathoadrenergic activation and immunological changes but no clinically relevant immunosuppression.     

Synthesis of nitrogen oxides from L-arginine by macrophage cytosol: requirement for inducible and constitutive components

Cytosols prepared from murine peritoneal macrophages and the RAW 264 macrophage cell line catalyzed conversion of L-arginine to the labile vaso-relaxant nitric oxide and its accumulating endproducts, nitrite and nitrate. This activity required previous exposure of the cells to interferon-gamma and bacterial lipopolysaccharide. Nitrogen oxide synthetase activity was characterized further using nitrite + nitrate production as an indicator of the synthesis of all three nitrogen oxides. Nitrogen oxide synthetase activity was heat-sensitive, NADPH-dependent, and exhibited substrate stereospecificity. The nitrite + nitrate formation was proportional to time and concentration of cytosol. However, dilution decreased the specific activity, suggesting a cofactor requirement in addition to NADPH. Specific activity was restored by addition of cytosol from non-activated macrophages, which itself did not make nitric oxide. Both high and low molecular weight fractions of control macrophage cytosol were required to restore activity of cytosol from activated macrophages that had been either diluted or partially purified. Thus, the enzymatic system involved in nitric oxide synthesis by murine macrophages consists of at least one inducible and two constitutive components.     

T-cell-antigen positive, E-rosette negative acute lymphoblastic leukaemia (author's transl)]

The lymphoblasts from 100 patients with acute lymphocytic leukaemia were investigated for the expression of receptors for sheep erythrocytes (E) and of a specific heterologous T cell antigen (T). In 17 cases, both T cell markers were expressed simultaneously on the leukaemic cells. In 13 cases only T antigens could be demonstrated on the lymphoblasts. A quantitative analysis of T antigens by immunoautoradiography revealed that the T expression of E-T+ -lymphoblasts was in general like that of E+T+-lymphocytes in the blood of normal persons, in several cases even higher. Therefore, the failure of E-rosette formation cannot be correlated to a decrease of the other T cell differentiation marker. In 7 out of 9 tested cases, a strong acid phosphatase reaction product located paranuclearly could be demonstrated. Complement-receptors were expressed in 3 of 5 cases which were also demonstrated in some cases of the E+T+-ALL group. The latter group was characterized by a T antigen expression like that of thymocytes. 4 cases of the E-T+ALL group were adults. Since the leukaemia cells of 2 cases were negative for acid phosphatase, PAS and all surface markers including cALL antigen, the T antigen can classify undifferentiated and otherwise unclassificable leukaemias. The clinical signigicance of the E-T+-ALL seems to be important since 5 out of 9 children with this type of ALL died soon after diagnosis.     

Mutagenicity of 5,6-dimethoxysterigmatocystin, a metabolite from Aspergillus multicolor, in the Salmonella/microsome system.

The natural sterigmatocystin derivative, 5,6-dimethoxysterigmatocystin, was found to be a mutagen for Salmonella typhimurium strains TA98 and TA100 after metabolic activation in a mammalian microsome system.     

Purification and characterization of a 22-kDa microsomal protein from rat parotid gland which is phosphorylated following stimulation by agonists involving cAMP as second messenger

Stimulation of secretion in exocrine glands by agonists involving cAMP as second messenger leads to the phosphorylation of the ribosomal protein S6 (protein I) and two other particulate proteins with apparent molecular masses of 24 kDa (protein II) and 22 kDa (protein III) [Jahn, R., Unger, C. & S?ling, H. D. (1980) Eur. J. Biochem. 112, 345-352]. This report describes the purification and characterization of protein III. Solubilization studies indicate that protein III is an intrinsic membrane protein. It could be extracted from the endoplasmic reticulum membrane only with Triton X-100, SDS or concentrated formic or acetic acid. The purification of this protein involved extraction of the microsomes with Triton X-100, removal of the detergent by acetone precipitation, extraction of water-soluble proteins, lipids and lipoproteins, and preparative SDS polyacrylamide gel electrophoresis. The protein has a basic pI (greater than 8.7). For determination of the amino acid composition of protein III and for sequencing of its amino-terminal portion, the protein was electroeluted out off the gel, the detergent removed and the protein finally purified by reversed-phase HPLC. Protein III could be phosphorylated in vitro by the catalytic subunit of the cAMP-dependent protein kinase to a degree of approximately 0.14 mol phosphate/mol protein. The only phosphopeptide obtained after in vitro phosphorylation and subsequent tryptic or chymotryptic digestion was identical with the phosphopeptide obtained after stimulation of intact rat parotid gland lobules with isoproterenol. The sequence of this peptide was Lys-Leu-Ser(P)-Glu-Ala-Asp-Asn-Arg. It was confirmed by an analysis of the synthetic peptide following in vitro phosphorylation with cAMP-dependent protein kinase. The first 41 N-terminal residues of protein III were sequenced. So far no sequence homology with other known peptides or proteins could be found.     

Selective fetal malnutrition: The effect of ethanol and acetaldehyde upon in vitro uptake of alpha amino isobutyric acid by human placenta

Uptake of alpha amino isobutyric acid was measured in human placental villus tissue exposed $\text{in vitro}$ to ethyl alcohol (ethanol) (0.3 g/dl–2 g/d1) or acetaldehyde (50 μM-20 mM). Ethanol and acetaldehyde significantly inhibited uptake of amino acid at higher, pharmacologic concentrations (2 g/dl and 2–20 mM respectively). Inhibition by 10 mM acetaldehyde was partially reversible. The results suggest that the human placenta is resistant to acute ethanol-associated effects upon amino acid transport $\text{in vitro}$. However, both ethanol and its major circulating metabolite, acetaldehyde, may still alter placental function during $\text{in vivo}$ chronic exposure.     

Changes of telomere lengths in human intracranial tumours

The termini of human chromosomes comprise stretches of G-rich repeats that are about 5–20 kilobase (kb) in length. The size of the telomeres can be determined by hybridization with probes specific for these (ttaggg)_n sequences after digestion of chromosomal DNA with appropriate restriction enzymes and electrophoretic separation of the fragments. Here, probing with the ³²P-labelled synthetic (TTAGGG)₃ oligonucleotide revealed length changes of the telomeres occurring in intracranial tumours. Among 60 samples analysed, 41.7% showed telomere elongation, and 21.7% telomere reduction, whereas 36.7% of the tumours exhibited equal lengths compared with the patients' peripheral blood leukocytes. Most of the elongated glioma telomeres exceeded in length those of untransformed astrocytes derived from human fetal tissue.     

Auer bodies in acute lymphocytic leukaemia and B-cell lymphoma: evidence for a common progenitor of myeloid and lymphoid cells?

In a patient with acute lymphocytic leukaemia (pre-T ALL) and another patient with leukaemic generalization of B-cell lymphoma Auer bodies were found in a few immature cells. The diagnosis in both cases was based on clinical grounds, morphology, cytochemistry, and immunological marker analysis of the blasts. Auer bodies are known to be a marker of high significance for acute non-lymphocytic leukaemias. Therefore the findings described suggest mixed leukaemias with either T-cell or B-cell predominance. It provides further evidence for the existence of a common progenitor of myeloid and lymphoid cells.