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Biomedical subjects

K George

Publications and source records attributed to K George.

At least 91 records · Page 5Linked to original sources
PubMed1997

7-ketocholesterol, a specific indicator of lipoprotein oxidation, and malondialdehyde in non-insulin dependent diabetes and peripheral vascular disease.

Increased free radical-mediated lipoprotein oxidation may contribute to the increased prevalence of atherosclerosis in non-insulin dependent diabetes. We have determined levels of malondialdehyde (MDA) and 7-ketocholesterol, a specific indicator of free radical-mediated oxidation of lipoprotein cholesterol, in serum in very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein (LDL) and high density lipoprotein fractions of serum separated by sequential flotation ultracentrifugation. Four groups of male subjects were studied: normal controls, diabetic patients with no evidence of microvascular complications or macrovascular disease, diabetic and non-diabetic patients with peripheral vascular disease (PVD). MDA was increased in vascular disease patients (diabetic 4.5 (3.7-5.8), non-diabetic 4.4 (3.2-5.7) mumol/l, median (2.5-97.5 percentiles)) than controls (3.6 (2.9-5.0) mumol/l) (P < 0.01), but was not increased in uncomplicated diabetic patients (3.8 (3.0-4.8) mumol/l). There were no significant differences in 7-ketocholesterol concentration in LDL, but calculated total 17-ketocholesterol was lower in non-diabetic vascular patients than controls (P < 0.01). Vitamin C concentration was reduced in diabetic and non-diabetic patients with vascular disease. No significant difference in concentration of vitamin E or A was found. In six normal subjects the concentration of MDA was low in lipoproteins separated by ultracentrifugation but high in the residue following lipoprotein fractionation (70-80% total serum MDA). In conclusion, the concentration of MDA by the thiobarbituric acid assay in untreated serum may not reflect free radical damage to lipoproteins. There was no evidence of increased lipoprotein oxidation using 7-ketocholesterol in NIDDM or PVD.

Adult↗
PubMed1997

Peripartum ovarian masses.

The presentation and management of ovarian tumours complicating pregnancy may have altered with changes in obstetric practice and developments in diagnostic imaging and pathology. A retrospective review of the presentation, management, pathological findings and pregnancy outcome of all women whose pregnancies were complicated by an ovarian tumour was undertaken. We found 84 cases where ovarian masses complicated pregnancy. Thirteen presented in association with an ectopic pregnancy. Forty-seven cases were asymptomatic and 29 of these were discovered incidentally at caesarean section despite the routine use of ultrasound. Twenty-two cases were symptomatic, presenting with mass, pain or bleeding. Aspiration cytology was helpful in only 53% while histology allowed definitive diagnosis for all tumours. Benign cystic teratoma was the most common tumour found. There was one tumour of borderline malignancy in this series. Examination of the ovaries at the time of caesarean section should be a routine practice since the majority of asymptomatic ovarian masses were discovered incidentally and not antenatally, having been missed at the time of routine ultrasound. Although differentiation of functional from neoplastic lesions can be difficult, most lesions are benign and selective conservative management may be considered.

Journal Article↗
PubMed1997

Cytogenetic effects of space radiation in lymphocytes of MIR-18 crews.

For assessing health risk, the measurement of physical dose received during a space mission, as well as the LETs, energies and charges of particles is important. It is also important to obtain quantitative information regarding the effectiveness of space radiation in causing damage to critical biological targets, e.g., chromosomes, since at present the estimated uncertainty of biological effects of space radiation is more than a factor of two. Such large uncertainty makes accurate health risk assessment very difficult. For this very reason, a study on cytogenetic effects of space radiation in human lymphocytes was proposed and done for MIR-18 mission. This study used FISH technique to score chromosomal translocations and C-banding method to determine dicentrics. Growth kinetics of cells and SCE were examined to ensure that chromosomal aberrations were scored in first mitosis and were induced not by chemical mutagens. Our results showed that chromosomal aberration frequency of post-flight samples was significantly higher than that of pre-flight ones and that SCE frequency was similar between pre- and post-flight samples. Based on a dose-response curve of preflight samples exposed to gamma rays, the absorbed dose received by crews during the mission was estimated to be about 14.5 cSv. Because the absorbed dose measured by physical dosimeters is 4.16 cGy for the entire mission, the RBE is about 3.5.

Chromosome Aberrations↗
PubMed1997

Biodosimetry results from space flight Mir-18.

Astronauts are classified as radiation workers due to the presence of ionizing radiation in space. For the assessment of health risks, physical dosimetry has been indispensable. However, the change of the location of dosimeters on the crew members, the variation in dose rate with location inside the spacecraft and the unknown biological effects of microgravity can introduce significant uncertainties in estimating exposure. To circumvent such uncertainty, a study on the cytogenetic effects of space radiation in human lymphocytes was proposed and conducted for Mir-18, a 115-day mission. This study used fluorescence in situ hybridization (FISH) with whole-chromosome painting probes to score chromosomal exchanges and the Giemsa staining method to determine the frequency of dicentrics. The growth kinetics of cells and sister chromatid exchanges (SCEs) were examined to ensure that chromosomal aberrations were scored in the first mitosis and were induced primarily by space radiation. Our results showed that the frequency of chromosomal aberrations increased significantly in postflight samples compared to samples drawn prior to flight, and that the frequency of SCEs was similar for both pre- and postflight samples. Based on a dose-response curve for preflight samples exposed to gamma rays, the absorbed dose received by crew members during the mission was estimated to be about 14.75 cSv. Because the absorbed dose measured by physical dosimeters is 5.2 cGy for the entire mission, the RBE is about 2.8.

Astronauts↗
PubMed1997

Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes.

Painting of interphase chromosomes can be useful for biodosimetric purposes in particular cases such as radiation therapy, accidental exposure to very high radiation doses and exposure to densely ionizing radiation, for example during space missions. Biodosimetry of charged-particle radiation is analyzed in the present paper. Target cells were human peripheral blood lymphocytes irradiated in vitro with gamma rays, protons and iron ions. After exposure, lymphocytes were incubated for different times to allow repair of radiation-induced damage and then fused to mitotic hamster cells to promote premature condensation in the interphase chromosomes. Chromosome spreads were then hybridized with whole-chromosome DNA probes labeled with fluorescent stains. Dose-response curves for the induction of chromatin fragments shortly after exposure, as well as the kinetics of rejoining and misrejoining, were not markedly dependent on linear energy transfer. However, after exposure to heavy ions, more aberrations were scored in the interphase cells after incubation for repair than in metaphase samples harvested at the first postirradiation mitosis. On the other hand, no significant differences were observed in the two samples after exposure to sparsely ionizing radiation. These results suggest that interphase chromosome painting can be a useful tool for biodosimetry of particle radiation.

Animals↗
PubMed1997

Induction of chromosome aberrations in human cells by charged particles.

Chromosome aberrations induced by high-energy charged particles in normal human lymphocytes and human fibroblasts have been investigated. The charged particles included 250 MeV/nucleon protons, 290 MeV/nucleon carbon ions and 1 GeV/nucleon iron ions. The energies of the charged particles were higher than in most of the studies reported in the literature. Lymphocytes were stimulated to grow immediately after irradiation, while fibroblasts were incubated at 37 degrees C for 24 h for repair. Chromosomes were collected at the first mitosis after irradiation and chromosome aberrations were scored using the fluorescence in situ hybridization (FISH) technique with a whole-chromosome 4 probe. Chromosome aberrations were classified as reciprocal exchanges, incomplete exchanges, deletions and complex exchanges. The relative biological effectiveness (RBE) for each type of aberration was calculated by dividing a dose of 4 Gy by the dose of the charged particles producing the same effect as 4 Gy of gamma rays. Results of this study showed that complex aberrations have the highest RBE for radiation of high linear energy transfer (LET) for human lymphocytes, but for fibroblasts, the greatest effect was for incomplete exchanges. For both lymphocytes and fibroblasts, iron ions induced a similar fraction of aberrant cells.

Carbon↗
PubMed1996

Chronic exposure of LLC-PK1 epithelia to the phorbol ester TPA produces polyp-like foci with leaky tight junctions and altered protein kinase C-alpha expression and localization.

Acute exposure (up to 4 h) of LLC-PK1 epithelial cell sheets to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) causes a rapid decrease of transepithelial electrical resistance (TER) to less than 15% of initial value. As the TPA exposure period is continued by chronically passaging cells in the presence of TPA, TER begins to recover. By 6 weeks of exposure, TER recovers to almost 50% of its initial value, suggesting that tight junctions (TJs) are recovering barrier function even in the continued presence of TPA. Between 6 and 8 weeks, TER then decreases a second time to approximately 20 to 40% of initial values, and TER values remain at this level for at least 18 weeks of exposure. Transepithelial (paracellular) fluxes of D-mannitol inversely correspond with TER changes. Across chronically treated cell sheets, rates are higher than those across control cell sheets, but lower than those across acutely treated cell sheets. The decrease of TER at 6-8 weeks coincides with the appearance of multilayered, polyp-like foci (PLFs) on the otherwise one cell layer thick epithelium. Electron microscopy shows that the electron-dense dye ruthenium red cannot penetrate across TJs of control cells but passes across all of the TJs of a cell sheet treated acutely with TPA. In chronically treated cultures, ruthenium red penetrates TJs between most cells of PLFs, but not TJs of adjacent morphologically normal epithelium. A clonal subline derived from cells of a PLF (clone PLF-A) is multilayered almost throughout and exhibits ruthenium red penetration across nearly all of its tight junctions, monolayer or multilayer. Acute exposure of control cell sheets to TPA induces activation, translocation, and down-regulation of protein kinase C-alpha (PKC-alpha). In chronically TPA-treated and clone PLF-A cells, total PKC-alpha levels are reduced even further and almost all remaining PKC-alpha is found in the membrane-associated and Triton-insoluble fractions. Immunofluorescence shows that PKC-alpha expression is restricted to the PLFs in chronically TPA-treated cells and is more homogeneously distributed in clone PLF-A cultures. In summary, the data show that chronic treatment of epithelial cells with a tumor promoter induces the formation of abnormal cell architecture (PLFs) associated with increased leakiness of TJs and membrane translocation of PKC-alpha. Recovery of barrier function in portions of chronically TPA-treated cultures does not correlate with up-regulation of PKC-alpha nor translocation back to the cytosolic compartment.

Animals↗
PubMed1996

Biological dosimetry by interphase chromosome painting.

Both fluorescence in situ hybridization of metaphase spreads with whole-chromosome probes and premature chromosome condensation in interphase nuclei have been used in the past to estimate the radiation dose to lymphocytes. We combined these techniques to evaluate the feasibility of using painted interphase chromosomes for biodosimetry. Human peripheral lymphocytes were exposed to gamma rays and fused to mitotic Chinese hamster cells either immediately after irradiation or after 8 h incubation at 37 degrees C. Interphase or metaphase human chromosomes were hybridized with a composite probe specific for human chromosomes 3 and 4. The dose-response curve for fragment induction immediately after irradiation was linear; these results reflected breakage frequency in the total genome in terms of DNA content per chromosome. At 8 h after irradiation, the dose-response curve for chromosome interchanges, the prevalent aberration in interphase chromosomes, was linear-quadratic and similar to that observed for metaphase chromosomes. These results suggest that painting prematurely condensed chromosomes can be useful for biological dosimetry when blood samples are available shortly after the exposure, or when interphase cells are to be scored instead of mitotic cells.

Animals↗
PubMed1996

Rejoining and misrejoining of radiation-induced chromatin breaks. I. experiments with human lymphocytes.

Fluorescence in situ hybridization with a composite probe for human chromosome 4 and a probe that stained all centromeres was used to study gamma-ray induced breakage, rejoining and misrejoining in prematurely condensed chromosomes in human lymphocytes. Dose-response curves for the induction of all types of aberrations in prematurely condensed human chromosomes 4 were determined immediately after irradiation and after 8 h postirradiation incubation. In addition, aberrations were measured after various incubation times from 0 to 18 h after a dose of 7 Gy. Unrejoined chromosome breaks were the most frequent type of aberration observed immediately after irradiation. Approximately 15% of total aberrations observed were chromosome exchanges. After 8 h postirradiation incubation, the frequency of breaks in prematurely condensed chromosomes declined to about 20% of the initial value, and chromosomal exchanges became the most frequent aberration. Results of metaphase analysis were similar to those for prematurely condensed chromosomes after 8 h incubation with the exception that a significantly lower frequency of fragments was observed. Symmetrical and asymmetrical interchanges were found at similar frequencies at all doses. No complex exchanges were observed in lymphocyte chromosomes immediately after exposure. They accounted for about 1% of total exchanges in metaphase chromosomes at doses <3 Gy and about 14% at 7 Gy. Incomplete exchanges amounted to approximately 15% of total exchanges at all doses. The kinetics of break rejoining was exponential, and the frequency of exchanges increased with kinetics similar to that observed for the rejoining of the breaks. This increase in the total exchanges as a function of the time between irradiation and fusion was due to a rapid increase in reciprocal interchanges, and a slower increase in complex exchanges; the frequency of incomplete exchanges increased initially, then decreased with prolonged incubation to the level observed in metaphase. It is concluded that the formation of each kind of chromosome aberrations follows different kinetics.

Cells, Cultured↗
PubMed1996

Rejoining and misrejoining of radiation-induced chromatin breaks. II. Biophysical Model.

A biophysical model for the kinetics of the formation of radiation-induced chromosome aberrations is developed to account for the recent experimental results obtained with a combination of the premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) techniques. In this model, we consider the broken ends of DNA double-strand breaks (DSBs) to be reactant and make use of the interaction distance hypothesis. The repair/misrepair process between broken ends is suggested to consist of two steps; the first step represents the two break ends approaching each other, and the second step represents the enzymatic processes leading to DNA end-to-end rejoining. Only the second step is reflected in the kinetics observed in experiments using PCC. The model appears to be able to fit existing data for human cells. It is shown that the kinetics of the formation of chromosome aberrations can be explained by a single rate that characterizes both rejoining and misrejoining of DSBs, suggesting that repair and misrepair share the same mechanism. Fast repair (completed in minutes) in a subset of DSBs is suggested as an explanation of the complete exchanges observed with PCC in human lymphocytes immediately after irradiation. The fast repair component seems to be absent in human fibroblasts.

Cell Line↗
PubMed1995

Doppler velocimetry and fetal heart rate pattern observations in acute cocaine intoxication. A case report.

While the use of cocaine in pregnancy continues to be a significant contributor to adverse maternal and perinatal outcomes, systematic study of the physiologic effects of cocaine in human gestation remains difficult. In a case of acute cocaine intoxication in the third trimester, Doppler velocimetry suggested a physiologic response from the uterine artery but not the umbilical artery. Furthermore, the abnormal uterine artery velocimetry was associated with a positive nonreactive contraction stress test, which became negative and reactive as the effects of the cocaine wore off and the velocimetry returned to normal. These observations suggest that the uterine arteries are more sensitive to cocaine than are the umbilical arteries and that abnormal fetal heart rate patterns during acute cocaine intoxication may be transitory.

Adult↗
PubMed1994

Effects of dogfish urotensin II on lipid mobilization in the fasted dogfish, Scyliorhinus canicula.

Previous studies, both in vitro and in vivo, have shown that urotensin II stimulates hepatic release of nonesterified fatty acids in teleost fish, but the effects of the peptide on lipid mobilization in elasmobranchs are unknown. Infusions of synthetic dogfish urotensin II (40 pmol/min/kg for 30 min followed by 400 pmol/min/kg for 30 min) into the first afferent gill artery of the fasted, unrestrained dogfish, Scyliorhinus canicula (n = 6), produced no significant change in the circulating concentrations of acetoacetate, 3-hydroxybutyrate, and triacylglycerols. Circulating nonesterified fatty acids were undetectable (< 0.1 mmol/liter) both before and after the urotensin II infusions. There was no significant change in the circulating concentrations of glucose and lactate during either the low- or the high-dose infusions. The data support the hypothesis that lipid is converted primarily to ketone bodies in the livers of elasmobranch fish and do not indicate a role for urotensin II in regulating either lipid or glycogen mobilization.

3-Hydroxybutyric Acid↗
PubMed1994

Maternal serum alpha-fetoprotein levels in chorioangiomas.

It has been suggested that chorioangiomas should be added to the list of causes of elevated maternal serum alpha-fetoprotein levels. We undertook a review of maternal serum alpha-fetoprotein levels in chorioangiomas histologically diagnosed in our department, and a review of the literature. Maternal serum alpha-fetoprotein level was elevated in only 1 of our 11 cases of chorioangioma. To date, there have been 14 case reports of chorioangiomas in which maternal serum alpha-fetoprotein levels have been recorded; 12 of these were associated with elevated maternal serum alpha-fetoprotein levels. We consider that, although chorioangiomas may be a cause of elevated maternal serum alpha-fetoprotein levels, it is likely to be infrequently a cause of such elevations in our population.

Female↗
PubMed1994

Clinical and microbiological status of osseointegrated implants.

Peri-implantitis, an inflammatory response around implants, has a poorly defined etiology and pathogenesis. To better understand the role of specific microorganisms in this disease process, clinical and microbiological parameters were examined in 24 patients with 98 osseointegrated implants. Sites were evaluated for probing depth (PD), plaque/calculus index (PI), gingival bleeding index (GBI), mobility, and crevicular fluid flow rate (CFFR). Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in subgingival plaque were identified by latex agglutination assays. Clinically, a statistically significant correlation (P < 0.001) was observed between probing depth and the length of time an implant was present. Mobility was also significantly greater (P < 0.001) in the maxillary than in the mandibular implants. Subgingival sites harboring one of the three microorganisms had significantly greater PD, GBI, and CFFR than non-colonized sites. Implants in partially edentulous patients more frequently were colonized with P. gingivalis/P. intermedia than edentulous patients. The incidence of these microorganisms also correlated with fixture longevity. Implants present for 3 to 4 years had a significantly greater frequency of test microorganisms than implants present for 1 to 2 years. These findings suggest that microbial pathogens associated with periodontitis occur more commonly around implants exhibiting gingival inflammation (GBI) and may contribute to peri-implantitis.

Adult↗
PubMed1992

Effects of acute vs. chronic phorbol ester exposure on transepithelial permeability and epithelial morphology.

In previous experiments we have shown that acute (30 minutes) exposure to phorbol esters or other protein kinase C activators causes increased transepithelial permeability, specifically by the increased paracellular permeability through tight junctions. However, the role of protein kinase C activators in carcinogenesis is predicted upon a chronic exposure of an effective dose at frequent intervals for a prolonged period of time. We therefore sought to determine the effect of chronic phorbol ester exposure on transepithelial permeability by exposing cells of the polar renal epithelial cell line, LLC-PK1, to phorbol esters for time periods as long as 16 weeks. The following changes ensued: (1) after the initial drop in transepithelial resistance due to phorbol ester exposure, i.e., an increase in transepithelial permeability (in the acute phase of exposure), an adaptive response occurs as transepithelial resistances in chronically exposed cultures recover to approximately 50% of control values, (2) the cell sheets in chronically exposed cultures lose their acute responsiveness of transepithelial permeability to phorbol ester exposure, (3) cell sheet architecture changes as cells occasionally multilayer and actual polyp-like cell masses appear at high frequency, and (4) cytosolic protein kinase C activity decreases to 50% of control level with acute exposure and then is further decreased to less than 1% of control level in chronically treated cells; membrane-associated PKC activity is not as sharply decreased. The possible role of transepithelial permeability in carcinogenesis and the value of chronically treated epithelial cell cultures as a model for two-stage carcinogenesis are discussed.

Animals↗
PubMed1992

Chromosomal abnormalities associated with a single umbilical artery.

A single umbilical artery was seen in 10 out of 117 cytogenetically abnormal pregnancies. The abnormal karyotypes found to be associated with a single umbilical artery were trisomy 18 (n = 5), monosomy X (n = 2), triploidy (n = 1), sex chromosome (47,XYY; n = 1) and translocation (46t(X,5)(q13p15);n = 1). With the exception of the translocation case, all cases with a single umbilical artery had anatomical defects which were detectable ultrasonographically. This suggests that a single umbilical artery alone is not an indication for prenatal fetal karyotyping.

Chromosome Aberrations↗
PubMed1992

Regulation of expression of the reovirus receptor on differentiated HL60 cells.

The reovirus receptor on mammalian cells has not been fully characterized and controversy exists over the nature of this receptor. We report here that the expression of this receptor is dependent on the differentiation status of a human promyelocytic leukaemia cell line (HL60). Phorbol treatment of HL60 cells for 24 h, at a concentration range of 160 nM down to 1 nM, led to differentiation of these cells towards monocytes and a loss of approximately 80% of their ability to bind reovirus in a fluorescence assay. These cells also lost their susceptibility to T1 and T3 reovirus infection. DMSO treatment for 24 h at a concentration of 1.25% (v/v) led to differentiation towards granulocytes. This was accompanied by an increase of approximately 15% in binding of reovirus to these cells. After being infected by T1 or T3 reovirus, the granulocytes produced higher titres of progeny virus than did untreated HL60 cells. Similar differences were noted when virus binding to HL60 cells was assayed using radiolabelled reovirus. These effects were not detected when murine L fibroblasts were treated with DMSO or phorbol. ATCC-derived murine R1.1 cells did not bind reovirus. Competition data indicated that there may be two reovirus receptors on HL60 cells, and that T1 can bind to only one receptor whereas T3 can bind to both receptors. Our data also suggested that the beta-adrenergic receptor was unlikely to act as the reovirus receptor on HL60 cells.

Animals↗