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Biomedical subjects

D Dimitrov

Publications and source records attributed to D Dimitrov.

At least 19 recordsLinked to original sources
PubMed1999

Rapid telomere shortening in children.

Telomere shortening may reflect the total number of divisions experienced by a somatic cell and is associated with replicative senescence. We found that the average rate of telomere shortening in peripheral blood mononuclear cells (PBMCs) obtained longitudinally from nine different infants during the first 3 years of life (270 bp per year) is more than fourfold higher than in adults and does not correlate with telomerase activity. These results show that the rate of telomere loss changes during ontogeny, suggesting the existence of periods of accelerated cell division. Because human immunodeficiency virus (HIV) preferentially infects actively dividing cells, our observation suggesting accelerated cell division in children may provide an explanation for some of the distinctive pathogenic features of the HIV disease in infants, including higher viral loads and more rapid progression to acquired immunodeficiency syndrome (AIDS).

Adult↗
PubMed1999

Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma.

The concentration of human immunodeficiency virus type 1 (HIV-1) particles in blood plasma is very predictive of the subsequent disease course in an infected individual; its measurement has become one of the most important parameters for monitoring clinical status. Steady-state virus levels in plasma reflect a balance between the rates of virions entering and leaving the peripheral blood. We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell-free particles in the presence and absence of virus-specific antibodies. Here we show, by measuring virion RNA, particle-associated p24 Gag protein and virus infectivity, that the clearance of physical and infectious particles from a primary, dual-tropic virus isolate, HIV-1DH12, is very rapid in naive animals, with half-lives ranging from 13 to 26 minutes. In the presence of high-titer HIV-1DH12-specific neutralizing antibodies, the half-life of virion RNA was considerably reduced (to 3.9-7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV-1 infectivity due to antibody binding.

Animals↗
PubMed1999

Cancer incidence in Republic of Bulgaria aircrew, 1964-1994.

BACKGROUND: This study includes all cases of cancer among Republic of Bulgaria Air Force and civil aviation aircrew. Cancer incidence, Standardized Incidence Ratios (SIRs) and 95% confidential intervals were calculated for the pilots, using data about cancer incidence in the same age groups of the male population of the Republic of Bulgaria for the same period of time, taken from the National Cancer Register. RESULTS: The results show a considerable difference in the structure of cancer among males in Bulgaria, as compared to male pilots (r<0.0001). While cancer of the respiratory system has the greatest incidence among the civil population, cancer of the bladder has the greatest incidence among pilots, followed by testicular and skin cancer. For the period under consideration there is a lower risk of malignant diseases in pilots as compared to the rest of the population. There is a higher risk of testicular cancer only in civil aviation pilots. For Air Force aircrew there is a 10-fold higher risk of bladder cancer as compared to the rest of the population. CONCLUSION: We established an interdependence between age and cancer incidence, cancer incidence being higher among pilots in the age group from 20-40 yr. For the remaining age groups, cancer incidence among the civil population is approximately 2.5 times higher. Of the pilots with cancer, 73.53% returned to a flying career after an average of 7 mo treatment.

Adult↗
PubMed1998

HIV infection: how effective is drug combination treatment?

The rate of decline of plasma HIV RNA in patients treated with anti-retroviral drugs has been postulated to reflect the half-lives of previously HIV-infected cells. Here, Zvi Grossman and colleagues argue that the observed decline is explained by the kinetics of ongoing infection cycles. Residual cell-to-cell infection that becomes increasingly difficult to block could stabilize cellular provirus reservoirs.

Anti-HIV Agents↗
PubMed1997

A computed tomography method for studying the degree of postoperative aeration of maxillary sinuses.

Most patients with chronic odontogenic sinusitis experience aeration problems which remain unresolved even after classic radical antrotomy has been performed. The aim of this study was to create a high-yield diagnostically feasible and accurate CT technique which would allow the evaluation of the degree of postoperative changes of maxillary sinus aeration and overcome the limited value of traditional imaging modalities. We studied the aeration sequelae in the maxillary sinus following antrotomy in thirty-five patients employing Sytec 3000 CT scan equipment with modern densoprofile software. We found a prevalence of 62.92% for minor complications following antrotomy--a reduction in the volume of the maxillary sinus up to 25%, whereas the more serious complications accounted for 5.72%. Conventional radiologic modalities demonstrated only 25% of these changes. Our results underscore the importance of the densoprofile CT technique as a valuable and accurate diagnostic tool in detecting the changes consistent with the postantrotomy syndrome.

Adult↗
PubMed1996

First aid and transportation of burned patients during mass disasters.

Twenty-eight mass burn disasters in Bulgaria with 381 injuries in the last 27 years (1968-1994) were reviewed. Mass burn disasters were classified as follows: industrial accidents, 23, with 273 injured and 103 dead; traffic accidents, 2, with 97 injured and 30 dead; domestic accidents, 2, with 11 injured and 6 dead. Organization of first aid at the disaster site and in the regional hospitals is described, as well as the time of transport of the patients to major hospitals near the site of the accident. As a priority, the injured were transported early to the biggest center for burns and plastic surgery in the capital.

Bulgaria↗
PubMed1996

Seroprevalence of human parvovirus B19 in children of a desert region.

A seroepidemiological study was conducted in Kuwait to evaluate the pattern of acquisition of human parvovirus B19 by children in Kuwait and to compare it with patterns described in other regions in different climatic zones. A total of 218 serum samples from children less than 16 years of age were tested for the presence of anti-B19 IgG by enzyme immunoassay. The overall seroprevalence was 17.4%. Infants in Kuwait had low levels of maternally-acquired anti-B19 IgG (8.6%). The age of peak exposure to parvovirus B19 was 10-15 years compared with less than 10 years in England and Wales and more than 20 years in Singapore. The results of this study indicate an influence of geographic differences on transmission of parvovirus B19.

Antibodies, Viral↗
PubMed1996

Interlaboratory comparison of sequence-specific PCR and ligase detection reaction to detect a human immunodeficiency virus type 1 drug resistance mutation. The AIDS Clinical Trials Group Virology Committee Drug Resistance Working Group.

Sequence-specific PCR was used in six laboratories and a ligase detection reaction was used in one laboratory to detect the zidovudine-resistance mutation at codon 215 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase DNA. The genotypes of 27 different clinical samples, including cultured HIV-1 isolates, peripheral blood mononuclear cells, and plasma, were correctly identified by 140 of 154 (91%) assays. The sensitivity for detecting a mutation was 96% for HIV-1 reverse transcriptase DNA clone mixtures containing 30% mutant DNA and 62% for mixtures containing 6% mutant DNA.

Antiviral Agents↗
PubMed1995

Life span of circulating membrane CD4 inserted into the plasma membranes of autologous red blood cells of HIV-infected subjects.

Membrane recombinant CD4 was electroinserted into the plasma membrane of red blood cells (RBCs) from four HIV patients. CD4 had been labeled with 125I before electroinsertion. The RBCs-CD4-125I were labeled with 51Cr and autotransfused to the donor patients. The hematological indexes and the P50 value of the RBCs were not modified by the electroinsertion of CD4. The life span of the RBCs was not affected by electroinsertion of CD4 (t1/2 approximately 30 days), whereas the exposed CD4 showed a kinetics of disappearance characterized by two half-life times: a short one (t1/2 approximately 1 day) and a long one approximately equal to that of the RBCs. No side effects or anti-CD4 immune responses were observed in patients over a period of 28 days. The RBC-CD4 entity appears to be long-lived and has no adverse effect in HIV patients.

Adult↗
PubMed1995

Exit from G0 and entry into the cell cycle of cells expressing p21Sdi1 antisense RNA.

p21Sdi1 (also known as Cip1 and Waf1), an inhibitor of DNA synthesis cloned from senescent human fibroblasts, is an inhibitor of G1 cyclin-dependent kinases (Cdks) in vitro and is transcriptionally regulated by wild-type p53. In addition, p21Sdi1 has been found to inhibit DNA replication by direct interaction with proliferating cell nuclear antigen. In this study we analyzed normal human fibroblast cells arrested in G0 and determined that an excess of p21Sdi1 was present after immunodepletion of various cyclins and Cdks, in contrast to mitogen-stimulated cells in early S phase. Expression of antisense p21Sdi1 RNA in G0-arrested cells resulted in induction of DNA synthesis as well as entry into mitosis. These results suggest that p21Sdi1 functions in G0 and early G1 and that decreased expression of the gene is necessary for cell cycle progression.

Adenovirus E1A Proteins↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗