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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 199 records · Page 11Linked to original sources
PubMed2000

Inactivation of Bacillus subtilis spores on aluminum and polyethylene preformed cartons by UV-excimer laser irradiation.

The efficacy of UV KrF-excimer laser light (at 248 nm) to inactivate Bacillus subtilis spores loaded onto preformed cartons was found to be dependent on the interior carton coating and scheme by which the irradiation was applied. When the carton was held static during UV laser treatment, the majority of the dose was delivered to the base of the carton and to a lesser extent to the upper part of the pack. In this arrangement no irradiation of the interior sides of the carton was observed. A more even distribution of dose was achieved, however, by moving the carton within the laser beam during irradiation treatment. The distribution of UV was also found to be dependent on the type of carton interior coating. With aluminum cartons the dose measured was found to be significantly greater (P < 0.01) and more evenly distributed across the interior compared to when polyethylene packs were tested. Under optimized conditions no spore survivors were detected on aluminum cartons preloaded with 9.5 x l0 B. subtilis spores by applying a UV laser output dose of 160 J. In comparison, the same conditions only achieved a significantly lower (P < 0.01) reduction in spore numbers (log count reduction 4.2) when polyethylene cartons were used. This difference in lethality and UV distribution of laser light was associated with the higher internal reflection of photons with aluminum cartons. The suitability of UV-excimer lasers for sterilizing preformed cartons over traditional germicidal lamp-based methods is discussed.

Aluminum↗
PubMed2000

Cancer risk estimates for family members of a population-based family registry for breast and ovarian cancer.

Population-based breast and ovarian cancer family registries can facilitate studies to evaluate genetic and environmental factors in the etiology of these malignancies. The purpose of this study is to describe what is, as far as we know, the first population-based breast and ovarian cancer family registry and to estimate breast and ovarian cancer risk in relatives of breast and ovarian cancer probands. Population-based consecutive incident cases of breast and ovarian cancer were invited to participate in the University of California, Irvine breast and ovarian family registry. In this study, we report data on 1567 breast cancer and 328 ovarian cancer probands. The operational components of this family registry include enrollment of probands, family history interviewing, confidentiality, pathology, verification and review, biospecimen bank, statistical/genetic analysis, and special studies on positional cloning of known genes. All of the components are tracked through the University of California, Irvine Genetic Research Information System. In non-Hispanic-white breast cancer probands, relative risk (RR) of breast cancer in mothers and sisters is significantly elevated [RR = 1.7 and 95% confidence interval (CI) = 1.4-2.0 and RR = 2.8 and 95% CI = 2.3-3.3, respectively]. In families of ovarian cancer probands, mothers are at increased risk of ovarian cancer (RR = 4.6; 95% CI, 2.1-8.7). RR of breast cancer in mothers of Hispanic breast cancer probands is significantly elevated (RR = 4.9; 95% CI, 2.6-8.5). No elevation of breast or ovarian cancer risk was observed among relatives of Asian probands. In general, there is a decrease in RR among mothers and sisters with increase in age of onset of probands. In second-degree relatives and first cousins, the breast cancer hazards ratios increase with increase in the number of affected first-degree relatives and decrease with increase in age at onset of the proband.

Adult↗
PubMed2000

Reiter's syndrome and reactive arthritis.

Reactive arthritis is an infection-induced systemic illness characterized by an inflammatory synovitis from which no viable microorganisms can be cultured. The paradigm of reactive arthritis is an infectious trigger that occurs in a genetically susceptible individual in whom the immune system continues to be stimulated or "react" to an ongoing or cleared infection, resulting in intermittent exacerbations of a variety of immune-mediated signs and symptoms. Although the terms Reiter's syndrome and reactive arthritis are sometimes used interchangeably, Reiter's syndrome is actually the complete clinical triad of urethritis, conjunctivitis, and arthritis. Some patients will never fulfill all three components of Reiter's triad, however, and although the term incomplete Reiter's syndrome is often used in such cases, the authors believe that the term reactive arthritis should be used, as it is less confusing and is inclusive of any extra-articular manifestations.

Arthritis, Reactive↗
PubMed2000

[Echocardiographic diagnosis of left intraventricular thrombi: contribution of high frequency probes].

Two-dimensional echocardiography is the reference technique for the diagnosis of left ventricular thrombi. However, it has some limitations due to poor imaging of the apex; location of many thrombi. Apical resolution improvement is possible using a 5 MHz ultrasonic transducer, which may identify 3.5MHz ultrasonic transducer false positive results. In a series of 53 patients with left ventricular dysfunction, we detected 11 thrombi. Using the 5MHz ultrasonic transducer as a reference the sensitivity of the 3.5MHz ultrasonic transducer was 100%, and much greater than that of the 2.5MHz ultrasonic transducer (55%), which was associated with 4 false positive results. The increased sensitivity associated with transducers of higher frequency was however limited by the echogenicity of patients, all the more since we used a medium instead of a short focalisation. Due to its therapeutic consequences, the detection of left ventricular thrombi must be enhanced using 5 MHz ultrasonic transducer, all the more in echogenic patients.

Echocardiography↗
PubMed2000

Radiology turf wars and antitrust law.

Nonradiologist health care providers have enjoyed the privilege of film interpretation without the assistance of radiologists. However, encroachment on the radiologist's turf of radiological image interpretation by nonradiologist physicians and radiographer technicians is reminiscent of recent antitrust battles between anesthesiologists and nurse anesthetists. Numerous antitrust issues are relevant to radiology; however, the scope of this article is limited to antitrust issues most relevant to radiology turf battles. Such battles often raise antitrust issues of group boycotts, tying arrangements, and exclusive contracts.

Antitrust Laws↗
PubMed2000

[Paralysing hypokalemic thyrotoxicosis].

Thyrotoxicosis is a rare cause of hypokalaemia. The clinical presentation associates signs of thyrotoxicosis which may be discrete, with severe hypokalaemia and peripheral muscular weakness with paralysis of the lower limbs. It is important not to miss this diagnosis because of the therapeutic implications. Treatment of this form of hypokalaemia is that of hyperthyroidism.

Adult↗
PubMed1999

Oligomerization state of MIP proteins expressed in Xenopus oocytes as revealed by freeze-fracture electron-microscopy analysis.

The MIP (major intrinsic protein) family is a widespread family of membrane proteins exhibiting two major types of channel properties: aquaporins and solute facilitators. In the present study, freeze-fracture electron microscopy was used to investigate the oligomerization state of two MIP proteins heterologously expressed in the plasma membrane of Xenopus laevis oocytes: AQPcic, an aquaporin from the insect Cicadella viridis, and GlpF, a glycerol facilitator from Escherichia coli. Swelling assays performed on oocytes 48 and 72 h following cRNA microinjections showed that these proteins were functionally expressed. Particle density determinations indicated that expression of proteins is related to an increase in particle density on the P fracture face of oocyte plasma membranes. Statistical analysis of particle sizes was performed on protoplasmic fracture faces of the plasma membrane of oocytes expressing AQPcic and GlpF 72 h after cRNA microinjections. Compared to control oocytes, AQPcic-expressing oocytes exhibited a specific population of particles with a mean diameter of 8.7 +/- 0.1 nm. This value is consistent with the previously reported tetrameric organization of AQPcic. In addition, AQPcic particles aggregate and form orthogonal arrays similar to those observed in native membranes of C. viridis, consisting of homotetramers of AQPcic. On the protoplasmic fracture face of oocytes expressing GlpF, the particle density is increased by 4.1-fold and the mean diameter of specifically added particles is 5.8 +/- 0.1 nm. This value fits with a monomer of the 28-kDa GlpF protein plus the platinum-carbon layer. These results clearly demonstrate that GlpF is a monomer when functionally expressed in plasma membranes of Xenopus oocytes and therefore emphasize the key role of the oligomerization state of MIP proteins with respect to their function.

Animals↗
PubMed1999

Conjugative plasmid transfer between Pseudomonas strains within alginate bead microcosms: effect of the internal gel structure.

Because microorganisms frequently live in an immobilized state in natural habitats, a cell-confined system was used to study bacterial conjugation. Two Pseudomonas putida strains were introduced together within calcium alginate gels. Different alginate beads were designed by varying the polysaccharide and the gelation solution concentrations. Microscopic examinations showed that 2% gels were quite homogeneous, but that 1.5% and 1% gels were rather heterogeneous. In these two last cases, shaft-shaped macrostructures were present. They were colonized during the culture by great densities of highly motile bacteria. Gene transfers due to conjugation were investigated in such alginate gel bead microcosms, in batch and continuous cultures. High-initial transfer frequencies were detected whatever the gel, but no conjugation events seemed to occur with further growth in the beads. Transfer frequency values were roughly similar in the different tested systems. Alginate gels used as artificial microcosms may be valuable to study the effect of cell microenvironment on genetic transfers in complex systems.

Alginates↗
PubMed1999

Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia.

BACKGROUND: L-asparaginase in combination with methotrexate has synergistic antileukemic activity in a schedule-dependent fashion. A new preparation of L-asparaginase, polyethylene-glycol conjugated (PEG)-asparaginase, is a pharmacologically different formulation of L-asparaginase with distinct properties including a longer half-life and less immunogenic properties. METHODS: Patients with refractory or recurrent acute lymphoblastic leukemia (ALL) were treated with a combination of methotrexate (MTX), vincristine, PEG-asparaginase, and prednisone (MOAP). The treatment was comprised of MTX, 100 mg/m(2) intravenously (i.v.), over 15 minutes on Days 1 and 14; PEG-asparaginase, 2500 IU/m(2), with a maximum dose of 3750 IU i.v. approximately 4-6 hours after MTX on Days 1 and 14; vincristine, 1.4 mg/m(2) (maximum dose, 2 mg) i.v., over 15 minutes on Days 1, 7, and 14; and prednisone, 200 mg daily orally, on Days 1-5 and 14-19. RESULTS: Thirty-two patients with a median age of 34 years (range, 20-74 years) were treated. Eight patients (25%) had ALL that was refractory to prior therapy and 24 patients (75%) had recurrent disease. Seven patients (22%) achieved a complete remission (CR). Five patients (16%) died early due to infections. Features associated with a poor response were high pretreatment lactate dehydrogenase levels and Philadelphia chromosome positive disease. The median duration of CR was 16 weeks and the overall median survival after MOAP therapy was 12 weeks. Anaphylactic reactions were not observed during MOAP combination therapy. CONCLUSIONS: MOAP is an active regimen in patients with refractory or recurrent ALL. This regimen is well tolerated and is not associated with allergic reactions. However, further studies regarding the pharmacologic interaction of MTX with PEG-asparaginase are needed to optimize this regimen.

Adult↗
PubMed1999

Transport of sulfonium compounds. Characterization of the s-adenosylmethionine and s-methylmethionine permeases from the yeast Saccharomyces cerevisiae.

We report here the characterization and the molecular analysis of the two high affinity permeases that mediate the transport of S-adenosylmethionine (AdoMet) and S-methylmethionine (SMM) across the plasma membrane of yeast cells. Mutant cells unable to use AdoMet as a sulfur source were first isolated and demonstrated to lack high affinity AdoMet transport capacities. Functional complementation cloning allowed us to identify the corresponding gene (SAM3), which encodes an integral membrane protein comprising 12 putative membrane spanning regions and belonging to the amino acid permease family. Among amino acid permease members, the closest relative of Sam3p is encoded by the YLL061w open reading frame. Disruption of YLL061w was shown to specifically lead to cells unable to use SMM as a sulfur source. Accordingly, transport assays demonstrated that YLL061w disruption mutation impaired the high affinity SMM permease, and YLL061w was therefore renamed MMP1. Further study of sam3Delta and mmp1Delta mutant cells showed that in addition to high affinity permeases, both sulfonium compounds are transported into yeast cells by low affinity transport systems that appear to be carrier-facilitated diffusion.

Amino Acid Sequence↗
PubMed1999

Chicken ovalbumin upstream promoter-transcription factor II, a new partner of the glucose response element of the L-type pyruvate kinase gene, acts as an inhibitor of the glucose response.

Transcription of the L-type pyruvate kinase (L-PK) gene is induced by glucose in the presence of insulin and repressed by glucagon via cyclic AMP. The DNA regulatory sequence responsible for mediating glucose and cyclic AMP responses, called glucose response element (GlRE), consists of two degenerated E boxes spaced by 5 base pairs and is able to bind basic helix-loop-helix/leucine zipper proteins, in particular the upstream stimulatory factors (USFs). From ex vivo and in vivo experiments, it appears that USFs are required for correct response of the L-PK gene to glucose, but their expression and binding activity are not known to be regulated by glucose. A genetic screen in yeast has allowed us to identify a novel transcriptional factor binding to the GlRE, i.e. the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII). Binding of COUP-TFII to the GlRE was confirmed by electrophoretic mobility shift assays, and COUP-TFII-containing complexes were detectable in liver nuclear extracts. Neither abundance nor binding activity of COUP-TFII appeared to be significantly regulated by diets. In footprinting experiments, two COUP-TFII-binding sites overlapping the E boxes were detected. Overexpression of COUP-TFII abrogated the USF-dependent transactivation of an artificial GlRE-dependent promoter in COS cells and the glucose responsiveness of the L-PK promoter in hepatocytes in primary culture. In addition, a mutated GlRE with increased affinity for USF and very low affinity for COUP-TFII conferred a dramatically decreased glucose responsiveness on the L-PK promoter in hepatocytes in primary culture by increasing activity of the reporter gene in low glucose condition. We propose that COUP-TFII could be a negative regulatory component of the glucose sensor complex assembled on the GlRE of the L-PK gene and most likely of other glucose-responsive genes as well.

Animals↗
PubMed1999

Deletion of protein kinase A phosphorylation sites in the HERG potassium channel inhibits activation shift by protein kinase A.

We investigated the role of protein kinase A (PKA) in regulation of the human ether-a-go-go-related gene (HERG) potassium channel activation. HERG clones with single mutations destroying one of four consensus PKA phosphorylation sites (S283A, S890A, T895A, S1137A), as well as one clone carrying all mutations with no PKA phosphorylation sites (HERG 4M) were constructed. These clones were expressed heterologously in Xenopus oocytes, and HERG potassium currents were measured with the two microelectrode voltage clamp technique. Application of the cAMP-specific phosphodiesterase (PDE IV) inhibitor Ro-20-1724 (100 microM), which results in an increased cAMP level and PKA stimulation, induced a reduction of HERG wild type outward currents by 19.1% due to a shift in the activation curve of 12.4 mV. When 100 microM Ro-20-1724 was applied to the HERG 4M channel, missing all PKA sites, there was no significant shift in the activation curve, and the current amplitude was not reduced. Furthermore, the adenylate cyclase activator forskolin that leads to PKA activation (400 microM, 60 min), shifted HERG wild type channel activation by 14.1 mV and reduced currents by 39.9%, whereas HERG 4M channels showed only a small shift of 4.3 mV and a weaker current reduction of 22.3%. We conclude that PKA regulates HERG channel activation, and direct phosphorylation of the HERG channel protein has a functional role that may be important in regulation of cardiac repolarization.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1999

Measles virus infection in a transgenic model: virus-induced immunosuppression and central nervous system disease.

Measles virus (MV) infects 40 million persons and kills one million per year primarily by suppressing the immune system and afflicting the central nervous system (CNS). The lack of a suitable small animal model has impeded progress of understanding how MV causes disease and the development of novel therapies and improved vaccines. We tested a transgenic mouse line in which expression of the MV receptor CD46 closely mimicked the location and amount of CD46 found in humans. Virus replicated in and was recovered from these animals' immune systems and was associated with suppression of humoral and cellular immune responses. Infectious virus was recovered from the CNS, replicated primarily in neurons, and spread to distal sites presumably by fast axonal transport. Thus, a small animal model is available for analysis of MV pathogenesis.

Animals↗
PubMed1999

Prospective study of HTLV-I infection in an initially asymptomatic cohort.

A prospective clinical study of 20 initially asymptomatic HTLV-I-seropositive carriers was commenced in 1991 to determine the natural history of the infection in relation to HTLV-I proviral load, immune responses, and lymphocyte phenotype. Proviral load varied widely between carriers but was relatively constant within an individual over time. The lymphocyte phenotype and prevalence of activated lymphocytes were not predictive of disease and the magnitude of the cytotoxic T-lymphocyte response to HTLV-I was independent of proviral load. Incident conditions, some related to HTLV-I infection, including a case of HTLV-I-associated myelopathy (HAM), were documented in 9 carriers. Development of myelopathy and uveitis was associated with high peripheral blood HTLV-I proviral load that predated symptoms. Persistently high proviral load appears to predate the development of HTLV-I-associated inflammation in neuro-ophthalmic tissue.

Adult↗
PubMed1999

An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation.

Invasive breast cancer cells have the ability to extend membrane protrusions, invadopodia, into the extracellular matrix (ECM). These structures are associated with sites of active matrix degradation. The amount of matrix degradation associated with the activity of these membrane protrusions has been shown to directly correlate with invasive potential. We demonstrate here that microinjection of polyclonal anti-cortactin antibodies blocks matrix degradation at invadopodia supporting the hypothesis that cortactin has a direct role in invasive behavior. MDA-MB-231, invasive breast cancer cells were sheared from the surface of a gelatin matrix to isolate invadopodia. Cortactin, paxillin and protein kinase C (PKC) mu, a serine kinase, were co-immunoprecipitated as a complex from invadopodia-enriched membranes. We confirmed the subcellular distribution of these proteins by immunolocalization and Western blotting. We also determined that, in contrast to its presence in invasive cells, this complex of proteins was not detected in lysates from non-invasive cells that do not form invadopodia. Taken together, these data suggest that the formation of this cortactin-containing complex correlates with cellular invasiveness. We hypothesize that this complex of molecules has a role in the formation and function of invadopodia during cellular invasion.

Actins↗
PubMed1999

Efficiency of physical (light) or chemical (ABA, tetracycline, CuSO4 or 2-CBSU)-stimulus-dependent gus gene expression in tobacco cell suspensions.

In this study, the efficiency of inducible promoters to switch on gene expression in the presence of inducer or to switch it off in its absence was evaluated in tobacco cell suspensions transformed with the gus gene coding sequence. Either plant (pats1A, pSalT, pIn2-2) or microbial (pMre, pTet) inducible promoters were used to drive gus expression. The inducers were light, abscisic acid, 2-CBSU, CuSO4, tetracycline, respectively. For each construct (inducible promoter-gus coding sequence), the optimal induction conditions were determined (inducer concentration, induction time, and age of cells in culture cycle before induction). The efficiency of the inducible promoter was then evaluated under optimal induction conditions. GUS-expression levels obtained under non-inducing and inducing conditions were systematically compared. Thirty or forty percent of the clones transformed with the pSalT-gus or pTet-gus construct, respectively, showed high induction rates (>1000) and GUS activities of the same order as those obtained with a constitutive system. However, basal GUS levels were always high for the pTet-gus cell lines. Seventy or eighty-five percent of the cell lines transformed with the pMre-gus or pln2-2-gus construct, respectively, had induction rates of 1.5 to 1000. The pats1A-gus construct gave very low induction rates-55% of cell lines had induction rates less than 1.5. Only the pSalt-gus construct gave both the highest induction rates and basal GUS-levels equivalent to the endogenous GUS background.

Abscisic Acid↗