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Biomedical subjects

R E Lynch

Publications and source records attributed to R E Lynch.

At least 37 records · Page 2Linked to original sources
PubMed1993

Distribution of gallium-67 in normal and hypotransferrinemic tumor-bearing mice.

The mechanism by which 67Ga accumulates in tumors is controversial. The most popular theory is that 67Ga binds to transferrin and gains access to cells by the transferrin receptor. However, substantial evidence suggests that uptake of 67Ga may not be universally mediated by transferrin in tumors. To determine whether transferrin is required for uptake of 67Ga in vivo, we compared the uptake of 67Ga by two types of implanted tumors and by normal tissues in normal and severely hypotransferrinemic strains of Balb/C mice. One type of tumor was strongly gallium-avid in normal mice; the other was not. Uptake of 67Ga by normal soft tissues was markedly less in hypotransferrinemic than in normal mice. Uptake of 67Ga by bone was equivalent in the two types of mice. For the more gallium-avid tumor, uptake of 67Ga was similar and the ratio of tumor-to-background activity was substantially higher in the hypotransferrinemic than in the normal mice. For the less gallium-avid tumor, uptake was significantly less in hypotransferrinemic than in normal mice. These data suggest that uptake of 67Ga by bone and by some tumors may be a transferrin-independent process.

Animals↗
PubMed1992

Uptake of cadmium is diminished in transfected mouse NIH/3T3 cells enriched for metallothionein.

To determine the relationship between cellular uptake of cadmium and content of metallothionein, we measured uptake of 109Cd in cells that differed in content of metallothionein (MT). MT cells were derived from NIH/3T3 cells by transfection with a plasmid containing the genome of bovine papilloma virus and the mouse metallothionein-I gene, driven by the promotor for the glucose-regulated protein of 78 kDa. Control cells were similarly transfected with bovine papilloma virus-based plasmids with the gene for metallothionein inverted and thus separated from the promoter (TM), or deleted, along with the promoter (BPA). The number of copies of bovine papilloma virus-based plasmids was similar in MT, TM, and BPA cells, approximately 100 per cell. MT cells were more than 10 times more resistant to the lethal effect of cadmium than were the control cells. Synthesis of metallothionein was 15-fold greater in the MT cells than in the TM or BPA cells. The uptake of 109Cd by the cells enriched in metallothionein was 4-fold less than by the control cells. These data suggest that an increased content of metallothionein may protect some cells from the toxic effects of cadmium, in part, by diminishing uptake of the metal.

3T3 Cells↗
PubMed1992

Intravenously administered labetalol for treatment of hypertension in children.

Thirteen children (ages 9.2 +/- 3.7 years, mean +/- SD) received intravenous doses of labetalol, an alpha 1- and beta-adrenergic blocker, on 15 separate occasions for treatment of hypertension. In 12 of 15 episodes an initial dose of 0.55 +/- 0.34 mg/kg was given; in all 15 a continuous infusion of 0.78 +/- 0.39 mg/kg per hour was utilized for 67.3 +/- 57.1 hours. A significant decrease in systemic blood pressure occurred in all episodes (143/99.1 +/- 17.7/11.1 vs 115.6/72.4 +/- 7.7/9.5; p less than 0.01). A clinically unimportant yet statistically significant decrease in heart rate occurred during labetalol infusion (116.3 +/- 19.8 vs 107.8 +/- 11 beats/min; p less than 0.01). The episodes in children with creatinine clearances greater than 50 (n = 6) were compared with those with creatine clearances less than 20 ml/min per 1.73 m2 (n = 9); similar doses of labetalol were required for control of blood pressure. We conclude that infusion of labetalol is effective for control of blood pressure in children with hypertension, regardless of renal function.

Adolescent↗
PubMed1991

Paraquat-resistant HeLa cells: increased cellular content of glutathione peroxidase.

Paraquat-resistant HeLa cells were selected and characterized to determine the mechanism(s) of the toxic action of paraquat for cultured mammalian cells. From HeLa cells already selected for resistance to the toxicity of 40 microM paraquat more resistant cells were selected in 90 microM paraquat. In these more resistant cells (PQRHM90) one adaptation which occurred at the lesser concentration of paraquat, magnification of the cellular content of both the CuZn- and the Mn-containing superoxide dismutases, did not increase further. Instead, the cellular content of catalase and of glutathione peroxidase increased. The increased cellular content of glutathione peroxidase appeared more likely to have produced increased resistance to paraquat than did the augmented content of catalase because, after cultivation in the absence of paraquat, the cells retained both resistance to 90 microM paraquat and the increased content of glutathione peroxidase, while the content of catalase declined. The cellular content of reduced glutathione in the PQRHM90 cells grown in paraquat was diminished in comparison with that in the cells from which they derived. The data suggest that the PQRHM90 cells resisted the toxicity of paraquat by increasing the cellular activity of glutathione peroxidase as a means of detoxifying the H2O2 produced by paraquat.

Catalase↗
PubMed1991

Pretreatment of formula with sodium polystyrene sulfonate to reduce dietary potassium intake.

Sodium polystyrene sulfonate (SPSS) is commonly administered for the acute and chronic treatment of hyperkalemia. Its oral intake is complicated by poor compliance due to multifaceted reasons. We therefore analyzed a method of reducing potassium (K) in formula by pretreatment with SPSS. If effective, this would bypass complications of enterally administered SPSS and provide low-K formula. Thirteen formulas and nutritional supplements were pretreated with SPSS to determine if one could bind K and provide formulas with decreased K contents. Using an SPSS concentration of 1 g/l mEq K in the formula, 62 +/- 2.6% (P less than 0.01, mean +/- SEM) of the K was removed in 30 min, while the sodium (Na) concentration was increased by 234 +/- 37% (P less than 0.01). Analysis suggests that the disproportionate increase in Na is due to exchange for calcium (Ca) and magnesium (Mg), interaction with proteins, and Na suspended with SPSS in the formula. Thus, SPSS pretreatment of formula is an effective method of making low-K formula, but the increase in Na exceeds the K reduction. Attention to possible complications of increased Na intake as well as decreased Ca and Mg intake is warranted.

Humans↗
PubMed1991

Ultrafiltration using low volume peritoneal dialysis in critically ill infants and children.

Ultrafiltration (UF) using dialysate volumes of less than 20 ml/kg was assessed in 12 critically ill infants and children with hypervolemia as the primary indication for dialysis. Ten of the 12 required mechanical ventilation (O2 requirements 45-100%). Seven, all infants, received at least one pressor intravenously in attempts to maintain systolic blood pressure of 60. Age was 22 +/- 11.5 mos. (mean +/- SE) with weight of 11.1 +/- 4.3 kg (range 2.4-50 kg). Dialysis prescription was as follows: Volume of 10.1 +/- 1.3 ml/kg/exchange; dwell time 30-45 minutes; drain time 15-20 minutes. Glucose concentration ranged from 1.5-4.25%. Drained dialysate volume expressed as a percent of volume instilled was 133.5 +/- 3.4%. When calculated for body weight and time, UF was 3.0 +/- 0.3 ml/kg/hour. UF was not significantly different in patients requiring pressors versus those not requiring blood pressure support. Although minor ventilatory changes were required, significant deterioration of blood gases did not occur during the first 3-6 hours of PD, nor did significant changes in blood pressure develop. Hyperkalemia, present in 1 patient prior to PD, resolved using this regimen. Low volume PD was a viable alternative to hemodialysis or hemofiltration for control of hypervolemia in this small group of very ill infants and children.

Acute Kidney Injury↗
PubMed1991

Gastric emptying after gastric interposition for cancer of the esophagus or hypopharynx.

Transhiatal esophagectomy with primary anastomosis to the stomach (gastric pull-up) is an attractive surgical alternative to colic interposition in patients with cancer of the esophagus and hypopharynx. However, the lack of intrinsic gastric peristalsis and complaints by patients of postprandial regurgitation prompted us to measure the effect of body posture on the rates of gastric emptying in these patients. The rates of solid and liquid gastric emptying were measured in 14 patients who had undergone gastric interposition for esophageal and hypopharyngeal carcinoma. Rates of emptying were measured in both the supine and upright position using a dual-isotope radiolabeling technique. In these patients, the rate of gastric emptying of both solids and liquids was significantly slower in the supine position than in the upright position. Emptying in supine patients was also prolonged when compared with supine normal volunteers. Conversely, the upright rate of solid and liquid emptying in the patients was accelerated when compared with published values for upright normal volunteers. We conclude that gastric emptying after gastric interposition is dependent on upright posture after meals.

Adult↗
PubMed1990

Ionized calcium: pediatric perspective.

Ionized calcium is a physiologically critical calcium pool. It is easily determined, although accuracy depends on sample handling. As a clinical parameter, directly measured ionized calcium has particular import in the care of neonates, patients with sepsis or other cardiovascular instability, massively transfused patients, and those undergoing cardiopulmonary bypass or liver transplantation. Disturbances of calcium occur in many other settings, however, and accurate diagnosis and research conclusions may depend on using the best measurement available. Clinical and investigational use of ionized calcium determinations represent appropriate applications of current proven technology. In the future, clinical calcium manipulation may include modifying specific transmembrane transport processes and intracellular calcium pools and movements. At the current time we are largely restricted to studies of extracellular calcium concentration and its interactions. Much is known, but Mother Nature still has too many secrets. The interested reader is referred to discussions of ionized calcium and hemodynamics, reviews of the endocrine disturbances of calcium and phosphorus, textbook discussions pertinent to general calcium disturbances, and critical care issues.

Animals↗
PubMed1990

Complications of nasogastric and gastrostomy tube feedings in children with end stage renal disease.

Twelve children with end stage renal disease requiring dialysis received enteral feedings via nasogastric (NG) or gastrostomy (G) tube between 1984 and 1989 for provision of adequate nutrition. Records were reviewed for frequency and types of complications seen. Six patients, ages 1 week to 16 months received NG feedings for a total of 32 months. Complications included persistent vomiting with recurrent aspiration (2), persistent vomiting with peritoneal dialysis (PD) exit site leak (1), sinusitis (1), and refusal to continue NG feeds because of patient/parental anxiety (1). Three of the 6 were changed to G tube feedings after 2 days to 3 months. The complication rate was 1 per 6.4 patient months. Nine patients, ages 4 days to 11 years, received G tube feedings for 64 months. The complication rate was similar, 1 per 7.1 months. Complications were PD fluid leak around G tube exit site (1), G tube infection (2), G tube obstruction requiring tube replacement (3), tube migration producing intestinal obstruction (1), and gastrocutaneous fistula (2). Both methods were associated with similar complication rates, although somewhat different types of complications were seen. The young dialysis patient may have certain unique risks in addition to the complications generally associated with enteral feedings.

Child↗
PubMed1990

Comparison of methods for calculating glomerular filtration rate: technetium-99m-DTPA scintigraphic analysis, protein-free and whole-plasma clearance of technetium-99m-DTPA and iodine-125-iothalamate clearance.

True glomerular filtration rate (GFR) was measured in normal volunteers and in patients with normal and impaired renal function by the iothalamate clearance (IC) method of Sigman. Within 24 hr, GFR was also determined by two other methods: technetium-99m- (99mTc) DTPA scintigraphic analysis (SA) utilizing a modification of the Gates computer program, and by measuring disappearance of 99mTc-DTPA from whole plasma (WPC) and from protein-free ultrafiltered plasma (PFPC). Determinations of GFR by IC and by PFPC methods were virtually identical (mean absolute error 5.36 ml/min, r = 0.99, p greater than 0.05). GFRs measured in protein-free, ultrafiltered plasma differed significantly from those obtained from whole plasma only in sicker patients and in those taking multiple medications (in whom alterations in protein-binding of DTPA may be seen). The SA method correlated less well with the iodine-125-(125I) IC method than did either the protein-free or whole-plasma clearance methods (mean absolute error 32.36 ml/min, r = 0.74, p less than 0.05). However, the SA method provided useful information with respect to differential (split) renal function.

Adult↗
PubMed1988

Superoxide mediates the toxicity of paraquat for cultured mammalian cells.

To establish some of the necessary steps in the toxic action of paraquat for cultured mammalian cells, we isolated paraquat-resistant HeLa cells after lethal increments in concentration of paraquat in the medium. The paraquat-resistant cells had increased the cellular content of both the Mn-containing and the CuZn-containing superoxide dismutases. The effect of paraquat on the consumption of oxygen by the wild-type and the resistance cells was similar; in both cases exposure to paraquat for 24 or more hours produced similar proportions of cyanide-resistant consumption of oxygen, suggesting that paraquat entered both cells, underwent reduction, and donated electrons to molecular oxygen. When cultivated for 5 months in the absence of paraquat the paraquat-resistant cells maintained the increased cellular content of superoxide dismutases and remained resistant to paraquat. This observation suggested that resistance to paraquat might be caused by enrichment for the two superoxide dismutases and, further, that the increased cellular content of the two enzymes was not a response to growth under stressful conditions. NIH/3T3 cells whose content of superoxide dismutase was increased by transcription of the transfected cDNA for the human CuZn superoxide dismutase were also resistant to paraquat, suggesting strongly that paraquat promotes the formation of O2- as a necessary part of its cytotoxic effects in two types of cultured mammalian cells.

Base Sequence↗
PubMed1988

Expression of transfected human CuZn superoxide dismutase gene in mouse L cells and NS20Y neuroblastoma cells induces enhancement of glutathione peroxidase activity.

The human CuZn superoxide dismutase (superoxide dismutase 1) a key enzyme in the metabolism of oxygen free-radicals, is encoded by a gene located on chromosome 21 in the region 21 q 22.1 known to be involved in Down's syndrome. A gene dosage effect for this enzyme has been reported in trisomy 21. To assess the biological consequences of superoxide dismutase 1 overproduction within cells, the human superoxide dismutase 1 gene and a human superoxide dismutase 1 cDNA were introduced into mouse L cells and NS20Y neuroblastoma cells. Both cell types expressed elevated levels (up to 3-fold) of enzymatically active human superoxide dismutase 1. These human superoxide dismutase 1 overproducers, especially neuronal cell lines, showed an increased activity in the selenodependent glutathione peroxidase. These data are consistent with the possibility that gene dosage of superoxide dismutase 1 contributes to oxygen metabolism modifications previously described in Down's syndrome.

Animals↗
PubMed1988

Uptake of cadmium-109, a metallothionein-binding radiometal, by tumors in mice as a function of the transformed phenotype.

Metallothionein (MT) is an intracellular protein that binds many metals with isotopes having imaging or radiotherapeutic potential. To determine whether uptake of radioisotopes that bind to MT is increased in tumors, we measured the uptake of cadmium-109 (Cd-109) in tumors and in normal tissues of mice. Tumors were grown in Balb/C mice from cultured Balb/3T3 cells transformed by the Moloney murine sarcoma virus (MMSV). Uptake of Cd-109 by MMSV tumors exceeded that by normal tissues examined, with the exception of liver and kidney (the organs known to be richest in metallothionein). The MMSV tumor:background ratios of activity were greater for Cd-109 than for gallium-67 for many of the normal tissues examined. The magnitude of uptake of Cd-109 by tumors from four related cell lines paralleled their degree of expression of two indices of the transformed, or malignant, phenotype. We conclude that metals that bind to MT may be useful for imaging or radiotherapy of cancer.

Animals↗
PubMed1986

Superoxide mediates the toxicity of paraquat for Chinese hamster ovary cells.

The roles of superoxide and H2O2 in the cytotoxicity of paraquat were assessed in Chinese hamster ovary cells. Neither catalase nor superoxide dismutase inhibited the loss of ability to form colonies when added to the medium. When introduced into the cells, superoxide dismutase but not catalase inhibited the toxicity of paraquat. That superoxide dismutase acted by its known catalytic action is shown by the loss of inhibition when the enzyme was inactivated by H2O2 before being introduced into the cells. The lack of inhibition by catalase, by dimethyl sulfoxide, and by desferoxamine suggests that the toxicity is not mediated by a reaction between H2O2 and superoxide to engender the hydroxyl radical. Exposure of Chinese hamster ovary cells to paraquat may be a suitable means to determine the effects of superoxide anion in cultured cells and the ways in which cells can resist this toxic action.

Animals↗
PubMed1983

Catalase and superoxide dismutase in Escherichia coli.

We assessed the roles of intrabacterial catalase and superoxide dismutase in the resistance of Escherichia coli to killing by neutrophils. E. coli in which the synthesis of superoxide dismutase and catalase were induced by paraquat 10-fold and 5-fold, respectively, did not resist killing by neutrophils. When bacteria were allowed to recover from the toxicity of paraquat for 1 h on ice and for 30 min at 37 degrees C, they still failed to resist killing by neutrophils. Induction of the synthesis of catalase 9-fold by growth in the presence of phenazine methosulfate did not render E. coli resistant to killing by either neutrophils or by H2O2 itself. The lack of protection by intrabacterial catalase from killing by neutrophils could not be attributed to an impermeable bacterial membrane; the evolution of O2 from H2O2 was no less rapid in suspensions of E. coli than in lysates. The failure of intrabacterial catalase or superoxide dismutase to protect bacteria from killing by neutrophils might indicate either that the flux of O-2 and H2O2 in the phagosome is too great for the intrabacterial enzymes to alter or that the site of injury is at the bacterial surface.

Catalase↗