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Biomedical subjects

M J Thomas

Publications and source records attributed to M J Thomas.

At least 73 records · Page 4Linked to original sources
PubMed1997

Blood transfusion in disasters, war, and emergencies.

Historically, the needs of those wounded in war have led to many major advances in blood transfusion. The most important of these is probably the ability to draw blood in one location and transfuse it, at a later time, in a distant location. Another important lesson is the need for meticulous planning. Every hospital and blood center should have a disaster plan consisting of five components. What fluids to use, from where are they to be obtained, to what degree are they to be tested, how will they be transported to the disaster scene, and, once there, how will they be stored. Once drawn up, this plan must be regularly exercised and periodically revised. This will ensure rapid and efficient implementation when an emergency arises. Triage is vital in mass casualty situations, ensuring that scarce resources are used for those with the best chance of recovery. Although patients survive with low hemoglobin levels for considerable periods, speedy treatment of hypovolemia is imperative. When perflourochemicals and hemoglobin solutions are available for general clinical use, they will have a major role to play in disasters. Similarly, a simple method for the cryopreservation of red cells will allow stockpiles to be established. Unfortunately, none of these are presently available, although some are undergoing clinical trials.

Blood Preservation↗
PubMed1997

Effects of leptin on insulin sensitivity in normal rats.

To determine whether leptin has insulin sensitizing effects in normal rodents, we measured plasma glucose and insulin concentrations in male Sprague-Dawley rats treated with leptin or vehicle by continuous s.c. infusion for 48 h. In additional experiments, we examined the acute effect of i.v. leptin upon insulin sensitivity under conditions of clamped glycemia. Subcutaneous leptin was administered at 10.0 and 1.0 microg/h. To avoid confounding effects of differences in food intake, both leptin- and vehicle-treated rats were fasted during the 48-h period of infusion. Infusion of leptin, 10 microg/h, significantly reduced both plasma glucose and insulin. Leptin, 1.0 microg/h, also decreased plasma glucose and insulin, although the effects on insulin did not achieve statistical significance. Leptin at either dose did not alter body weight or epididymal fat mass compared with vehicle treated controls. Leptin, 10 microg/h, decreased circulating insulin-like growth factor-1 levels. No differences in GLUT-4 content in either in brown or epididymal fat were observed as a result of leptin-treatment. Leptin, 10 microg/h, significantly decreased urine osmolality, increased water intake, and reduced renal potassium excretion compared with vehicle-infused rats. In additional rats, we measured the acute effect of i.v. leptin on insulin sensitivity determined as whole body glucose utilization during hyperinsulinemic glucose clamps performed at glucose targets of 60 and 90 mg/100 ml. Glucose utilization was increased by 29% during the last 135 min of glycemia clamped at 60 mg/100 ml (P < 0.05) and by 30% during the last 135 min of glycemia clamped at 90 mg/dl (P < 0.01) in rats infused with leptin compared with vehicle. In summary, leptin increased insulin sensitivity in normal rats both under fasting conditions and in the presence of hyperinsulinemia at clamped glucose. These effects did not appear dependent on altered body weight. Leptin also altered salt and water metabolism under fasting conditions resulting in increased water intake and more dilute urine.

Adipose Tissue, Brown↗
PubMed1997

Short-term insulin therapy and normoglycemia. Effects on erythrocyte lipid peroxidation in NIDDM patients.

OBJECTIVE: To evaluate erythrocyte lipid peroxidation (LPO) before and after an adaptive short-term insulin therapy in NIDDM patients who were chronically hyperglycemic. RESEARCH DESIGN AND METHODS: Twenty-six patients with NIDDM (mean HbA1c, 11.28%) aged 53.04 +/- 2.03 years were submitted for 3 days to constant intravenous glucose and continuous insulin perfusion at an adaptable rate to maintain glycemia within the normal range. An evaluation of LPO at baseline and after euglycemic insulin therapy was determined by erythrocyte free and total malondialdehyde (MDA) levels, polyunsaturated fatty acid (PUFA) percentage, vitamin E and glutathione content, and the following antioxidant enzymatic activity determinations: glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). Fasting serum glucose, HbA1c, triglycerides, cholesterol, and HDL cholesterol levels were also determined at these time points. RESULTS: At baseline, erythrocyte free and total MDA were significantly higher in NIDDM patients than in control subjects (11.14 +/- 0.80 vs. 1.74 +/- 0.11 nmol/g Hb [P < 0.0001] for free MDA; 18.04 +/- 1.79 vs. 7.85 +/- 0.55 nmol/g Hb [P < 0.0001] for total MDA). PUFAs, particularly C20:4 and C22:5, were increased (14.69 +/- 0.34 vs. 12.03 +/- 0.31 and 2.31 +/- 0.04 vs. 1.71 +/- 0.03% of total fatty acids, respectively). Vitamin E and glutathione were reduced significantly (6.16 +/- 0.61 vs. 14.84 +/- 0.64 nmol/g Hb and 0.42 +/- 0.04 vs. 0.97 +/- 0.06 mmol/l, respectively). No difference was observed for the enzymatic activities. After euglycemic insulin therapy, triglycerides significantly decreased compared with baseline concentrations (1.55 +/- 0.13 vs. 2.42 +/- 0.22 mmol/l; P < 0.001), whereas other lipidic parameters were unchanged. Free MDA significantly decreased (8.60 +/- 0.76 vs. 11.14 +/- 0.80 nmol/g Hb [P < 0.01]), while vitamin E increased (7.93 +/- 0.73 vs. 6.16 +/- 0.61 nmol/g Hb [P < 0.05]). No difference was observed for PUFAs, glutathione, or total MDA. CONCLUSIONS: The observed erythrocyte LPO in NIDDM decreased after a short-term adaptive insulin therapy. This decrease could be principally attributed to the normalized glycemia that reduces reactive oxygen species (ROS) production, which in turn may explain the increase in erythrocyte membrane vitamin E and the decrease in MDA. This study shows the value of a euglycemic environment in NIDDM to reduce LPO and, at long range, to minimize clinical diabetes complications.

Adult↗
PubMed1997

Effect of porcine somatotropin administration in young pigs during the growth phase from 10 to 25 kilograms.

We conducted two experiments to determine the efficacy of exogenous porcine somatotropin (pST) on enhancing performance during an early phase of growth (10 kg initial BW) when pigs are already growing efficiently and have high rates of lean deposition and low rates of lipid deposition. In Exp. 1, performance was measured on 45 barrows that received one of five daily doses (0, 50, 100, 150 and 200 microg/kg BW) of recombinant pST. In Exp. 2, 27 barrows were used in a slaughter-balance study in which two groups received daily either buffer (control) or 120 microg/kg BW of pST and the third group was slaughtered for initial body composition. In both experiments, pigs received daily i.m. injections of their respective dose for 20 d. The diet was fed for ad libitum consumption and calculated to contain 3.5 Mcal DE/kg, 22.3% CP, and 1.5% lysine. Administration of pST failed to alter overall growth rate or efficiency of gain in either experiment. However, in Exp. 2 pigs treated with pST had increased deposition rates of protein and water but reduced lipid deposition rates. Furthermore, pST treatment resulted in characteristic reductions in plasma urea nitrogen and elevations in glucose and NEFA. Plasma concentrations of insulin and IGF-I were also increased, but pST reduced IGF-II and IGF binding protein-2. Overall, the data demonstrated that very young pigs respond to pST with enhanced lean tissue accretion and metabolic changes, but the response is attenuated compared with previous studies in older growing pigs.

Animals↗
PubMed1997

Differential expression of messenger ribonucleic acids encoding 11beta-hydroxysteroid dehydrogenase types 1 and 2 in human granulosa cells.

In glucocorticoid target organs 11beta-hydroxysteroid dehydrogenase (11betaHSD) regulates the levels of active glucocorticoids available to glucocorticoid receptors. To date two isoforms of 11betaHSD, NADP-dependent type 1 11betaHSD (11betaHSD1) with predominant reductase activity and NAD-dependent type 2 11betaHSD (11betaHSD2) with dehydrogenase activity have been identified. Human ovarian granulosa cells have been shown to possess both dehydrogenase and reductase 11betaHSD activities and express 11betaHSD1 mRNA. However, whether 11betaHSD2 mRNA is also present or if the expression of either mRNA is developmentally regulated in the human ovary is unknown. We therefore used northern analysis to examine 11betaHSD1 and 11betaHSD2 mRNA levels in non-luteinized and luteinizing granulosa cells, corpora lutea (CL) and ovarian stroma obtained from human ovaries. Here we show that non-luteinized granulosa cells express relatively high levels of 11betaHSD2 mRNA but not 11betaHSD1. Conversely, luteinizing granulosa cells abundantly express 11betaHSD1 mRNA but not 11betaHSD2. CL also expresses 11betaHSD2 to lesser extent. Neither 11betaHSD mRNA is detectable in ovarian stroma. These results indicate that mRNAs encoding both 1lbetaHSD isozymes are present in human granulosa cells and they are developmentally--but differentially--regulated during preovulatory follicular development. The existence of developmentally regulated 11betaHSD in human granulosa cells is important new evidence that glucocorticoids, acting directly on the ovary, serve physiologically significant roles in the regulation of folliculogenesis.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Identification of the cAMP response element that controls transcriptional activation of the insulin-like growth factor-I gene by prostaglandin E2 in osteoblasts.

Insulin-like growth factor-I (IGF-I), a multifunctional growth factor, plays a key role in skeletal growth and can enhance bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other agents that increase cAMP activated IGF-I gene transcription in primary rat osteoblast cultures through promoter 1 (P1), the major IGF-I promoter, and found that transcriptional induction was mediated by protein kinase A. We now have identified a short segment of P1 that is essential for full hormonal regulation and have characterized inducible DNA-protein interactions involving this site. Transient transfections of IGF-I P1 reporter genes into primary rat osteoblasts showed that the 328-base pair untranslated region of exon 1 was required for a full 5.3-fold response to PGE2; mutation in a previously footprinted site, HS3D (base pairs +193 to +215), reduced induction by 65%. PGE2 stimulated nuclear protein binding to HS3D. Binding, as determined by gel mobility shift assay, was not seen in nuclear extracts from untreated osteoblast cultures, was detected within 2 h of PGE2 treatment, and was maximal by 4 h. This DNA-protein interaction was not observed in cytoplasmic extracts from PGE2-treated cultures, indicating nuclear localization of the protein kinase A-activated factor(s). Activation of this factor was not blocked by cycloheximide (Chx), and Chx did not impair stimulation of IGF-I gene expression by PGE2. In contrast, binding to a consensus cAMP response element (CRE; 5'-TGACGTCA-3') from the rat somatostatin gene was not modulated by PGE2 or Chx. Competition gel mobility shift analysis using mutated DNA probes identified 5'-CGCAATCG-3' as the minimal sequence needed for inducible binding. All modified IGF-I P1 promoterreporter genes with mutations within this CRE sequence also showed a diminished functional response to PGE2. These results identify the CRE within the 5'-untranslated region of IGF-I exon 1 that is required for hormonal activation of IGF-I gene transcription by cAMP in osteoblasts.

Animals↗
PubMed1996

Products of ozonized arachidonic acid potentiate the formation of DNA single strand breaks in cultured human lung cells.

In this study we examined the potential for environmental levels of ozone (03) to degrade arachidonic acid (AA), a polyunsaturated fatty acid abundantly present in the lung, into products that can produce DNA single strand breaks (ssb) in cultured human lung cells. Human lung fibroblasts were incubated with 60 microM AA that had been previously exposed to and degraded by 0.4 ppm 03 (1 hr.) Incubation of the cells with 03-exposed AA (but not with vehicle alone) for 1 hr at 4 degrees C and 37 degrees C produced 555 and 245 rad-equivalents of DNA ssb, respectively, as determined by the DNA alkaline elution technique. These breaks were completely eliminated when the ozonized AA solution was incubated with catalase prior to cell treatment, indicating that h202 was solely responsible for damaging DNA. Superoxide dismutase bovine serum albumin, or heat-inactivated catalase showed little, if any, inhibitory activity. The H202 content of the ozonized AA (31 +/- 4 microM) could account for only about 40% of the observed breaks. Potentiation of the H202-induced DNA ssb persisted after removal of the carbonyl substances by chromatographic procedures, suggesting that the non-carbonyl component of ozonized AA was the responsible component for inducing augmentation of the observed increases in DNA ssb. Ozonized AA also induced DNA ssb in cultures of the human bronchial epithelial cell line BEAS-2B. Again, these breaks were shown to exceed levels that could be attributed to the presence of H202 alone. These results indicate that products of ozonized AA can interact to potentiate DNA ssb in human lung cells.

Animals↗
PubMed1996

A method for the cryopreservation of red blood cells using hydroxyethyl starch as a cryoprotectant.

A simple, quick, inexpensive and long term method of cryopreserving human red cells using hydroxyethyl starch (HES) as a cryoprotectant is described. No sophisticated equipment or skilled labour is required. As HES is a plasma expander, it does not have to be removed prior to transfusion, thereby obviating the requirement for a washing stage. This allows 60 units/h to be prepared. As the microbiological integrity of the system is maintained, there is potential for prolonged storage post-thaw at 4 degrees C. Recoveries of 99% and 30 min saline stabilities in excess of 91% have been consistently achieved. P50O2 and 2,3DPG values are not significantly decreased.

Cryopreservation↗
PubMed1996

Activity-dependent beta-adrenergic modulation of low frequency stimulation induced LTP in the hippocampal CA1 region.

beta-Adrenergic receptor activation has a central role in the enhancement of memory formation that occurs during heightened states of emotional arousal. Although beta-adrenergic receptor activation may enhance memory formation by modulating long-term potentiation (LTP), a candidate synaptic mechanism involved in memory formation, the cellular basis of this modulation is not fully understood. Here, we report that, in the CA1 region of the hippocampus, beta-adrenergic receptor activation selectively enables the induction of LTP during long trains of 5 Hz synaptic stimulation. Protein phosphatase inhibitors mimic the effects of beta-adrenergic receptor activation on 5 Hz stimulation-induced LTP, suggesting that activation of noradrenergic systems during emotional arousal may enhance memory formation by inhibiting protein phosphatases that normally oppose the induction of LTP.

Animals↗
PubMed1996

Noninvasive and minimally invasive carcinoma ex mixed tumor: a clinicopathologic and ploidy study of 12 patients with major salivary tumors of low (or no?) malignant potential.

We studied 12 histologically malignant salivary tumors that showed complete encapsulation or only limited microscopic invasion. Most cases were histologically characterized by atypical and mitotically active luminal cells forming dilated, angular, variably sized glands in the subcapsular region, varying proportions of nonluminal tumor cells, and a background of central fibrosed hyalinized stroma. The appearance is that of a low-grade carcinoma. Focal higher grade carcinoma was superimposed on this histologic data in three cases. Neither recurrences nor metastases were seen in 11 of 12 patients after surgical resection with a follow-up of 1.2 to 13 yrs (mean, 4.2 years). Ploidy studies were performed on the paraffin-embedded tissue in 11 cases and yielded results for 7 cases. Aneuploid cell populations were found in five tumors; two had normal diploid populations; and the ploidy results are not predictive of tumor behavior. This type of salivary gland tumor fits diagnostically within the category of noninvasive and minimally invasive carcinoma ex pleomorphic adenoma (also referred to as in situ and low-grade malignant mixed tumors), a class that requires additional awareness and precise recognition as it signifies a good prognosis after surgical resection.

Adenoma, Pleomorphic↗
PubMed1996

Consensus conference on autologous transfusion. Acute normovolaemic haemodilution.

ANH is a relatively cheap and logistically straightforward method of autologous transfusion which is attractive in that it may be applied to a wide cross-section of patients, many of whom will not be suitable for pre-deposit. There are, however, concerns about the safety of the procedure, and doubts have been expressed about its efficacy in reducing allogeneic transfusion requirements and, therefore, its cost-effectiveness. Assessment of the value of the procedure is hampered by the lack of large scale prospective, controlled trials. In the present state of knowledge it seems that ANH is most likely to be safe, efficacious and cost-effective when undertaken aggressively (target haematocrit < 0.20) in otherwise healthy, young patients undergoing elective surgery with large expected blood losses.

Adult↗
PubMed1996

Dietary fatty acids, low density lipoprotein composition and oxidation and primate atherosclerosis.

Low density lipoproteins (LDL) were isolated from nonhuman primates fed isocaloric diets rich in different types of fatty acids. These diets contained 35% of calories as fat enriched in fatty acids from the following sources: lard that is rich in saturated fatty acids, safflower oil rich in oleic acid, safflower oil rich in linoleic acid and menhaden oil that is rich in n-3 fatty acids. LDL composition reflected the dietary fats. LDL were subjected to oxidation using copper ions and azobis(2-amidinopropane) x 2HCl. In general, the sensitivity of LDL to oxidation depended on both the poly-unsaturated fatty acid and vitamin E content. However, the lag times calculated for the copper ion catalyzed oxidations did not show the linear dependence on vitamin E content that was found for azobis(2-amidinopropane) catalyzed oxidation.

Animals↗
PubMed1996

Effects of doxorubicin, 4'-epirubicin, and antioxidant enzymes on the contractility of isolated cardiomyocytes.

The purpose of this study was to determine the acute effects of doxorubicin and its less cardiotoxic epimer, 4'-epirubicin, on the contractile response of isolated myocytes, and to assess similarities or differences with respect to active oxygen-derived mechanisms. Calcium-tolerant myocytes from rat ventricle were field stimulated at 1.0 Hz, and the maximum extent of cell shortening, peak shortening velocity, and peak relaxation velocity of single twitches were measured by video edge detection. The contractile responses of the myocytes to the two anthracyclines were approximately equal. Exposure of the cells to 10 microM of either anthracycline for 20 min decreased all indices of contractility by 28% (p < 0.05). The active oxygen scavengers, superoxide dismutase and catalase, distinguished the extent to which active oxygen was involved in modifying cellular contractility. Paradoxically, superoxide dismutase alone (10 U/mL) decreased contractility by 21%. Nevertheless, superoxide dismutase (10 U/mL) prevented the decreases in contractility produced by doxorubicin. In contrast, superoxide dismutase only mildly (32%) protected against 4'-epirubicin. Catalase (10 U/mL), however, provided substantial (82-93%) protection against both anthracyclines. Hydrogen peroxide therefore, and presumably hydroxyl radicals, were involved in mediating the decreases in contractility from both doxorubicin and 4'-epirubicin. These results show that an acute exposure to clinically relevant concentrations of these anthracyclines significantly depresses myocyte contractility and that, in this respect, 4'-epirubicin is as potentially cardiotoxic as doxorubicin. The results with antioxidant enzymes also strongly support a free radical mechanism for the toxicity of doxorubicin and 4'-epirubicin to cardiomyocytes.

Animals↗