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Biomedical subjects

A Ivanova

Publications and source records attributed to A Ivanova.

At least 19 recordsLinked to original sources

A theoretical study of model lipid monolayers.

Studies of pure phospholipid monolayers or various well defined lipid mixtures have greatly contributed to the current knowledge of the relationship between monolayer composition and its properties and to understand how their physicochemical properties, e.g. refraction, polarization, are controlled by structural variations at the molecular level. Therefore, an attempt was made to investigate model lipid molecules adsorbed on the air/water interface. Semi-empirical (AM1) quantum chemical calculations were performed for several clusters and were compared with experimental data. The optimized acidic molecules show a marked tendency to group forming domains. An increase in the number of surfactant molecules in the cluster leads to a decrease in the effective headgroup area. On the other hand, the area grows with the increase of the degree of ionization. Both relations are in accordance with the experimental trends and the electrostatic theory. The employed theoretical approach proves to be applicable to the study of monolayers, thus providing a reliable description at molecular level of the traditionally phenomenological investigations in the field.

Cell Membrane↗

Niels Stensen--prestigious scholar of the 17th century.

The authors present a biography of modest, extraordinary educated Danish scholar Niels Stensen, who gave his life to anatomy, geology and finally to theology. His anatomical studies of salivary glands, lymphatic system, muscles and heart, and also of other organs of human body, based on study of contemporary anatomy classify him among most important scholar of 17th century. The truth, scientific approach and his method of explaining anatomical structures in a connection with physiological notes are original and valid from a todays point of view. (Fig. 3. Ref. 8.)

Anatomy↗

Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer.

An acidic extracellular pH is a fundamental property of the malignant phenotype. In von Hippel-Lindau (VHL)-defective tumors the cell surface transmembrane carbonic anhydrase (CA) CA9 and CA12 genes are overexpressed because of the absence of pVHL. We hypothesized that these enzymes might be involved in maintaining the extracellular acidic pH in tumors, thereby providing a conducive environment for tumor growth and spread. Using Northern blot analysis and immunostaining with specific antibodies we analyzed the expression of CA9 and CA12 genes and their products in a large sample of cancer cell lines, fresh and archival tumor specimens, and normal human tissues. Expression was also analyzed in cultured cells under hypoxic conditions. Expression of CA IX and CA XII in normal adult tissues was detected only in highly specialized cells and for most tissues their expression did not overlap. Analysis of RNA samples isolated from 87 cancer cell lines and 18 tumors revealed high-to-moderate levels of expression of CA9 and CA12 in multiple cancers. Immunohistochemistry revealed high-to-moderate expression of these enzymes in various normal tissues and multiple common epithelial tumor types. The immunostaining was seen predominantly on the cell surface membrane. The expression of both genes was markedly induced under hypoxic conditions in tumors and cultured tumor cells. We conclude that the cell surface trans-membrane carbonic anhydrases CA IX and CA XII are overexpressed in many tumors suggesting that this is a common feature of cancer cells that may be required for tumor progression. These enzymes may contribute to the tumor microenvironment by maintaining extracellular acidic pH and helping cancer cells grow and metastasize. Our studies show an important causal link between hypoxia, extracellular acidification, and induction or enhanced expression of these enzymes in human tumors.

Biomarkers, Tumor↗

Characterization of novel methyl-branched chain fatty acids from a halophilic Bacillus species.

The 4-methylated fatty acids 4,9-dimethyldecanoic, 4,11-dimethyldodecanoic, 4,10-dimethyldodecanoic, and 4,13-dimethyltetradecanoic acid as well as the 2-methylated fatty acids 2,13-dimethyltetradecanoic and 2,12-dimethyltetradecanoic acid were identified for the first time in nature in the halophilic bacterium Bacillus sp. isolated from the salt pans of Burgas in Bulgaria. The principal fatty acids in this bacterium were a series of iso-anteiso fatty acids with chain lengths between C11 and C19, but an interesting series of linear alkylbenzene fatty acids with chain lengths between C10 and C14, such as 12-phenyldodecanoic acid, were also identified. The novel 4-methylated fatty acids were characterized using a combination of GC-MS and chemical transformations such as N-acylpyrrolidide derivatization. The 2-methylated fatty acids were also identified by GC-MS and gas chromatographic coelution with synthetic samples. The novel methyl-branched fatty acids probably originated from the selective incorporation of methylmalonyl-CoA by one of the fatty acid-synthesizing enzymes of the bacterium.

Bacillus↗

Mutant Plp/DM20 cannot be processed to secrete PLP-related oligodendrocyte differentiation/survival factor.

Most of the mutations within the PLP gene result in degeneration of oligodendrocytes and this is believed to be caused by intracellular trafficking defects. Previous studies have demonstrated that cells expressing the wild type PLP gene release a factor promoting differentiation/survival of oligodendrocyte and that this factor is the C-terminal portion of the protein itself. In this study we asked how the naturally occurring mutations of the PLP gene (jimpy, jimpy msd, and rumpshaker) affect this activity. We developed a transient expression system for retroviral production and transduction that enabled the expression of mutant PLP/DM20 cDNAs in NIH3T3 cells. None of the NIH3T3 cells producing mutant PLP/DM20s secreted the PLP-related factor that increases the number of oligodendrocytes. Since it has been shown that rumpshaker DM20 can be transported to the cell surface, but its folding is incorrect, absence of secretion of this factor is more heavily attributable to incorrect protein folding than to the defect in the PLP/DM20 trafficking.

3T3 Cells↗

Drawbacks to integer scoring for ordered categorical data.

Linear rank tests are widely used when testing for independence against stochastic order in a 2 x J contingency table with two treatments and J ordered outcome levels. For this purpose, numerical scores are assigned, possibly by default, to the J outcome levels. When the choice of scores is not apparent, integer (equally spaced) scores are often assigned. We show that this practice generally leads to unnecessarily conservative tests. The use of slightly perturbed scores will result in a less conservative and uniformly more powerful test.

Biometry↗

Optimal adaptive designs for binary response trials.

We derive the optimal allocation between two treatments in a clinical trial based on the following optimality criterion: for fixed variance of the test statistic, what allocation minimizes the expected number of treatment failures? A sequential design is described that leads asymptotically to the optimal allocation and is compared with the randomized play-the-winner rule, sequential Neyman allocation, and equal allocation at similar power levels. We find that the sequential procedure generally results in fewer treatment failures than the other procedures, particularly when the success probabilities of treatments are smaller.

Biometry↗

Anaerobic mineralization of toluene by enriched sediments with quinones and humus as terminal electron acceptors.

The anaerobic microbial oxidation of toluene to CO(2) coupled to humus respiration was demonstrated by use of enriched anaerobic sediments from the Amsterdam petroleum harbor (APH) and the Rhine River. Both highly purified soil humic acids (HPSHA) and the humic quinone moiety model compound anthraquinone-2,6-disulfonate (AQDS) were utilized as terminal electron acceptors. After 2 weeks of incubation, 50 and 85% of added uniformly labeled [(13)C]toluene were recovered as (13)CO(2) in HPSHA- and AQDS-supplemented APH sediment enrichment cultures, respectively; negligible recovery occurred in unsupplemented cultures. The conversion of [(13)C]toluene agreed with the high level of recovery of electrons as reduced humus or as anthrahydroquinone-2,6-disulfonate. APH sediment was also able to use nitrate and amorphous manganese dioxide as terminal electron acceptors to support the anaerobic biodegradation of toluene. The addition of substoichiometric amounts of humic acids to bioassay reaction mixtures containing amorphous ferric oxyhydroxide as a terminal electron acceptor led to more than 65% conversion of toluene (1 mM) after 11 weeks of incubation, a result which paralleled the partial recovery of electron equivalents as acid-extractable Fe(II). Negligible conversion of toluene and reduction of Fe(III) occurred in these bioassay reaction mixtures when humic acids were omitted. The present study provides clear quantitative evidence for the mineralization of an aromatic hydrocarbon by humus-respiring microorganisms. The results indicate that humic substances may significantly contribute to the intrinsic bioremediation of anaerobic sites contaminated with priority pollutants by serving as terminal electron acceptors.

Anaerobiosis↗

Anatomic nomenclature by Vesalius.

Our paper deals with the situation of medieval anatomy language in the pre-Vesalian period. It also explains the necessity of terminology reform undertaken by Vesalius in his De humani corporis fabrica. It describes formation principles of the scientific language of anatomy based on pure classical Latin while eliminating Arabic and Greek elements. Emphasis is laid on Vesalius' effort to unify terms as far as their meaning is concerned, to record lexical items and to create a permanent nomenclature in order to eliminate discrepancies in this field of communication. Our paper contains a lot of information on terminology demonstrating Vesalius' language reform and reminding us of his great achievement, for which he is considered a forerunner of anatomy nomenclature codification. (Ref. 5.)

Anatomy↗

Andreas Vesalius--the reformer of anatomy.

This paper deals with two main topics. The first part provides data on the life of Andreas Vesalius, a scholar and anatomist of the 16th century, and describes the environment in which he lived and worked. It highlights his personality of a great doctor and teacher and points out the importance of his scientific methods and techniques as opposed to speculative methods that were prevalent in the scientific research in those days. The second part of the paper is devoted to the characteristics and description of his famous and, given the times he lived in, grand work called "De Humani Corporis Fabrica", which opened a new epoch in the history of anatomy. Andreas Vesalius is considered to be the founder of the science of anatomy which is based on observation and experience gained by using scalpel on dead bodies of humans. This is how he proved the then valid statements wrong. This complex view of life and work of Andreas Vesalius is aimed at highlighting the milestone which he represents in this traditional science of anatomy that has been conscientiously developed since the Classical times. (Fig. 4, Ref. 6.)

Anatomy↗

Dorsal spinal cord inhibits oligodendrocyte development.

Oligodendrocytes are the myelinating cells of the mammalian central nervous system. In the mouse spinal cord, oligodendrocytes are generated from strictly restricted regions of the ventral ventricular zone. To investigate how they originate from these specific regions, we used an explant culture system of the E12 mouse cervical spinal cord and hindbrain. In this culture system O4(+) cells were first detected along the ventral midline of the explant and were subsequently expanded to the dorsal region similar to in vivo. When we cultured the ventral and dorsal spinal cords separately, a robust increase in the number of O4(+) cells was observed in the ventral fragment. The number of both progenitor cells and mature cells also increased in the ventral fragment. This phenomenon suggests the presence of inhibitory factor for oligodendrocyte development from dorsal spinal cord. BMP4, a strong candidate for this factor that is secreted from the dorsal spinal cord, did not affect oligodendrocyte development. Previous studies demonstrated that signals from the notochord and ventral spinal cord, such as sonic hedgehog and neuregulin, promote the ventral region-specific development of oligodendrocytes. Our present study demonstrates that the dorsal spinal cord negatively regulates oligodendrocyte development.

Animals↗

Unusual lipid composition of a Bacillus sp. isolated from Lake Pomorie in Bulgaria.

The lipid composition of a Bacillus sp., isolated from Lake Pomorie in Bulgaria, was unusual and consisted of 26 different fatty acids between C12 and C26, with anteiso C15-C17 saturated fatty acids predominating. The furan fatty acid, 10,13-epoxy-11-methyloctadeca-10,12-dienoic acid, was also identified, a new finding for this genus. The hydrocarbons consisted of 30 different monounsaturated hydrocarbons, between C25 and C30, with the iso-iso, iso-anteiso, anteiso-anteiso, iso-normal, and anteiso-normal methyl branching for odd-numbered chains, and the iso-iso, iso-anteiso, iso-normal, and anteiso-normal methyl branching for even-numbered chains. The double bond positions in these hydrocarbons were determined by dimethyl disulfide derivatization followed by GC-MS, and the double-bond cis configuration was confirmed by infrared spectroscopy. Some previously unknown hydrocarbons in bacteria, such as (Z)-3,21-dimethyl-9-tricosene, (Z)-3,21-dimethyl-10-tricosene, (Z)-2,24-dimethyl-11-pentacosene, and (Z)-2,25-dimethyl-13-hexacosene were identified. Sterols were detected and were based on the sitosterol nucleus.

Bacillus↗

Two novel iso-branched octadecenoic acids from a Micrococcus species.

The novel fatty acids 16-methyl-6(Z)-heptadecenoic acid and 16-methyl-8(Z)-heptadecenoic acid were identified for the first time in nature in a species of the bacterium Micrococcus isolated from Lake Pomorie in Bulgaria. The principal fatty acids in this bacterium were a series of iso-anteiso fatty acids with chain lengths between C(14) and C(24), while the most interesting series of monounsaturated fatty acids was a family of Delta(6) fatty acids with chain lengths between C(14) and C(17). The novel compounds were characterized using a combination of GC-MS and chemical transformations, such as dimethyl disulfide derivatization and catalytic hydrogenation. The results established for the first time a bacterial origin for some of these Delta(6) fatty acids.

Fatty Acids, Monounsaturated↗

A comparison of urn designs for randomized clinical trials of K > 2 treatments.

Response-adaptive designs in clinical trials involve incorporating accruing information from patient responses to treatment into the randomization scheme in order to assign more patients to the treatment that has performed better in the trial up to that point. One probability model useful in generating an adaptive randomization scheme is an urn model. We will give a short overview of such adaptive models and compare four of them. We will be interested in how these four models minimize the number of treatment failures in a clinical trial with dichotomous response treatments. Comparison will be done via simulations for four treatments and exactly for three treatments for moderate sample sizes. We compare designs under the assumption that the results of treatments are known immediately, and we also allow some delay in response. Power is analyzed under various alternatives. Our results indicate that a birth and death urn with immigration is the best unless success probabilities are very small, in which case a randomized version of Polya's urn is preferred.

Algorithms↗

Proteolipid protein gene product can be secreted and exhibit biological activity during early development.

A gene encoding myelin proteolipid protein (PLP) and its smaller isoform DM20 is expressed at least 1 week before myelination. Mutations within the gene cause abnormalities in the development of premyelinating oligodendrocytes, resulting in hypomyelinating disorders. These findings suggest a premyelinating function of the PLP gene products. We previously demonstrated that PLP gene expression is directly associated with secretion of a factor that increases the number of oligodendrocytes. Here we show that this activity is mediated by a secreted fragment containing the C-terminal portion of PLP. This factor increased the bromodeoxyuridine incorporation rate in both oligodendrocyte and astrocyte lineage cells; a synthetic peptide (PLP 215-232) exhibited a similar activity. Dose-response curves of PLP and PLP peptide showed maximum activities at a concentration in the picomolar range, which decreased at higher concentrations. These observations demonstrate that a secreted PLP gene product exerts biological activity at a premyelinating stage before the major induction of the gene.

3T3 Cells↗

Potential acuity pinhole: a simple method to measure potential visual acuity in patients with cataracts, comparison to potential acuity meter.

OBJECTIVE: To describe the potential acuity pinhole (PAP) test and compare its accuracy to the potential acuity meter (PAM) in predicting visual outcome after cataract surgery. STUDY DESIGN: Prospective case series. PARTICIPANTS: A total of 56 preoperative patients with cataracts participated. MAIN OUTCOME MEASURES: Accuracy of predicting postoperative distance visual acuity was measured. METHODS: Lines of inaccuracy were calculated by subtracting actual postoperative best-corrected distance visual acuity (BCVA) from predicted values. Variables analyzed were method of prediction, preoperative BCVA, and preoperative spherical equivalent. RESULTS: The PAP test predicted visual outcomes within 2 lines in 100%, 100%, and 56% of eyes with preoperative BCVA of 20/50 and better (group 1), 20/60 to 20/100 (group II), and 20/200 and worse (group III), respectively. The PAM predictions within 2 lines for the same groups were 42%, 47%, and 0%, respectively. Mean lines of inaccuracy of PAP predictions were 0.83, 1.11, and 3.50 lines for groups I, II, and III, respectively. Mean lines of inaccuracy for PAM predictions were 2.50, 2.68, and 6.22 lines for the same groups. Differences in lines of prediction between PAM and PAP were 1.67 (P = 0.004), 1.58 (P = 0.0002), and 2.72 lines (P = 0.0001) for groups I, II, and III, respectively. There was no statistically significant correlation between PAP predictions and preoperative myopic spherical equivalent. CONCLUSIONS: The PAP test is a simple, inexpensive, and relatively reliable method to estimate visual outcome after uncomplicated cataract surgery in eyes with no coexisting disease. It is less accurate in patients with preoperative BCVA worse than 20/200. It appears to be more predictive than PAM.

Adult↗