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Biomedical subjects

M Nikolova

Publications and source records attributed to M Nikolova.

At least 19 recordsLinked to original sources
PubMed2006

Motor cortex excitability changes preceding voluntary muscle activity in simple reaction time task.

The effect of transcranial magnetic stimulation (TMS) on reaction time (RT) and motor cortex excitability in the premovement period was investigated. Single and paired-pulse TMS with 3 and 13 ms interstimulus intervals (ISI) were applied to the left motor cortex at different delays after a visual command for isometric right hand index finger abduction. Motor evoked potentials (MEPs) recorded from the right first dorsal interosseous (FDI) were analysed to assess cortex excitability. The MEPs in response to single pulse TMS were gradually increased in the premovement period in general, but strongly augmented in a period of 90-100 ms before the voluntary myoelectrical activity (EMG) onset. In paired-pulse TMS (13 ms ISI), the MEP augmentation was smaller but started earlier before the EMG burst, and a gradual increase of MEP amplitudes was not evident. In case of 3 ms ISI, the expected intracortical inhibition (ICI) was evident only when TMS preceded the voluntary EMG by an interval of more than 60 ms, but at shorter intervals, rather some MEP augmentation was observed. Generally, the augmentation of MEPs in the premovement period was more pronounced in single pulse TMS. Most strikingly, a dead band period without MEP occurrences was observed within an interval of 30-50 ms before the voluntary EMG. In conclusion, parallel action of intracortical facilitation (ICF) and ICI as well as different dynamic behaviour of ICF and pre movement facilitation may explain the earlier mentioned effects. Moreover, this leads to an extended description of the rather subtle TMS influence on RT.

Adaptation, Physiological↗
PubMed2006

Surface flavonoid aglycones in newly studied plant species.

Several newly studied species of the Scrophulariaceae, Lamiaceae, and Ranunculaceae spread in Bulgaria have been analyzed for their surface flavonoid profiles. Except Pulsatilla montana (Hope) Rchb. (Ranunculaceae) all taxa now studied accumulated mainly apigenin, luteolin, and it's derivatives. This is the first report for the presence on external flavonoid aglycones in genus Pulsatilla. Quercetin-3'-methyl ether is a new citation for P. montana. The presence on surface flavonoid aglycones in species Veronica bellidioides L., V. persica Poir., Odontites verna (Bell.) Dum., Laminiastrum galeobdolon Heist ex Fabr., Glechoma herbaceae L., Ajuga genevensis L., and A. reptans L. are reported for the first time too.

Flavonoids↗
PubMed2006

IgM-enriched human intravenous immunoglobulin suppresses T lymphocyte functions in vitro and delays the activation of T lymphocytes in hu-SCID mice.

Previous studies of an experimental human immunoglobulin preparation for intravenous use, containing normal pooled IgM (IVIgM), have shown its beneficial therapeutic effect in experimental autoimmune diseases. The mechanisms of its immunomodulatory activity remain however, poorly understood. In the experiments reported here, IVIgM inhibited the proliferation of various autonomously growing human lymphoid cell lines in vitro, as well as of MLR- and of PHA-stimulated human T-lymphocytes. These effects of IVIgM were observed at non-apoptotic concentrations and were stronger on a molar basis than those of normal pooled IgG for intravenous use (IVIg). Both preparations, when administered to SCID mice, repopulated with human peripheral blood mononuclear cells, delayed the expression of the early activation marker CD69 on both human CD4+ and CD8+ T-lymphocytes, activated by the mouse antigenic environment. The data obtained show that normal pooled human IgM exerts a powerful antiproliferative effect on T-cells that is qualitatively similar but quantitatively superior to that of therapeutic IVIg. Our results suggest that infusions with IVIgM might have a significant beneficial immunomodulating activity in patients with selected autoimmune diseases.

Animals↗
PubMed2006

[A rare case of ovarian carcinosarcoma with metastasis in the uterine cervix--diagnostic and therapeutic problems].

Carcinosarcomas are rare malignant neoplasms that histologically contain both epithelial and mesenchymal components. In the female genital tract they occur mainly in uterus and rarely in cervix, ovaries and omentum. A rare case of ovarian carcinosarcoma is presented. Because of the presence of a solitary, massive metastasis in the uterine cervix, it created some serious diagnostic and therapeutic problems.

Aged↗
PubMed2005

[Gynecological laparoscopy and treatment of ectopic pregnancy].

The aim of the present study is to show the advantages of the gynecologic laparoscopy for the diagnosis and treatment of the intact tubal pregnancy. For the fulfillment of this aim was made a prospective study for 5 years' period of the patients with diagnosis "Ectopic pregnancy", treated in Gynecological clinic of UMBAL-Pleven. The objects of observation were 33 women with diagnosis: "Intact ectopic pregnancy". Methotrexate was used by plan for 6 patients, in 7 patients was made laparotomy, and in 20 patients--gynecological laparoscopy. From the performed 20 gynecological laparoscopy, 16 women were recovered laparoscopically, in 14 of which was made partial salpingectomy, and in 2--milking. In one of the last two patients was injected Methotrexate in the bed of the gestational bag. In 4 women was necessary laparotomy, because of impossibility of performing of laparoscopic surgery. The authors emphasized the advantages of the gynecological laparoscopy for precise diagnosis and contemporary treatment of the intact ectopic pregnancy.

Antimetabolites, Antineoplastic↗
PubMed2005

[Microglandular endocervical hyperplasia and endocervical adenocacinoma in pregnant--description of two cases].

Two clinically identical cases of young, pregnant women, presented with exocervical polypoid masses are described. Because of beginning delivery in both cases, the diagnoses are made on frozen sections. In the first case histological examination reveals microglandular endocervical hyperplasia. A successful delivery by caesarian section and no more operations is performed. In the second case, an endocervical adenocarcinoma is diagnosed and after a successful delivery by caesarian section, a laparohysterectomy with bilateral adnexectomy and lymph node dissection is performed. Detailed histological examination of the endocervical neoplasm discloses a well differentiated papillary villoglandular adenocarcinoma, containing minor elements of more aggressive serous carcinoma, which may adversely affect the outcome. Three consequent recurrences are found in this patient for a period of 5 years and 3 months after the operation.

Adenocarcinoma↗
PubMed2004

[The role of polyclonal anti-T-lymphocyte antibodies (ATG) in the kidney transplantation].

UNLABELLED: The successes in the kidney transplantation are closely connected with the successes of the immunology and the advance of the immunosuppressive therapy. The main task of the modern immunosuppressive therapy is the insurance of medicines with a minimum nephro-toxicity, and the optimum protection regarding the adoptive body against an early reaction of rejection. The polycomponent anti-T-limphocitic antibodies (ATG) give us the opportunity of that. The polycomponent anti-T-limphocitic antibodies or the antilimphocitic serum (ALS) are xenogenetic polycomponent antibodies, that are directed to the human T-limphocites, i.e. antitimocitic globuline (ATG). They are received by immunization of rabbits or horses with human thymus limphoid cells. They are received for the first time by horses, and later on by rabbits. The last patent medicines have more powerful effect. In spite of the side effects of the polycomponent ATG, the patent medicine is used for inductive treatment after transplantation of organs and for a treatment of acutely rejection of the graft. We have treated 15 patients after kidney transplantation with ATG for a period of an year in the ward of kidney transplantation in The Clinic of Urology. The patients with transplantation are at the age of 21 to 50 years old, and by sex--11 male and 4 female patients. 9 of them are transplanted from alive donor and 6--from a dead body. We have applied the patent medicine of ATG Timoglobuline in a phial of 5 mg\ml intravenally in a bank of 500 ml physiological solution according to the weight and the blood test of the patients. We have applied a fourfold immunosuppressive therapy: Urbazon, Imuran, CyA(Neoral) +ATG. CONCLUSIONS: ATG is a mixture of monocomponent polyspecific antibodies, which, in spite of its side effects, has been applied successfully in transplantation for more than 30 years. In the course of many years anti-CD3 patent medicine OKT3 has been the only one monocomponent antibody for the treatment of an acute rejection of the graft for inductive therapy in transplanted patients.A chimerical (baziliksimab) and humanized (daklizumab) monocomponent antibodies of the alpha-chain of the receptor for IL-2 (CD25) are used for the prophylaxis of the episodes of acutely rejection of the transplanted kidney during the last 10 years. ATG does not consists of anti-CD25 antibodies. That is why the simultaneously application of ATG with baziliksimab or daklizumab is expected to have an additional effect with a complementary mechanism of efficacy.

Adult↗
PubMed2004

[Clotting induction in the mesenterium and erosive stomach mucosa in wistar rats as the result of a catenoidal ultrasonic transducer].

The ultrasonic transducers and instruments used in surgery operate in the range of 1-10 MHz and release significant heat in the surroundings. They need additional cooling system which significantly raises the cost and impedes the equipment operation. Hemostasis can be successfully achieved by employing ultrasonic transducers that operate in the kilohertz range, avoiding the occurrence of inadmissible tissue overheat outside the area of the transducer performance. The paper presents results of the approbation of the effect of a periodical acoustic signal with frequency of 60 kHz over the erosive stomach mucosa and mesenterium of 28 rats, "Wistar" breed, and the period of tissue exposure is 1-10 min. A transducer-catenoidal semi-wave concentrator that provides maximum emitted power of the ultrasonic wave is used and thermal effects are avoided. It is proved that the use of a powerful and localized ultrasonic signal results in erythrocyte diapedesis and forms microhaemorrhagies together with an out-vessel coagulation in the rat stomach mucosa The tissue damages are strictly limited within the area of the emitter contact and they are subject to control during the ultrasonic performance.

Animals↗
PubMed2003

Isolation of a CD8alphaalpha+ CD4- tumour T-cell clone with cytotoxic activity from a CD4+ CD8- cutaneous T-cell lymphoma.

BACKGROUND: We have previously established tumour T-cell lines, both from the skin and from the blood of patients with a cutaneous T-cell lymphoma (CTCL). In one patient, the tumour cells and the derived cell lines had a CD3+ CD4+ CD8- phenotype and a trisomy of chromosome 7. They expressed three T-cell receptor (TCR) beta-chain transcripts, but only one was productively rearranged and expressed at the cell membrane. OBJECTIVES: In the present study, we tried to isolate a fast-growing new tumour T-cell line from the same patient. PATIENTS/METHODS: We performed direct cell cloning of the skin tumour lymphocyte population, which led to the isolation of an interleukin-2-dependent highly proliferative T-cell subclone, named Cou-L3, with a CD3+ TCR-Vbeta13+ CD4- CD8alphaalpha+ phenotype. RESULTS: We demonstrated that Cou-L3 was identical to the original clonal tumour CD3+ Vbeta13+ CD4+ CD8- cells, as it expressed the same rearranged TCR-Vbeta13 chain. We further studied the functional activity of these CD8alphaalpha+ Vbeta13+ Cou-L3 cells. We found that these cells exhibited CD3-redirected cytotoxic activity. CONCLUSIONS: An immunophenotypic shift, with a change from a CD4+ to a CD8+ phenotype, has been already reported in association with disease progression in CTCL. However, in these cases, there has been no demonstration that the phenotypic change involved the same T-cell clone. The present study is the first report of the phenotypic heterogeneity of the tumour clonal cell population in CTCL.

Aged↗
PubMed2002

Identification of cell surface molecules characterizing human cutaneous T-cell lymphomas.

Primary cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignant mature T-cell proliferations most often presenting as mycosis fungoides (MF) or its leukemic variant, Sezary syndrome (SS). No specific cell surface markers are presently available to distinguish the circulating malignant clone from normal lymphocytes. Using the previously established CTCL cell lines, Cou-LS and Pno, we have detected two leucocyte cell surface antigens with aberrant expression on CTCL cells. The NK-receptor (NKR) p140/KIR3DL2 normally expressed by NK and CD8+ T-cells was detected on the surface of CTCL cell lines as well as on freshly isolated CD4+PBL from SS patients. Further on, p140 marked in situ SS cells, distinguishing them from p140-negative tumor cells of patch plaque MF. SC5 is a newly described activation-related intracellular inhibitory receptor expressed on the surface of a minor PBL subset. We found that SC5 expression was significantly increased in SS cells and correlated to p140 expression. Moreover, cross-linking of SC5 molecules inhibited the malignant cell proliferation induced by anti-CD3 mAbs. The identification of these new structures on circulating SS tumor cells seems to be important both for the understanding of CTCL pathophysiology and for the clinical management of SS patients.

Antigens, Surface↗
PubMed2001

Functional characterization of neurotensin receptors in human cutaneous T cell lymphoma malignant lymphocytes.

Cutaneous T cell lymphomas are a clonal proliferation of CD4+ T lymphocytes primarily involving the skin. Mycosis fungoides is an epidermotropic CD4+ cutaneous T cell lymphoma, and a more aggressive form, Sezary syndrome, occurs when the malignant cells become nonepidermotropic. The role of neuropeptides in the growth and chemotaxis capacity of cutaneous T cell lymphoma cells remains unknown. In this report, we found that cutaneous T cell lymphoma cells, similarly to normal resting or activated peripheral lymphocytes, were able to bind neurotensin. We used an interleukin-2-dependent cutaneous T cell lymphoma malignant T cell line derived from cutaneous T cell lymphoma lesions in order to study the role of neurotensin in the proliferation and migration of these malignant cells. First, we determined that the malignant cells expressed neurotensin receptors on their cell membrane. Functional results indicated that neurotensin did not stimulate the growth of the cell line. In contrast, this neuropeptide inhibited the proliferation of the tumor cells in response to exogenous interleukin-2. Furthermore, we found that neurotensin enhanced both spontaneous and chemoattractant-induced migration of the malignant cells. This suggests that neurotensin in skin can play a role in the disease by locally limiting the growth of the cutaneous T cell lymphoma tumor cells in response to cytokines and by enhancing their chemotaxis capacity.

CD4-Positive T-Lymphocytes↗
PubMed2001

Increased expression of a novel early activation surface membrane receptor in cutaneous T cell lymphoma cells.

Using a newly generated monoclonal antibody we identified the 96 kDa transmembrane receptor SC5 expressed simultaneously on a human Sezary cell line and a minor T cell subset in normal individuals. SC5 antigen was detected mostly on CD45RO+ lymphocytes from both CD4+ and CD8+ subsets as well as on natural killer and B lineage cells. SC5 surface expression increased very early after polyclonal stimulation of CD3+ cells due to the transfer of intracellular SC5 molecules to the cell membrane. Engagement of SC5 receptor by its monoclonal antibody inhibited the anti-CD3-induced proliferation and cytokine secretion of peripheral blood T cells and cell clones, whereas SC5 monoclonal antibody did not affect the cytotoxic activity of CD8+ T cell clones. Extensive phenotypic analysis revealed that the percentage of SC5+ CD4+ circulating lymphocytes in Sezary syndrome patients was significantly increased in comparison with controls (p < 0.01) and correlated with the morphologically detected percentage of Sezary syndrome cells in peripheral blood (p < 0.001). In one patient we clearly demonstrated that the circulating malignant T cells coexpress SC5 molecules. Importantly, ligation of SC5 receptor in a cutaneous T cell lymphoma cell line profoundly inhibited the anti-CD3-induced proliferation. Consequently, the expression of SC5 receptor in the peripheral blood of Sezary syndrome patients may serve not only to detect the presence of circulating malignant CD4+ cells but also as a target for immunotherapy.

Antibodies, Monoclonal↗
PubMed2001

Crosstalk between tumor T lymphocytes and reactive T lymphocytes in cutaneous T cell lymphomas.

We have established several tumor T cell lines, both from the skin and from the blood of a patient with an MHC class II-/class I+, CD4+ cutaneous T cell lymphoma (CTCL). These cell lines, like the initial tumor cells, had a CD3+CD4+CD8- phenotype. We also isolated two cytotoxic T lymphocyte clones from the tumor site of this CTCL patient. These clones displayed a CD4+CD8dim+ (TC5) and CD4+CD8- (TC7) phenotype and mediated a specific MHC class I-restricted cytotoxic activity toward noncultured tumor cells and autologous tumor cell lines. Despite surface expression of Fas on tumor cells and Fas-L induction on TC5 and TC7 cell membrane after coculture with autologous tumor cells, the CD4+ CTL clones did not use this cytotoxic mechanism to lyse their specific target. TC7 used a granzyme/perforin-dependent pathway, whereas TC5 used a TRAIL-dependent mechanism. Quantitative analysis of cytokine mRNA expression indicated that while the tumor cells displayed a Th2-type profile, the CTL clones expressed Th1-type cytokines. Preincubation of TIL clones with autologous tumor cells in a short-term culture induced their activation and subsequent amplification of the Th1-type response, which indicates a direct contribution of the malignant cells in the Th1/Th2 imbalance. However, we found that tumor cells produced high amounts of TGF-beta, which could explain the inhibition of a specific antitumor immune response. Another mechanism to avoid the host immune response was the expression of CD158a, CD158b, p70, and CD94/NKG2A inhibitory receptors by tumor-specific lymphocytes. Finally, we present recent data on new antigen structures expressed both by long-term CTCL lines and uncultured tumor cells.

Antigens, Neoplasm↗
PubMed2001

The receptors regulating natural cytotoxic effector functions.

Natural cytotoxic effector functions are regulated by a multitude of opposing signals provided by immunoglobulin and lectin-like functional molecules. While inhibitory receptors possess immunoreceptor tyrosine-based inhibition motif (ITIM) cytoplasmic sequences recruiting tyrosine phosphatases, activatory receptors require association with accesory immunoreceptor tyrosine-based activation motif (ITAM)-bearing molecules. One considerable group of natural cytotoxic cell receptors are specific for classical and non-classical class I antigens and detect both qualitative and quantitative changes in the autologous MHC-I phenotype. Non-MHC-I-specific receptors provide signaling in the absence of MHC-I antigens or in response to not well-known stress-induced antigens. NK cell receptors may equally participate in the regulation of target cell functions through contact or souble mediator-dependent mechanisms. The identification of NK cell regulating molecules has led to the elucidation of more general principles underlying immune homeostasis.

Animals↗
PubMed1999

G10.3 monoclonal antibody identifies novel functional cell surface structures expressed by normal B lymphocytes and various malignant cell lines.

G10.3, a unique monoclonal antibody (mAb), was produced to better characterize lymphocyte subsets. In the present study, we show that this mAb identifies 118, 83 and 51 kDa cell surface sialylated glycoproteins on the immunizing cell line YTindi. The reactivity of G10.3 mAb is restricted in normal cells to B lymphocytes, whereas within tumoral cell lines various lymphoid and non-lymphoid cells were found positive. Interestingly, functional studies revealed that triggering G10.3 mAb reactive molecules with soluble antibody led to an inhibition of growth and to an induction of programmed cell death in tumor cell lines expressing high levels of reactive molecules.

Antibodies, Monoclonal↗