Human breast epithelium transplanted into nude mice

Summary Epithelial components of the normal human breast and their response to hormonal manipulation have been studied in the nude mouse. Six to eight week-old female athymic nude mice were used as the recipients of enzymatically prepared breast organoids, composed of ductal and lobuloalveolar structures. After 12 weeksin situ in the mouse mammary fat pad the human breast tissue retains its normal morphology as demonstrated by the presence of myosin positive myoepithelial cells and keratin positive luminal cells. Monoclonal antibodies M8 and M18 raised to components of the human milk fat globule membrane give a similar staining pattern in the xenografted organoids to that seen in the donor tissue. On mating the recipient female nude mice, the human breast tissue responds with both an increased³H-thymidine labeling index and -lactalbumin production. This model in conjunction with in vitro studies is, therefore, suitable for the study of extrinsic and intrinsic factors controlling differentiation and morphogenesis in the human breast.     

Malignant pheochromocytoma. Effect of oral α-methyl-p-tyrosine upon catecholamine metabolism

Summary In a patient with malignant pheochromocytoma treated unsuccessfully with propranolol and phenoxybenzamine the additional therapy with -methyl-p-tyrosine resulted in a substantial decrease of the blood pressure to almost normal values. His general condition improved considerably. During therapy the urinary excretion rates of catecholamines and all their metabolites dropped to about 50% of control values. O-Hydroxylation of -methyl-p-tyrosine could be demonstrated by the isolation of -methyldopa and -methylnormetanephrine. After discontinuation of treatment with -methyl-p-tyrosine blood pressure and catecholamines returned to control values within two days.     

Effect of intermediates of the krebs cycle on blood supply and energy metabolism of the ischemized myocardium

The effect of -ketoglutarate and of sodium succinate on the collateral coronary circulation (CCC) of the ischemic myocardium, the systemic arterial pressure, and the concentrations of lactic and pyruvic acids and glucose in the blood flowing from the zone of ischemia was investigated in acute experiments on dogs. A positive effect of -ketoglutarate in doses of 6 mg/kg (into the coronary artery) and 60 mg/kg (intravenously) on CCC and on contraction was discovered. Intravenous injection of -ketoglutarate (12 mg/kg) and succinate (100 mg/kg) considerably reduced the glucose consumption of the ischemized myocardium, which was increased after ligation. Succinate, in all doses, prevented the increase in the lactate concentration in the blood flowing from the zone of ischemia more intensively than -ketoglutarate. Consequently, -ketoglutarate and succinate, in certain doses, can be used to correct CCC and the energy provision for the ischemized myocardium.Department of Pharmacology, Kursk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 317–319, September, 1978.     

Adenosine as inhibitor of myocardial effects of catecholamines

Summary Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dosedependent inhibition of dP/dt_max caused by bolus injections of isoproterenol (4×10^–11 moles). Threshold concentration of adenosine was 10^–7 M and maximal inhibition (90%) occurred at 10^–5 M. Coronary dilation induced by, papaverine did not influence the contractile response to catecholamines. In addition to its influence on cardiac performance, adenosine (10^–5 M) effectively inhibited the isoproterenol (10^–7 M) induced initial rise in myocardial levels of cyclic 35-AMP, glucose-1-phosphate and glucose-6-phosphate. Adenosine also antagonized the effect of isoproterenol on adenylate cyclase activity in a crude membrane preparation from guinea pig ventricles; it was without effect on the activity of the membrane phosphodiesterase. Theophylline inhibited the actions of adenosine both on adenylate cyclase activity and on contractile force development.-Upon infusion of isoproterenol (3×10^–7 M) into the coronary arteries of the isolated heart (perfusion at constant pressure), the adenosine concentration in the effluent perfusate increased within 45 s from 10^–8 M to about 10^–6 M. It thus appears conceivable that in ventricular myocardium endogenously formed adenosine may serve 2 functions: dilation of the coronary arteries and limitation of the inotropic and metabolic effects of catecholamines.A preliminary report of these studies was presented at the 47th Meeting of the German Physiological Society in Regensburg, Germany [Pflügers Arch.365, R4 (1976)]     

Anticholinesterase Mechanism as a Factor of Immunotoxicity of Various Chemical Compounds

Experiments on Wistar rats showed that acute poisoning with chemicals in a dose of 0.75 LD₅₀ (dimethyl dichlorovinyl phosphate, sarin, VX substance, sulfur yperite, lewisite, tetraethyl lead, dichloroethane) inhibiting platelet acetylcholine esterase, -naphthyl-AS-acetate esterase, and -naphthyl-butyrate esterase suppressed T cell-mediated immune reactions.     

Effect of α-fetoprotein on reparative regeneration of the skin and long bones

The effect of human, canine, and feline -fetoprotein on reparative regeneration of the skin and long bones of mice and rats was studied. -Fetoprotein has a stimulating action, through the formation of young connective tissue, on regeneration but without strict species-specificity. Of the various -fetoproteins studied, a commercial preparation of human -fetoprotein had the highest physiological activity.Department of Biochemistry and Anatomy, Astrakhan' Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 362–365, March, 1978.     

Synthesis and localization of α-fetoprotein during regeneration of the liver in mice

The main site of localization of -fetoprotein (FP) in mouse liver regenerating after CCl₄ poisoning or partial hepatectomy was in the typical mature hepatocytes that account for not more than a few per cent of the total number of residual hepatocytes. Morphologically they were indistinguishable from the main mass of hepatocytes and they retained on their surface bile capillary antigen. The change in their number and in the brightness of their fluorescence in liver sections corresponded to the dynamics of the FP level in the animals' serum. During regeneration of the liver in mice FP is evidently produced mainly by mature hepatocytes.Laboratory of Immunochemistry and Diagnosis of Tumors, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR. Laboratory of Clinical Immunology, Institute of Experimental and Clinical Oncology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. V. Baroyan.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1251–1254, October, 1976.     

Proteinase — Antiproteinase imbalance in meningitis: Determination of α 1 proteinase inhibitor (α 1PI), elastase — α-1PI complex,and elastase inhibition capacity in cerebrospinal fluid

Summary Mortality and long-term neurologic sequelae are still frequent complications of meningitis despite effective antibiotic treatment. This suggests that pathogen-independent inflammatory mechanisms may play an important role in the course of this illness.Neutrophil granulocytes form the primary immune defense in meningitis. Once activated, these cells release elastase into the cerebrospinal fluid (CSF). Elastase may induce tissue damage if local antiproteinase capacity is low as under normal conditions.To define the relevance of this mechanism we studied 22 patients with meningitis. Concentrations of elastase in complex with the main antiproteinase 1-proteinase inhibitor (elastase- 1PI), 1-proteinase inhibitor ( 1PI), and elastase inhibition capacity (EIC) were measured in CSF of 9 patients with bacterial meningitis (BM), aged 1 month-214 years; 13 patients with non-bacterial meningitis (NBM), aged 1 month–15 years; and 20 patients in whom meningitis was excluded after spinal tap (control group), aged 6 months–15 years. The concentration of elastase- 1PI in the BM group (median 552 g/l) was significantly higher than in either the NBM group (median 30 g/l,p<0.01) or the control group (median 30 g/l,p<0.01). Similarly, the 1PI-concentration in the BM group was significantly higher (median 113 mg/l) than either the NBM group (median 13.7 mg/l,p<0.025) or the control group (median 6.3 mg/l,p<0.001). The concentration of elastase- 1PI shows a significant correlation with the duration of the infectious symptoms before admission to the hospital (r=0.51,p<0.02), but not with the number of neutrophil granulocytesr=0.23, p=0.21).Free elastolytic capacity in CSF could be demonstrated in 4 patients: 1 with BM, 2 with NBM, and 1 with pertussis pneumonia and enzephalitis.The measured insufficiency of the proteinase-antiproteinase system may indicate high-risk patients in need of additional anti-inflammatory therapy, e.g., with corticosteroids, during the initial phase of meningitis.Abbreviations 1PI 1-proteinase inhibitor, 1-antitrypsin - elastase- 1PI complex elastase- 1-proteinase inhibitor complex - EIC elastase inhibition capacity - BM group: bacterial meningitis - NBM group: non-bacterial meningitis - CSF cerebrospinal fluid     

Presence of two isoforms of Na,K-ATPase with different pharmacological and immunological properties in the rat kidney

Previous studies have demonstrated the presence of two populations of Na,K-ATPase with distinct kinetic, pharmacological and immunological characteristics along the rabbit nephron, indicating that the proximal segments of the nephron express exclusively the ₁ isoform of the catalytic subunit, whereas the collecting duct expresses an ₃-like isoform. Because pharmacological studies have shown the existence of two populations of Na,K-ATPase with different sensitivities to ouabain in the rat cortical collecting duct, which may result from the presence in the same nephron segment of the two isoforms demonstrated in the different segments of the rabbit nephron, the present study was undertaken to characterize the properties of Na,K-ATPase along the rat nephron. Results indicate that each segment of the rat nephron contains two subpopulations of Na,K-ATPase: a component highly sensitive to ouabain (IC₅₀ 5.10^–6 M) which is recognized by an anti- ₃ antibody and another moiety of lower affinity for ouabain (IC₅₀ 5.10^–4 M) which is recognized by an anti- ₁ antibody. Whether these two subpopulations correspond to different isoforms of the subunit of Na,K-ATPase ( ₁ and ₃-like) remains to be determined.     

Protection of monoamine oxidase in brain synaptosomes by lipid- and water-soluble antioxidants during lipid peroxidation

I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 2, pp. 169–171, February, 1989.     

Expression of Estrogen Receptors-β and Aromatase Activity in Primary Mammary Gland Tumors

Expression of estrogen receptors alpha and beta was studied by the PCR method in 22 primary receptor-positive or receptor-negative breast carcinomas obtained during surgical intervention from patients aged 41-77 years and activity of aromatase in the same specimens was evaluated by the formation of tritiated water from labeled androgen precursor. Expression of estrogen receptors alpha and beta was more often detected in receptor-positive tumors characterized by lower aromatase activity. The authors conclude that the intensity of local production of estrogens can be one of the regulators of their expression, limiting this expression in case of more active production of estrogen in the tumor. On the other hand, there were no differences in the expression of estrogen beta-receptor gene or in detection of this receptor by immunocytochemical method in primary tumors lacking one of these receptors, and hence, this form of estrogen receptors is less involved in induction of progesterone receptors than alpha-receptors.     

Role of adrenergic structures in functional control over the cerebral circulation

An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with and adrenoblockers showed that the constrictor response of the cerebral vessels is due to excitation of-adrenergic structures and the dilator response to excitation of-adrenergic structures. A possible mechanism of these changes is postulated.Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 1, pp. 9–12, January, 1976.     

Synthesis of tumor necrosis factor α (TNF-α) by human monocytes in vitro

Research Institute of Hematology and Blood Transfusion, Ministry of Health of the Belorussian SSR, Minsk. Institute of Experimental Hematology and Biotechnology, All-Union Hematologic Scientific Center, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. A. Zotikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 9, pp. 287–289, September, 1991.