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Biomedical subjects

D Dimitrov

Publications and source records attributed to D Dimitrov.

At least 37 records · Page 2Linked to original sources

Evidence for a p53-independent pathway for upregulation of SDI1/CIP1/WAF1/p21 RNA in human cells.

SDI1 is an inhibitor of DNA synthesis that we isolated by expression screening cDNAs prepared from senescent, terminally nondividing human cells. Other groups then cloned this gene as a cyclin-dependent kinase (cdk)-interacting protein (CIP1, p21) that inhibits cdks; the gene was also isolated by screening for genes transactivated by p53 (WAF1). p53 levels are low in senescent and quiescent contact-inhibited or serum-deprived normal human cells, which we have found express high levels of SDI1 mRNA. This indicates that alternate pathways for upregulation of message level of this gene may exist. We therefore proceeded with the study presented here, treating human cells with a variety of growth-arrest-inducing agents, including some that damaged DNA, and found that RNA levels of SDI1 were increased in all cases that resulted in growth inhibition. More important, with the exception of gamma-radiation, most of these agents were able to elevate SDI1 message levels in cells lacking wild-type p53. At least two distinct kinetic profiles for RNA induction were observed, one that implicated p53 transactivation and occurred early enough to cause arrest, and another that clearly was p53 independent and suggested a role for the SDI1 gene product in the maintenance rather than in the cause of inhibition of DNA synthesis.

Antimetabolites↗

Atrial natriuretic peptide and dopamine in a dog model of acute renal ischemia.

Atrial natriuretic peptide (ANP) has been shown to reverse functional impairment in ischemic acute renal failure (ARF). To prolong and/or to enhance the effects of peptide, in this investigation dopamine (D) (3 micrograms/kg BW/min) was applied together with ANP (100 ng/kg BW/min) after 90 min unilateral renal artery occlusion in anesthetized dogs. ANP significantly increased creatine clearance, filtration fraction, diuresis, sodium excretion, sodium reabsorption, and free water clearance, as in postinfusion period only V remained elevated. D alone did not effect renal function beneficially. ANP+D improved kidney function impairment to a level comparable with that of ANP alone, but V and UNa.V remained increased in the postinfusion period. MAP was elevated during ANP+D infusion as compared to ANP alone and was sustained to the end of the experiment. We conclude that D does not potentiate the positive effects of ANP on postischemic kidney, but prolongs its action on UNa.V, possibly by maintenance of high MAP after renal ischemia.

Acute Kidney Injury↗

A new approach to measure fusion activity of cloned viral envelope proteins: fluorescence dequenching of octadecylrhodamine-labeled plasma membrane vesicles fusing with cells expressing vesicular stomatitis virus glycoprotein.

Fusion between fluorescently labeled plasma membrane vesicles (PMV) and cells expressing vesicular stomatitis virus (VSV) glycoprotein (G-protein) was investigated by utilizing a lipid mixing assay based on fluorescence dequenching of octadecyl rhodamine (R18). The PMVs were prepared from Vero cells by hypotonic lysis. The G-protein was expressed on the cell surface either following infection with intact VSV or with an adenovirus vector (AdG12) containing the gene for the G-protein. Fusion was temperature and pH dependent and was inhibited by VSV G-antiserum. The pH dependence of PMV fusion paralleled that observed for VSV-cell fusion and VSV-induced syncytia formation. The kinetics of fusion followed an exponential dependence on time without an observable time lag after lowering pH. These findings indicate that dequenching R18-labeled PMV reliably represents the basic features of fusion of VSV with cells and can be used as a new tool in the study of fusion activity of virus envelope proteins expressed in cells.

Animals↗

Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor.

Vascular endothelial cell growth factor (VEGF), also known as vascular permeability factor, is an endothelial cell mitogen which stimulates angiogenesis. Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. Expression of KDR in CMT-3 (cells which do not contain receptors for VEGF) allows for saturable 125I-VEGF binding with high affinity (KD = 75 pM). Affinity cross-linking of 125I-VEGF to KDR-transfected CMT-3 cells results in specific labeling of two proteins of M(r) = 195 and 235 kDa. The KDR receptor tyrosine kinase shares structural similarities with a recently reported receptor for VEGF, flt, in a manner reminiscent of the similarities between the alpha and beta forms of the PDGF receptors.

Amino Acid Sequence↗

Cell-to-cell spread of HIV-1 occurs within minutes and may not involve the participation of virus particles.

Although virus infections have been classically studied with "cell-free" virion preparations, many animal viruses are able to spread both in vitro and in vivo by inducing cell-cell fusion. An efficient system to monitor the cell-to-cell spread of HIV-1 has been developed employing chronically infected H9 donor cells. Under appropriate conditions of cocultivation with uninfected cells, the synthesis of unintegrated viral DNA, monitored by Southern blot hybridization, occurred between 2 and 4 hr following infection; viral proteins were detected 8 to 12 hr following cocultivation and progeny virions were released into the medium by 16 hr. The use of metabolic inhibitors or specific envelope/receptor antibodies revealed that the cell-to-cell spread of HIV required: (1) gp120-CD4 interaction and (2) reverse transcription. Light and electron microscopy, fluorescent dye redistribution, and soluble CD4 competition experiments all demonstrated that the HIV-induced cell-cell fusion began within 10 to 30 min of cocultivation. Surprisingly, the electron microscopic analyses also suggested that budding or mature virus particles did not participate in this process. Thus the virus-induced cell-cell fusion observed is very likely the result of gp120/gp41 proteins, on the surface of infected cells, interacting with CD4 molecules on uninfected cells. These findings are of immediate importance in understanding the mechanism(s) of HIV-1 transmission in vivo and for the design of effective vaccines and antiviral agents.

Blotting, Western↗

[Lipid and mineral metabolism and morbidity with temporary loss of work capacity in miners].

Examination is performed on 87 miners from mine for copper production subject to intensive local vibrations with average rate of increase (K) of the norms for the individual octave frequencies 2.4 times for 3 h exposure of the working shift, as well as to intensive noise--113-115 dB/A equivalent level, general dust--23 mg/m3, fine dust--3.5 mg/m3 and fine quartz--0.43 mg/m3. There are data for vibration effect--changes in the cold test, vibration sensoriness, ultra sound sonometry, in all miners. In a significant part of them are established dyslipoproteinemia--increase of triglycerides, total and LDL cholesterol, values beyond reference (mainly above the norm) of 10 electrolytes and microelements in blood serum (blood). An extremely high prevalence of the cases and the days of total morbidity with temporary disability (respectively 189.7 and 2935 per 100), with predominance in its structure of diseases of the central and peripheral nervous systems, hypertension disease, etc. The importance of vibrations for disorder in the metabolic processes in the organism and development of temporary diseases are underlined.

Absenteeism↗

Immunology and immunopathology of reproduction.

This review is dealing with the roles of the immune system in the development and functions of the male and female reproductive systems. Further, it describes the topical views on the roles of immunopathologic events and mechanisms involved in the male and female infertility, recurrent abortions, endometriosis, EPH gestosis and disorders of fetal development. Particular attention is paid to the complicated immunological cross-talk and interplay between the mother and its offspring, including the active role played by the placenta and mainly the trophoblast tissue, in the course of gestation. In the light of the "immunotrophic theory", maternal immune responses to foreign fetal components, occurring in normal pregnancies, within the limits of "tolerated" or even beneficial levels, are described. Emphasis is given on the possible deregulation of materno-fetal immunological balance, leading to immunopathological events and putting in danger the overall reproductive capacity of the couple. The contemporary therapeutic--mainly immunological--approaches to the main reproductive failures are also mentioned.

Female↗

Electrolytic exchange in organism under the conditions of vibration. Experimental studies.

The study deals with a wide spectrum of indices of the electrolytic metabolism--sodium, potassium, calcium, chlorides, magnesium, iron, copper, zinc, cobalt and manganese--in blood, organs and tissues under the conditions of experimental chronic exposure of whole-body vibration frequency of 50 and 150 Hz and velocity of 85 mm.s-1 during a three months experiment (3 h daily) Reference methods were used for the determination of the indices--atom absorption spectrophotometry (variants with flame and without flame), coulometric chlorine titrator, flame photometry, etc. The indices were examined three times (1, 2 and 3rd months). Statistic analysis of the data showed significant changes in the number and the values of the indices and their character (increase or decrease) in comparison with the control values. The indices modifications occur early (at the end of the first month) and they proceed till the end of the experiment (till the end of the 3rd month) during the exposure to both frequencies, but are strongly expressed in the case of high frequency vibrations. The disorders in electrolytic metabolism established in the experiment testify that people exposed to vibrations are likely to suffer analogical changes and develop other pathologies--diseases of cardiovascular system, of blood and haematopoietic organs, etc. as well as an increase of specific disorders in connection with vibration exposure.

Animals↗

[Experimental and clinical analysis with the reconstruction of the fenestrated anterior wall of the sinus maxillaris].

A comparative macroscopie and hystomorphological analysis of shutting the fenestrated front wall of the maxillary sinus is done with 34 rabbits. An autogenic bony cover and grates made of chromium cobaltomolybdenum and non-coloured plastic. Are used 30 patients are operated on with the same materials with tracing the process of reparation and the aeration of the operated sinuses. The results are compared with another group of patients operated without a reconstruction of the facial bony defect. The importance of reconstruction for reparation of the ventilation ability of the operated sinuses in the after-operational period is proved.

Animals↗

[Choice of x-ray diagnostic methods in chronic odontogenic sinusitis].

On the basis of our experiences the selection of diagnostic methods for chronic odontogenic sinusitis is discussed. The selection is based on the primary sign, the reduced transparency of the sinus, detected with conventional radiography. Its purpose is the determination of the extent and nature of the opacity. Conventional methods, contrast investigations, conventional and computed tomography are used.

Humans↗