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Biomedical subjects

J T Davis

Publications and source records attributed to J T Davis.

At least 55 records · Page 3Linked to original sources

Retinol processing by the peritubular cell from rat testis.

The cells that surround and support the seminiferous epithelium of the tubules in the testis, i.e., the peritubular or myoid cells, are known to contain relatively high amounts of cellular retinol-binding protein (CRBP). This suggests that they may play an important role in the movement or metabolism of retinol (vitamin A alcohol), which is required for the maintenance of spermatogenesis. Peritubular cells in culture, isolated from the testes of the 20-day-old rat, maintained high levels of CRBP and had the ability to internalize retinol from retinol-binding protein (RBP), the blood transport protein for retinol, in a manner suggesting a receptor-mediated process. Little of the internalized retinol was esterified, in contrast to what occurs in other cell types that contain high amounts of CRBPs, and very little, if any, lecithin-retinol acyltransferase activity was present in microsomes obtained from the cultured cells. The cells did, however, have the ability to synthesize and release their own RBP to the medium. This suggests that retinol from the blood may actually reach the seminiferous epithelium by passing across the peritubular cell, released on a new molecule of RBP, rather than by entering into the tubule bound to the preexisting RBP present in the interstitial fluid.

Acyltransferases↗

Standardizing care delivery for infants and children with common congenital cardiac lesions.

The emergence of managed care is influencing the practices of pediatric cardiology and cardiac surgery. The need for efficiencies brought about by standardizing care whenever possible has led to the development of care guidelines and clinical pathways. Care guidelines are general algorithms mapping the care of a specific problem. They are patient oriented and cover all aspects of care from diagnosis onward. National task forces have recently published guidelines for the care of children with specific congenital cardiac defects, and some of these are reviewed. Clinical pathways are more specific to an episode of inpatient or outpatient care. They consist of expected defined outcomes of care, including all tests, monitoring, and intervention. In other fields, clinical pathways have been developed for specific diagnoses or procedures. However, in pediatric cardiac surgery, the variety of conditions and operations is so great that two different methods of acuity-based, rather than disease-based, clinical pathway methodologies were developed that have been shown to decrease lengths of stay and hospital charges. Refinement of the system will require more sophisticated data, including the delineation of actual costs rather than charges, along with refinement and standardization of outcomes measurements. With fundamental changes in the delivery system, the roles of the specialist and the primary care physician have undergone changes that will continue to evolve. Vigilance on the part of all providers will be necessary to assure quality of care in this new milieu.

Cardiac Surgical Procedures↗

Synthesis and secretion of retinol-binding protein and transthyretin by cultured retinal pigment epithelium.

Recent studies indicate that the retinal pigment epithelium (RPE) may serve as an extrahepatic source of retinol-binding protein (RBP) and transthyretin (TTR) for the retina by virtue of the fact that this cell layer is the exclusive retinal location for mRNA coding for these proteins [Herbert, J., et al. (1991) Invest. Ophthalmol. Vis. Sci. 32, 302-309; Cavallaro, T., et al. (1990) Invest. Ophthalmol. Vis. Sci. 31, 497-501], although the proteins themselves are present in a variety of retinal neurons. It is therefore necessary to determine whether these mRNAs are translated and whether their translated products are secreted like hepatic RBP and TTR. Metabolic labeling of cultured bovine RPE with [35S]cysteine and [35S]methionine and subsequent analysis of newly synthesized proteins in the conditioned medium by affinity chromatography, gel filtration, partial amino acid sequence analysis, and autoradiography of electrophoretograms indicate that both RBP and TTR are synthesized and secreted by the RPE. Moreover, for cells grown in chambers with permeable supports, the predominant direction for secretion was into the apical medium. The mean apical:basal ratio after 72 h of incubation was 9.2 for TTR and 4.5 for RBP. A function for these proteins in the neurosensory retina remains speculative. They could be involved in the delivery of all-trans-retinol to amacrine and Müller cells as a precursor for retinoic acid, since these cells are known to contain cellular retinoic acid binding protein [Gaur, V.P., et al. (1990) Exp. Eye Res. 50, 505-511; Milam et al. (1990) J. Comp. Neurol. 296, 123-129].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

1H NMR studies on an Asn-linked glycopeptide. GlcNAc-1 C2-N2 bond is rigid in H2O.

The conformation of an Asn-linked glycopeptide in H2O was studied by two-dimensional 1H NMR. Nonexchangeable proton and exchangeable amide (NH) proton resonances were assigned for the hen ovomucoid glycopeptide 1, Ser-Ile-Glu-Phe-Gly-Thr-Asn Ile-Ser-Lys, with pentasaccharide Man alpha 1-3 (Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4GlcNAc beta 1-NH attached to the Asn7 gamma-carboxamide. The pentasaccharide increases the local correlation times of amino acid residues near the N-glycosylation site. Nuclear Overhauser effect (NOE) measurements on 1 and the corresponding Man3-GlcNAc2 pentasaccharide 3 show that the attached peptide does not perturb O-glycoside conformation. Sequential dNN (i, i + 1) NOEs in the Thr6-Ser9 region indicate populations of folded structure near the N-glycosylation site of both glycopeptide 1 and aglycosyl peptide 2. However, the Man3GlcNAc2 pentasaccharide does not dramatically affect the average conformation of either the peptide backbone or the Asn7 side chain. GlcNAc NH protons were studied at pH 3.0; and NOE and 3JNH data were used to constrain the glycopeptide's GlcNAc-1 side chain dihedral angle (tau) (C1-C2-N2-C7(Ac)). The glycopeptide's core GlcNAc-1 C2-N2 side chain bond is not flexible in H2O. A strong GlcNAc-1 NH2-H3 NOE, a medium strength NH2-H1 NOE, and a weak NH2-H2 interaction suggest that GlcNAc-1 has a rigid C2-N2 bond, with tau between 95 and 115 degrees. No evidence was found for intramolecular hydrogen bonds restricting this C2 side chain torsion. It may be that GlcNAc-1's rigid planar N-glycosidic linkage limits the conformational space available to the adjacent C2 acetamido side chain.

Acetylglucosamine↗

Cavopulmonary anastomotic aneurysm: a complication in pulsatile pulmonary arteries.

An aneurysm of a left superior vena cava developed after anastomosis to the left pulmonary artery during repair of an atrioventricular septal defect with a persistent left superior vena cava entering directly into the left atrium. We believe this implies caution should be used in accepting the recent suggestion of using a bidirectional cavopulmonary connection to a pulsatile pulmonary arterial circuit as a way of allowing anatomic correction of atrioventricular septal defect with a small right ventricle.

Aneurysm↗

Coronary artery fistula in the pediatric age group: a 19-year institutional experience.

Ten patients with coronary artery fistulae were identified from records at Columbus Children's Hospital between 1974 and 1993. Clinical presentations of patients were quite variable, from 1 day to 20 years of age. Symptoms ranged from none to severe cardiorespiratory failure requiring extracorporeal membrane oxygenation. Long term follow-up revealed one sudden death and one spontaneous closure of the fistula. This lesion should be ruled out in patients who present as extracorporeal membrane oxygenation candidates. Patients with mild forms of this lesion may be followed up medically if the left to right shunt is inconsequential, because spontaneous closure is a possibility. Because of the risk of sudden death, close long-term follow-up is mandatory even for operated patients, and antiplatelet therapy should be considered for these patients.

Adult↗

Use of cardiac catheterization in pediatric cardiac surgical decisions.

Current practice patterns relating to pediatric cardiac catheterization (Cath) have considerable economic implications. The decreased cost and risk of noninvasive methods such as echocardiography (ECHO) and magnetic resonance imaging (MRI) make them attractive alternative diagnostic methods if they can sufficiently define cardiac anatomy and the need for surgical intervention. We reviewed a recent cardiac surgical series of 465 cases in 1.5 years to determine how often a Cath was performed prior to surgery. Overall, 59.4% of the procedures were preceded by a Cath (76% of open heart operations, and 26.7% of closed heart operations). We specify the situations where we feel enough information is available for preoperative decision making from non-invasive testing, and we present some diagnostic pitfalls that have been encountered.

Cardiac Catheterization↗

Mobility at the TpA cleavage site in the T3A3-containing AhaIII and PmeI restriction sequences.

Lefevre et al. originally observed conformational transitions at the TpA step in the TTAA Pribnow box sequence of the trp promoter [Lefevre, J.-F., Lane, A. N., & Jardetzky, O. (1985) FEBS Lett. 190, 37-40]. In 500-MHz 1H NMR studies on the TnA(n)-containing DNA oligonucleotides [d(CGAGGTTTAAACCTCG)]2, [d(GCTCCTTTAAAGGAGC)]2, and [d(GCCGTTAACGGC)]2, we observe that, in addition to the H2 proton (which resides in the minor groove of DNA), the H8 proton of the first adenine (which resides in the major groove) is also broadened due to motion at the TpA junction. In analogous 16-mers where the T3A3 segment has been replaced by an A3T3 sequence, and therefore contains CA, GA, and AT steps (but no TA steps), all adenine proton resonances are narrow, indicating that the broadening occurs only at TpA steps. Assuming chemical exchange in the form of conformational dynamics, e.g., oscillation of the purine base about the glycosidic torsion angle, the experimental 500-MHz 1H T1 rho and 2D-NOESY data were used to constrain the correlation time of the internal motion to a range between the T1 and T1 rho minima. Calculated line shapes using a two-site exchange model indicate that the motion has an amplitude of 20-50 degrees with an associated tau c of ca. 1.6 x 10(-4) to 1.0 x 10(-5) s rad-1, respectively. The mobility appears to be a consequence of the structure at the TpA junction which is characterized by (1) a wide minor groove between two regions of narrow minor groove, (2) an unusual average orientation of the adenine heterocycle probably resulting from a poor base-stacking interaction of the adenine with the preceding thymine, and (3) a sharp discontinuity in the sugar conformation at the TpA step.

Base Sequence↗

Sequence-selective metal ion binding to DNA oligonucleotides.

Metal ion titrations of several DNA oligonucleotides, 10 dodecamers and one decamer have been monitored by 1H NMR spectroscopy in order to elucidate metal ion binding patterns. Also, the effects of paramagnetic impurities on resonance linewidths and NOESY cross-peak intensities have been reversed by EDTA back-titration experiments. 1H 1D NMR spectra were recorded after successive additions of aliquots of different metal salts to oligonucleotide samples. Paramagnetic manganese(II) salts were used in most cases, but a few samples were also titrated with diamagnetic zinc(II). From this study, we conclude that there exists a sequence-selective metal ion binding pattern. The metal ions bind predominantly to 5'-G in the contexts 5'-GC and 5'-GA. The order of preference seems to be GG > or = GA > GT > > GC. No evidence of metal ion binding to 5'-G in 5'-GC steps or to non-G residues was found. The H6 or H8 resonances on preceding (5'-) bases were affected by the adjacent bound paramagnetic metal ion, but no effect was observed on the protons of the succeeding (3'-) base. The metal binding site in the duplexes is most likely at G-N7, as manifested by the pronounced paramagnetic line broadening or diamagnetic shift of the G-H8 signal. This sequence selectivity may be qualitatively explained by a sequence-dependent variation in the molecular electrostatic potentials of guanine residues (MEPs) along the oligonucleotide chain.

Base Sequence↗

Myxoid heart disease: an assessment of extravalvular cardiac pathology in severe mitral valve prolapse.

Because of the microscopic features of the affected leaflets in mitral valve prolapse (MVP), myxoid degeneration of the valve is a common pathologic designation applied to this condition. We undertook this study as a means of gaining an insight into the occurrence and prevalence of extravalvular cardiac alterations in hearts with severe MVP. Tissues of 24 hearts with severe myxomatous transformation of the mitral valve as the sole cardiac abnormality were examined. Eighteen of the 24 subjects with severe MVP died suddenly. Only two of these had pathologic evidence of severe mitral insufficiency. Twenty-four normal hearts served as controls. The two groups of hearts came from victims of homicide, suicide, accident, or natural death. Sections of the mitral valve, working myocardium, conduction system, and cardiac nerves and ganglia were studied by routine and special connective tissue and proteoglycan stains. Similar to the findings in severely affected mitral valves, prominent deposits of proteoglycans in neural and conduction tissue readily distinguished hearts with myxomatous valve changes from the control hearts. We conclude that the commonly recognized local derangement of valvular tissue in MVP is but one specific reflection of a more general myxomatous alteration in cardiac connective tissue.

Adolescent↗

Synthesis and secretion of retinol-binding protein by cultured rat Sertoli cells.

We report here that retinol-binding protein (RBP) is synthesized and secreted by rat Sertoli cells in culture. This was demonstrated in four ways. First, transthyretin (TTR) bound to Sepharose 4B retained a labeled protein from media collected from Sertoli cells provided with 35S-methionine, under the same conditions as authentic RBP is bound. The protein was co-eluted with authentic RBP by pure water. Second, this same radioactive protein co-eluted with pure RBP upon gel filtration. Third, when subjected to SDS-PAGE, the protein again migrated with pure RBP, as shown by radioautography. Finally, Sertoli cells were incubated with 35S-cysteine and the conditioned medium was put over a TTR-Sepharose column to isolate the radioactive protein, as characterized above. Cysteine residues were oxidized to cysteic acid residues, and the protein was submitted for sequencing through the first ten residues. Radioactivity was located only in the fourth residue, where a cysteine residue is found in rat RBP. This indicates that RBP is secreted by the Sertoli cell and may serve as the carrier of retinol to the developing germ cells, which are known to be dependent upon vitamin A.

Amino Acid Sequence↗

The application of the Screening Cerebral Assessment of Neppe (BROCAS SCAN) to a neuropsychiatric population.

Assessments of higher cortical functioning are often neglected in patients with possible coarse neurobehavioral psychiatric disease, such as dementia, stroke, or focal cerebral lesions. When performed, the short Folstein Mini-Mental State Exam (MMSE) is typically used. The authors' research on 45 neuropsychiatric patients compared the MMSE with a new 20-30-minute bedside examination, the Screening Cerebral Assessment of Neppe (BROCAS SCAN). This screens 10 areas: recall, recognition, orientation, organization of thought, concentration, calculation, agnosia, apraxia, speech, and sensory-motor-reflex phenomena. The BROCAS SCAN (total) correlated extremely well with neuropsychiatric prediction, MRI changes, and neuropsychological testing, and distinguished diagnoses, demonstrating construct and face validity. It also accounted for a larger proportion of variance than the MMSE in correlating with these parameters and was more sensitive in mildly cognitive impaired patients. The briefer first section of the BROCAS SCAN, the core SCAN, also showed statistically relevant relationships to age, diagnosis, MRI, and neuropsychiatric prediction.

Adolescent↗

Prevalence of paediatric cardiac disease in rural Kenya.

A series of 31 patients referred for evaluation of paediatric cardiac disease in rural Kenya is reported. The prevalence of symptomatic rheumatic heart disease is unchanged from previous data in the literature which is well over a decade old. We can conclude that recent improvements in medical care in Kenya have not yet reached certain rural areas as far as rheumatic fever is concerned. In addition, a significant number of children presumed to have had no discernible heart disease at this evaluation, suggesting the need for critical re-evaluation of this population at intervals. Finally, cyanotic disease seems under-represented in the series, suggesting that infants with certain cyanotic lesions may have been selected out and hence not referred to us.

Child↗

Congenital heart disease in Down's syndrome patients: a decade of surgical experience.

Patients with Down's syndrome represent a significant subset of patients with congenital heart disease. Fifty-five patients with Down's syndrome have undergone surgical treatment for congenital heart disease at our institution in the past decade. Twenty-six had atrioventricular canal, 11 had ventricular septal defect, 7 had secundum atrial septal defect, 7 had tetralogy of Fallot, 3 had primum atrial septal defect and 1 patient had double outlet right ventricle. The thirty day mortality following operative intervention was 16.4%. Mortality was highest for tetralogy of Fallot followed by atrioventricular canal and ventricular septal defect. Long term mortality for all lesions was 27.3% over our follow-up period which averaged 33 months. Thirty day mortality compared similarly to previous reports of surgically treated Down's syndrome patients. When compared to our patients without Down's syndrome, the Down's population did not exhibit an increased risk for surgical treatment of congenital heart disease.

Adolescent↗

The cardiac apex and its superficial blood supply.

The cardiac apex was defined and 3 types were presented: the anatomical apex, the base of which was established at the incisura apicis cordis; the amplified anatomical apex, twice the volume of the preceding; and the geometric apex, the distal third of the ventricles. These types of cardiac apex were studied in connection with the superficial branches of the coronary arteries at their level. The investigation was conducted on 81 normal hearts (56 males and 25 females) of 60 Caucasian and 21 non-Caucasian individuals. The arteries were injected with colored gelatine mixed with a radiopaque substance. The number of branches decreased from the geometric (the largest type) to the anatomical apex (the smallest): 27 on the surface of the geometric apex, 14 on the surface of the amplified anatomical apex, and 7 on the surface of the anatomical apex. The sternocostal aspect had a higher number of superficial branches than the diaphragmatic aspect in all types of cardiac apex. Sexual differences were found in the incidence of the r posterior ventriculi sinistri intermedius on the amplified anatomical apex as it was more frequent in females than in males. In the geometric apex there were 3 branches also more frequent in females: r anterior ventriculi sinistri inferior, r posterior ventriculi sinistri lateralis I, and r posterior ventriculi sinistri lateralis IV.

Adolescent↗