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Biomedical subjects

J Magner

Publications and source records attributed to J Magner.

At least 19 recordsLinked to original sources
PubMed1998

Induction of mortality and malformation in Xenopus laevis embryos by water sources associated with field frog deformities.

Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species.

Animals↗
PubMed1998

Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes.

OBJECTIVE: To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and metformin (2,000 or 2,500 mg/day in divided doses). RESEARCH DESIGN AND METHODS: This study had a multicenter randomized double-blind placebo-controlled parallel-group comparison design. The trial lasted 31 weeks and consisted of a 1-week screening period, a 6-week placebo pretreatment period, and a 24-week period of acarbose or placebo, with a forced titration from 25-50 mg t.i.d. and a titration of 50-100 mg tid that was based on glucose control. The primary efficacy variable was the mean change from baseline in HbA1c. Secondary efficacy variables included mean changes from baseline in fasting and postprandial plasma glucose, serum insulin, and triglyceride levels. RESULTS: The addition of acarbose to patients on background metformin and diet therapy showed a statistically significant reduction in mean HbA1c of 0.65%. There were statistically significant reductions in fasting and postprandial plasma glucose and serum insulin levels compared with placebo. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. No significant differences in liver transaminase elevations were observed between patients treated with acarbose and those treated with placebo. CONCLUSIONS: The results of this study demonstrate that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with metformin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and fasting and postprandial glucose and insulin levels.

Acarbose↗
PubMed1998

Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes.

OBJECTIVE: To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and insulin. RESEARCH DESIGN AND METHODS: A multicenter randomized double-blind placebo-controlled parallel-group comparison study was conducted. The trial was 26 weeks with a 2-week screening period and a 24-week period of treatment with acarbose or placebo, with forced titration from 25 mg t.i.d. to 50 mg t.i.d. after 4 weeks, and titration of 50 mg t.i.d. to 100 mg t.i.d. after 12 weeks based on glucose control. The dosage of insulin was to remain stable. The primary efficacy variable was mean change from baseline in HbA1c, and secondary efficacy variables included mean changes in fasting and postprandial plasma glucose and triglyceride levels. RESULTS: The addition of acarbose to the treatment of patients receiving background insulin and diet therapy resulted in a statistically significant reduction in mean HbA1c of 0.69% compared with placebo. There were statistically significant reductions in postprandial plasma glucose and glucose area under the curve, and in postprandial serum triglyceride levels in the acarbose-treated patients. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. There were no significant differences in hypoglycemic events or liver transaminase elevations between groups. CONCLUSIONS: This study demonstrated that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with insulin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and postprandial glucose levels.

Acarbose↗
PubMed1997

Transiently decreased sialylation of thyrotropin (TSH) in a patient with the euthyroid sick syndrome.

A 60-year old woman was admitted to the medical intensive care unit with respiratory distress and worsening renal function, and was found to have bilateral renal artery occlusion. Aggressive nutrition per nasogastric tube was begun on day 8 of her illness, and she eventually recovered after bilateral renal artery bypass surgery, which was performed on day 15. She developed the euthyroid sick syndrome. Levels of serum TSH, T3, and T4 fell during the first few days of her illness, then all trended to normal levels by day 28. The TSH level declined from 1.6 microU/mL on day 2 to 0.2 microU/mL on day 5, then rose to 4.5 microU/mL on day 10, and was 3.8 microU/mL on day 14. The ratios of free T4/TSH, a crude measure of the bioactivity of TSH, were 1.4, 8.0, 0.16, 0.32, and 1.14 on days 2, 5, 10, 14 and 28, respectively. TSH was immunoaffinity concentrated from serum collected on four dates. The TSH oligosaccharides were enzymatically released, treated with or without neuraminidase, labeled with a fluorescent probe, and analyzed by gel electrophoresis. The TSH oligosaccharides were found to be transiently less sialylated on day 13 as compared to days 2, 4, and 24. Three gel bands representing poorly sialylated oligosaccharides represented a mean of 20.6% of TSH oligosaccharides on days 2, 4, and 24, but represented 33.7% of TSH oligosaccharides on day 13. This is the first report of altered TSH oligosaccharide sialylation in the euthyroid sick syndrome. If confirmed by studies of additional patients, altered TSH sialylation may, in part, explain the altered TSH bioactivity that has been described in the euthyroid sick syndrome.

Chromatography, Affinity↗
PubMed1997

Intra-ocular pressure changes following laryngeal mask airway insertion: a comparative study.

We compared the effects of the Brain laryngeal mask airway with a tracheal tube on intra-ocular pressure. Propofol was used as induction agent and atracurium as relaxant. Twenty-six patients with normal intra-ocular pressure undergoing cataract surgery were randomly allocated to two groups. Group A (n = 13) had a laryngeal mask airway inserted and Group B (n = 13) had a tracheal tube inserted. Intra-ocular pressure was measured just before insertion of the airway, 20 s after insertion and at 2 min. In the laryngeal mask airway group there were no significant changes in mean intra-ocular pressure. In the tracheal tube group there was a significant rise in mean intra-ocular pressure at 20 s (p = 0.0056) which returned to pre-insertion levels at 2 min. We conclude that the laryngeal mask airway continues to have advantages over the tracheal tube for ophthalmic surgery despite the use of propofol and atracurium as anaesthetic agents.

Aged↗
PubMed1996

Smallpox.

Explore the source record for details and available documents.

England↗
PubMed1992

Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors.

Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms from the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures.

Adult↗
PubMed1992

Fucosylation of glycoproteins begins in the rough endoplasmic reticulum of mouse active thyrotrophs.

Our aim was to determine whether fucosylation of glycoproteins begins in the rough endoplasmic reticulum (RER) of active thyrotrophs. This would contrast with most cells studied, in which fucosylation generally is associated with the Golgi apparatus. Mouse thyrotropic tumor tissue was incubated with [35S]methionine for 2, 5, 7, 10, 30, and 90 minutes. TSH and free alpha-subunits were immunoprecipitated from cell lysates, and they displayed a time-dependent increase in affinity for lentil lectin (which binds oligosaccharides having core fucose), even at short times. Since no 20-30 minute lag in onset of TSH- and free alpha-subunit-lentil binding was appreciated, as might have been expected had fucosylation begun only in the Golgi, it appeared that fucosylation was beginning in the RER of thyrotrophs. Pituitary tissue from euthyroid and hypothyroid mice was incubated with [3H]fucose, then subjected to electron microscopic autoradiography. The pituitaries of hypothyroid mice had numerous "thyroidectomy cells," which had 40% of silver grains over dilated cisternae of RER. "Nonthyroidectomy" cells had few silver grains over RER; most were over secretory granules and Golgi areas. Thus, active mouse thyrotrophs appear to shift the subcellular site of fucosylation partially from Golgi to RER, and this phenomenon may represent one cellular mechanism whereby the endocrine regulation of the structure of TSH oligosaccharides is accomplished.

Animals↗
PubMed1991

Effect of anaesthesia on intraocular blood flow.

Pulsatile ocular blood flow, intraocular pressure, systemic blood pressure, and heart rate was measured in two groups of 15 patients. One received lignocaine 1.5 mg/kg intravenously prior to induction. There was a significant increase in intraocular pressure after suxamethonium, which was not associated with any rise in ocular blood flow. Both the IOP and ocular blood flow increased significantly after tracheal intubation. A rise in ocular blood flow reflects the stress response associated with intubation. Lignocaine failed to attenuate either response.

Anesthesia, General↗
PubMed1988

Metabolic labeling of human thyroglobulin with [35S]sulfate: incorporation into chondroitin 6-sulfate and endoglycosidase-F-susceptible carbohydrate units.

To study the incorporation of sulfate into thyroglobulin, human thyroid tissue was incubated with [35S]sulfate. Labeled thyroglobulin was purified by ammonium sulfate precipitation, gel exclusion chromatography, and equilibrium density gradient centrifugation, the last of these specifically to remove proteoglycans. [35S]Sulfate was found in thyroglobulin with low density, indicating that sulfate was incorporated into newly synthesized molecules before their iodination. Chondroitin ABC lyase and chondroitin AC lyase released equal amounts of [35S]sulfate, demonstrating the presence of chondroitin units, and TLC showed this to be predominantly chondroitin 6-sulfate. Additional [35S]sulfate was released by endoglycosidase-F (Endo-F), but not by Endo-H. The Endo-F-sensitive sulfate-labeled complex carbohydrate units were heterogeneous, one fraction passing through a Concanavalin-A-Sepharose column without delay and another fraction showing weak affinity for the lectin. More than 90% of the incorporated [35S]sulfate was accounted for by the chondroitin ABC lyase and Endo-F-sensitive fractions. Thus, human thyroglobulin contains sulfate in at least three types of carbohydrate units, 1) chondroitin 6-sulfate units, 2) complex units with no affinity for Concanavalin-A (tri- or tetraantennary forms), and 3) complex units with weak affinity for Concanavalin-A (biantennary forms).

Ammonium Sulfate↗
PubMed1986

Early kinetics of human macrophage apolipoprotein E synthesis and incorporation of carbohydrate precursors.

Apolipoprotein E was detected in human macrophage lysates after 4-120-min pulses with [35S]methionine. Significant levels of apolipoprotein E were not found in the media until 120 min. Incorporation of N-[3H]acetylmannosamine, a sialic acid precursor, into apolipoprotein E was measurable after 120 min, whereas no [3H]mannose incorporation could be observed. These methods will be useful for examining the regulation of apolipoprotein E secretion and carbohydrate processing.

Acetylglucosaminidase↗
PubMed1986

Studies of double-labeled mouse thyrotropin and free alpha-subunits to estimate relative fucose content.

The composition and structure of the complex oligosaccharides of thyrotropin (TSH) and free alpha-subunits are not well established, but are believed to be important determinants of the biological properties of these glycoproteins. We employed a simple double-label technique to learn the relative fucose content of mouse thyrotropin and free alpha-subunits. Thyrotropic tumor minces were incubated simultaneously with [35S]methionine and [3H]fucose. Thyrotropin and free alpha-subunits were labeled with both isotopes, and the ratio of 3H/35S was higher in free alpha-subunits than in thyrotropin; free alpha-subunits were approximately fivefold richer in fucose than was thyrotropin. The 3H/35S ratio was not substantially altered in TSH or free alpha-subunits secreted after a brief incubation with 10(-7) M thyrotropin-releasing hormone. Species which incorporated [3H]fucose were resistant to endoglycosidase H. Thus, mouse free alpha-subunits secreted by thyrotropic tumor are relatively rich in fucose. Double-isotope labeling using an amino acid and a sugar appears to be a useful technique for studies of the glycoprotein hormones.

Animals↗