Ras proteins in developmental pattern formation in Caenorhabditis elegans and Drosophila. Recent studies of genetically isolated mutants in Caenorhabditis elegans and Drosophila have revealed ras functions in developmental pattern formation. The ras proteins act as genetic switches to determine cell fates between two alternative choices during C elegans vulval development (vulval versus hypodermal cells) and during Drosophila eye development (R7 versus cone cell). In both cases, ras proteins act downstream of a receptor tyrosine kinase in a signal transduction pathway that mediates cell-cell interactions. These genetic systems may allow the further elucidation of ras-mediated developmental regulatory pathways.


ras activation in experimental carcinogenesis. We review experimental models of carcinogenesis in which the role of ras activation has been most thoroughly studied: skin, thymus, mammary gland and liver. Qualitative changes (point mutations), as well as quantitative changes (over-expression, increased gene dosage) contribute to the transforming phenotype induced by ras genes. The activation of the three different ras family members is associated with particular tumor types, carcinogenic agents, and carcinogenic stages, suggesting the ras proteins may be involved in different biological functions. Depending on the system, ras activation has been shown to be an early and/or a late event in the multi-step process of carcinogenesis. These data underscore the possible relationship between ras activation and cell type specificity, proliferation, differentiation or cell-cell interaction.


ras and human tumors.

ras and human tumors. Mutational activation of ras oncogenes is frequently encountered in human tumors. For unexplained reasons, K-ras mutations are predominantly found in pancreatic cancer, colorectal cancer and adeno-carcinoma of the lung, N-ras is predominantly found in a subset of acute leukemias and in myelodysplastic syndromes, while H-ras mutations are rare. In most tumors, ras mutations are not clearly associated with specific clinical or biological features, but in lung cancer, childhood lymphoblastic leukemia and possibly in myelodysplastic syndromes ras mutations may predict a poor prognosis. Accumulating evidence suggests that exposure to chemical carcinogens is responsible for many ras mutations in humans.


Regulation of DNA replication by the nuclear envelope. Recent evidence suggests that the nuclear envelope is directly involved in regulating DNA replication. It does this in at least three ways. First, replication is dependent on assembly of an intact nuclear envelope capable of nuclear transport. Second, the nuclear membrane defines the nucleus as the fundamental unit of replication and determines the timing of initiation. Third, the nuclear membrane is essential for coupling DNA replication to the cell cycle. Thus, regulated DNA replication in eukaryotic cells depends on a structurally intact and functional nuclear envelope.


Assembly and cell cycle dynamics of the nuclear lamina. The nuclear lamina is a karyoskeletal structure composed of intermediate filament type proteins. It underlies the inner nuclear membrane and confers mechanical stability to the nuclear envelope. In addition, it interacts with chromatin and may thereby participate in determining the three-dimensional organization of the interphase nucleus. During mitosis, the nuclear lamina is transiently disassembled, most probably through hyperphosphorylation of lamin proteins by the protein kinase p34cdc2, a key regulator of the eukaryotic cell cycle. Mitotic disassembly of the lamina is necessary but not sufficient for nuclear envelope breakdown. Electron microscopic analyses have begun to provide insights into the principles that govern lamina assembly in vitro, and sequence motifs required for targeting newly synthesized lamins to the nuclear envelope have been identified. Of particular interest, lamins were shown to undergo a type of hydrophobic modification known as isoprenylation. Finally, recent studies addressing the nature of lamin-chromatin interactions may provide the basis for elucidating the role of lamins in organizing the distribution of interphase chromatin.


An extended view of nuclear lamin structure, function, and dynamics. Molecularly-based studies of nuclear lamins have progressed at a rapid rate in the last decade. However, we still have no answer to the most important question: what are the functions of lamins? In this review we describe recent experiments which challenge traditional views of lamin function and structure. These surprising results indicate that much lamin functionality remains to be discovered, and that more global approaches to lamin structure and function are especially appropriate at this time.


Nuclear pore structure and function.

Nuclear pore structure and function. Nuclear pores are huge macromolecular assemblies, approximately 120 nm in diameter, that perforate the nuclear membrane and mediate nucleocytoplasmic transport. Nuclear pores are constructed from a cylindrical spoke-plug complex sandwiched between nucleoplasmic and cytoplasmic rings. The spoke-plug complex has pronounced 8-fold rotational symmetry, which is also present in the rings. Nucleocytoplasmic transport is an energy-requiring process that takes place through the centre of the pores and can accommodate particles up to about 25 nm diameter. Translocation is preceded by a separate binding step which does not require energy. Several nuclear pore proteins have been isolated and characterized. Many of these proteins contain O-linked N-acetyl glucosamine residues and may have similar modular domain structures.


A high frequency of N-RAS oncogene mutations in multiple myeloma. Mutation of the RAS oncogene was studied in ten patients with multiple myeloma, and the DNA from nude mouse tumors formed by cells obtained from tumorigenecity assays (in vivo selection assays) in these patients was analyzed by PCR and oligonucleotide hybridization. Mutations of the N-RAS oncogene were identified in two of three patients investigated by in vivo selection assay and in five of ten patients investigated by PCR analysis of DNA from myeloma cells. In the two former patients, mutation of the N-RAS oncogene was observed at the 61st codon. Of the five N-RAS mutant-positive patients investigated by the PCR analysis, one had a mutation at codon 12, two had mutations at codon 13, and two had mutations at codon 61. None of the patients had mutations of the K-RAS oncogene. These results suggest that the frequency of RAS gene mutation in multiple myeloma is higher than in other lymphoid malignancies such as acute lymphocytic leukemia, chronic lymphocytic leukemia, and malignant lymphoma. As the mutation was observed only at the N-RAS oncogene level, it is speculated that N-RAS oncogene activation might play an important role in the progression of multiple myeloma.


Gene analyses of abnormal fibrinogens with a mutation in the gamma chain. In four abnormal fibrinogens with a point mutation in the gamma chain, all characterized by impaired fibrin polymerization, we identified single base exchanges in the respective mutant gamma chain genes by polymerase chain reaction followed by DNA sequence analysis. These base exchanges accounted for the amino acid substitutions previously reported from our laboratory. They were exchanges of C to T (CGC for gamma Arg-275 to TGC for Cys) in fibrinogen Osaka II, T to G (AAT for gamma Asn-308 to AAG for Lys) in fibrinogen Kyoto I, T to C (ATG for gamma Met-310 to ACG for Thr) in fibrinogen Asahi, and G to T (GAT for gamma Asp-330 to TAT for Tyr) in fibrinogen Kyoto III. These base exchanges were found to reside in exon VIII of the gamma chain gene. Since many abnormal molecules are associated with polymerization defects, unless associated with the impaired release of fibrinopeptides A and/or B, exon VIII of the gamma chain gene may deserve careful study to define the structural alterations.


Altered expression of protein kinase C in adult T-cell leukemia cells. Protein kinase C (PKC) has been shown to be involved in the mitogenic response and in oncogenic cell transformation in many experimental models. We analyzed the expression of PKC in both highly purified leukemic T cells freshly isolated from adult T-cell leukemia (ATL) patients and control T lymphocytes obtained from healthy volunteers. PKC activity was decreased in the ATL cells as compared with the control T cells. Cytosolic PKC activity in the ATL cells was remarkably decreased, whereas particulate membrane PKC activity was similar to the control level. The percentage of PKC activity in the particulate fraction was 34% in the ATL cells and 19% in the control cells. Regarding the altered subcellular localization of PKC activity, phorbol ester-induced translocation of cytosolic PKC was inhibited in some ATL cases. Similarly to the decrease in PKC activity, there was a decrease in the expression of the major PKC isozymes II(beta) and III(alpha) in ATL cells. These results suggest impaired regulation of PKC expression in ATL as well as in many experimental cancers.


Hirudin and sulotroban improve coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary artery thrombosis. Thrombus formation in anesthetized, open-chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery. One-hour postocclusion, administration of vehicle to heparinized dogs (n = 12) did not induce reperfusion despite concomitant treatment with acetylsalicylic acid (ASA), sulotroban, or saline. Intravenous bolus injection of 140 kU/kg (= 0.24 mg/kg) of the unglycosylated t-PA variant BM 06.022 induced reperfusion in 4 out of 6 dogs, followed by flow deterioration. Pretreatment with i.v. ASA did not improve coronary blood flow (CBF). Conjunctive treatment with the thromboxane A2-receptor antagonist, sulotroban, (10 mg/kg i.v. bolus, followed by 10 mg/kg/h) or with recombinant hirudin, a specific thrombin inhibitor, (1 mg/kg/h) 30 min prior to i.v. injection of BM 06.022, prolonged (p < 0.01) the cumulative patency time (sum of time-intervals in which the coronary artery was patent) to 147.4 +/- 9.2 min in 4 out of 6 reperfused dogs and 129.9 +/- 12.3 min in 7 out of 8 dogs, respectively, compared to the saline plus BM 06.022 treatment (47.5 +/- 13.1 min) in 4 out of 6 dogs. The terminal CBF was higher (p < 0.01) after sulotroban plus BM 06.022 (7.0 +/- 1.7 ml/min) and hirudin plus BM 06.022 (6.3 +/- 1.5 ml/min) than after saline plus BM 06.022 (0.8 ml/min). These findings demonstrate that drugs with antithromboxane or antithrombin activity may improve CBF after reperfusion.


Rapid prenatal diagnosis of Hb Bart's hydrops fetalis in southeast Asia area by polymerase chain reaction. We used the polymerase chain reaction (PCR) to amplify the breakpoint area of alpha-thalassemia-1 of Southeast Asia type and several parts of the alpha-globin gene cluster to make a differential diagnosis between alpha-thalassemia-1 and Hb Bart's hydrops fetalis. The procedure involved three primers to detect the homozygote of alpha-thalassemia-1, then amplifies the other alpha-globin gene cluster with three other pairs of primers to double check the results. The PCR products were checked again by allele specific probes. Twenty-two cases were diagnosed prenatally, two were normal, 17 were alpha-thalassemia-1, and three Hb Bart's hydrops fetalis. All cases were confirmed either by Southern blot hybridization or follow-up by sonography or after delivery. No false positive or false negative results were obtained by our strigent procedure. We conclude it to be a rapid, accurate and economic method.


Circulating transferrin receptor in acute leukemias. Serum transferrin receptor (s-TR) levels in acute leukemia patients were measured by a recently developed sandwich radioimmunoassay. The mean s-TR level for normal subjects (n = 205) was 246 +/- 79 (mean +/- 1 SD) ng/ml. The values for patients with untreated acute myelocytic leukemia (AML, n = 18) and untreated acute lymphocytic leukemia (ALL, n = 14) were 398 +/- 175 ng/ml and 479 +/- 176 ng/ml, respectively, both of which were significantly higher than those for the normal subjects (AML, p < 0.02; ALL, p < 0.05). When complete remission was achieved with initial remission induction therapy, s-TR decreased to 262 +/- 47 ng/ml (n = 22, 12 AML and 10 ALL), returning to normal levels. There was a good correlation between s-TR levels and the number of leukemic cells in peripheral blood (r = 0.743, n = 32, p < 0.01). In two patients with AML, serial changes of s-TR values and numbers of blast cells in the peripheral blood and bone marrow occurred in a parallel manner. If, therefore, this assay for s-TR can be made more sensitive, it may become useful for assessing acute leukemia activity and for monitoring the effects of therapy.


Effects of cobalamin, cobalamin analogues and cobalamin binding proteins on P388D1 mouse leukemic cells in culture. Cobalamin-deficient P388D1 mouse leukemic cells were created by propagation in a cyanocobalamin-free medium in which the original fetal bovine serum was replaced by bovine serum albumin. These cobalamin-deficient cells gradually ceased to multiply when the medium contained 5-methyltetrahydrofolate. The growth of cells that had been cultured with this coenzyme was recovered following the addition of cyanocobalamin (CNCbl), at concentrations above 37 pM. In contrast to the effect of CNCbl, cobinamide, and cobalamin analogues prepared from hydroxy cobalamin by reaction with ascorbic acid, did not have a growth-inducing effect on these cells, nor did these analogues inhibit CNCbl-dependent growth. Transcobalamin II-cobalamin complex had a remarkably stimulating effect on cell growth. The growth inducing effect became apparent with a cobalamin concentration of only 0.37 pM. This was about 1/100th the level of free cobalamin required for cell growth. However, no growth-inducing effect was seen at an R protein-bound cobalamin concentration of 37 pM, indicating that once cobalamin has been bound to R protein, it loses its growth-promoting effect on these cells in culture.


Primary extramedullary plasmacytoma of the small intestine. We report a case of primary extramedullary plasmacytoma (PEMP), IgA kappa type, with a long clinical history, in a 64-year-old Japanese woman. In this case, PEMP occurred primarily in the jejunum and then recurred in several organs, specifically the spleen and stomach, and in the subcutaneous tissue, over a period of about 16 years. However, examination of bone marrow aspirates on several occasions continued to show no plasmacytoma involvement. The patient is still living. Immunohistochemical examinations revealed monoclonal IgA kappa immunoglobulin in the cytoplasm of infiltrating plasma cells in all surgical specimens examined. Immunoelectrophoresis revealed serum M-component only when the patient had a splenic tumor. Soon after splenectomy, the serum M-component disappeared. PEMP of the small intestine is rare.


Monitoring hemangioblastoma tumor burden using plasma erythropoietin levels. We report a 39-year-old female patient with a hepatic hemangioblastoma, polycythemia and elevated plasma erythropoietin (Epo) levels. Following orthotopic liver transplantation (OLTx), her plasma Epo levels and hematocrit normalized but began to rise several months later. This rise correlated with the appearance of multiple lung metastases. The tumor was implicated as the source of excess Epo production using Northern analysis of a resected metastatic lung nodule. Based on our results, the measurement of plasma Epo levels in patients with Epo secreting tumors could be of general utility in assessing tumor burden.


[The determination of myocardial mass by cardiac magnetic resonance tomography. The effect of section alignment and section distance]. The effect of section alignment and distance in volumetric determination of myocardial mass by means of cardiac magnetic resonance imaging (MRI) was studied in 19 isolated pig hearts. Double angulated views taken through the short axis of the heart with a slice thickness of 10 mm and slices at a distance of 0 mm, 1 mm, 3 mm and 5 mm produced accurate left ventricular measurements with cardiac MRI. Measurements in the long axis of the heart resulted in a marked underestimation of myocardial mass; depending on slice intervals, there was an error between 13% and 20%. In vivo measurements in 35 subjects confirmed the effect of section alignment. Measurements in the long axis of the heart produced results of 139.9 +/- 31.7 g, significantly less than measurements in the short axis of the heart of 157.8 +/- 32.3 g.


[Measurement error estimation in MR tomographic volumetry of the left ventricle with the multisection technic]. A multi-slice technique for MRT measurements of the left ventricular volume is much faster than the use of single-slice methods and is therefore better tolerated, leaving time for additional measurements. The end-diastolic left ventricular volume can be reliably measured by this method (123.3 +/- 13.5 ml vs. 124.1 +/- ml). The end-systolic volume is consistently overestimated by 23.7 +/- 18.3% compared with the reference value obtained by single slice measurements (47.9 +/- 8.9 ml vs 39.1 +/- 7.9 ml). Correspondingly, stroke volume and ejection fraction is underestimated on average by 10.6 +/- 9.7% and 10.6 +/- 7.6% respectively).


[The direct measurement of the spin-grid-relaxation times of phosphorus metabolites in the human myocardium]. The T1 relaxation times of the phosphorus metabolites in human heart muscle measurable by 31P-MR spectra were determined in 12 individuals using a 1.5 Tesla system. Several spectra were recorded consecutively with a pulse repetition time of 1.6 s to 24 s. The T1 times of creatine phosphate (CP), of gamma-, alpha-, beta-adenosintriphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG) together with anorganic phosphate) and phosphodiester (PDE) showed mean measurements of 6.1 +/- 0.5, 5.4 +/- 0.5, 5.0 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s (M +/- SE). The accuracy of the ISIS technique was tested with a special phantom. T1 times were also measured in standard solutions (20 mM CP, 10 mM ATP); CP was 8.7 +/- 0.2 s and gamma-ATP was 9.9 +/- 0.7 s. Corrections for partially saturated 31P-MR spectra--at least for CP/ATP ratios--are relatively small.


[In-vivo 31P-NMR-spectroscopy in patients with dilated cardiomyopathy]. In vivo 31P-NMR spectra of heart muscle were obtained in 7 patients with dilating cardiomyopathies and in 10 normal subjects, using an ISIS technique with a 1.5 Tesla body scanner (Philips Gyroscan S15) and the results of the two groups were compared. These results were easily reproduced. In patients with cardiomyopathy there was a significant (p < 0.05) reduction of the PCr/ATP ratio as an expression of abnormal energy metabolism. Two patients with mild clinical symptoms and only slightly reduced functional measurements showed no significant changes in the 31P-NMR spectrum. The patients with the largest reduction of the PCr/ATP index also showed the most marked changes in functional measurements. The PCr/ATP ratio (as also suggested by animal experiments) appears to be a suitable non-invasive indicator for the diagnosis and staging of myocardial changes in dilating cardiomyopathies.


[MR tomographic volumetry of the subarachnoid space in HIV-associated brain atrophy]. The CSF volume of 45 patients with HIV infection was measured at various clinical stages and the results compared with 24 normals. 60% of all patients showed increased CSF spaces as an indication of cerebral atrophy. Serial measurements were particularly valuable during the early stages of atrophy since there is marked variation in the normal CSF volume. Conventional measurements, with the exception of the width of the third ventricle, were much less sensitive than these quantitative measurements. Classification of HIV infection according to the clinical stage was useful since CSF volume and volume increase correlated with the stage of HIV infection.


[Magnetic resonance tomography in the follow-up after the embolization of arteriovenous malformations of the central nervous system]. Interventional embolisation is an accepted treatment for intracranial or spinal arteriovenous malformations. Since multiple embolizations are often required, noninvasive repeatable follow-up studies are desirable. The aim of this study is to demonstrate the usefulness of T2-weighted images, MR angiography, and gadolinium-DTPA first-pass studies for post-embolisation follow-up studies. Five patients with arteriovenous malformations, four cerebral and one spinal, were studied prospectively before and repeatedly after single or multiple embolizations. A total of 26 MRI studies (1.5 T Magnetom, Siemens AG) were performed. The combination of T2-weighted images, MR angiography, and gadolinium-DTPA first-pass studies nicely demonstrated the arteriovenous malformations and the effect of embolisation which ranged from negligible to almost complete. While contrast-enhanced T1-weighted images and contrast-enhanced MR-angiography seemed to be of little more value than unenhanced studies, gadolinium-DTPA first-pass studies appeared to be more sensitive than T2-weighted images or MR-angiography because of their high intrinsic sensitivity to regional blood flow and volume. In the spine, T2-weighted images and MR-angiography were too insensitive to detect arteriovenous malformations, whereas gadolinium-DTPA first-pass studies sensitively detected the malformation and the changes after embolizations.


[A prospective study to determine the recanalization time with a guide wire/recanalization catheter system in arterial occlusions]. The success rate and time taken for recanalization was determined in a prospective study of 82 consecutive unselected patients (53 men, 29 women; mean age 65.7 +/- 13, from 28 to 88 years). There were 106 complete occlusions of infrarenal arteries and a hydrophilic guide wire with a special 5-F recanalization catheter was used. Mean occlusion length was 12.97 +/- 10 cm (from 1 cm-45 cm). 79.3% of occlusions were in the femoro-popliteal territory, 6.6% were iliac and 14.1% tibial. 101 of the 106 occlusions were recanalized (95.3%). Mean recanalization time was 120.8 +/- 228.1 s (from 1 s-1440 s), mean recanalization velocity was 0.11 cm/s. The majority of obstructions could be recanalized in less than one minute. The five occlusions which could not be recanalized were distal lesions in the superficial femoral artery and which were longer than 10 cm; two were calcified. There were no complications resulting from the recanalization apart from three perforations which were clinically not apparent. Consequent angioplasty proved successful in 78.1% of these patients.


[Long-term observation after percutaneous transluminal angioplasty in the pelvic and leg areas]. In this study 163 patients had long term follow ups after PTA; the value of a test which had previously hardly been used, the "Cox proportional hazards model", for prognostic purposes is stressed. In this test account is taken of the severity of the stenosis before PTA, the extent of re-stenosis following PTA and the distance of the occlusion from the aorta and these are related to the likelihood of success. The use of the Cox proportional hazards model with an accurate description of the clinical material and the use of the Kaplan-Meier method is recommended in order to obtain comparable figures for the results obtained in various centres. In this study patency after six months was 77%, after a year 67%, after three years 46% and after five years 37%.


[The catheter embolization of acute hematuria after percutaneous nephrostomy and nephrolitholapaxy]. Angiography was performed on 6 patients with acute haematuria following percutaneous nephrostomy and nephrolitholapaxy; in 3, vessel damage with leak of contrast into the nephrostomy canal or renal parenchyma was demonstrated and in 3 there were one or more pseudoaneurysms with or without arteriovenous fistula. All patients were successfully treated by catheter embolisation. Various catheter techniques (monaxial, coaxial) and embolic materials (Spongostan, Ivalon, coils) were used. The use of a Tracker-18 catheter with micro coils is the method of choice and permits superselective embolisation of bleeding from small peripheral branches with maximal preservation of the renal parenchyma.


[The imaging diagnosis of acute renal transplant obstruction with special reference to antegrade pyelography]. 30 patients with an acute build-up of renal transplant were examined comparatively via antegrade pyelography (AP), computed tomography (CT) and sonography (SONO). In the proof of obstructions and compressions of the ureter of renal transplant, antegrade pyelography was superior to sonography and computed tomography. Perirenal collections of fluids were recognised correctly via sonography by 73% (11/15) and computed tomography by 87% (13/15). The computer tomogram is superior in the differentiation of perirenal collection of fluids. In establishing proof of the cause of an acute build-up of renal transplant it was evident that computed tomography with a sensitivity of 64% and a specificity of 94% was slightly superior.


[Renal osteodystrophy: the spectrum of the x-ray symptoms in modern forms of kidney transplantation and long-term dialysis therapy]. Plain film radiography and microradioscopy represent standard imaging for diagnosis and grading of renal osteodystrophy. The aim of this retrospective study was to evaluate the effects of modern therapeutic regimens on skeletal abnormalities as diagnosed radiographically. 198 patients were investigated. X-ray findings of 38 patients from 1981-1983 (16-66 years, 40.1 +/- 13.4; 23 male, 15 female) were compared with those of 160 patients from 1991 (20-71 years, 48.4 +/- 12.5; 98 male, 62 female). We found significant differences in respect of the spectrum and the degree of skeletal abnormalities. The prevalence of phalangeal resorptions lowered from 87 to 50%, the prevalence of soft tissue calcification from 68 to 57%. Therefore, renal osteodystrophy is not as extensive as it was ten years ago, but it still continues to be an unavoidable complication of renal insufficiency.


[The imaging diagnosis of sclerosing peritonitis (SP) following continuous ambulatory peritoneal dialysis (CAPD)]. Sclerosing peritonitis is a serious complication of CAPD characterised by thickened peritoneal membranes which lead to decreased ultrafiltration and intestinal obstruction. The roentgenographic signs of SP were analysed in 11 patients who underwent plain x-ray of the abdomen, follow-through examinations of the small bowel, ultrasonography and computed tomography. Results were correlated with the histological degree of SP. Besides the non-specific findings of intestinal obstruction, patients with histologically marked SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications and thickened peritoneal membranes. Due to the fact that postoperative complications often occur in patients with SP, detection of the radiological signs should lead to cautious surgical interventions and changeover to haemodialysis.


[The preoperative marking of nonpalpable breast lesions: the technic and results]. 189 non-palpable breast lesions in 182 patients were localized using conventional mammographic apparatus, a wire grid compression plate and a cannula with a hooked mandrin. The technique of the examination for defining the lesion in three planes and fixation of the lesion with the wire is described. In 173 instances (91.5%), the lesion was found at the first biopsy and subsequent biopsies were necessary on only 24 occasions. One lesion (0.5%) was missed completely. 47 carcinomas were found (24.9%) and the incidence of malignancy increased from 14.3% to 33.3% during the series. The mean ratio defining the size of the biopsy and the size of the lesion was 3.3 and indicates good preservation of breast tissue. Radiographs of the specimen taken with compression showed 186 lesions (98.4%). The method, which is comfortable for the patient, provides satisfactory detection and localization of the lesions; results are similar to those of stereotactic methods but this method is quicker and much less expensive.


Changes in the blood-brain transfer of L-phenylalanine elicited by arginine vasopressin. Arginine vasopressin (AVP) coinjected into the carotid artery in physiological concentrations (0.1 nmol/l) with L-[3H]phenylalanine changed the kinetic parameters of blood-brain barrier (BBB) transport of this neutral amino acid. The half-saturation constant (Km) and the maximum velocity of transport (Vmax) were estimated in nine brain regions of male Wistar rats anaesthetized with ether. In the cerebral hemisphere Km decreased significantly from 0.107 to 0.061 mmol/l and Vmax from 37.6 to 27.4 mmol/min/g. Comparing the kinetic constants for the phenylalanine transfer of corresponding regions of control animals and those coinjected with the amino acid and AVP, 8 out of 9 (Km) and 7 out of 9 (Vmax) regions were found significantly lowered. The findings support the hypothesis that AVP binding to the endothelial cell layer of the brain capillaries induces alterations of the transfer of at least the large neutral amino acids (LNAAs) from blood to brain. The kinetic parameters estimated for L-phenylalanine favour the assumption that in vivo AVP induces a preferred transport of this amino acid across the BBB compared to L-leucine.


Effect of mesulergine on prolactin secretion and dopamine D2 receptors-adaptive changes in diethylstilbestrol-induced hyperplasia of the rat anterior pituitary. Mesulergine (N,N-dimethylsulphamide-N'-1,6-dimethyl-ergoline-8 alpha-yl) is an active semisynthetic ergot derivative with lower antiprolactin potency compared with bromocriptine or pergolide. Since no data are yet available on the effects of mesulergine on pituitary dopamine receptors, the present study has been designated to elucidate the influence of this drug on prolactin secretion in vivo and in vitro and 3H-spiperone binding by the anterior pituitary gland in female Wistar rats with experimentally induced hyperprolactinemia. Three weeks after bilateral ovariectomy and subcutaneous implantation of silastic tubes, containing 10 mg of diethylstilbestrol, a dramatic rise in serum prolactin levels was observed (1.67 +/- 0.23 vs. 80.82 +/- 3.80 ng/ml; P less than 0.001). Mesulergine attenuated the stimulatory effect of diethylstilbestrol on serum prolactin level in a time- and dose-dependent fashion. At concentration range between 10(-5) and 10(-7) M it also inhibited prolactin secretion from cultured rat pituitary cells to the medium during 180 min incubation in a dose-dependent manner. Scatchard analyses performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture, prepared from the pituitaries from rats treated for four weeks with diethylstilbestrol, showed that chronic mesulergine treatment (in dose of 3.0 mg/kg injected s.c. for 10 days) induced a significant decrease in the number of dopamine D2-binding sites (Bmax 28.00 +/- 4.20 vs. 42.80 +/- 4.76 fmol/10(6) cells; P less than 0.01) without any changes in D2-receptor affinity. Our results suggested that antiprolactin activity of mesulergine in vivo and in vitro is probably associated with agonistic effect of this drug on D2-dopamine receptors.


Low concentrations of oxytocin suppress lordosis when infused into the lateral ventricle of female rats. The first experiment was undertaken to compare the effects on lordosis of the infusion of oxytocin into the lateral versus the third ventricle. Female rats fitted with bilateral cannulae aimed at these ventricles were primed with 5 micrograms estradiol benzoate and 150 micrograms progesterone and received an infusion of 0.34 ng oxytocin into either the left lateral or the third ventricle. The infusion of 0.34 ng oxytocin into the left lateral ventricle inhibited lordosis behavior, while the same dose infused into the third ventricles of the same animals did not. Since a facilitation of lordosis in response to the infusion of oxytocin into the lateral ventricle has been reported in other studies, it seemed possible that the inhibition and facilitation could be produced by different doses of oxytocin. In the second experiment this hypothesis was tested in another set of female rats fitted with unilateral cannulae aimed at the left lateral ventricle, primed with 5 micrograms estradiol benzoate and 150 micrograms progesterone and infused with different doses of oxytocin. In these animals the inhibition occurred with 0.34 ng but not with 3.4 ng or 34 ng of oxytocin. No facilitation was observed at any of these doses.


Effects of dexamethasone on TRH and TRH precursor peptide (Lys-Arg-Gln-His-Pro-Gly-Arg-Arg) levels in various rat organs. The effect of an acute dexamethasone administration on thyrotropin-releasing hormone (TRH) and TRH precursor peptide (Lys-Arg-Gln-His-Pro-Gly-Arg-Arg) (p-8) levels in various rat organs has been studied. Rats were injected i.p. with 25 micrograms of dexamethasone/100 g body weight (group A), 500 micrograms of dexamethasone/100 g body weight (group B) or saline (group C). The rats were serially decapitated after the injection. TRH and p-8 levels in the hypothalamus, cerebrum, cerebellum and brain stem, stomach and eye and plasma TRH and thyrotropin (TSH) levels were measured by individual radioimmunoassays. P-8 levels in the hypothalamus decreased significantly in both group A and B at 1-4 hours after the injection, and then returned to pretreated levels at 24 hours after the injection. TRH levels in the hypothalamus increased significantly in both group A and group B at 1-4 hours after dexamethasone injection. No changes in p-8 and TRH levels were observed in other organs. In group A, plasma TRH levels tended to decrease at 1-2 hours, then to increase at 3 hours. In group B, plasma TRH levels decreased 1-4 hours after the dexamethasone injection, then increased at 24 hours. The plasma TSH levels decreased significantly at 1-4 hours in group A and group B, returned to pretreatment levels at 24 hours in group A, and increased significantly in group B at 24 hours after dexamethasone injection.(ABSTRACT TRUNCATED AT 250 WORDS)


Single point estimation of glucocorticoid receptors in lymphocytes of normal subjects and of children under long term glucocorticoid treatment. A single point assay of glucocorticoid receptors (GR) in human lymphocytes based on the measurement of specific dexamethasone binding has been developed and compared with a common multi-point Scatchard analysis. The assay conditions-concentration of the ligand 20 nmol/l, incubation time 2 h and the cell count 2-6 mil. cells/tube in the assay volume 0.25 ml were found to be optimal. An attempt was also undertaken to use a cell harvester for the separation of cells from unbound ligand. Though specifically bound dexamethasone measured by whole-cell assay and that using cell harvester correlated well, almost by one order lower values obtained with the latter method render it non-applicable for receptor quantitation. The results from 9 healthy volunteers (average GR concentration 7131 +/- 1256 sites/cell) correlated excellently with those obtained by the Scatchard analysis. The single point assay has been also applied for determination of GH in 10 children treated with large doses of prednisone. The average values from healthy volunteers did not differ significantly from those found in these children, though much broader range was found in patients.


Androgen hydroxysteroid dehydrogenases under the influence of pyridoxine derivatives. The metabolism of testosterone in the rat ventral prostate, anterior pituitary, basal hypothalamus and amygdala was studied in vitro under the influence of vitamin B6 compounds. The influence of these compounds on the activity of 5 alpha-reductase (5 alpha-R), 3 alpha- and 17 beta-hydroxysteroid dehydrogenase (3 alpha-HSD, 17 beta-HSD) was determined for all the examined tissues. Pyridoxine hydrochloride significantly increased the activity of 5 alpha-R, 3 alpha- and 17 beta-HSD, but pyridoxal hydrochloride had an inhibitory influence on 5 alpha-R and showed no effect on 3 alpha-HSD activity at the prostate level. Male rat anterior pituitary, basal hypothalamus or amygdala incubated with pyridoxal phosphate and pyridoxal hydrochloride showed modified enzymatic activities. Pyridoxal hydrochloride showed an inhibitory effect on 5 alpha-R in the rat pituitary and basal hypothalamus as well as in the rat prostate.


Inhibition of human serum oxytocinase (cystine aminopeptidase, E. C. 3.4.11.3) by GnRH peptides. The hydrolysis of H-Cys(Bzl)-NH-Meq by human serum oxytocinase (E.C. 3.4.11.3) was inhibited non-competitively by various pyroglutamyl peptides. The most effective were the chicken GnRH II (Ki = 6 x 10(-6) mol l-1) and salmon GnRH (Ki = 12 x 10(-6) mol l-1), while the inhibitory potency of human GnRH was substantially lower (Ki = 60.0 x 10(-6) mol l-1). Variations in inhibitory potency of individual peptides reflected mostly the differences in N-terminal and C-terminal parts of the molecules.


[Changes in impulse activity of neurons of the CA3 area of the hippocampus under the effects of neuromodulator neurotropin]. Neurotropin (Nippon Zoki Co, Ltd) effects on firing patterns of the CA 3 hippocampus neurons in rabbits under a 24-h food deprivation was studied. Neuronal firing was recorded in a state of hunger (40 neurons) and under neurotropin (27 neurons) injected through a catheter implanted into the lateral brain ventricles. Initially, in 20% of neurons histograms had a bimodal interspike interval distribution: 1.5-25 ms and 100-400 ms. Neurotropin (50 microliters) increased the baseline spike rate regularity of hippocampus neurons. Histograms had a monomodal interspike interval distribution. Neurotropin (70 microliters) inhibited firing patterns and histograms, had trimodal interspike interval distribution: 1.5-5 ms; 250-400 ms and 1000 ms. Thus, these data suggested the involvement of neuro-immuno-modulator mechanisms in organization of firing patterns in rabbits.


[Diurnal dynamics of red blood indicators after carotid glomectomy in rats]. After bilateral carotid glomectomy the rat resistance to acute hypoxia reduces and phenomena of anemia arise. There appear correlations between resistance to hypoxia and red cell count, hemoglobin and hematocrit. The diurnal fluctuation of rat resistance to acute hypoxia after the glomectomy does not change while hemodynamics undergo marked changes.


[Features of changes in bioelectric reactions of the cerebral cortex in rats with deafferentation pain syndrome]. In rats with pain syndrome after sciatic nerve section the authors studied spontaneous and evoked bioelectric activity in sensomotor cerebral cortex of both hemispheres. Electrocorticogram showed the presence of hyper-synchronic discharges and paroxysmal peak-wave (700-800 mV) activity in contralateral hemisphere. While stimulating the injured limb the threshold of evoked potentials (EP) was observed to decrease, its amplitude to increase and focus maximum EP activity to extend.


[Effects of neurotropin on seizure activity in picrotoxin kindling]. It is shown that both intracerebral and intraperitoneal neurotropin administration resulted in a decrease of seizure susceptibility of preliminary picrotoxin--kindled rats. On the other hand, neurotropin did not change the course of kindling development. Under conditions of acute picrotoxin--induced seizures it was observed that preliminary cycloheximide (protein-synthesis blocker) administration abolished anticonvulsant properties of neurotropin. It is concluded that anticonvulsant effects of neurotropin are realized via modulation of endogenous peptides synthesis and, in particular, cerulein.


[Relations between disorders of the intestinal-hepatic basin hemodynamics and absorption function in hemorrhage]. Chronic dog experiments showed that blood loss of 30 ml/kg or an intravenous injection of 1 microgram/kg norepinephrine did not markedly change small intestinal absorption. Blood supply to the liver was maintained at the expense of restricted portal circulation. Adaptation in blood loss seems to support arterial blood supply to the liver and absorbing epithelium of the small intestine to warrant their resistance to circulatory hypoxia and to promote their functional activity.


[Changes in EEG and higher nervous activity of rats during cerebral anti-ischemic protection by acelysin]. The water-soluble aspirin (acelysin) has been used as an anti-ischaemic protector when injected in the dose of 150 mg/kg 30 min before ischaemia. The EEG has been registered during the whole period of experiment and the total EEG power index has been calculated. The higher nervous activity has been evaluated during analysis of rat's abilities for elaboration of conditional reflex of an active escape reaction in Y-labyrinth. The results have demonstrated the complete rehabilitation and restoration of brain functional activity 8 days after endurance of brain ischaemia under protection of acelisin.


[Use-dependent inhibition of C-axon multimodal units of cat skin by lidocaine and N-propyl-ajmaline]. Subcutaneous application of local anesthetic drug lidocaine and cardiac antiarrhythmic n-propyl-ajmaline produced the reversible use-dependent inhibition of feline polymodal mechano-heat C-fiber cutaneous sensory units (CMH-units) excited by moderate noxious mechanical stimulus. The discharge rate as well as the number of evoked spikes of polymodal sensory units treated with the drugs decreased below the values observed under noxious chemical excitation of CMH-units. The repeated mechano-stimulation with 5 to 30 sec interval between stimuli produced complete though a reversible block of the treated units. Quaternary amine n-propyl-ajmaline induced use-dependent inhibition of CMH-units in lower concentrations than tertiary amine lidocaine. The use-dependent inhibition of CMH-units is discussed in connection with nociception and local analgesia.


[Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes]. The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy.


[Effects of ubiquinone-9 on lipids of nuclei and chromatin of the rat liver under continuous irradiation]. The influence of continuous gamma irradiation on the lipids of nuclei and chromatin of rat liver at a dose-rate of 0,129 Gy/day for 155 days (a total dose of 20 Gy) and by feeding of ubiquinone-9 has been studied. The amount of phosphatidylcholine with phosphatidylserine and phosphatidyl-ethanolamine in liver nuclei of irradiated rats was found to increase. Ubiquinone-9 had a normalizing effect. A decrease of cardiolipin was observed in the liver chromatin of irradiated rats. The amount of free fatty acids had a tendency to decrease in homogenate, nuclei and liver chromatin of irradiated rats. Ubiquinone was found to increase the amount of free fatty acids up to the control level. The amount of cholesterol in nuclei was increased after irradiation and that in chromatin tended to rise. Ubiquinone-9 significantly decreased the amount of cholesterol in nuclei and chromatin of irradiated rats.


[Participation of tyrosine residues of myoglobin in the disproportionateness reaction of heme iron (II) and (IV)]. By means of the comparison of the constant oxidation reactions of both the myoglobin modified by N-acetylimidazole and the intact myoglobin in the presence of H2O2 or ferrylmyoglobin we characterized the role of the tyrosine residues (Tyr) of myoglobin in the synproportionation reaction between heme iron (II) of one molecule and heme iron (IV)--of another. It was demonstrated that Tyr derivatization resulted in the decrease of the velocity of redox interaction between deoxymyoglobin (II) and ferrylmyoglobin (IV) and led to the decrease of the efficiency of oxymyoglobin deoxygenation. The effects were shown to be independent on Tyr quantity in myoglobin molecule and to have the same character for both the sperm-whale myoglobin and the horse myoglobin.


[Periodicity of changes in the concentration of cholesterol and blood serum proteins in dynamics of hypercholesterolemia]. During 30-week hypercholesterolemia in rabbits and guinea pigs the differences in cholesterol dynamics manifested themselves in quantitative variations of blood serum proteins. Five weeks after the beginning of the experiment a sharp increase of cholesterol level corresponded to the equally sharp decrease of the quantity of blood serum total and cation proteins. The variation of protein and cholesterol concentrations in guinea pigs during 17 weeks is similar to the development of early stages of cholesterolemia (4 weeks) in rabbits. It can be supposed that there is a connection between metabolic systems involved in the transformation of blood serum cholesterol and blood serum.


[Changes in the organization of the intermediate filament system of human fibroblasts in lysosomal storage diseases and their modeling]. The organization of the system of the vimentin intermediate filaments (IFs) in human fibroblasts in lysosomal storage diseases (Fabry's disease, mannosidosis) and their modelling has been studied in vitro. It was shown that during accumulation of nonhydrolyzable compounds, hypertrophy of the lysosomal compartment is accompanied by formation of ring-shaped bundles IFs, surrounding apparently these increased organelles. The changed organization of IFs is characteristic of polarised pathological cells in monolayer, and after repassage it is retained only at the spreading state; on transition from the discoid to extended cellular form there occurred the centrifugal shift of ring-shaped structures of IFs to active cell border and gradual restoration of radial fibrillar state of IFs. It is suggested that on intralysosomal storage of unsplit compounds reorganization of the vimentin-type IFs in ring-shaped structure is necessary for optimal distribution and stabilization into the cytoplasm of large amounts of increased lysosomes with exo- and endogenous contents. In condition of free spreading (i. e. with diminished cell density) the restoration of normal fibrillar IF organization may be due to the loss of considerable number of hypertrophied lysosomes; the involvement of lysosomal membrane in formation of active cellular border is not to be ruled out.


[A comparison of 3 methods of lipoprotein (a) isolation from human plasma]. Three methods for purification of lipoprotein (a) [Lp(a)] from human plasma were compared. Method I: two-stage ultracentrifugation with subsequent gel-filtration of Lp(a) containing fractions (1.063-1.090 g/ml) on Sepharose CL-4B. Method II: ultracentrifugation followed by affinity chromatography of plasma fraction (1.063 g/ml) on anti-apoB sorbent. Method III: affinity chromatography of the whole plasma on anti-apo(a) sorbent. The Lp(a) yield of these methods is 35, 54 and 41%, respectively. The method III is preferable of these three because it permitted high purification of a large amount of Lp(a) by single-step chromatography.


[Increase of seizure threshold and resistance to stress in rats after immunization against fragment of diazepam-binding inhibitor]. White rats were immunized against fragment of diazepam-binding inhibitor octadecaneuropeptide (ODN) with conjugate ODN bovine serum albumin. This rats have reduced reactions of fear and anxiety in stress model of "open field" and in conflict Vogel test; their pain sensitivity ("tail flick" test) was lowered. The number and intensity of generalized seizure reactions after injection of pentylenetetrazole were decreased. The results show that active immunization to endogenous ODN has stress--protective and anti-seizure effects.


[Elimination of the atherogenic effect of beta blocker propranolol by papaverine]. Recently, the ability of beta-blockers to stimulate proliferative activity and induce lipid accumulation in cultured human aortic intimal cells has been demonstrated. Moreover, the addition of calcium antagonists completely blocked the increase in proliferative activity and abolished cholesterol accumulation caused by propranolol. In this study blood serum of rabbits treated with 20 mg of propranolol induced 2-fold cholesterol accumulation in mouse peritoneal macrophages. Papaverin did not influence this effect. In case of simultaneous administration of propranolol and papaverin rabbit serum did not exhibit the ability to accumulate intracellular lipids. Propranolol substantially stimulated the formation of myointimal thickening and neutral lipid accumulation in denuded rabbit aorta. Papaverin completely blocked the propranolol-produced atherogenic changes. The data suggest that in vitro and in vivo atherogenic effects of beta-blockers may be prevented by papaverin.


[Toxic effects of heavy metal salts on intact and irradiated cultured mammalian cells]. The toxicity of solutions of K2Cr2O7 and NiSO4.8H2O for cultivated Chinese hamster fibroblasts and murine lymphoma Sp-2 cells was determined using three criteria of damage: cell death (dyeing with trypan blue), inhibition of cell proliferation and their colony-forming activity. It was shown that both salts have equal toxicity in (10(-3)-10(-2)) M interval for both culture investigated relative to inhibition of cell proliferation. The threshold of toxicity of K2Cr2O7 relative to reproductive cell death (10(-4) M is smaller than to the inhibition of cell proliferation. The nontoxic concentration of K2Cr2O7 enhanced the radiation-induced reproductive death of fibroblast culture at doses 2 and 4 Gy.


[Disorders of bone marrow hematopoiesis long time after the action of cytostatic preparations]. We studied the condition of CBA mice bone marrow hemopoiesis and functional activity of adherent cells 6 months after a single treatment with vinblastine (VB), doxorubicin (DR) and cyclophosphamide (CP) in LD10 dose (6, 22 and 250 mg/kg, respectively). There was a long-term disorganization of bone marrow cell composition. The damage may be attributed to exhaustion of the pools of stem cells and changes in function of the cells formed by hemopoiesis induction microenvironment.


[Antipyrine metabolism and rat liver ultrastructure in single and combined action of trichlorodiphenyl and dioctyl phthalate]. As shown by animal experiments, low-dose trichlorodophenyl and dioctyl phthalate induce microsomal cytochrome P-450-dependent enzymes and ultrastructural changes in hepatocytes. This evidences hepatotoxicity of the compounds.


[Febrifugal activity of acupuncture and its strengthening by the effects of anaprilin]. The power and duration of antipyretic actions of acupuncture under single or repeated stimulation of Shaoshang (Lu-11) and Shangyang (LI-1) acupoints were studied in rabbits. Under conditions of preliminary i. v. injection of propranolol (1-2 mg/kg), strengthening of acupuncture antipyretic activity was revealed. This effect suggests participation of norepinephrine system in mechanism of febrifugal action of acupuncture.


[An experimental study of anti-amnestic activity of piracetam in orchidectomized rats]. The decrease of learning ability by 50% as assessed by passive avoidance test and the increase 28% of microviscosity of synaptosomal membranes from brain cortex were observed in rats in a month after orchidectomy as compared with that of intact or sham--operated animals. The treatment of orchidectomized rats with piracetam either by single application or in the course of 10 days applications in the daily dose of 250 mg/kg intraperitoneally failed to improve learning ability of animals in passive avoidance test and to produce a normalizing effect on the structure of membrane lipid matrix. The testosterone content in blood of orchidectomized rats was 10 times lower as compared with control and was not affected by treatment with piracetam.


[Effects of nitroglycerin on intracellular concentration of calcium in human blood platelets]. It is shown that nitroglycerin has a calcium-blocking property in human platelets both at basal and ADP-induced calcium level, determined by fluorescence techniques (Fura-2). The study demonstrated a dose-dependent inhibitory effect of nitroglycerin on calcium rise, induced by ADP. 30-min preincubation with 60 microM nitroglycerin increased IC50 from 44 (without preincubation) to 320 microM, indicating the development of nitrate tolerance. It was suggested, that human platelet may be used as an experimental model of nitrate tolerance.


[Characteristics of immunomodulating effect of histamine in inbred strain mice]. The activity of 5'-nucleotidase of peritoneal exudate in subcutaneous injection of histamine in a dose of 1.0-100 microliters was studied in mice of different lines (CBA, C57, B1/6, Balb/c, NFS/n, NFR/n). There were interline differences in the influence of histamine on this metabolic index.


[Sensitivity to mouse toxin and level of macrophage 5-nucleotidase activity]. It is shown that immunomodulator of bacterial origin salmozan causes alternations of sensitivity to mouse toxin in mice CBA. A correlation exists between the sensitivity to mouse toxin and the level of 5-nucleotidase of peritoneal exudate macrophages.


[Characteristics of lymphoid subpopulations of peripheral blood of patients with shigellosis]. This work presents some investigation results of lymphoid subpopulation functional activity: Tg+1, Tg-1, Theophylline-resistant and Theophylline-sensitive lymphocytes and O-1 isolated from the peripheral blood of patients with bacterial dysentery (BD) in local xenogenic GVHD. It has been established that Tg+1 and Tg-1 have stimulating effect on local xenogenic GVHD, but O-1 are inert though the quantity of Fcg+--receptor carrying lymphocytes among O-1 in BD and nonspecific ulcerative colitis is increased compared with donors. Theophylline-resistant and Theophylline-sensitive lymphocytes demonstrated inhibiting effect on GVHD formation which was evident in the latter case.


[Immunomorphological studies of the antigen associated with squamous cell cancer of the human cervix uteri]. The existence of the antigen associated with human cervical squamous cell cancer in normal and pathologically changed cervical epithelium was studied. Immunocytochemical and immunohistochemical methods were used. It is shown that the levels of the antigen increase significantly as the severity of dysplastic changes in epithelial stratum grows and tumor invasive growth begins. The data obtained indicate that the above tumor-associated marker can be useful in the follow-up for prognosticating a course of cervical cancer and dysplasia.


[Seasonal characteristics of the circadian rhythm of peripheral blood leukocyte content in Wistar rats]. In Wistar rats, the seasonal variability of acrophase position, mesor value and circadian rhythm amplitudes of total leukocyte count, as well as of percentage and absolute lymphocyte count was revealed. The leukocyte count and absolute lymphocyte content were found highest in spring, while eosinophils--in autumn, neutrophils and monocytes--in winter.


[Seasonal changes in amine-containing structures of the thymus during the 1st hour of antigen effects]. Using luminescent-histochemical and microspectrofluorimetric techniques, the combination of early visual and quantitative changes of catecholamine and serotonin content in biogenic amine-containing thymus structures during the first hour contact of the body with the T-dependent antigen (sheep red blood cells) has been studied. The experiments were made on 60 male rats of Wistar-2 line, white laboratory rats in spring and autumn. The degree and direction of the changes were found to depend on the baseline neuromediator levels.


[Effects of nerve growth factor on the development of the dendritic system of cholinergic neurons in dissociated culture of the rat septum]. Neurons dissociated from septal area of fetal (E18-19) rat brain were grown 14-days in culture. Cholinergic neurons were identified by cytochemical demonstration of acetyl cholinesterase. It was shown that the nerve growth factor added to the culture medium (50 u/ml) has increased the size of cell body of AchE-positive neurons, mean total length and arborization of dendrites and also the dendritic tree area.


[Histological manifestations of the sparing effect of cooling in heat dissection of the cerebral cortex and liver]. A new method of heat dissection of tissues combined with application of cooling was studied experimentally in white rats. Histologic changes of tissues of the cerebrum cortex and the liver wounds were investigated. It was found out that automatic selection of temperature regimen in combination of heat and cold ensured stable effect which was well balanced from the point of view of its depth and prevented overheating of tissues surrounding a wound channel. In comparison with cut wounds the above mentioned method allowed to gain better safety of cells.


[Phosphate metabolism in the mineral matrix of intact bones and after single and multiple fractures]. The level of mineral matrix phosphates in unbroken bones was investigated in rats with isolated and multiple fractures. It was found out that in bones lying close to the broken one the phosphates exchange shifts were similar to the changes happening in the region of the trauma. On the resorption stage the phosphates level in the nearby intact tissue decreases, during the bone callus formation it increases, and in the process of remodelling decreases again. The authors suggest that this zone should be identified under the term "trauma field".


[Morphofunctional analysis of zinc-accumulating capacity of digestive system organs]. The distribution of zinc and related changes have been studied in zinc--loaded chick pancreas, ileum and liver at the ultrastructural level by sulphide--silver method. White Leghorn chicks fed a high zinc diets (50, 500, 1000, 2000 and 4000 mgZn/kg diet) for 6 weeks, were killed at intervals; portions of their organs were fixed for light and electron microscopy; other samples were analyzed for zinc by AA spectrophotometry. A drastic increase of zinc level in chick pancreas fed 2000 mg Zn/kg diet (as ZnCl2) was associated with acinar cell degeneration. Apoptosis was the predominant form of acinar cell deletion. This study provides support for a previously proposed theory that cell injury stimulates passive zinc accumulation.


[Structural-metabolic changes in the ventricular myocardium in massive experimental pulmonary embolism]. A comparative study of hemodynamic and structural-metabolic changes in myocardium of right (RV) and left (LV) ventricles by compensative massive pulmonary embolism (MPE) and decompensated MPE was made in 29 mongrel dogs. By decompensated MPE the histoenzymological and ultrastructural methods reveal changes in RV which are not adequate to its high hemodynamic load: the catabolic enzymes activity decreases, the numeral density of mitochondrial profiles decreases too, the fraction of damaged mitochondria increases. By decompensated MPE the myocardial metabolism shifts from catabolic to biosynthetic processes, the activity of NADP.H-D and G-6-PDG increase in both ventricles.


[Wound epithelialization in rats depending on the quantity and orientation of microautotransplants]. Patches of autoskin (0.5 x 1.0 mm) were grafted on a full-thickness rat back skin wound (5.4 cm2). As a result of "island" epithelialization from microautotransplants (MATR), the skin defect underwent repair. It is shown that the advance of the wound re-epithelialization did not depend on MATR number and their orientation in relation to the wound surface. The use of MATR allows to restore the skin defect with the plastic coefficient 1:100. This reduces the deficiency of donor skin at extensive burns.


[Evoked potentials and electric resistance of the cerebral cortex under the effects of strychnine and atropine]. The effect of strychnine and atropine on the amplitude of the evoked potentials (EP) of the cerebral cortex was studied. It was shown, that both drugs increased amplitude of the EP. When we used strychnine, increased amplitude of the EP determined modification of the electrical resistance and current sources of the electrical field of the EP. Atropine did not change electrical resistance and in this case only electrical current sources determined modification of the EP.


[Changes in the bioelectrical activity of the brain cortex in rats with infraorbital nerve compression]. Bioelectrical activity of the somatosensory cortex was studied in the Wistar rats with chronic (1.5-2 months) compression of the infraorbital nerve produced by two partial ligations. In 20% of rats spike-slow wave complex and slow waves were observed. Electrostimulation of the skin on the injured nerve side resulted in a considerable increase in the amplitude of early components of the contralaterally evoked potentials in comparison with the non-injured side stimulation in 75% of rats. A decrease in the evoked potential thresholds on the injured nerve stimulation was shown in both hemispheres. In most of the animals a hypersynchronous late component of the evoked potential was observed.


[Relationship between functional activity of the adrenal glands and gonads in monkeys during puberty]. Testicular and adrenal cortex endocrine functions were simultaneously tested in pubertal baboons (papio hamadryas) during one year. Concentrations of androgens (testosterone, 5 alpha-dihydrotestosterone, dehydroepiandrosterone), corticosteroids (cortisol, progesterone, 17-hydroxyprogesterone, 17-hydroxypregnenolone) and aldosterone were determined in blood of the experimental monkeys by radioimmunoassay. It was shown that with increasing androgen (testosterone and dihydrotestosterone) levels in blood of the pubertal monkeys there was a significant decrease of corticosteroid concentration which was most pronounced in the monkeys with maximum increase of testosterone level. Described hormonal changes did not influence aldosterone concentration.


[Mechanism of the antiarrhythmic effect of laser irradiation]. Acute experiments were performed to study the role of afferent impulses from the heart receptors which pass by different vagal fibers during intraatrial laser irradiation. Double laser irradiation of the right atrium seemed more effective than a single one as to decreasing ventricular arrhythmias during cardiac ischemia. It is shown that the antiarrhythmic effect of intraatrial laser irradiation may be due to the change of the afferent information passing by myelinated vagal fibers.


[Interatrial differences of myocardial reactivity and its changes in adaptation of rats to physical exercise]. The myocardial reactivity to main regulatory influences (changes of stimulation rate, superfusion of acetylcholine, adrenaline, noradrenaline) was to be higher in right than in left rat atrium. The training-induced increase of some interatrial differences in myocardial reactivity suggests their essential physiological significance.


[Effects of taurine and dipeptide Tyr-Tyr on ventricular defibrillation]. Results of the study of taurine and dipeptide Tyr-Tyr effect on the threshold values of functional lesions of the myocardium and heart defibrillation are reported. The experiments were carried out on 27 narcotized mongrel dogs weighing 12-30 kg. Defibrillation was performed using Lifepak-7 defibrillator (USA). Lesion threshold (LT), defibrillation threshold (DT) and electrotherapeutic index (ETI) as a LT:DT ratio were determined. In 14 experiments (control group) these parameters were evaluated during 3 h. In group 1 (6 experiments) taurine (100 mg/kg) was infused intravenously by the end of the 1st hour, in group 2--Tyr-Tyr (25 mg/kg). It was shown that infusion of taurine did not have a noticeable effect of the LT, DT and ETI values. Infusion of Tyr-Tyr resulted in an increase in LT and DT. The possibility to use dipeptide Tyr-Tyr in the complex of measures aimed at ceasing ventricular fibrillation is discussed.


[Role of the vagus nerve in mechanisms of the modulation of afferent duodenal effects]. The electrostimulation of vagal nerves, the effect of naloxone and atropine on duodenal afferentation by registering evoked potential (EP) at cortex on direct electrostimulation of duodenum have been studied in acute experiments on cats. It has been established that the stimulation of afferent portion of vagal nerves causes the effect of deprivation of EP, whereas the stimulation with certain intensity of efferent portion of vagal nerves intensifies the duodenal afferentation. The effect of afferentation easeness (relief) has been blocked by the application of naloxone 10-20 microgram on duodenal bulbus, but not on it's i. v. injection and without effect on local application of atropine. It is concluded that the role of vagal nerves on the modulation of duodenal nociception is due to the activation of opiate terminals of the efferent vagal nerve portions.


[Functional state of the endogenous opioid peptide system in traumatic shock in rats]. The experiments have been performed on 120 Wistar rats and 546 CBWH mice. Met-enkephalin (ME) and beta-endorphin (BE) levels were determined to increase in blood and mid-brain 3 hours later after soft tissue compression of pelvic extremities. 48 hours later after six-hour compression BE and ME level in blood was increased, BE concentration in blood was also increased, and enkephalins' content in brain and blood was decreased as against the control. Opioid peptides influence on the host compression period has been studied. D-agonists were established to decrease, but mu-agonists were established to increase mice survival in shock. Opioid peptides' significance in traumatic shock pathogenesis is being discussed.


[Study of axodendritic synapses of the hippocampal CA3 field in experimental uremia and administration of exogenous parathyroid hormone]. The effect of parathyroid hormone intraperitoneal injection at different stages of experimental uremia induced by subtotal nephrectomy on ultrastructural morphofunctional characteristics of hippocampus Ca3 field axospinal synapses was studied. A conclusion is made that the decrease of synaptic activity in the hippocampus field due to redistribution of calcium ions between spine cytoplasm and spine apparatus may take place after PTH injection and during uremia development.


[Effects of prolonged hyperbarism on lipid peroxidation and structural-functional state of erythrocytes]. Prolonged helium-oxygen hyperbaric (pressure 3,6 MPa) increased diene conjugate and Schiff's base level in plasma and erythrocyte membranes of mice. In those conditions SOD and glucose 6-phosphate dehydrogenase activities were inhibited in erythrocytes. Lipid bilayer microviscosity and cholesterol content of erythrocyte membranes were increased.


[Antiatherogenic action of corn oil in experimental atherosclerosis]. Therapeutic effect of corn oil was studied in rabbits with alimentary atherosclerosis. Corn oil was administered (2 ml/kg, 30 days) after the completion of cholesterol diet unlike studies, where they were administered simultaneously. Total cholesterol, apoB-lipoprotein cholesterol and triglycerides decreased more intensively in rabbits fed by corn oil than in control group. No changes in high-density lipoprotein cholesterol were observed. The most pronounced effect was noted in aorta morphological analysis: an aorta damage degree was 4.8% as compared with 52.9% in the control group. The results show that available plant oils with omega-6 polyunsaturated fatty acids (PUFA), in particular corn oil, may as well as omega-3 PUFA be used as the base for antiatherogenic preparations.


[Antiradical activity of complex copper compounds (II) on coumarin ligand base]. The antioxidant capacity of copper chelates with coumarins has been studied by the method of iron-induced chemiluminescence. All substrates studied were potent antioxidants, comparable to butylated hydroxytoluene. The mechanism of the antioxidant action of these copper-coumarin chelates was similar to that of Cu-Mn-superoxide dismutase, with a coumarin part of the complex being involved as a free radicals trap.


[Content of cholesterol extracted from human skin surface--a possible discriminant of atherosclerosis?]. Basing on the data of Bouissou et al. on an increase of cholesterol content in the skin biopsies in atherosclerosis patients, the cholesterol amount was evaluated after superficial atraumatic rapid treatment of patients palm skin. The optimization of the extraction conditions was performed: the surface skin cholesterol value was constant for individual subjects (variability factor 5%). The range of this value was 1.5-6 Mg/cm2 and it was higher for atherosclerotic patients. No correlations with any conventional plasma lipoprotein parameters were observed. At the same time positive correlation (r = 0.54. p < 0.01) was observed with dyslipoprotein coefficient--(Ch+TG/alpha-Ch). Possible diagnostic significance of this skin cholesterol parameter is discussed.


[Relaxant effects of oligopeptides isolated from the tracheal mucosa and pulmonary parenchyma on the smooth muscle of isolated rat trachea]. Relaxant effect of oligopeptides extracted from tracheal mucosa (PTM), lung parenchyma (PLP), aortal wall (PAW) and thymic gland (PTG) was investigated using acetylcholine-induced constriction of tracheal strips. Time of 50 percent relaxation of constricted strips treated with saline, atropine or peptides was measured. Both PTM and PLP in concentrations 10(-6)-10(-3) g/ml accelerated relaxation in dose-dependent manner, however this effect was less prominent compared with atropine. Relaxant effect of PTM was found using different parts of trachea (cervical of thoracal), indicating independence of PTM action of intramural ganglia which are present only in the thoracal part. PAW and PTG did not show any significant effect on relaxation time. These results suggest the presence of oligopeptides, capable to relax airways smooth muscle, in tracheal mucosa and lung parenchyma.


[Increased lipid peroxidation in the rat hypothalamus after short-term emotional stress]. Concentrations of TBA-reactive substances (TBARS) were measured spectrophotometrically in homogenates of small samples of the brain (hypothalamus, parieto-occipital, sensori-motor and limbic cortex), heart, liver and adrenals of male August and Wistar rats; the former strain is more susceptible to emotional stress than the latter one. Forced isolation of the rats in the restraining plastic cages for 1 h increased the TBARS concentrations in the hypothalamus and liver in August rats only. TBARS accumulation in some tissues correlated with such indices of emotional stress as the changes in relative weight of thymus and adrenals. As regards the brain regions, after 1-hour emotional stress the TBARS levels were no longer different because of an increment in hypothalamic TBARS concentration. However, in control conditions the hypothalamus had significantly lower TBARS levels than any other brain structure both in Wistar and August rats.


[Role of leukocyte adhesion in filterability of blood cell suspensions]. We investigated blood cells suspension filterability of 16 donors. The filtration was performed trough 5 microns-pore nuclear filters at constant perfusion pressure 10(5) din/cm2. We estimated also the adherence of leukocytes and platelets on nylon. The adherence of platelets and mononuclear leukocytes reduced the level of the suspension filterability only by 21% (p > 0.05). The presence of nonadhesive polynuclear leukocytes in the suspensions did not change practically their filterability. The addition in the suspensions of adhesive polynuclear leukocytes reduced suspension filterability dramatically.


[Effects of peginol C-2000 on respiration and oxidative phosphorylation in liver mitochondria of rats poisoned with butylcaptax]. The data on the effect of synthetic antioxidant Paginol C-2000 on respiration and oxidative phosphorylation in liver mitochondria of rats primed with butylcaptax are given. It is shown that intoxication of organism with butylcaptax in the dose of 1/10 LD50 during 5 days resulted in suppression of respiration and oxidative phosphorylation in rat liver mitochondria. It is found, that administration of Raginol C-2000 into organisms of primed animals leads to the reduction of succinate pathway of oxidation, that, in its turn, results in the normalization of functioning level of ATP-synthesizing system of mitochondria.


[DNA-protein interactions in CpG islands and DNAse I sensitive chromatin]. DNA-protein interactions were studied in the chromatin preparations obtained according to different procedures by means of nucleoprotein-celite chromatography. Three discrete fractions dissociating in 1M, 2M and 3M NaCl were observed in all preparations. The 1M fraction prevails in DNaseI-sensitive chromatin and the 2M fraction--in the resistant. Chromatin solubilized by MspI restrictase (the active chromatin) contains the 1M and 3M fractions, one solubilized by AluI (inactive)--the 2M fraction. Distribution of the fractions is different in proliferating and quiescent cells.


[Post-intoxication hypothermia and processes of free radical lipid peroxidation in the rat brain and heart in organophosphorus cholinesterase inhibitor poisoning]. The activity of lipid peroxidation (LP) of the brain and myocardium as well as the intensity of the body hypothermia during 30 days after a single introduction of poisons at a dose < D50 were studied on the models of induced toxicosis in rats due to two organophosphorus compounds (malathion and armin). It has been established that the maximums of diene conjugates and Schiff's bases accumulation in the rat organs poisoned with malathion and the intensity of hypothermic response on days 14 and 21 after intoxication coincided. The similar elevated lipid peroxidation was associated with esophageal hypothermia on day 14 after armin administration. Therefore, because of hypothermia, the influence of organophosphorus compounds on lipids of the rat brain and heart in the post-intoxication period may include the free radical ways of their peroxidation.


[Lipid peroxidation in the aorta of normotensive and spontaneously hypertensive rats with diabetes mellitus]. We have studied the effects of streptozotocin-induced (STI) diabetes on the lipid peroxidation in the aorta from normotensive (NTR) and spontaneously hypertensive (SHR) rats. In the control SHR quantity of malonyldialdehyde (MDA), conjugated dienes (CD) and arterial pressure where higher than in NTR analogous group. It has been shown that Diabetes in NTR results in significantly increased arterial pressure and quantity of MDA and CD. Under certain conditions in SHR arterial pressure and the other factors remain almost unchanged. It is likely that completely different changes in intensity of lipid peroxidation may evidence breaking adaptation mechanism in diabetic SHR.


[Effects of arginine on properties of the erythrocyte membrane in hypoxia]. The antioxidant effect of arginine evident from stabilization of membrane structure and properties and activation of oxygen-toxicity-protecting enzymes was demonstrated in hypoxia. The intraperitoneal injection of L-arginine-HCl in a dose of 120 mg per 100 g body mass prevented the increase of microviscosity, membrane permeability and lipid peroxidation products level in hypoxia. At the same time the activity of the antioxidant enzymes--superoxide dismutase and catalase--was increased in red blood cells by 64 and 46%, respectively.


[Activity of cytochromes P-450p and P-450h in liver microsomes and blood corticosteroid levels in experimental animals under the action of physical factors]. In experiments on male Wistar rats it has been found that physical factors applied in medicine (laser radiation of low intensity with wave length 0.89 microns, microwaves of centimeter range of 2450 MHz, and ultrasound of low intensity 880 KHz) changed catalytic activity of liver microsomal and rostenedione 16 alpha- and 6 beta-hydroxylating cytochromes P-450h and P-450p and blood corticosteroids level. Activities of these two steroid-metabolizing cytochromes decreased under ultrasonic skin application on liver region and increased under microwave and laser action. Contents of physiologically inactive form of corticosterone were not changed by the physical factors action while level of active hormone was increased under ultrasonic and microwave action. These findings suggest association of the activity of liver steroid-metabolizing cytochromes P-450 and level of physiologically active form of corticosterone in blood under physical factors skin application on liver region.


[Lipid peroxidation changes in the brain in fetal alcohol syndrome]. The study was performed upon three groups of 12-week-old male rats. The first group of rats received ethanol/9 g/kg/day as 6% aqueous solution/during pregnancy and lactation, the second group received ethanol only during lactation and the third group, controls, received equicaloric sucrose solution. The concentrations of LPO products were determined in the homogenates of tissue from frontal cortex, striatum, hypothalamus, hippocamp and cerebellum. The concentration of fluorescent products in the brain structures of rats treated perinatally with ethanol was several-fold increased as compared with controls. The levels of diene conjugates were increased in most brain structures of rats with FAS. It should be pointed out that there was the same degree of increase of the levels of both fluorescent products and diene conjugates in two groups of rats with FAS. Having in mind that in the rat the increased growth of the brain occurs during the first 10 postnatal days, it might be assumed that this period is favorable for LPO.


[Anticalcium activity of several antidepressive agents]. In experiments in white mice and rats the antidepressants pyrazidol (pirlindole), moclobemide and especially tetrindole possess anticalcium activity in tests of calcium chloride-induced lethality in mice and arrhythmia in rats. Tetrindole is as active as verapamil. Imipramine, azaphen and incazane were not active in these experiments. In vitro on isolated intestinal segments of guinea-pigs tetrindole exerts anticalcium action, but in less degree than verapamil. In all probability the anticalcium activity of tetrindole may play some role in the mechanism of action of this compound on the central nervous system.


[Antioxidant effects of antihypoxic drugs in cerebral ischemia]. Cerebral ischemia in rats (both carotid arteries occlusion) during 30 min, 3 hours and recirculation (1 hour) after ischemia (30 min) stimulated diene conjugates and fluorescent products accumulation in brain tissue. Intraperitoneal injection of sodium hydroxybutyrate (100 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) reduced brain lipid peroxidation and did not yield in this respect to emoxypin (5 mg/kg). In contrast to emoxypin, sodium hydroxybutyrate, bemitil and ethomersol had no antiradical activity.


[Participation of protein synthesis in brain cell structures in the action of antifeins on long-term memory]. Incorporation of 3H-leucine into proteins of rat brain cell structures during application of antifeins (compounds of alternative action on memory processes) has been studied. No correlation was observed between changes in protein synthesis in nuclei, mitochondria, components of endoplasmic reticulum and memory effects of ethyl-, allyl- and propylnorantifeins. Only M1 and M2-demethylated structural analogs of ethylnorantifeins (exerting the most effective action on RNA synthesis and retention of conditional reflexes) enhanced the synaptosomal protein synthesis.


[Analysis of the role of calcium in analgesic action of non-narcotic analgesics and calcium channel blockers]. In the mice hot-plate test we have compared analgesic effect of calcium channel blockers and new non-narcotic analgesic antiinflammatory agent PV-107: verapamil > fenigidin > PV-107. Simultaneously we have shown strong correlation (r - 0.82) between analgesic effect and 45Ca2+ efflux of cardiac membrane in depolarizing media in vitro.


[Mechanism of prolonged hypocoagulation appearing after intratracheal administration of heparin]. The comparative study of intratracheal and intravenous effect of administration of heparin on blood clotting and mast cell population condition was carried out in experiments. Unlike intravenous bolus injection of heparin, which induced fast short-time inactivation of all enzyme clotting factors, a single intratracheal injection inactivated "internal" rout of thrombin production. It was shown, that long-term hypocoagulability effect and inhibition of factors of blood coagulation after intratracheal administration of heparin correlated with accumulation of heparin in mast cell.


[Role of T-lymphocytes in the mechanisms of hemopoiesis-inducing microenvironment activation in inflammation]. On the model of acute infectious peritonitis in mice, the inflammation was shown to accompany pronounced activation of bone marrow haemopoiesis. The increased number of committed precursor cells of erythro- and granulomonocytopoiesis, morphologically differentiated elements and enhancing colony-stimulating and erythropoietic activities of GIM cells origin were shown as well. Thy 1.2+ cells, migrating to bone marrow, were shown to play an important role in hemopoiesis stimulation inflammation. These stimulate the processes of myeloid precursor proliferation directly (by means of lymphokines) and in cooperation with monocytes-macrophages of GIM.


[Characteristics of the mitogenic activity of purified thymocyte growth factor]. Being purified by gel filtration and reverse phase HPLC the thymocyte growth factor from the supernatant of the cell line of intrathymic precursors of T-lymphocytes can stimulate the growth of splenocytes and thymocytes nonactivated by mitogen. Addition of suboptimal doses of mitogen or phorbol myristate acetate does not enhance the cell response to the thymocyte growth factor. The thymocyte growth factor in capable of stimulating the growth of thymocytes synergistically with interleukin-2, but the direct action of the thymocyte growth factor is not mediated by the production and reception of interleukin-2 and interleukin-4.


[A simple method of continuous passage of human tumors in immunocompetent mice]. A simple procedure is described for the continuous passage of a human tumor in immunocompetent mice. The BRO human melanoma was transplanted consecutively 25 times by implanting tumor tissue under the sub--renal capsule of mice which had been immunosuppressed by a single dose of whole--body irradiation or by cytosine arabinoside followed by irradiation. The tumor grew continuously for 14 days, and cytological examination showed that the growth consisted almost entirely of tumor cells.


[Immunomodulating activity of exogenous ceruloplasmin in experimental tumor growth]. Immunomodulating properties of ceruloplasmin were determined in vivo on healthy mice line C57BL/6 and mice with Lewis carcinoma. It was established, that ceruloplasmin at the concentration of 1-40 mg/kg stimulated both T- and B--systems of immunity and prevented immunodepression activity of tumor growth.


[Inhibition of phospholipid reacylation in oxidative damage of tumor cells]. In this study we examined the effect of oxidative stress on phospholipid reacylation and [1-14C]arachidonic acid uptake by murine mastocytoma P815 cells. Tert-butyl hydroperoxide inhibited arachidonic acid uptake by P815 cells and incorporation of fatty acid into main cellular phospholipids. Specific activity of control phosphatidylcholine was about 15-fold higher than that of phosphatidylcholine from tert-butyl hydroperoxide-treated cells. For phosphatidylethanolamine and phosphatidylinositol this inhibition was about 7-fold and 12-fold, respectively. Thus, oxidative stress causes the drastic changes in the process of phospholipid repair, which may significantly disorder membrane stability.


[Effects of human defensin HNP-1 on the production of tumor necrosis factor-alpha by human blood monocytes in vitro]. The influence of human defensin HNP-1 on the synthesis of tumor necrosis factor-alpha (TNF-alpha) by human blood monocytes was studied. It was shown that TNF-alpha production by human monocytes activated by SAC or PMA was augmented in the presence of HNP-1 concentrations of 10(-8)-10(-9) M. HNP-1 alone induced no synthesis of TNF-alpha. High concentration of HNP-1 (10(-4) M) was cytotoxic for human monocytes.


[Thiol-induced fragmentation of chromosomal DNA]. Supramolecular complexes of DNA (SC DNA) were isolated from loach sperm, loach erythrocytes and hen erythrocytes by the phenol method. By the use of UV-sedimentation on neutral 5-20% sucrose gradient, we studied the effect of 2-mercaptoethanol (ME), dithiothreitol (DTT) and NaBH4 on SC DNA at different pH and long-time incubation (5 and 10 days). It appeared that ME treatment at pH 4.4 fragmented SC DNA of three objects into subunits of size 5 x 10(5)D. Incubation with DTT at pH 8 in the presence of EDTA resulted in subunits of size 1-2 x 10(7)D. However, NaBH4 at pH 8 failed to induce fragmentation of SC DNA. It is shown that ME-induced at pH 4.4 fragmentation is accompanied by a decrease in hyperchromatic effect of subunits, indicating the presence of "sticky" ends. Thus, ME-induced fragmentation of SC DNA results from a "clayting" double-strand break, involving, on an average, 180 bp.


[Delayed hypersensitivity to house dust-storage mites Thyrophagus putrescentiae in experimental allergic dermatoses]. House dust mites and storage mites proved to be one of the main allergens causing hypersensitivity in atopic dermatitis in allergic patients. The authors reproduced experimental allergic dermatosis on the model of delayed type hypersensitivity in guinea pigs, caused by sensitization to the allergen from the mite's bodies Tyrophagus putrescentiae--species having wide distribution in the country. The results characteristic for T-cell type hypersensitivity have been obtained: delayed positive skin tests after 24 hours, typical histomorphological picture (strong allergic alteration, epidermis desquamation, vasculitis, dermis T-cell infiltration and spongiosis--Waksman's syndrome). It is concluded that side by side with humoral IgE-mediated reaction there is strong delayed T-cell hypersensitivity to the storage mites Tyrophagus putrescentiae.


[Testing of promising dressing materials in cultures of fibroblasts and keratinocytes of human skin]. Cell cultures of epidermal keratinocytes and dermal fibroblasts were used to test collagen dressings in vitro. It was shown that effects of the dressings on skin major cell types might be differentially evaluated.


[Clinico-experimental study of histoenzymological changes in the ventricular myocardium in pulmonary embolism]. The SDH and LDH activity in ventricular myocardium was studied in early autopsies of 16 patients, which died from acute pulmonary thromboembolism, and also in 17 dogs with experimental pulmonary embolism. In general the data of histoenzymological study of experimental and sectional material were identical. We revealed some factors, which correlated with low activity of catabolic enzymes in ventricular myocardium of the patients with pulmonary embolism: small volume of embolic occlusion (the thromboembolism of lobar and segmental pulmonary arteries); the presence of prior chronic cardiopulmonary disease; the advanced age and the female sex. Preexisting cardiopulmonary disease, as well as age and sex changes of myocardial metabolism, may assist the development of heart failure by relatively small volume of embolic obstruction.


[Development of interfollicular epidermis on the surface of collagen framework of the dermis in experimental animals]. The fate of interfollicular epidermis keratinocytes which filled the hair follicles bursas of collagen dermis framework was investigated in the autotransplantation experiment. Collagen dermis framework was prepared from the skin flap. Interfollicular epidermis was detached with the help of suction method and transferred to the collagen dermis framework surface which was placed previously on the full thickness skin defect surface. It was established that in this environment keratinocytes not only developed, but some of them migrated into the hair follicle bursas cavities. It resulted in the follicular-like structures formation, cell elements of which differentiated in the manner characteristic of interfollicular epidermis. However, in spite of the fact that the epidermal cells partially retained their proliferating ability, ingrowing would completely disappear by the 15th to 20th day after the transplantation.


[Effects of antibodies to lysosomal enzymes on the course of experimental burn shock]. On the model of burn shock in rats, the influence of antibodies to lysosomal enzymes has been studied in respect to the cathepsin D activity, oxygen regimen, acid-base equilibrium in blood, and animal survival. It has been shown that the antibodies inactivate the cathepsin D activity which is increased in burn shock. Because of the decreased cardiodepressant action of the lysosomal enzymes, the blood circulation improves, the manifestations of hypoxia and metabolic acidosis are attenuated. The results obtained confirm an important role of the lysosomal in the pathogenesis of bur, shock and permit one to consider its therapy using antibodies to the lysosomal enzymes to be promising.


[Flavobion and thioctacid lessen irradiation-induced latent injury of the liver]. The effect of hepatoprotective drugs (flavobion and thioctacid) and a single whole-body irradiation (5.7 Gy of gamma radiation) on the regeneration of rat liver was examined. Liver regeneration was estimated on the basis of chosen morphological parameters on hour 30 after partial hepatectomy. Radiation-induced latent injury to intact rat liver 30 min before partial hepatectomy manifested in remaining regenerating liver by slowing-down of the increase in liver weight, cellularity and inhibition of the mitotic activity and in more frequent chromosome aberrations. Both hepatoprotective agents, especially thioctacid, used i.p. 60 min before irradiation, i.e. 90 min before partial hepatectomy, alleviate the manifestations of latent injury in this low proliferating organ as indicated by an increase in cellularity and mitotic index as compared with unprotected animals. Furthermore, the preparations tested decreased the frequency of radiation-induced chromosome aberrations.


[Ultrastructural changes in interneuron connections in intramural ganglia of the small intestine in suckling rabbits with experimental cholera]. Data, received in investigation of the small intestine intramural ganglia of 34 suckling rabbits show, that development of experimental cholera induce in the neurons reactive shifts, changed by dystrophic alterations. Prevaluation of cholinergic influences in autonomic ganglia in small intestine promotes enterocytes hypersecretion and accelerating of motor activity.


[Functional morphology of resistant pulmonary vessels and capillaries in individual and species adaptation to high altitude]. Morphological and structural rearrangement of resistant pulmonary vessels and alveolar capillaries was assessed in lowland animals (rabbits) during high-altitude adaptation, in aboriginal high-altitude species (yaks, mountain goats) and on native highlanders. Structural adaptive developments in pulmonary vessels and capillaries of high-altitude animals contribute to maximal facilitation of gas diffusion. Similar adaptive changes in pulmonary resistant vessels and capillaries of laboratory animals and in native highlanders are associated with pathological alterations manifest in the elevation of pulmonary vascular resistance, right ventricular hypertrophy, increases in the thickness of the basal membrane of the air-blood barrier. In all the subjects studied the process of high-altitude adaptation is associated with hypertrophy of pulmonary endothelium. The intensification of pulmonary endothelium. The intensification of pulmonary endothelium metabolic activity may be directed at regulation of vascular tone.


[Changes in adhesive interactions of keratinocytes during regeneration of the rat skin]. The values of adhesion between keratinocytes as dermo-epidermal junction in the skin decreased after UV-irradiation, heating to 60 degrees C or sodium dodecyl sulfate action. The results suggest the existence of nonspecific adaptive reactions of keratinocytes adhesive interactions in response to different irritative stimulants.


[Reparative changes in the sensorimotor cortex of the offspring in moderate prenatal alcoholism]. Sensorimotor cortex of 21-, 30-, 60-day-old offspring given prenatally moderate alcohol (2 g/kg) manifested signs of compensatory type: double nerve and glial cells, open capillaries, nearby nerve and glial cell bodies with basal membrane of capillaries. Intracellular reparative processes in dystrophic neurons were observed: nuclear activation, hyperplasia of cytoplasmic organelles, hypertrophy of some of them. Reparative processes are more distinct in 30-day-old rat offspring In 60-day-old offspring a polymorphic pattern of cortical synapses ultrastructure was found. However, dystrophic changes of neurons and interneuronal connections still remain.


[A new method of assessing anxiety-phobic states in rats]. A new multiparameter method for evaluating anxiety-phobic states in rats is elaborated. The method is based on the ranged scale consisting of parameters which characterize the species-specific rat response to the series of ethologically adequate test-stimuli inducing manifestation of the anxiety-phobic states. The method makes it possible to evaluate individual anxiety-phobic level in rats, to form experimental groups with rats of known individual anxiety-phobic level, to conduct repeated observations in the same animals. The method is easy to perform in laboratory and makes it possible to get the results quickly.


[Opposite effects on antioxidant enzymes of adaptation to continuous and intermittent hypoxia]. Adaptation to continuous hypoxia under mid-mountain conditions (altitude 2100 m) decreases the content of lipid peroxidation products and the activity of superoxide dismutase and catalase in rat heart, liver, and brain, with a concomitant decline in the resistance to reperfusion arrhythmias. On the contrary, adaptation to intermittent hypoxia in the altitude chamber increases the activity of the antioxidant enzymes in the same organs, while the content of peroxidation products remains normal; at the same time, the heart becomes more resistant to reperfusion arrhythmias. The mechanism is discussed that ensures enhanced antioxidant protection in adaptation to intermittent hypoxia.


[Effectiveness of artificial ventilation in oil microembolism followed by pulmonary edema]. In experiments on sodium pentobarbital (40 mg/kg, i.p.) anesthetized mongrel cats of either sex weighting from 2.0 to 4.0 kg, it was found, that in conditions of oil pulmonary microembolization, followed by pulmonary edema, the most suitable is rapid and shallow pattern of ventilation, ensuring optimal ventilation/perfusion interrelation. The oil microembolization was introduced with intravenous administration (1 mg per kg of body weight during 2 min) of olive oil. It is necessary to provide flexible regimens of artificial ventilation and conformity of respiratory pattern and body's demands can be controlled according to pHa and PaO2. It is desirable that pH and pO2 can be evaluated continuously.


[Dynamics of coronary circulation in rats]. The blood flow velocities in left anterior descending coronary artery and ascending aorta have been measured in anesthetized rats by high frequency Doppler technique. The measurement of coronary blood flow velocity by miniature ultrasonic probe (2.0 x 1.5 mm) was performed through myocardial surface. Two different forms of coronary blood flow curves were recorded. These forms of the curves depend on the value of the coronary blood flow velocity and are connected with the ascending aorta blood flow velocity. The dynamics of the coronary blood flow reactions under coronary artery occlusion and asphyxia in the rat is similar to the one in the cat and the dog, but less expressive. In experiments with vasodilators the direct dependence between linear and volume coronary artery velocities under the measurement through myocardial surface was found.


[Functional state of the hematopoietic system in different stages of CCL4-induced liver fibrosis in mice]. The state of hemopoietic system at different stages of CCL4-induced liver fibrosis in mice and its reaction to stimuli was examined. At early stages of liver fibrosis (2 weeks of CCL4-administration) we observed a disinhibition of granulo-monocytopoiesis. This is manifested in an increase of the number of immature granulocytes, monocytes/macrophages and CFU-GM in the bone marrow. After 24 h of zymosan injection in this stage an increase of both bone marrow CFU-GM and CFU-E, and the rate of serum colony stimulating activity (CSA) occurred. On the contrary, in advanced liver fibrosis (16 weeks of CCL4 administration), the rate of both granulo-monocytopoiesis and erythropoiesis were decreased as compared with the preceding stage of the process and the response to zymosan became perverted: the number of CFU-GM was paradoxically decreased, while the number of CFU-E remained practically unchanged. The rate of serum CSA increased very poorly too. Thus, in advanced liver fibrosis the hemopoietic system is functionally defective and this factor may be important in development of fibrotic process in the liver.