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Biomedical subjects

J Carver

Publications and source records attributed to J Carver.

At least 19 recordsLinked to original sources
PubMed1996

The effects of acetyl-L-carnitine and sorbinil on peripheral nerve structure, chemistry, and function in experimental diabetes.

Nerve conduction velocity (NCV) increased with age in nondiabetic male Wistar rats for the first 26 weeks of life. The NCV of animals made hyperglycemic at age 6 weeks by administration of streptozotocin (STZ) also increases, but at a slower rate. Animals with 4 weeks of hyperglycemia and reduced NCV treated with an aldose reductase inhibitor (sorbinil) or a short-chain acyl-carnitine (acetyl-L-carnitine [ALC]) daily for 16 weeks showed an improvement in NCV. Morphometric studies of tibial nerves collected from animals after 20 weeks of hyperglycemia (age 26 weeks) showed a consistent reduction in the width of the myelin sheath and little change in axon area. The number of large myelinated fibers (>6.5 microns) found in nerves collected from hyperglycemic animals was less than the number found in nondiabetic animals. Treatment of hyperglycemic rats with either sorbinil or ALC was associated with increased NCV, myelin width, and large myelinated fibers. The apparent metabolic effect of these agents was similar for fatty acid metabolism, but different for polyol pathway activity. We conclude that in animals hyperglycemic long enough to slow NCV, sorbinil and/or ALC treatment reduces the functional, structural, and biochemical changes associated with hyperglycemia that occur in the myelin sheath.

Acetylcarnitine↗
PubMed1996

Rapid placement of transpyloric feeding tubes: a comparison of pH-assisted and standard insertion techniques in children.

OBJECTIVE: To compare transpyloric feeding tube placement using a pH-assisted placement technique versus a standard placement technique in pediatric patients requiring enteral nutrition. METHODS: Critically ill children younger than 4 years were prospectively and randomly assigned to either a pH-assisted or a standard feeding tube placement group. Identical pH-assisted feeding tubes were used in both groups; however, feeding tubes in the standard group were not attached to a portable pH meter. Successful transpyloric placement was confirmed by radiography before beginning feedings. If placement was not successful, a second placement attempt was made after metoclopramide administration. Information regarding tube placement success, number of radiographs, time to initiation of feedings, and daily caloric intake was collected. A cost comparison between the two groups was performed. RESULTS: Thirty-four patients were enrolled in the pH-assisted group, and 34 were enrolled in the standard feeding tube group. Ninety-seven percent of patients in the pH-assisted group had successful placement after the first attempt, compared with 53% of patients in the standard group. The average time to successful placement of pH-assisted feeding tubes was 6 minutes. All patients in the pH-assisted group had successful placement after the second attempt, compared with 78% of patients in the standard group. A pH of greater than 5.6 accurately predicted transpyloric placement in 97% (33 of 34) of individuals in the pH-assisted group. Children in the pH-assisted group required significantly fewer radiographs than those in the standard group. Hospital costs were $114 per patient in the pH-assisted group and $135 per patient in the standard group. CONCLUSIONS: Our findings indicate that bedside transpyloric placement of pH-assisted feeding tubes can be accomplished rapidly and with a high success rate. This method is associated with decreased radiation exposure and economic savings when compared with a standard placement technique.

Child, Preschool↗
PubMed1995

Comparison of gastric intramucosal pH and standard perfusional measurements in pediatric septic shock.

OBJECTIVE: To examine the utility of gastric tonometry as an early indicator of morbidity and mortality in pediatric patients with septic shock. DESIGN: Prospective clinical study. SETTING: Multidisciplinary pediatric ICU. PATIENTS: Eight critically ill pediatric patients with septic shock and with pulmonary artery and gastric tonometry catheters in place. INTERVENTIONS: Standard perfusional data including cardiac index, oxygen content (arterial, mixed venous), oxygen delivery, oxygen consumption, urine output, capillary refill, and lactate value were measured every 4 h. Intramucosal pH (pHi) was calculated from simultaneous tonometric measurements of gastric intramucosal PCO2 (PiCO2). Mean pHi values were compared between survivors and nonsurvivors. Tonometric data were compared with standard perfusional data by regression analysis. Low pHi values (< 7.35) were temporally compared with occurrence screens for adverse clinical events, (cardiopulmonary arrest, acute hemorrhage, and significant hypotension or dysrhythmias). MEASUREMENTS AND MAIN RESULTS: Sets (n = 108) of paired data were collected from 8 patients (age 7 to 168 months) representing 4 deaths. The mean pHi in nonsurvivors (7.32 +/- 0.18) was significantly lower than that in survivors (7.48 +/- 0.07). Both pHi and PiCO2 were correlated with urine output by regression analysis. The pHi, but not PiCO2 correlated with extraction ratio and lactate level. There were no other significant correlations noted. Analysis of the ability of pHi values to predict adverse clinical events revealed that pHi less than 7.35 accurately predicted 26 of 39 concurrent or subsequent adverse clinical events. However, 24 of 50 pHi values less than 7.35 showed no association with similar adverse events, either concurrent or subsequent. The pHi had a sensitivity of 67%, a specificity of 74%, a positive predictive value of 52%, and an efficiency of 72% in predicting these adverse events. CONCLUSION: Use of gastric tonometry in pediatric septic shock patients appears to distinguish survivors from nonsurvivors. However, in general, tonometric assessment of splanchnic perfusion correlates poorly with standard clinical, hemodynamic, oxygen transport, or metabolic measurements of perfusion. Low pHi measurements are not predictive of concurrent or subsequent adverse clinical events.

Adolescent↗
PubMed1993

Expression and dynamic modulation of the human granulocyte colony-stimulating factor receptor in immature and differentiated myeloid cells.

In this study we have examined the expression and modulation of the human granulocyte colony-stimulating factor (G-CSF) receptor (R) in immature and differentiated myeloid cells using a 125I labelled human G-CSF analogue (TG50). Equilibrium binding data revealed a single affinity class of receptor on all cell types expressing G-CSFR (KD 235-606 pM) with neutrophils expressing 2883 +/- 672 Rs/cell. Rapid internalization of surface receptor-bound ligand at 37 degrees C was detected in both immature cells (U937) and neutrophils with > 70% of specifically bound ligand internalized within 5 min. Concentration-response data showed that the level of occupancy of neutrophil G-CSFRs by ligand at 37 degrees C was approximately 5-fold greater than predicted by equilibrium binding data and correlated closely with concentration-response data for biological activity. Re-expression of G-CSFRs following down-regulation by internalization was not detected. Down-regulation of the neutrophil G-CSFR by several agents including granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF), lipopolysaccharide (LPS), f-met-leu-phe (fMLP), phorbol ester (TPA) and C5a was observed at 37 degrees C but not at 4 degrees C. In contrast, G-CSFRs on immature myeloid cells were significantly down-regulated by TPA only. Differentiation of myeloid leukaemic cell line HL-60 with DMSO, a frequently used model of granulocytic differentiation, was associated with a significant reduction in G-CSFR expression (11 +/- 5% of control) whereas treatment with retinoic acid led to increased G-CSFR expression (161 +/- 3%).

Binding, Competitive↗
PubMed1993

Dynamic modulation of the cell surface expression of the granulocyte-macrophage colony-stimulating factor receptor.

The GM-CSF receptor (GM-CSFR) is composed of alpha and beta subunits. Surface expression of the alpha chain alone leads to low affinity GM-CSF binding and of both subunits to high affinity binding; the beta chain is required for transducing a proliferative signal. Studies of GM-CSFR expression have concentrated largely on static events occurring under conditions of binding equilibrium. We have examined the dynamic regulation of high and low affinity GM-CSFR expression in neutrophils (1100 +/- 200 R/cell, KD 50 +/- 15 pM) and a GM-CSF dependent human leukaemic cell line, TF-1 (2000 +/- 450 R/cell KD 15 +/- 5 pM) and 8600 +/- 1150 R/cell KD 1.8 +/- 0.3 nM). The addition of GM-CSF to TF-1 cells (350 pM, 4 h at 37 degrees C) caused a reduction in subsequent binding of 125I-GM-CSF at low ligand concentration (100 pM) (following a low pH wash to remove surface bound ligand) to 16 +/- 4% and a reduction in binding at high ligand concentration (2 nM 125I-GM-CSF) to 36 +/- 9% of control. Scatchard analysis showed complete down-regulation of high affinity GM-CSFR and a significant reduction in low affinity GM-CSFR. In neutrophils, concentration-response curves of ligand induced receptor down-regulation at 37 degrees C showed that observed down-modulation was more than 10-fold greater than predicted by static equilibrium binding data and correlated closely with GM-CSF priming of the neutrophil respiratory burst. The addition of IL-3 to TF-1 cells at 37 degrees C reduced 100 pM 125I-GM-CSF binding to 18 +/- 4% and 2 nM 125I-GM-CSF binding to 46 +/- 5% of control. TF-1 cells, but not neutrophils, were able to re-express GM-CSFR following removal of GM-CSF from medium. TF-1 proliferation assays showed that pulsed GM-CSF (0.35-3.5 nM) for up to 4 h did not cause a significant increase in 3H-thymidine incorporation which required the continued presence of GM-CSF (control 2875 +/- 208 cpm, pulsed GM-CSF 5 ng/ml 4972 +/- 1344, continuous GM-CSF 5 ng/ml 17249 +/- 2982). Therefore, proliferation of TF-1 cells required the continued presence of GM-CSF at a time when there was no detectable surface high affinity GM-CSFR.(ABSTRACT TRUNCATED AT 400 WORDS)

Cells, Cultured↗
PubMed1993

Fetal hemoglobin and sudden infant death syndrome.

Chronic hypoxemia has been suggested as an unrecognized condition that may result in sudden infant death syndrome. Fetal hemoglobin has been shown to be increased in infants suffering from chronic hypoxemia. We examined fetal hemoglobin levels in 54 cases of sudden infant death syndrome, 17 infants dying of other causes, and 22 live, healthy control infants. Fetal hemoglobin in infants with sudden infant death syndrome was found to be elevated when compared with our control infants as well as when compared with literature-based normal values. These findings indicate that fetal hemoglobin measurements may be a valuable aid in identifying cases of sudden infant death syndrome at autopsy and supports the hypothesis that this group of victims of sudden infant death syndrome are not normal before death but have an underlying condition resulting in chronic hypoxemia.

Age Factors↗
PubMed1992

Developmental changes in hepatic basolateral membrane lipid composition and fluidity.

Membrane fluidity and lipid composition influence the activity of a variety of membrane proteins. Decreased rates of hepatic ion clearance are associated with the neonatal period. We postulated that hepatic basolateral membranes derived from suckling animals might be less fluid than those from adult animals. Basolateral membrane vesicles were prepared from the livers of 1-week-old (SBLMV) and adult (ABLMV) rats by a Percoll gradient method. Na+/K(+)-ATPase activities were similar in the two groups. Double bond index, cholesterol and cholesterol/phosphorus ratios were significantly higher in SBLMV compared with ABLMV, while lipid phosphorus and relative percentages of phospholipid subclasses did not differ. Fluorescence anisotropy measured using diphenylhexatriene as well as 2-(9-anthroyloxy)stearate was significantly greater in SBLMV compared with ABLMV, while measurements made with 12-(9-anthroyloxy)stearate were similar in both age groups. Mean excited state lifetimes, lifetime distributions, and rotational correlation times were similar in both groups. These data suggest that hepatic basolateral membranes derived from suckling rats are less fluid than those from adult animals and further suggest that this difference may be due to increased cholesterol in hepatic basolateral membranes derived from suckling animals.

Animals↗
PubMed1983

alpha Chain and gamma chain abnormal hemoglobins in newborn babies: structural and genetic aspects.

Structural studies and quantitative analyses were conducted on the hemoglobin of 55 newborn babies. Seven alpha chain variants (G-Philadelphia, Montgomery, Inkster, I-Philadelphia, Matsue-Oki, Winnipeg, and O-Indonesia) were present in 26 heterozygous newborns (17 black, eight Caucasian, and one Indonesian). The relative amount of the alpha X containing abnormal Hb F of the Hb G-Philadelphia and Hb Winnipeg babies was less than observed in heterozygous adults, which may indicate a decreased rate of assembly of the alpha X-gamma dimer over that of the alpha X-beta dimer. Of the 29 newborns with gamma chain variants, 16 were Caucasian babies; of these 15 had a Hb A gamma F-Hull heterozygosity and one a Hb G gamma F-Marietta heterozygosity. Six black babies were heterozygous for Hb A gamma F-Texas-I and six for Hb G gamma F-Port Royal. One Japanese baby had a heterozygosity for A gamma F-Iwata and a second was heterozygous for A gamma TF-Yamaguchi. Quantitative analyses of the isolated normal Hb Fo as well as an evaluation of the relative amounts of the Hb Fx in the red cell lysates gave data useful for a speculation of the genetic condition in each of these babies. It was concluded that the babies with the Hbs F-Texas-I, F-Iwata, F-Hull, and F-Marietta were simple heterozygotes with either the G gamma x A gamma/G gamma x A gamma X or the G gamma x A gamma/G gamma X x A gamma genic arrangement. The babies with Hb F-Port Royal had a G gamma x G gamma X/G gamma x A gamma arrangement, which may result from a (to be determined) gene conversion. The newborn baby with Hb F-Yamaguchi has the G gamma x A gamma x/A gamma T-X.-. genic arrangement, suggesting the presence of three distinctly different gamma chain genes of which one, the A gamma T-X gene, produces an A gamma chain (with threonyl at position gamma 75 and an Asn at position gamma 80) at a level usually seen for G gamma rather than A gamma chains. These studies were greatly facilitated by the use of high pressure liquid chromatographic methods.

Amino Acid Sequence↗
PubMed1983

A survey of hospital audiovisual services.

A survey of 305 potential audio-visual (A/V) service users from 17 disciplines in 7 teaching hospitals determined awareness of A/V services offered, use, and evaluation of these services. Ninety-nine percent of those surveyed were aware of the A/V services. The services most used were equipment loan, overhead transparency production, and slide/print production from type. Services most needing improvement were those providing patient education materials and facilities. Slide libraries and instruction in use of audiovisuals were perceived to need improvement. Conclusions are drawn about services that are best decentralized, or centralized and developed for sharing among hospitals.

Audiovisual Aids↗
PubMed1982

Further studies on the quantitation of the hemoglobins A, S, C, and F in newborn babies with different hemoglobinopathies using high pressure liquid chromatography.

High pressure liquid chromatography (HPLC) has been used for the detection and quantitation of the beta chain variants Hb S and Hb C in blood samples of newborn babies with different hemoglobinopathies. The complete separation of the Hbs C, S, A, and F made it possible to diagnose conditions such as AS AC, SS, CC, SC and even S(C)-beta+ thalassemia. The procedure is fast (62 min) and ideally suited for the quantitation of Hb F at birth. Data for a few hundred cord blood samples indicate a great variability in the relative quantities of Hb S or Hb C in heterozygotes which prevents a definitive diagnosis of a simultaneously occurring alpha-thalassemia except perhaps of the homozygous form of alpha-thalassemia-2 (alpha o alpha/alpha o alpha). The large spread in the data also shows some overlap between the quantitative results in Hb S (or Hb C) heterozygotes and in babies with the Hb S (Hb C)-beta-thalassemia condition.

Chromatography, High Pressure Liquid↗
PubMed1981

Application of high-field proton magnetic resonance spectroscopy in the structural determination of membrane-derived Sindbis virus glycopeptides.

Sindbis virus membrane glycopeptides have ben purified in chemical quantities and their oligosaccharide structures analyzed by 1H NMR spectroscopy at 360 MHz. Interpretable spectra could be obtained with approximately 100 micrograms of oligosaccharide. Spectral analysis of the sialyl glycopeptides S1, S2, and S3 at high and low temperatures confirms their structures to be NANA alpha (2,3)Gal beta (1,4)-GlcNAc beta (1,2)Man alpha (1,6)-[NANA alpha (2,3)Gal beta (1,4)-GlcNAc beta (1,2)Man alpha (1,3)]-Man beta (1,4)GlcNAc beta (1,4)-[Fuc alpha-(1,6)]-GlcNAc beta 1-Asn. These are heterogeneous with respect to sialic acid (NANA). Spectra of two endo-beta-N-acetylglucosaminidase products of the S4 glycopeptides are reported. The interpretation of these spectra is consistent with Man5GlcNAc and Man7GlcNAc oligosaccharide structures. Their chemical shifts are essentially identical with those reported for ovalbumin glycopeptides of the same composition, with exception to the perturbations arising from their oligosaccharide nature.

Animals↗