Biomedical subjects

T Ivanova

Publications and source records attributed to T Ivanova.

At least 19 recordsLinked to original sources

PubMed2003

Persistence of chromosome aberrations in peripheral lymphocytes from Hodgkin's lymphoma remission patients.

PURPOSE: To analyse spontaneous and in vitro bleomycin-induced chromosome aberrations in peripheral lymphocytes taken from Hodgkin's disease patients after prolonged (up to 31 years) remission periods, and to consider these data from the point of view of the carcinogenic potential of anticancer therapy. MATERIALS AND METHODS: Conventional analysis of chromosome preparations stained with azure-eosin. RESULTS: The mean frequency and patterns of both spontaneous and induced aberrations in remission patients were significantly different from comparison groups (healthy donors and primary Hodgkin's disease patients). Individual values were characterized with high variation and did not show correlation with post-therapy time. New cancer cases diagnosed in remission patients were more frequent in subjects with high chromosome sensitivity to in vitro bleomycin challenge than in patients whose sensitivity to bleomycin was at a control level. CONCLUSIONS: The results are interpreted as suggesting that the tumorigenic potential of radiochemotherapy is mediated via induction of genetic instability in exposed cells. Long after the therapy, the instability may become an initiating event in the development of new malignancies in affected tissues, whereas the instability induced in haemopoietic stem cells may reveal itself in peripheral lymphocytes derived from formerly exposed precursors.

Adult↗

PubMed2002

Rapid stimulation of the PI3-kinase/Akt signalling pathway in developing midbrain neurones by oestrogen.

Oestrogen promotes the differentiation of neurones in the central nervous system. In the rodent midbrain, the maturation of dopaminergic neurones appears to be under oestrogen control. This is supported by the fact that dopaminergic cells contain nuclear oestrogen receptors-alpha/beta (ER). Second, aromatase is transiently expressed in the developing midbrain. In previous studies, we have shown that oestrogen increases dopamine synthesis and plasticity of dopamine cells. These effects are transmitted through classical nuclear ER but require also the stimulation of nonclassical signalling pathways involving the activation of membrane receptors. This study attempted to identify nonclassical oestrogen-dependent signalling cascades which might be stimulated downstream of membrane ERs. Using cultured mouse midbrain cells, we could demonstrate by Western blotting, that oestrogen rapidly phosphorylates Akt, a kinase which is implicated in the phosphatidylinositol 3 (PI3)-kinase pathway. This effect was only seen in midbrain neurones but not astrocytes. Oestrogen-induced Akt phosphorylation was time- and dose-dependent, showing highest responses after 30 min and at a steroid concentration of 10(-8) and 10(-6) M. Immunocytochemistry for phosphorylated Akt (pAkt) demonstrated that pAkt is predominantly found in a nuclear/perinuclear position and that oestrogen exposure increased the number of pAkt-positive cells. To investigate the mechanisms which are involved in transmitting oestrogen effects on the cellular level, cells were treated with antagonists for distinct signalling pathways. The application of the nuclear ER antagonist ICI 182 780 did not abolish the oestrogen-induced Akt phosphorylation. In contrast, interrupting intracellular calcium signalling with BAPTA completely prevented this effect. The PI3-kinase inhibitor LY294002 also inhibited the activation of Akt by oestrogen. Our study clearly indicates that oestrogen can rapidly stimulate the PI3-kinase/Akt signalling cascade in differentiating midbrain neurones. This effect requires the intermediate activation of calcium-dependent signalling pathways. In conclusion, oestrogen effects in the developing midbrain appear to be connected with the PI3-kinase/Akt signalling mechanism.

Animals↗

PubMed2002

Nonmelanoma skin cancers and risk of subsequent malignancies: a cancer registry-based study in Bulgaria.

Analysis of new primary tumors following nonmelanoma skin cancers (NMSC) has a public health and risk assessment interest, as well as potential implications for etiologic inference. The aim of this study is to evaluate the risk of the second primary tumors occurrence after NMSC development. A cohort of 2620 cases (1335 males and 1285 females) with nonmelanoma skin cancers registered in Bulgarian National Cancer Registry in 1993 was examined. The follow-up period represented a total of 15,856 person-years at risk. Over this period 128 (83 in men, 45 in women) new secondary tumors were established. After NMSC appearance, both genders show higher risk for the second primary tumors occurrence. This risk is greater for men. For both sexes after NMSC development there is increased risk for occurrence of second primary cancers of head and neck, thyroid, lung, larynx, bladder, colon, as well as cutaneous malignant melanoma, non-Hodgkin's lymphoma and leukemias. The results of considering only basal cell carcinomas show an elevated risk in patients of both sexes for appearance of second primary tumors of head and neck, bladder, larynx, lung and colon as well as non-Hodgkin's lymphoma and cutaneous malignant melanoma. The results of considering only squamous cell carcinomas show an increased risk in persons of both sexes for development of second primary cancers of head and neck, skin, thyroid, lung, stomach, as well as leukemias, non-Hodgkin's lymphoma and cutaneous malignant melanoma. The association between NMSC and subsequent increased risk for appearance of second primary skin and visceral tumors determine the necessity of monitoring the patients with NMSC.

Bulgaria↗

PubMed2001

Estrogen stimulates brain-derived neurotrophic factor expression in embryonic mouse midbrain neurons through a membrane-mediated and calcium-dependent mechanism.

We have provided evidence that 17beta-estradiol (E) synthesized in the midbrain promotes the differentiation of midbrain dopamine neurons through nonclassical steroid action. Because these developmental effects resemble those reported for brain-derived neurotrophic factor (BDNF), we hypothesized that E influences dopaminergic cell differentiation through a BDNF-dependent mechanism. Competitive RT-PCR and ELISA techniques were employed to study first the developmental pattern of BDNF and trkB expression in the mouse midbrain. BDNF protein/mRNA levels peaked postnatally, whereas trkB did not fluctuate perinatally. To prove the hypothesis that E regulates BDNF expression in vivo, fetuses and newborns were treated with the aromatase antagonist CGS 16949A. CGS 16949A exposure reduced midbrain BDNF mRNA/protein levels. The coapplication of CGS 16949A and E abolished this effect. Midbrain cultures from mouse fetuses were used to investigate intracellular signaling mechanisms involved in transmitting E effects. Estrogen increased expression of BDNF but not of other neurotrophins. As concerns the related signaling mechanism, these effects were antagonized by interrupting intracellular Ca(2+) signaling with BAPTA and thapsigargin but not by the estrogen receptor antagonist ICI 182,780. Insofar as E effects on BDNF mRNA expression were inhibited by cycloheximide, it appears likely that other, not yet characterized intermediate proteins take part in the estrogenic regulation of BDNF expression. We conclude that E exerts its stimulatory effect on the differentiation of dopaminergic neurons by coordinating BDNF expression. This particular E effect appears to be transmitted through Ca(2+)-dependent signaling cascades upon activation of putative membrane estrogen receptors.

Animals↗

PubMed2001

Muscle vibration sustains motor unit firing rate during submaximal isometric fatigue in humans.

1. In keeping with the 'muscular wisdom hypothesis', many studies have documented that the firing rate of the majority of motor units decreased during fatiguing isometric contractions. The present study investigated whether the application of periodic muscle vibration, which strongly activates muscle spindles, would alter the modulation of motor unit firing rate during submaximal fatiguing isometric contractions. 2. Thirty-three motor units from the lateral head of the triceps brachii muscle were recorded from 10 subjects during a sustained isometric 20 % maximal voluntary contraction (MVC) of the elbow extensors. Vibration was interposed on the contraction for 2 s every 10 s. Twenty-two motor units were recorded from the beginning of the fatigue task. The discharge rate of the majority of motor units remained constant (12/22) or increased (4/22) with fatigue. Six motor units demonstrated a reduction in discharge rate that later returned toward initial values; these motor units had higher initial discharge rates than the other 16 motor units. 3. In a second series of experiments, four subjects held a sustained isometric 20 % MVC for 2 min and then vibration was applied as above for the remainder of the contraction. In this case, motor units initially demonstrated a decrease in firing rate that increased after the vibration was applied. Thus muscle spindle disfacilitation of the motoneurone pool may be associated with the decline of motor unit discharge rate observed during the first 2 min of the contraction. 4. In a third set of experiments, seven subjects performed the main experiment on one occasion and repeated the fatigue task without vibration on a second occasion. Neither the endurance time of the fatiguing contraction nor the MVC torque following fatigue was affected by the application of vibration. This finding calls into question the applicability of the muscular wisdom hypothesis to submaximal contractions.

Adult↗

PubMed2001

Pre- and postnatal expression of brain-derived neurotrophic factor mRNA/protein and tyrosine protein kinase receptor B mRNA in the mouse hippocampus.

Brain-derived neurotrophic factor (BDNF) is implicated in the control of hippocampal development. In this study, we have analyzed the developmental expression of BDNF mRNA/protein and its receptor tyrosine protein kinase receptor (trk) B mRNA in the mouse hippocampus by competitive reverse transcription/polymerase chain reaction and enzyme-linked immunoassay. Cell-type specificity of BDNF/trkB expression was studied in primary hippocampal cultures. BDNF levels increased stepwise from embryonic day 15 until the second postnatal week, whereas trkB expression was stable throughout development. Neurons and astrocytes expressed both BDNF and trkB. Our data suggest that developmental BDNF action mainly occurs postnatally and indicates that hippocampal neurons and astroglia not only produce BDNF but also appear to be targets for BDNF.

Aging↗

PubMed2001

Vps9, Rabex-5 and DSS4: proteins with weak but distinct nucleotide-exchange activities for Rab proteins.

The activities of three Rab-specific factors with GDP/GTP exchange activity, Vps9p, Rabex-5 and DSS4, with their cognate GTPases, Ypt51p, Rab5 and Ypt1p, have been analysed quantitatively. In contrast to other exchange factors examined and to DSS4, Vps9p, and by analogy probably Rabex-5, have considerably lower affinity than GDP to the respective GTPases. In keeping with this, they are relatively weak exchangers, with a maximal rate constant for GDP release from the ternary complex between exchange factor, GTPase and GDP of ca 0.01 s(-1), which is several orders of magnitude lower than for other exchange factors examined. If interaction with these proteins is a mandatory aspect of the Rab cycle, this suggests that the overall rate of cycling might be controlled at this point of the cycle. Surprisingly, DSS4, which has the thermodynamic potential to displace GDP effectively from Ypt1p, also does this very slowly, again with a maximal rate constant of ca 0.01 s(-1). An additional, and based on present knowledge, unique, feature of the Ypt1p.DSS4 complex, is that the association of GTP (or GDP) is more than 10(3)-fold slower than to Ypt1p, thus leading to a long life-time of the binary complex between the two proteins, even at the high nucleotide concentrations that prevail in the cell. This leads to the conclusion that the protein-protein complex is likely to have an important biological significance in addition to its probable role in GTP/GDP exchange.

Carrier Proteins↗

PubMed2001

Estrogen stimulates the mitogen-activated protein kinase pathway in midbrain astroglia.

Estrogen stimulates the development of midbrain dopamine neurons predominantly by acting through membrane receptors coupled to Ca(2+)-signaling. In this report, we describe that estrogen activates extracellular signal-regulated kinases (ERK1/2) in midbrain astrocytes but not neurons. This effect was inhibited by BAPTA which interrupts Ca(2+)-signaling but not by antagonists specific for other signaling pathways. The activation of the MAP kinase pathway suggests a potential role for astrocytes in mediating estrogen effects in the midbrain.

Animals↗

PubMed2001

Classical and nonclassical estrogen action in the developing midbrain.

There is widespread acceptance that estrogen is involved in various steps of cellular differentiation during brain development. In the past years, we have demonstrated such a developmental role for estrogen in the rodent midbrain. Precisely, estrogen affects midbrain dopamine neurons with respect to functional and morphological maturation. On the cellular level, estrogen may act classically by binding and activating its respective nuclear receptors, thereby controlling the transcription of target genes. On the other hand, many estrogen effects in the CNS are transmitted nonclassically by interactions with putative membrane receptors and by stimulating distinct intracellular signaling cascades. In the midbrain, classical and nonclassical estrogen signaling routes operate side by side to ensure the proper development of dopaminergic cells. In the present report, we detail some of the cellular and molecular events which are activated by estrogen and are thought to take part in the estrogen-mediated stimulation of dopamine neuron differentiation.

Animals↗

PubMed2001

Blood flow in the triceps brachii muscle in humans during sustained submaximal isometric contractions.

The main purpose of this study was to determine the extent to which blood flow through the profunda artery within the triceps brachii muscle may be compromised during maintained low-force isometric fatiguing contractions. Doppler ultrasound techniques were used to record mean blood velocity and arterial diameter of the profunda brachii artery during sustained isometric contractions of 20% maximal voluntary contraction. The arterial diameter did not change throughout the contraction. Thus, blood velocity was considered to be an indicator of blood flow. The mean blood velocity increased initially and then remained constant during the contraction period. When compared to rest [0.06 (SD 0.03) m s-1] mean blood velocity was significantly larger at the start of the contraction [0.13 (SD 0.07) m s-1] and larger yet during recovery following the contraction [0.30 (SD 0.14) m s-1]. Although blood flow through the conduit artery did not drop during the contraction, the post-contraction hyperaemia suggested that circulatory compromise might have occurred at the level of the capillary beds.

Adult↗

PubMed2000

Role of limb movement in the modulation of motor unit discharge rate during fatiguing contractions.

Motor unit firing rates of the triceps brachii muscle have been shown to decline during sustained isometric contractions, but not if the fatiguing contraction incorporates arm movements. The purpose of this study was to determine the impact of the actual physical displacement of the limb on the maintenance of motor unit discharge rate during dynamic muscle fatigue. An isometric force pulse paradigm was used to recreate the motor unit activity patterns that occur during a dynamic contraction. With this paradigm, the variable force output that would occur during a dynamic contraction remained intact, but the movement of the limb was eliminated. Motor unit firing rates declined in the isometric force pulse protocol. Thus, factors related to the actual movement of the limb appear to enable the maintenance of motor unit discharge rates during fatigue.

Adult↗

PubMed2000

Ontogenetic expression and sex differences of aromatase and estrogen receptor-alpha/beta mRNA in the mouse hippocampus.

Estrogen plays an important role during brain development interfering with the maturation of distinct neural systems and, in particular, with the sexual differentiation of brain structures and function. Similar to other brain regions, estrogen is known to influence neuronal differentiation and plasticity in the hippocampus. The present study is concerned with the developmental expression of mRNAs for the estrogen-synthesizing enzyme aromatase and the two known nuclear estrogen receptors (alpha/beta) in the male and female mouse hippocampus. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we found that aromatase as well as estrogen receptors (alpha/beta) are already expressed prenatally in the hippocampus of both sexes. Aromatase expression increased during the first two postnatal weeks and decreased, thereafter, to lower levels in adults. Sex differences in aromatase expression were observed postnatally with higher levels in males. Estrogen receptor-alpha/beta mRNAs did not fluctuate obviously throughout pre- and postnatal development but revealed a distinct sex-specific pattern at the end of the first postnatal week. Again, higher expression was detected in males. These findings clearly demonstrate the capacity of estrogen formation and the presence of both estrogen receptor subtypes in the developing hippocampus. Sex differences in aromatase mRNA levels paralleled the sex-specific pattern of estrogen receptor expression. Thus, our data support the idea that the developing hippocampus is a target for estrogen action and estrogen receptor-mediated sexual differentiation.

Animals↗

PubMed2000

Microgravity effects on water supply and substrate properties in porous matrix root support systems.

The control of water content and water movement in granular substrate-based plant root systems in microgravity is a complex problem. Improper water and oxygen delivery to plant roots has delayed studies of the effects of microgravity on plant development and the use of plants in physical and mental life support systems. Our international effort (USA, Russia and Bulgaria) has upgraded the plant growth facilities on the Mir Orbital Station (OS) and used them to study the full life cycle of plants. The Bulgarian-Russian-developed Svet Space Greenhouse (SG) system was upgraded on the Mir OS in 1996. The US developed Gas Exchange Measurement System (GEMS) greatly extends the range of environmental parameters monitored. The Svet-GEMS complex was used to grow a fully developed wheat crop during 1996. The growth rate and development of these plants compared well with earth grown plants indicating that the root zone water and oxygen stresses that have limited plant development in previous long-duration experiments have been overcome. However, management of the root environment during this experiment involved several significant changes in control settings as the relationship between the water delivery system, water status sensors, and the substrate changed during the growth cycles.

Carbon Dioxide↗

PubMed1999

The activities of Professor Curt Krause in Bulgaria.

Prof. C. Krause spent six years in Bulgaria, from 1928 to 1934. He officially assumed his position on October 10, 1928, as he delivered his opening lecture titled About the past, present and future of the general pathology and pathological anatomy. He worked skillfully and with utmost devotion on the organization of the department of General Pathology and Pathological Anatomy at the Veterinary Faculty. The educational process normalized. Seven students completed their doctoral theses under his leadership and first research assistants were prepared. He lay the foundations of the pathoanatomical museum in his department. Prof. Krauseus contributions to the development of the pathological anatomy in Bulgaria both as a scientific discipline and as a veterinary practice are substantial. In 1939, Prof. Krause received the highest honour for his work in Bulgaria - he was awarded the title of doctor honoris causa of veterinary medicine of the Sofia University.

Bulgaria↗

PubMed1998

Discharge patterns in human motor units during fatiguing arm movements.

The purpose of this study was to determine whether short interspike intervals (ISIs of <20 ms) would occur naturally during voluntary movement and would increase in number with fatigue. Thirty-four triceps brachii motor units from nine subjects were assessed during a fatigue task consisting of fifty extension and fifty flexion elbow movements against a constant-load opposing extension. Nineteen motor units were recorded from the beginning of the fatigue task; the number of short ISIs was 7.1 +/- 4.1% of the total number of ISIs in the first one-third of the task (unfatigued state). This value increased to 11.8 +/- 5.9% for the last one-third of the task (fatigued state). Fifteen motor units were recruited during the fatigue task and discharged, with 16.4 +/- 6.0% of short ISIs in the fatigued state. For all motor units, the number of short ISIs was positively correlated (r2 = 0.85) with the recruitment threshold torque. Short ISIs occurred most frequently at movement initiation but also occurred throughout the movement. These results document the presence of short ISIs during voluntary movement and their increase in number during fatigue.

Adult↗

PubMed1997

Motor unit discharge rate is not associated with muscle relaxation time in sustained submaximal contractions in humans.

The muscle wisdom hypothesis suggests that motor unit discharge rates decrease in parallel with the slowing of muscle contractile properties during fatigue. In this study, the discharge rates of single motor units and the muscle contractile properties were measured during a sustained submaximal contraction. The majority of motor units that were active from the beginning of the task demonstrated a decline in discharge rate in the absence of any slowing of muscle relaxation time. These findings suggest that the muscle wisdom hypothesis may not apply to sustained submaximal contractions.

Adult↗

PubMed1997

Preventive role of lyophilic dairy products bulgaricum and biostim.

The purpose of the study was to examine the protective role of lyophilic dairy products bulgaricum and biostim with active bacteria lactic acid strain. Protective effect was determined as a phagocytosis activity and activity of major immunoglobulins. In total 120 men aged 30-35 years were included in three groups (30 controls with placebo). Daily doses (50 g) of these products were taken during a month. Positive responses from investigation links of immune system and paraspecific resistance were observed. Immunologic response was significantly higher after lyophilic dairy diet and this indicates that bulgaricum and biostim are products with protective role due to specific influence of bacteria lactic acid.

Adult↗

PubMed1997

Motor unit recruitment and discharge behavior in movements and isometric contractions.

The purpose of this study was to contrast the discharge patterns of the same motor units during movements and during isometric contractions that were produced with comparable torque-time characteristics. Subjects performed elbow flexion and extension movements with predetermined acceleration characteristics. The average acceleration and deceleration profiles for the movements were reproduced in the isometric setting by presenting the kinematic profiles as templates for torque production. Trained subjects were able to match the first agonist (AG1) and antagonist (ANT) electromyographic (EMG) bursts, but tended to produce a smaller second agonist burst (AG2) in the isometric contraction. Twenty-five motor units from triceps brachii were studied. The same motor units (with one exception) were recruited and subsequently discharged in a similar fashion in both the isometric and movement tasks in the AG1 and ANT EMG bursts, with fewer motor unit discharges in the AG2 burst in the isometric contraction. The central control mechanisms appear to be the same for the acceleration phase of movement and isometric contraction, but differ during the deceleration phase.

Adult↗