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Biomedical subjects

V V Kalinichenko

Publications and source records attributed to V V Kalinichenko.

17 recordsLinked to original sources
PubMed2001

Defects in pulmonary vasculature and perinatal lung hemorrhage in mice heterozygous null for the Forkhead Box f1 transcription factor.

Decreased pulmonary expression of Forkhead Box f1 (Foxf1) transcription factor was associated with lethal alveolar hemorrhage in 55% of the Foxf1 +/- newborn mice. The severity of the pulmonary abnormalities correlates with the levels of Foxf1 mRNA. Defects in alveolarization and vasculogenesis were observed in subsets of the Foxf1 +/- mice with relatively low levels of expression from the normal Foxf1 allele. Lung hemorrhage was coincident with disruption of the mesenchymal-epithelial cell interfaces in the alveolar and bronchiolar regions of the lung parenchyma and was associated with increased apoptosis and reduced surfactant protein B (SP-B) expression. Finally, the lung defect associated with the Foxf1 +/- mutation was accompanied by reduced expression of vascular endothelial growth factor (VEGF), the VEGF receptor 2 (Flk-1), bone morphogenetic protein 4 (Bmp-4), and the transcription factors of the Brachyury T-Box family (Tbx2-Tbx5) and Lung Kruppel-like Factor. Reduction in the level of Foxf1 caused neonatal pulmonary hemorrhage and abnormalities in alveologenesis, implicating this transcription factor in the regulation of mesenchyme-epithelial interaction critical for lung morphogenesis.

Alleles↗
PubMed2001

Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury.

The forkhead box (Fox) proteins are a growing family of transcription factors that have important roles in cellular proliferation and differentiation and in organ morphogenesis. The Fox family members hepatocyte nuclear factor (HNF)-3beta (Foxa2) and HNF-3/forkhead homolog (HFH)-8 (FREAC-1, Foxf1) are expressed in adult pulmonary epithelial and mesenchymal cells, respectively, but these cells display only low expression levels of the proliferation-specific HFH-11B gene (Trident, Foxm1b). The regulation of these Fox transcription factors in response to acute lung injury, however, has yet to be determined. We report here on the use of butylated hydroxytoluene (BHT)-mediated lung injury to demonstrate that HFH-11 protein and RNA levels were markedly increased throughout the period of lung repair. The maximum levels of HFH-11 were observed by day 2 following BHT injury when both bronchiolar and alveolar epithelial cells were undergoing extensive proliferation. Although BHT lung injury did not alter epithelial cell expression of HNF-3beta, a 65% reduction in HFH-8 mRNA levels was observed during the period of mesenchymal cell proliferation. HFH-8-expressing cells were colocalized with platelet endothelial cell adhesion molecule-1-positive alveolar endothelial cells and with alpha-smooth muscle actin-positive peribronchiolar smooth muscle cells.

Animals↗
PubMed2001

Transcription factors in mouse lung development and function.

Development of the mouse lung initiates on day 9.5 postcoitum from the laryngotracheal groove and involves mesenchymal-epithelial interactions, in particular, those between the splanchnic mesoderm and epithelial cells (derived from foregut endoderm) that induce cellular proliferation, migration, and differentiation, resulting in branching morphogenesis. This developmental process mediates formation of the pulmonary bronchiole tree and integrates a terminal alveolar region with an extensive endothelial capillary bed, which facilitates efficient gas exchange with the circulatory system. The major function of the mesenchymal-epithelial signaling is to potentiate the activity or expression of cell type-specific transcription factors in the developing lung, which, in turn, cooperatively bind to distinct promoter regions and activate target gene expression. In this review, we focus on the role of transcription factors in lung morphogenesis and the maintenance of differentiated gene expression. These lung transcription factors include forkhead box A2 [also known as hepatocyte nuclear factor (HNF)-3beta], HNF-3/forkhead homolog (HFH)-8 [also known as FoxF1 or forkhead-related activator-1], HNF-3/forkhead homolog-4 (also known as FoxJ1), thyroid transcription factor-1 (Nkx2.1), and homeodomain box A5 transcription factors, the zinc finger Gli (mouse homologs of the Drosophila cubitus interruptus) and GATA transcription factors, and the basic helix-loop-helix Pod1 transcription factor. We summarize the phenotypes of transgenic and knockout mouse models, which define important functions of these transcription factors in cellular differentiation and lung branching morphogenesis.

Amino Acid Motifs↗
PubMed1999

Norepinephrine-mediated inhibition of antitumor cytotoxic T lymphocyte generation involves a beta-adrenergic receptor mechanism and decreased TNF-alpha gene expression.

We have previously shown that norepinephrine (NE) inhibits the in vitro generation of anti-MOPC-315 CTL activity by spleen cells from BALB/c mice rejecting a large MOPC-315 tumor as a consequence of low-dose melphalan (l -phenylalanine mustard (l -PAM)) treatment (l -PAM TuB spleen cells). Since TNF-alpha plays a key role in the generation of antitumor CTL activity in this system, we determined whether NE mediates this inhibition through inhibition of TNF-alpha production. Here, we show that NE inhibits the production of TNF-alpha protein and mRNA by l -PAM TuB spleen cells stimulated in vitro with mitomycin C-treated tumor cells. Flow cytometric analysis of intracellular expression of TNF-alpha revealed substantial NE-mediated decreases in the percentages of TNF-alpha+ cells among CD4+ and CD8+ T cells and F4/80+ activated macrophages. NE inhibition of CTL generation was largely overcome by addition of TNF-alpha to the stimulation cultures. When the beta-adrenergic antagonist propranolol was added to the stimulation cultures of l -PAM TuB spleen cells at a concentration that prevented NE-induced cAMP elevation, the NE-mediated decrease in TNF-alpha mRNA and NE-mediated inhibition of CTL generation were reversed. Collectively, these results suggest that NE inhibits antitumor CTL generation, at least in part, by inhibiting TNF-alpha synthesis through a mechanism(s) involving beta-adrenergic receptor signaling.

Animals↗
PubMed1995

Antagonistic interactions among T cell subsets of old mice revealed by limiting dilution analysis.

When CD4 spleen cells from old (but not young) mice are tested for Con A-induced proliferation in limiting dilution assays, the dose response curve shows a nonlinear relationship. We interpret these observations using a two-cell model, in which proliferation of one cell type (LPC1) can be blocked by a second cell type (LPC2), which can itself generate detectable proliferation only at high multiplicities. The two-cell model accounts for several observations: 1) the variation in curve shape as a function of incubation time; 2) the skewed distribution of wells scored as "negative" in cultures of old splenocytes; and 3) the initially antagonistic effects of old splenocytes titrated into cultures containing fixed numbers of young responders. To provide a further test of the two-cell model, ionomycin-resistant (CaR) and ionomycin-sensitive (CaS) cells were separated using a Percoll/ionomycin gradient. The CaR preparation, shown previously to consist largely of memory T cells, showed the dose curve predicted for the LPC2 cell type, whereas the CaS (naive) cells showed the single-hit kinetics postulated for LPC1 cells. Furthermore, mixtures of CaR and CaS cells from young mice reproduced the zigzag dose curve characteristically produced by unseparated cells from old mice. These data suggest that the spleens of both young and old mice contain two kinds of Con A-responsive CD4 cell: one that proliferates vigorously, and a second, calcium ionophore-resistant type that proliferates less well, that can interfere with proliferation of the first cell type, and whose frequency increases with age.

Aging↗
PubMed1991

About the great importance of venous blood circulation in the pathogenesis of spaceman state disturbances in weightlessness.

CVP increasing observed in OS "Mir" flights lets to consider it as one of the chief factors in stateman state disturbance. It is necessary to use prophylactic means to prevent pathological changes in long flights. The received data confirm physical training and clamping cuffs application efficiency as a blood volume decentring and CVP decreasing.

Blood Circulation↗
PubMedDate not supplied

[Postural reactions in cosmonauts after long flights aboard Salyut-6].

Tilt tests were used to study changes in cardiovascular responses to ortho- and antiorthostasis of four cosmonauts after their 96- and 140-day flights onboard Salyut-6. Preflight the cosmonauts were exposed to head-up and head-down tests in order to facilitate their readaptation to weightlessness. Postflight all cosmonauts exhibited a better cardiovascular capability to counteract cranial blood redistribution during antiorthostatic tilt tests. This can be considered as a result of their adaptation to weightlessness. After flight every crewmember showed a significant decrease of orthostatic tolerance. One of the factors responsible for the lower orthostatic tolerance is assumed to be inactivity of the vascular tone mechanisms. It is suggested that their better stimulation before reentry may improve the efficacy of countermeasures against postflight orthostatic disorders.

Adaptation, Physiological↗
PubMedDate not supplied

[Changes in cardiac output and orthostatic tolerance of astronauts].

Examinations of 14 cosmonauts who performed orbital flights of 14 to 175 days were used to correlate cardiac output (CO) inflight with orthostatic tolerance and LBNP reactions postflight. In 3 crewmembers CO was lower than or close to the preflight level. In 4 cosmonauts CO was higher thant preflight. The remaining 7 crewmembers showed lower orthostatic tolerance and stronger LBNP reactions. The difference between mean CO values before and during flight was in negative correlation with orthostatic tolerance (r = -0.6) and in positive correlation with LBNP reactions (r = 0.7). The correlation coefficients were derived from small samples but an identical relationship between the two different tests with inflight CO variations gives evidence that such a relationship actually exists.

Adaptation, Physiological↗
PubMedDate not supplied

[Results of vectorelectrocardiographic examinations during and after long space flights aboard the orbital complex "Sal'iut-6"--"Soiuz"].

In long-term space flights cardiac bioelectric activity was measured by vector-electrocardiography using ECG in 12 standard leads. Most marked changes in the form of a decrease in the integral spatial repolarization vector were seen postflight. This parameter did not return to normal during one month postflight. Depolarization vector and vector orientation remained essentially unchanged.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

Preliminary results of medical investigations during piloted flights in the Salyut-6 program.

The changes observed during flight on the whole corresponded with the preflight prognosis and reflected the phase nature of the processes of adaptation. They were shown by blood redistribution symptoms, fluctuations in the main indices of hemodynamics at rest not going beyond the limits of the physiological norm, an increase in the pulse-filling of the head with blood, and a decrease in that of the shank. The reaction of the blood circulation to a physical load and the application of negative pressure varied, and in a number of investigations during flight it was more pronounced than on Earth. The changes observed after the flight appeared regular for the period of readaptation of the reactions of the organism. These reactions bore a functional nature and qualitatively did not differ from reactions observed after other flights, and after the 140-day flight they were, on the whole, less pronounced than after the 96-day flight. In the postflight period to accelerate the process of adaptation a complex of restorative-healing measures was carried out, including mainly a regulation of motor activity, restorative massage of the muscles, remedial physical culture and aquatic procedures. The flight lasting 140 days revealed no contraindications to a further regular increase in the time of cosmic flights and demonstrates once again the possibility of the planned control of the state of a healthy subject in flight and the readiness of the organism for a return to the terrestrial force of gravity.

Blood Circulation↗
PubMedDate not supplied

[Dynamics of the orthostatic tolerance of cosmonauts after flights lasting from 2 to 63 days].

Changes in orthostatic tolerance were studied in 25 cosmonauts after their flights to 2 to 63 days in duration aboard the spacecraft Soyuz and the orbital station Salyut. Postflight orthostatic tolerance decreased to a greater extent in those cosmanauts in whom it was below the medium level preflight. Orthostatic intolerance increased with the flight time. The development of orthostatic intolerance in the crewmembers of the Salyut station was significantly delayed due to better environmental conditions and countermeasures against adverse effects of space flight. An application of countermeasures against postflight orthostatic intolerance and a gentle regimen of readaptation are indicated. An exposure to prolonged weightlessness changes significantly the structure of orthostatic responses. This ought to be taken into consideration when inflight orthostatic tests are being evaluated and when countermeasures against postflight orthostatic intolerance are developed.

Adult↗
PubMedDate not supplied

[Orthostatic stability in cosmonauts following 30- and 63-day flights in orbital station "Salyut-4"].

Reactions of the circulation system of cosmonauts to the up and down body movements were studied after 30-day and 63-day flights. All the four cosmonauts showed a decline in the orthostatic tolerance. An improved system of countermeasures against unfavourable effects of weightlessness used in the 63-day flight helped to maintain a better orthostatic tolerance of the crewmembers than that of the 30-day cosmonauts. It is assumed that a rapid increase of orthostaic tolerance postflight indicates an adequate maintenance of functional capabilities of circulation and suggests possible stimulation of its antigravity mechanisms prior to reentry in order to prevent postflight orthostatic disorders. An exposure to weightlessness increased the capacity of circulation to counteract the blood redistribution in the cranial direction in the head-down position. This capacity became more pronounced and stable with an increase in the flight time.

Adaptation, Physiological↗
PubMedDate not supplied

[Reactions of the cardio-respiratory system of cosmonauts to dosed physical loads following 30- and 63-day flights in orbital station "Salyut-4"].

Cardiorespiratory responses of Salyut-4 crewmembers to exercises of 600 kgm/min performed for 7 min on a bicycle ergometer in the supine position were studied. It was found that the 30- and 63-day flights induced a certain decrease in the body response which included a less economic functioning of the cardiorespiratory system during exercise. The degree of postflight changes of the 30- and 63-day crewmembers was similar. At the same time the cardiorespiratory system of the 63-day crewmembers returned to the preflight level more rapidly than that of the 30-day cosmonauts.

Blood Pressure↗