Search PubMed⌕ Search

Biomedical subjects

T Thomas

Publications and source records attributed to T Thomas.

At least 73 records · Page 4Linked to original sources
PubMed2000

Failure-free survival following brachytherapy alone or external beam irradiation alone for T1-2 prostate tumors in 2222 patients: results from a single practice.

PURPOSE: To evaluate failure-free survival (FFS) for brachytherapy (BT) alone compared to external beam radiotherapy (EBRT) alone for Stage T1-2 Nx-No Mo patients over the same time period by a single community-based practice in the prostate-specific antigen (PSA) era. MATERIALS AND METHODS: The database of Arizona Oncology Services (a multiphysician radiation oncology practice in the Phoenix metropolitan area) was reviewed for patients meeting the following criteria: (1) T1 or T2 Nx-No Mo prostate cancer; (2) no prior or concurrent therapy including hormones; (3) treatment period 12/88-12/95; and (4) treatment with either EBRT alone or BT alone ((125)I or (103)Pd). This yielded 1527 EBRT and 695 BT patients; no patients meeting the above criteria were excluded from analysis. Median follow-up for EBRT patients was 41.3 months and, for BT patients, 51.3 months. Patients were not randomized to either therapy but rather received EBRT or BT based upon patient, treating, and/or referring physician preference. PSA failure was defined according to the ASTRO consensus guidelines. The median patient age was 74 years for both groups. RESULTS: Failure-free survival at 5 years for EBRT and BT are 69% and 71%, respectively (p = 0.91). For T stage, no significant difference in FFS at 5 years is observed between EBRT and BT for either T1 (78% vs. 83%, p = 0.47) or T2 (67% vs. 67%, p = 0.89) tumors. Analysis by Gleason score shows superior outcomes for Gleason 8-10 lesions treated with EBRT vs. BT (5-year FFS 52% vs. 28%, p = 0.04); outcomes for lower grade lesions (Gleason 4-6) when analyzed by Gleason score alone do not significantly differ according to treatment received. Patients with initial PSA values of 10-20 ng/dL have an improved FFS with EBRT vs. BT at 5 years (70% vs. 53%, p = 0.001); outcomes for patients with initial PSA ranges of 0-4 ng/dL, of > 4-10 ng/dL, and > 20 ng/dL did not differ significantly by treatment received. FFS was also determined for presenting Gleason score/PSA combinations; all Gleason combinations in the initial PSA range >10-20 ng/dL had superior outcomes with EBRT compared to BT, and this reached statistical significance for Gleason scores of 2-4 (72% vs. 58%, p = 0.026), Gleason 7 (67% vs. 28%, p = 0.002), and Gleason 8-10 (63% vs. 23%, p = 0.05). CONCLUSION: In our patient population, either EBRT or BT appear equally efficacious for patients with T1/T2 disease with Gleason scores </= 6 or PSA </= 10 ng/dL. Patients with presenting Gleason scores of 8-10 or PSA > 10 ng/dL (but </= 20 ng/dL) appear to fare significantly worse with BT alone compared to EBRT alone. Neither EBRT nor BT alone was particularly effective for patients with a presenting PSA > 20 ng/dL, as would be anticipated from the significant risks of occult distant metastasis in this group. To our knowledge, this is the first report comparing the outcome of EBRT and BT treatment in patients treated concurrently by a single group, and these results, achieved in a community-based practice, compare favorably to data from academic centers regarding external beam, brachytherapy, or surgical outcomes and should be generalizable to the community at large.

Aged↗
PubMed2000

Sensing arterial CO(2) levels: a role for medullary P2X receptors.

ATP has been shown to act as an excitatory neurotransmitter in the central nervous system. In this review, evidence is presented to indicate that when ATP is micro-injected into the ventrolateral medulla (VLM) of the rat, changes in respiratory activity are elicited. These effects, and accompanying changes in heart rate and blood pressure are mediated by P2X purinoreceptors. Immunocytochemistry indicates a prevalence of P2X(2) and P2X(6) purinoreceptors in this region of the medulla. The P2 purinoceptor antagonists, suramin and PPADS blunt the respiratory responses to changes in arterial CO(2) levels when micro-injected into the VLM. This effect is shown electrophysiologically to be mediated by purinoreceptors located primarily on respiratory neurones of the VLM including the Bötzinger complex. As the effects of agonist activation of P2X(2) purinoceptors expressed in HEK293 cells and Xenopus oocytes are potentiated by lowering pH, these data imply that the central respiratory response to CO(2) depends in part on the pH sensitivity of purinoreceptors located on inspiratory neurones. The implications for respiratory activity and control are discussed.

Adenosine Triphosphate↗
PubMed2000

Coexpression of rat P2X2 and P2X6 subunits in Xenopus oocytes.

Transcripts for P2X(2) and P2X(6) subunits are present in rat CNS and frequently colocalize in the same brainstem nuclei. When rat P2X(2) (rP2X(2)) and rat P2X(6) (rP2X(6)) receptors were expressed individually in Xenopus oocytes and studied under voltage-clamp conditions, only homomeric rP2X(2) receptors were fully functional and gave rise to large inward currents (2-3 microA) to extracellular ATP. Coexpression of rP2X(2) and rP2X(6) subunits in Xenopus oocytes resulted in a heteromeric rP2X(2/6) receptor, which showed a significantly different phenotype from the wild-type rP2X(2) receptor. Differences included reduction in agonist potencies and, in some cases (e.g., Ap(4)A), significant loss of agonist activity. ATP-evoked inward currents were biphasic at the heteromeric rP2X(2/6) receptor, particularly when Zn(2+) ions were present or extracellular pH was lowered. The pH range was narrower for H(+) enhancement of ATP responses at the heteromeric rP2X(2/6) receptor. Also, H(+) ions inhibited ATP responses at low pH levels (<pH 6.3). The pH-dependent blocking activity of suramin was changed at this heteromeric receptor, although the potentiating effect of Zn(2+) on ATP responses was unchanged. Thus, the rP2X(2/6) receptor is a functionally modified P2X(2)-like receptor with a distinct pattern of pH modulation of ATP activation and suramin blockade. Although homomeric P2X(6) receptors function poorly, the P2X(6) subunit can contribute to functional heteromeric P2X channels and may influence the phenotype of native P2X receptors in those cells in which it is expressed.

Adenosine Triphosphate↗
PubMed2000

Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts.

BACKGROUND: Microgravity has been thought to induce osteoporosis because of reduced weight-bearing. However, up to now, few data have been available about its precise nature and timecourse. METHODS: We measured bone mineral density (BMD) at the distal radius and tibia in 15 cosmonauts of the Russian MIR space station who sojourned in space either 1 (n=two), 2 (two), or 6 months (11). After recovery periods of similar duration to the space missions, BMD was measured for the 2-month and 6-month crews. FINDINGS: Neither cancellous nor cortical bone of the radius was significantly changed at any of the timepoints. On the contrary, in the weight-bearing tibial site, cancellous BMD loss was already present after the first month and deteriorated with mission duration. In tibial cortices, bone loss was noted after a 2-month flight. In the 6-month group, cortical bone loss was less pronounced than that for cancellous bone. In some individuals, tibial deterioration was great. Actual BMD did not depend on preceding cumulative periods spent in space. During recovery, tibial bone loss persisted, suggesting that the time needed to recover is longer than the mission duration. INTERPRETATION: In space, despite physical training, bone loss is an adaptive process that can become pathological after recovery on Earth. Striking interindividual variations in bone responses seem to suggest a need for adequate crew preselection. Targeted treatment or prevention strategies would be useful, not only for space purposes, but also for the increasing number of osteoporotic patients on Earth.

Adult↗
PubMed2000

Low temperature regulated DEAD-box RNA helicase from the Antarctic archaeon, Methanococcoides burtonii.

DEAD-box RNA helicases, by unwinding duplex RNA in bacteria and eukaryotes, are involved in essential cellular processes, including translation initiation and ribosome biogenesis, and have recently been implicated in enabling bacteria to survive cold-shock and grow at low temperature. Despite these critical physiological roles, they have not been characterized in archaea. Due to their presumed importance in removing cold-stabilised secondary structures in mRNA, we have characterised a putative DEAD-box RNA helicase gene (deaD) from the Antarctic methanogen, Methanococcoides burtonii. The encoded protein, DeaD is predicted to contain a core element involved in ATP hydrolysis and RNA-binding, and an unusual C-terminal domain that contains seven perfect, trideca-peptide, direct repeats that may be involved in RNA binding. Alignment and phylogenetic analyses were performed on the core regions of the M. burtonii and other DEAD-box RNA helicases. These revealed a loose but consistent clustering of archaeal and bacterial sequences and enabled the generation of a prokaryotic-specific consensus sequence. The consensus highlights the importance of residues other than the eight motifs that are often associated with DEAD-box RNA helicases, as well as de-emphasising the importance of the "A" residue within the "DEAD" motif. Cells growing at 4 degrees C contained abundant levels of deaD mRNA, however no mRNA was detected in cells growing at 23 degrees C (the optimal temperature for growth). The transcription initiation site was mapped downstream from an archaeal box-A element (TATA box), which preceded a long (113 nucleotides) 5'-untranslated region (5'-UTR). Within the 5'-UTR was an 11 bp sequence that closely matches (nine out of 11) cold-box elements that are present in the 5'-UTRs of cold-shock induced genes from bacteria. To determine if the archaeal 5'-UTR performs an analagous function to the bacterial 5'-UTRs, the archaeal deaD 5'-UTR was transcribed in E. coli under the control of the cspA promoter and transcriptional terminator. It has previously been reported that overexpression of the cspA 5'-UTR leads to an extended cold-shock response due to the 5'-UTR titrating cellular levels of a cold-shock repressor protein(s). In our hands, the cold-shock protein profiles resulting from overexpression of Escherichia coli cspA and M. burtonii deaD 5'-UTRs were similar, however they did not differ from those for the overexpression of a control plasmid lacking a 5'-UTR. In association with other recent data from E. coli, our results indicate that the role of the 5'-UTR in gene regulation is presently unclear. Irrespective of the mechanisms, it is striking that highly similar 5'-UTRs with cold-box elements are present in cold induced genes from E. coli, Anabaena and M. burtonii. This is the first study examining low temperature regulation in archaea and provides initial evidence that gene expression from a cold adapted archaeon involves a bacterial-like transcriptional regulatory mechanism. In addition, it provides the foundation for further studies into the function and regulation of DEAD-box RNA helicases in archaea, and in particular, their roles in low temperature adaptation.

5' Untranslated Regions↗
PubMed2000

ATP as a mediator of mammalian central CO2 chemoreception.

1. A role for P2 purinoceptors in the chemosensory response of respiratory neurones localised in the ventrolateral medulla to changes in arterial CO2 levels was investigated in the anaesthetised rat. Extracellular recordings were made from different classes of respiratory neurone and the effects of P2 receptor blockade on CO2-evoked changes in activity investigated. 2. Increasing inspired CO2 excited 85 % of inspiratory neurones in the pre-Botzinger complex. In all cases, CO2-evoked excitation was blocked by ionophoretic application of the P2 receptor antagonists suramin (0.02 M) and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 100 microM), but not the adenosine receptor antagonist 8-phenyltheophylline (8-PT; 100 microM). Suramin and PPADS often reduced ongoing activity, and blocked the excitatory effects of ATP. Inspiratory neurones were also excited by the P2X receptor agonist alphabeta-methyleneATP, suggesting a specific role for P2X receptors. 3. Sixty-six per cent of pre-inspiratory neurones were also excited by CO2. This effect was reduced or abolished by prior application of P2 receptor antagonists. Although post-inspiratory and expiratory neurones were excited by increasing levels of CO2, and also by ionophoretically applied ATP, the CO2-evoked effects were unaffected by P2 receptor blockade. 4. We suggest that ATP, possibly acting via P2X purinoceptors localised within the ventral respiratory group, is involved in central chemoreception. Specifically, these distinctive CO2-P2X-mediated actions were observed only in inspiratory neurones (incrementing inspiratory neurones and pre-inspiratory neurones), which appear to have purinoceptors with pH sensitivity that can account for the actions of CO2 in modifying ventilatory activity.

Adenosine Triphosphate↗
PubMed2000

Muscle-specific transcriptional regulation of the slowpoke Ca(2+)-activated K(+) channel gene.

Transcriptional regulation of the Drosophila slowpoke calcium-activated potassium channel gene is complex. To date, five transcriptional promoters have been identified, which are responsible for slowpoke expression in neurons, midgut cells, tracheal cells, and muscle fibers. The slowpoke promoter called Promoter C2 is active in muscles and tracheal cells. To identify sequences that activate Promoter C2 in specific cell types, we introduced small deletions into the slowpoke transcriptional control region. Using transformed flies, we asked how these deletions affected the in situ tissue-specific pattern of expression. Sequence comparisons between evolutionarily divergent species helped guide the placement of these deletions. A section of DNA important for expression in all cell types was subdivided and reintroduced into the mutated control region, a piece at a time, to identify which portion was required for promoter activity. We identified 55-, 214-, and 20-nucleotide sequences that control promoter activity. Different combinations of these elements activate the promoter in adult muscle, larval muscle, and tracheal cells.

Animals↗
PubMed2000

Structural analysis of the elongation factor G protein from the low-temperature-adapted bacterium Arthrobacter globiformis SI55.

The first structural analysis of elongation factor G (EF-G) from a cold-adapted bacterium is presented. EF-G is an essential protein involved in the elongation process during protein synthesis and is therefore thought to play a crucial role in the low-temperature adaptation of cold-adapted microorganisms. To define its importance, the EF-G gene (fus) from the psychrotolerant bacterium Arthrobacter globiformis SI55 was cloned and sequenced. The deduced primary structure of the elongation factor is composed of 700 amino acids with a predicted molecular mass of 77.4 kDa. A three-dimensional model of the protein was constructed based on the known crystal structures of structurally homologous proteins. Structural features that might potentially be important for activity and flexibility at low temperature were deduced by comparisons with models of the EF-G proteins from the closely related mesophiles Micrococcus luteus and Mycobacterium tuberculosis. These features include a loss in the number of salt bridges in intradomain and interdomain positions, increased solvent interactions mediated by greater charge and polarity on domain surfaces, loop insertions, loss of proline residues in loop structures, and an increase of hydrophobicity in core regions. Specific changes have also been identified in the catalytic domain (G domain) and sites of potential ribosome interaction, which may directly affect guanosine triphosphate (GTP) hydrolysis and elongation rates at low temperature.

Amino Acid Sequence↗
PubMed2000

Cold stress response in Archaea.

We live on a cold planet where more than 80% of the biosphere is permanently below 5 degrees C, and yet comparatively little is known about the genetics and physiology of the microorganisms inhabiting these environments. Based on molecular probe and sequencing studies, it is clear that Archaea are numerically abundant in diverse low-temperature environments throughout the globe. In addition, non-low-temperature-adapted Archaea are commonly exposed to sudden decreases in temperature, as are other microorganisms, animals, and plants. Considering their ubiquity in nature, it is perhaps surprising to find that there is such a lack of knowledge regarding low-temperature adaptation mechanisms in Archaea, particularly in comparison to what is known about archaeal thermophiles and hyperthermophiles and responses to heat shock. This review covers what is presently known about adaptation to cold shock and growth at low temperature, with a particular focus on Antarctic Archaea. The review highlights the similarities and differences that exist between Archaea and Bacteria and eukaryotes, and addresses the potentially important role that protein synthesis plays in adaptation to the cold. By reviewing the present state of the field, a number of important areas for future research are identified.

Adaptation, Physiological↗
PubMed2000

Localization and action of adenosine A2a receptors in regions of the brainstem important in cardiovascular control.

In vitro autoradiography and central microinjections of a P1 adenosine A2a receptor antagonist have been employed to investigate a possible role for centrally located adenosine A2a receptors in modulation of the baroreceptor reflex. In vitro autoradiography using [125I]4-(2-[7-amino-2-[2-furyl][3,2,4]triazolol[2,3-a][1,3,5]tr iazin-5-yl-amino]ethyl)phenol ([125I]ZM241385), the high-affinity adenosine A2a receptor antagonist, revealed a heterogeneous distribution of adenosine A2a binding sites within the lower brainstem of the rat. Image analysis showed high levels of binding in rostral regions of both the nucleus tractus solitarius and the ventrolateral medulla. Intermediate levels of binding were observed in the commissural nucleus tractus solitarius and the dorsal vagal motor nucleus, with low levels of binding in caudal regions of the nucleus tractus solitarius and the ventrolateral medulla, and the hypoglossal nucleus. Unilateral microinjections of unlabelled ZM241385 into the nucleus tractus solitarius had no effect on baseline levels of arterial pressure, heart rate and phrenic nerve activity recorded in anaesthetized, artificially ventilated rats. However, microinjections of ZM241385 reduced the bradycardia evoked by stimulation of the ipsilateral aortic nerve. In contrast, ZM241385 had no effect on the depressor response or the reduction in phrenic nerve activity evoked by aortic nerve stimulation. Our results indicate that adenosine A2a binding sites are located in a number of brainstem regions involved in autonomic function, consistent with the idea that adenosine acts as a neuromodulator of a variety of cardiorespiratory reflexes. Specifically, the data support the hypothesis that adenosine A2a receptors located within the nucleus tractus solitarius are activated during baroreceptor stimulation and have an important modulatory role in the pattern of cardiovascular changes associated with this reflex.

Adenosine↗
PubMed2000

The intravenous use of coconut water.

Medical resources routinely used for intravenous hydration and resuscitation of critically ill patients may be limited in remote regions of the world. When faced with these shortages, physicians have had to improvise with the available resources, or simply do without. We report the successful use of coconut water as a short-term intravenous hydration fluid for a Solomon Island patient, a laboratory analysis of the local coconuts, and a review of previously documented intravenous coconut use.

Cocos↗
PubMed2000

Self-assembly of an oligodeoxyribonucleotide harboring the estrogen response element in the presence of polyamines: ionic, structural, and DNA sequence specificity effects.

Estrogenic regulation of gene expression is mediated by the binding of the hormone to its specific receptor, estrogen receptor (ER), which undergoes structural and conformational alterations to recognize specific DNA sequences, estrogen response elements (ERE), in responsive genes to trigger a series of events culminating in the transcription of these genes. Polyamines are ubiquitous cellular cations that are important for cell growth and differentiation, and have been shown to participate in estrogenic regulation of gene expression. Polyamine-mediated DNA condensation/aggregation has been studied to understand the ionic and structural requirements for the compaction of DNA. DNA condensation/decondensation may also play a role in transcription and replication. We studied the aggregation of a 38-mer oligonucleotide duplex (ODN) in the presence of natural and synthetic polyamines under different ionic conditions (NaCl, KCl, and K glutamate). Our results showed that an ODN harboring the consensus ERE (ODN1) was 2-fold more susceptible to precipitation by spermine compared to ODN2 containing scrambled sequences, or a mutant ODN (ODN3). The nature of the monovalent cations (Na+ vs K+), and anions (Cl- vs glutamate) also played an important role in the efficacy of a polyamine to precipitate ODNs: potassium glutamate being the least effective in suppressing the ability of spermine to precipitate ODNs. The concentration of polyamines required for precipitating the ODNs increased with monovalent ion concentration in the buffer. With ODN1, a plot of log[spermine4+] at the 50% precipitation concentrations against log[Na+/K+] yielded a straight line, with a slope of 1.8 +/- 0.18, a value comparable to that predicted by the counterion condensation theory (1.85). We also observed significant structural specificity effects of spermine and its analogues [NH2(CH2)3NH(CH2)nNH(CH2)3NH2, where n = 2-9; n = 4 for spermine] on aggregating the ODN1. These results demonstrate DNA sequence and polyamine structural specificity effects on the aggregation of ODNs, and suggest that the gene regulatory function of ERE may be linked to its ability to undergo facile condensation/decondensation in the presence of biological cations, such as polyamines.

Base Sequence↗
PubMed2000

A new gene trap construct enriching for insertion events near the 5' end of genes.

The gene trap approach is based on the integration of a gene trap vector into the genome. This can be done either by electroporation of a plasmid construct or by infection with a viral vector. Commonly used viral gene trap vectors have been shown to select for integrations near the 5' end of genes. To date, no plasmid vector with a similar tendency has been reported. In this paper we describe a new plasmid vector, pKC199beta geo. This vector contained a short splice acceptor fragment from the Hoxc9 gene, a full length lacZ gene, including an ATG, and a reduced activity, mutant neomycin phosphotransferase gene as a selectable marker. This vector enriched the population of trapped genes in our gene trap screen for insertion events in the 5' end of genes. In the two cases examined the beta-galactosidase activity pattern accurately reflected the endogenous promotor activity.

Animals↗
PubMed2000

Phylogenetic relationship and antifouling activity of bacterial epiphytes from the marine alga Ulva lactuca.

It is widely accepted that bacterial epiphytes can inhibit the colonization of surfaces by common fouling organisms. However, little information is available regarding the diversity and properties of these antifouling bacteria. This study assessed the antifouling traits of five epiphytes of the common green alga, Ulva lactuca. All isolates were capable of preventing the settlement of invertebrate larvae and germination of algal spores. Three of the isolates also inhibited the growth of a variety of bacteria and fungi. Their phylogenetic positions were determined by 16S ribosomal subunit DNA sequencing. All isolates showed a close affiliation with the genus Pseudoalteromonas and, in particular, with the species P. tunicata. Strains of this bacterial species also display a variety of antifouling activities, suggesting that antifouling ability may be an important trait for members of this genus to be highly successful colonizers of animate surfaces and for such species to protect their host against fouling.

Animals↗
PubMed2000

Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.

Whether the higher serum leptin levels in women are due to gender differences in fat mass or to other factors such as sex steroids remains unclear. In addition to sex steroids, serum insulin levels also appear to be related to leptin levels, although whether this effect is independent of the effects of body composition is unclear. The purpose of this study was to identify the major determinants of circulating serum leptin levels. We studied a large, population-based cohort of 345 men (23 to 90 years), 137 premenopausal women (21 to 54 years), and 212 postmenopausal women (34 to 94 years), including 47 women on hormone replacement therapy (HRT). Serum leptin levels were related to body composition as assessed by dual-energy x-ray absorptiometry (DEXA) and to circulating sex steroid and insulin levels. Serum leptin levels remained significantly higher in women versus men even after adjustment for fat mass, and leptin levels were significantly correlated with fat mass independently of age. By univariate analyses, logarithmically transformed serum leptin levels correlated positively with bioavailable estrogen ([E] estradiol plus estrone) in postmenopausal women not on HRT, and negatively with total and bioavailable testosterone (T) levels in men. Serum insulin levels were directly related to leptin levels regardless of gender and age. By multivariate analyses, fat mass, lean mass, and insulin levels were the strongest predictors of leptin levels in all groups. In addition, bioavailable E entered the model in the postmenopausal women not on HRT. These studies indicate that the fat mass, lean mass, and insulin level are the major determinants of the serum leptin level in adults. Moreover, after adjusting for these variables, bioavailable E also explains a significant proportion of the variance in leptin levels among postmenopausal women not on HRT.

Adult↗
PubMed2000

Cell separation improves the sensitivity of detecting rare human normal and leukemic hematopoietic cells in vivo in NOD/SCID mice.

BACKGROUND: This report describes a novel cell-separation procedure developed to improve detection and analysis of rare human hematopoietic populations, obtained from NOD/SCID mice engrafted with normal and/or leukemic stem cells. METHODS: In preliminary experiments, artificial mixtures of murine and human BM cells were labeled with a combination of Abs specific for murine hematopoietic cells, prior to immunomagnetic negative selection using StemSep. In subsequent experiments, BM was harvested from individual NOD/SCID mice transplanted 6-12 weeks earlier with either human cord blood or primary CML cells and a similar immunomagnetic selection procedure was applied to enrich human cells present. RESULTS: Application of this selection procedure to mixtures of murine and human hematopoietic cells using anti-mouse CD45 and Ter-119 allowed a > 1000-fold depletion of murine cells with > 50% recovery of human cells, including progenitors. This level of depletion and recovery were found to be reproducible for NOD/SCID mice transplanted and engrafted with human cord blood stem cells, thus facilitating detection of human progenitors, including colony-forming cells (CFC) and LTCIC. For NOD/SCID mice previously transplanted with CML cells, this procedure increased the sensitivity of detecting rare human cell subsets by up to > 100-fold. This, in turn, improved the sensitivity of RT-PCR for BCR-ABL and made possible the identification by FACS of various minor subsets of human cells, including CD34(-)CD19/20(+) B-lineage cells, CD34(+) progenitors, mature CD15(+) myeloid cells and CD3(+) T cells present in the mice. DISCUSSION: This simple cell-depletion procedure should facilitate future investigations of normal and CML stem cell populations in vitro and in NOD/SCID mice.

Animals↗
PubMed2000

Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver.

Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.

Aldehyde Reductase↗