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Biomedical subjects

C Deal

Publications and source records attributed to C Deal.

At least 19 recordsLinked to original sources
PubMed1996

Polymorphic functional imprinting of the human IGF2 gene among individuals, in blood cells, is associated with H19 expression.

In most non-neoplastic tissues studied to date, IGF2 is expressed only from the paternal allele and H19 is expressed only from the maternal allele. The choroid plexus, the only normal tissue to date where IGF2 is expressed from both parental alleles, does not express H19. We present an additional situation in which biallelic IGF2 expression is associated with the absence of H19 transcription in normal tissue: blood cells. In blood cells, functional IGF2 imprinting was found to be a polymorphic trait among individuals: expression was biallelic in 79 out of 85 individuals, but the remaining 6 expressed a single allele. Only the latter expressed H19. Finally, the familial clustering of functional IGF2 imprinting in blood cells suggests that the trait may be genotype-dependent.

Alleles↗
PubMed1996

Pharmacodynamics and enantioselective pharmacokinetics of carprofen in the cat.

The pharmacodynamics and enantioselective pharmacokinetics of the arylpropionic acid non-steroidal anti-inflammatory drug, carprofen, were investigated in cats after administration of the racemic mixture (rac-carprofen) at dose rates ranging from 0.7 to 4.0 mg kg-1 intravenously and subcutaneously. A low dose of rac-carprofen (0.7 mg kg-1) partially inhibited the rise in skin temperature at a site of acute inflammation but had no effect on the ex vivo synthesis of serum thromboxane (Tx) B2. A higher dose (4.0 mg kg-1) inhibited oedematous swelling, although the response was statistically significant at only one time, and also reduced the ex vivo synthesis of serum TxB2 for 12 hours after intravenous injection or 24 hours after subcutaneous injection. The main features of carprofen pharmacokinetics were a low distribution volume, a relatively long elimination half-life, the predominance of the R(-) enantiomer and a bioavailability (after subcutaneous dosing) of 100 per cent and 92 per cent, respectively, after doses of 0.7 and 4.0 mg kg-1. On the basis of these data, it is suggested that a dose of 4.0 mg kg-1 by both intravenous and subcutaneous routes should be evaluated in clinical subjects.

Animals↗
PubMed1996

Effects of 14-day infusions of growth hormone and/or insulin-like growth factor I on the obesity of growing Zucker rats.

The response of fat tissue to GH or insulin-like growth factor I (IGF-I) differs between humans with hypopituitarism and those with exogenous obesity; the effects of combined GH and IGF-I administration have not been compared in these two situations. In GH-deficient dwarf rats (who have a primary GH deficiency), the excessive fat deposition induced by a high fat diet is completely reversed by combined infusion of GH and IGF-I. Whether the same phenomenon would be observed in genetically obese Zucker rats (in whom, as in obese humans, the decrease in GH secretion is secondary to the obese state) remained to be determined. Growing (6-week-old) female obese Zucker rats received a continuous sc infusion of vehicle, recombinant human GH, recombinant human IGF-I, or GH plus IGF-I for 14 days (3 mg/kg x day for both GH and IGF-I). Combined GH and IGF-I stimulated body weight gain and in naso-anal length to the same extent as IGF-I alone, whereas GH alone was less potent. Because all treatments stimulated weight linear growth proportionately, the progression of obesity was similar in treated and control animals. However, GH plus IGF-I (but not either agent alone) induced a 25% decrease in the relative weight of inguinal fat. GH and IGF-I exerted distinct effects on the relative weights of liver, kidney, and spleen and on the circulating levels of IGF-I and IGF-binding protein-3. Circulating glucose and insulin levels did not change in any group. In summary, GH plus IGF-I infusions decrease the relative weight of inguinal fat in Zucker rats as in obese GH-deficient dwarf rats; however, this effect is of more modest magnitude despite the use of a 2- to 3-fold higher dose and is limited to the inguinal site. Thus, GH plus IGF-I infusions did not influence the obesity index in Zucker rats. Inasmuch as Zucker rats are a better model of childhood-onset obesity than dwarf rats fed a high fat diet, the present results do not appear promising for extrapolation to clinical studies in children. The mechanisms by which the primary vs. secondary nature of the decreased GH secretion influences the effect of GH plus IGF-I on obesity remain to be determined.

Analysis of Variance↗
PubMed1996

Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors.

Human cDNAs encoding N-methyl-D-aspartate receptor type (NMDAR)1A, NMDAR2A and NMDAR2B subunits were cloned and receptors encoded by these cDNAs were functionally expressed by injection of the respective mRNAs in Xenopus oocytes. The pharmacological properties of recombinant human N-methyl-D-aspartate (NMDA) receptors were characterized by profiling two agonists and four antagonists at both the NMDA and glycine sites in voltage-clamped oocytes. NMDA, glycine and D-serine were significantly more potent at human NMDAR (hNMDAR)1A/2B receptors than at nNMDAR1A/2A, whereas there was no detectable subtype-dependent difference in the potency of glutamate. Of the NMDA-site antagonists tested, CGP 43487 and 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonate exhibited 5.8- and 3.9-fold greater potency, respectively, at hNMDAR1A/2A receptors than at hNMDAR1A/2B. Of the four glycine-site competitive antagonists tested, L-689,560 displayed 5-fold greater potency at hNMDAR1A/2A, whereas 5,7-dichlorokynurenic acid, HA-966 and CGP 58411 did not discriminate between hNMDAR1A/2A and hNMDAR1A/2B. Receptors resulting from injection of hNMDAR1A, hNMDAR2A and hNMDAR2B transcripts in a 1:1:1 ratio were indistinguishable from hNMDAR1A/2B receptors in terms of their sensitivity to NMDA, glycine, D-serine, CGS 19755 and CGP 40116. Ifenprodil was approximately 350-fold more potent at hNMDAR1A/2B than at hNMDAR1A/2A receptors. Ifenprodil sensitivities of receptors formed in oocytes injected with a constant amount of hNMDAR1A mRNA but varying ratios of hNMDAR2A or hNMDAR2B mRNAs were compared. The receptors expressed at a 10:1 ratio of 2A:2B transcripts displayed an ifenprodil sensitivity that would be predicted for a population in which 51% was represented by hNMDAR(1A)2(2A)3 complexes. Our results underscore the need for subtype-selective compounds acting at novel sites to sufficiently probe the pharmacological differences between NMDA receptor subtypes formed by different subunit combinations.

Animals↗
PubMed1996

Stable expression and characterization of recombinant human heteromeric N-methyl-D-aspartate receptor subtypes NMDAR1A/2A and NMDAR1A/2B in mammalian cells.

The electrophysiological and pharmacological properties of two mammalian cell lines stably transfected with cDNAs encoding recombinant human N-methyl-D-aspartate (NMDA) receptor subtypes NMDAR1A/2A and NMDAR1A/2B are described. In whole-cell electrophysiological recordings, application of NMDA/glycine elicited inward currents at negative holding potentials in human NMDAR1A/2A (hNMDAR1A/2A)- and hNMDAR1A/2B-expressing cells. The current-voltage relationships determined in both cell lines in the presence and absence of external Mg++ were similar to those observed with recombinant rat NMDA receptors. Power spectra calculated from NMDA/glycine-induced currents for both NMDA receptor-expressing cell lines suggested a kinetically homogeneous population of channels. Immunoprecipitation with an anti-NMDAR1A antibody coprecipitated the corresponding NMDAR2 subunit with the NMDAR1A, suggesting that heteromeric complexes are formed in these stable cell lines. Stimulation of NMDA receptors evoked an increase in intracellular Ca++, which was used to characterize their pharmacological properties. NMDA displayed less intrinsic activity than did glutamate in both NMDA receptor-expressing cell lines and was a 4-fold more potent agonist at hNMDAR1A/2B than hNMDAR1A/2A. NMDA/glycine-evoked increases in Ca++ levels were inhibited by CGS 19755, (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate, MK-801, ketamine and ifenprodil. (+/-)-3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonate was a 3-fold more potent antagonist at hNMDAR1A/2A than hNMDAR1A/2B, whereas ifenprodil was markedly more selective toward hNMDAR1A/2B, being 250-fold more potent than against hNMDAR1A/2A. These data suggest that cells stably expressing recombinant heteromeric hNMDAR1A/2A and hNMDAR1A/2B represent pharmacologically valid experimental systems to study human NMDA receptors.

Animals↗
PubMed1995

The use of ultra-low-dose aprotinin to reduce blood loss in cardiac surgery.

One hundred patients due to undergo primary cardiac surgery were prospectively randomized to receive aprotinin or placebo. In the aprotinin group, 250,000 kallikrein inhibitory units (KIU) of aprotinin were added to the cardiopulmonary bypass prime solution. A further 250,000 KIU of aprotinin were infused intravenously over 30 minutes immediately before the start of cardiopulmonary bypass. The control group received 0.9% saline in equal volumes at identical times. The study was designed to have a 90% chance of demonstrating a 30% reduction in blood loss. No significant differences were found between the two groups. The median blood loss in the aprotinin group was 750 mL (interquartile range 556 to 1025 mL, 95% confidence interval 600 to 800 mL). In the control group, the median blood loss was also 750 mL (interquartile range 500 to 988 mL, 95% confidence interval 625 to 925 mL). In the aprotinin group, 12 patients received postoperative autotransfusion of shed mediastinal blood of median volume of 665 mL (interquartile range 500 to 925 mL, 95% confidence interval 450 to 1000 mL). In the control group, 14 patients received postoperative autotransfusion of mediastinal blood of median volume of 663 mL (interquartile range 600 to 800 mL, 95% confidence interval 600 to 700 mL). Five patients in the aprotinin group and seven patients in the control group required postoperative homologous blood transfusion. Reassessment of inclusion criteria showed a 19% reduction in blood loss in patients undergoing only aortocoronary bypass receiving aprotinin compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗
PubMed1994

Admissions to a pediatric intensive care unit for status epilepticus: a 10-year experience.

OBJECTIVE: To characterize the etiology, course, and prognosis in children admitted to a pediatric intensive care unit (ICU) for status epilepticus. DESIGN: Retrospective, descriptive study. SETTING: Pediatric ICU in a university hospital. PATIENTS: One hundred forty-seven children admitted with status epilepticus. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Status epilepticus was defined as a prolonged (> 30 mins) or repeated tonic or tonic-clonic seizure with a persistent altered state of consciousness. Over 10 yrs, 147 children 0 to 16 yrs of age (median 1; mean 3.4 +/- 3.9 [SD]) were admitted to a pediatric ICU for, or with, 153 episodes of status epilepticus. Status epilepticus was caused most often by epilepsy (n = 52), atypical febrile convulsions (n = 21), bacterial meningitis (n = 20), encephalitis (n = 20), intoxication (n = 8), or a metabolic disorder (n = 12). Two infants, 1 and 3 months of age, and a patient with intoxication by isoniazid, responded to pyridoxine. Among 114 previously normal children, 34 patients displayed a new neurologic problem on discharge from the ICU, among whom, 68% (23/34) still had some neurologic abnormality 1 yr after the episode of status epilepticus. Nine patients died during their ICU stay, mostly from underlying disease rather than from the status epilepticus itself. A normal neurologic status before status epilepticus and age < 4 yrs seem to be markers of good prognosis, while encephalitis and meningitis appear to be markers for morbidity and mortality. CONCLUSIONS: Most cases of status epilepticus were caused by epilepsy, atypical febrile seizure, encephalitis, meningitis, or metabolic disease. The mortality rate during the ICU stay was 6%. The prognosis was good in most surviving cases, more so if the neurologic development of the child was normal before the status epilepticus.

Adolescent↗
PubMed1993

Functional polymorphism in the parental imprinting of the human IGF2R gene.

The murine genes coding for insulin-like growth factor II (Igf2) and its specific receptor (Igf2r) are parentally imprinted, with exclusive expression from the paternal (Igf2) or maternal (Igf2r) gene copy. We have demonstrated that the human IGF2 gene is imprinted, like its murine homologue. To examine whether the human IGF2R is also imprinted, we used CA repeat polymorphisms of the cDNA sequence to distinguish expression from each copy. Unlike the mouse, most subjects equally expressed both gene copies. However, two out of 14 informative fetuses showed exclusive expression from the maternal gene copy. We conclude that the human IGF2R gene is parentally imprinted, like its murine homologue, but only in a minority of individuals. This is the first direct demonstration of imprinting as a polymorphic trait, a property that had been observed in transgene methylation and predicted from the behavior of certain human tumors.

Animals↗
PubMed1993

Parental genomic imprinting of the human IGF2 gene.

The mouse igf2 gene, coding for the insulin-like growth factor II (IGF-II) is parentally imprinted, only the gene copy derived from the father is expressed. To know whether IGF2, the human homologue, is also imprinted, we used an ApaI polymorphism at the 3' untranslated region in order to distinguish between mRNA derived from each copy of the gene in placentae from heterozygote human fetuses, studied after careful removal of the decidua. Six term and two pre-term placentae of heterozygotes were studied, and in each case the cDNA contained only one of the two alleles present in the genomic DNA. In three cases the mother was homozygous for the non-expressed allele, allowing assignment of paternal origin to the transcribed gene copy. We conclude that, as in the mouse, human IGF2 is parentally imprinted.

Alleles↗
PubMed1991

Pseudomonas aeruginosa exoenzyme S is an adhesion.

Exoenzyme S from Pseudomonas aeruginosa has been studied as an adhesion for glycosphingolipids and buccal cells. Binding of exoenzyme S to gangliotriosylceramide (GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer), gangliotetraosylceramide (Gal beta 1-3 GalNAcT beta 1-4 Gal beta 1-4Glc beta 1-1Cer), and lactosylceramide (Gal beta 1-4Glc beta 1-1Cer) separated on thin-layer chromatograms was observed. Binding curves for exoenzyme S with dilutions of gangliotetraosylceramide immobilized on plastic plates were similar to previously reported results for the intact bacteria. Binding of exoenzyme S to sialylated counterparts of these glycosphingolipids was not seen, indicating that the addition of a sialic acid residue interferes with binding. Exoenzyme S and monoclonal antibody to exoenzyme S inhibit the binding of P. aeruginosa to buccal cells. The presence of exoenzyme S on the surface of P. aeruginosa was detected by immunogold labeling of bacteria with antibodies to exoenzyme S. Results of these studies led us to conclude that exoenzyme S is an important adhesion of P. aeruginosa.

ADP Ribose Transferases↗
PubMed1989

Decompensated cardiomyopathy mimicking hepatitis in a 13-year-old girl.

The name of a 13-year-old girl diagnosed as having idiopathic dilated cardiomyopathy was removed from the cardiac transplant list because a hepatitis-like picture developed that coincided with evidence of decompensation of her cardiac function. On admission, there was only modest evidence of cytolysis (ALT level, 115 U/L) and of cholestasis (bilirubin level, 3.0 mg/dl), but there was severe prolongation of her prothrombin time (28 s). This was followed by elevation of both her transaminases and bilirubin levels. A liver biopsy sample showed extensive necrosis involving both the central and midlobular zones, while periportal areas revealed dilated sinusoids and steatotic multinucleated hepatocytes. A brief improvement of both her liver and her heart was followed by rapid deterioration of the functions of both. Attention is drawn to the relationship between reduced cardiac output and hepatic dysfunction secondary to massive cytolysis.

Adolescent↗
PubMed1988

Identification of carbohydrate structures that are possible receptors for Neisseria gonorrhoeae.

Different strains and isogenic variants of Neisseria gonorrhoeae were assayed for their ability to bind glycolipids extracted from various sources. Among a large number of reference glycolipids, binding was observed only to lactosylceramide [Gal(beta 1-4)Glc(beta 1-1)Cer], isoglobotriaosylceramide [Gal(alpha 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer], gangliotriaosylceramide [GalNAc(beta 1-4)Gal(beta 1-4)Glc(beta 1-1)Cer], and gangliotetraosylceramide [Gal(beta 1-3)GalNAc(beta 1-4)Gal(beta 1-4)Glc(beta 1-1)Cer]. The latter two glycolipids bound gonococci with the highest affinity. Lactosylceramide and gangliotriaosylceramide were found in glycolipid preparations from ME180 cells, an epithelial cell line derived from a human cervical carcinoma, and thus are possible receptors for gonococci. The gonococcal surface component that bound the above glycolipids is a protein distinct from pilin and protein II.

Animals↗
PubMed1988

Rheumatoid arthritis of the cervical spine: surface-coil MR imaging.

Fifteen patients with classic rheumatoid arthritis were investigated with plain films, pluridirectional tomography, and surface-coil T1-weighted MR imaging at 500/17 (TR/TE). We evaluated the atlantodental interval; basion-dental interval; density or intensity of the dens; dens erosion; cranial settling; anterior, posterior, lateral, or rotatory atlantoaxial subluxation; subaxial subluxation; ligamentous calcification or osteophytes; erosion; cystic changes; joint-space narrowing of the apophyseal articulations; and posterior spinous process erosion. In addition, the cervicomedullary angle and the neuraxis configuration were identified on MR images. To determine its normal range, the cervicomedullary angle was measured in 50 patients whose MR studies were unrelated to the craniovertebral junction. All patients with a cervicomedullary angle less than 135 degrees had evidence of brainstem compression, cervical myelopathy, or C2 root pain. Also, all patients with cervicomedullary junction compression were neurologically abnormal. MR was found to be as good as tomography in evaluating the atlantodental interval, dens erosion, ligamentous calcification or osteophytes of the upper spine, subaxial subluxation, and various subluxations that occur in the occiput-C2 area. MR was less effective than tomography in evaluating the basion-dental interval, erosion of the posterior spinous processes, apophyseal joint disease from C3 inferiorly, and cystic changes of the articular facets of C1-C2. The most clinically important parameters were well seen with MR. The data show that MR is an excellent imaging procedure for evaluating rheumatoid arthritis of the cervical spine.

Adult↗
PubMed1986

An improved technique for long saphenous vein harvesting for coronary revascularization.

A prospective study was undertaken to assess the functional quality of long saphenous vein for coronary revascularization when it has been harvested by means of multiple small incisions and use of the Mayo "stripper." This avoids a "long cut" and the major wound problems commonly associated with it. Between January, 1979, and July, 1984, 2,439 patients underwent coronary artery bypass graft with long saphenous vein harvested by this technique. No major wound problems occurred, and minor wound problems were seen in only 23 patients (0.9%). Vein quality was assessed by histological studies of veins, postoperative graft angiography, and exercise testing. Both light electron microscopy and scanning electron microscopy demonstrated that the vein was of good quality and that the intima had been preserved. Postoperative graft angiography and exercise testing confirmed high patency rates for the vein grafts (93%). Vein harvesting with this technique is easy, gives good quality vein, both morphologically and functionally, for grafting, is associated with a minimum of wound problems, and has cosmetically superior results.

Adult↗
PubMed1986

Long saphenous vein harvesting.

There is described an easy and rapid technique using the Mayo Vein Stripper to facilitate safe harvesting of the long saphenous vein for vascular reconstruction. It provides good quality vein and a superior cosmetic result without wound complications.

Coronary Artery Bypass↗