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Biomedical subjects

L Smith

Publications and source records attributed to L Smith.

At least 577 records · Page 32Linked to original sources

Benefits of early predoctoral experiences in longitudinal patient care.

A ten-year experience with a continuity clerkship taught to second-year medical students is described. Students enrolled in this course spend one half-day per week for nine months with a practicing family physician, attend a weekly seminar or workshop, and write a longitudinal patient care report. This comprehensive report summarizes their experience with a patient or a family and addresses pertinent medical and psychosocial issues. Forty-four of these reports were analyzed for the 1981-82 academic year. The analysis revealed that the main benefits to the students from the longitudinal experience were (1) recognizing the importance of continuity of care, (2) observing the interplay between the social environment, family, and the patient's health, (3) gaining insight into the role of the family physician, and (4) experiencing the difficulties of chronic disease management.

Adult↗

Reaction of cytochrome c in the electron-transport chain of Paracoccus denitrificans.

The reaction of the cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) of Paracoccus denitrificans cytoplasmic membranes with the endogenous cytochrome c of the membranes was studied, as well as its interaction with added exogenous cytochrome c from P. denitrificans or bovine heart. The polarographic method was employed, using N,N,N',N'-tetramethyl-p-phenylenediamine plus ascorbate to reduce the cytochrome c. We found that overall electron transport can proceed maximally while the cytochrome c remains membrane bound; NADH or succinoxidase activities were not inhibited by the addition of substances which bind the P. denitrificans cytochrome c strongly. In contrast to our observations with the spectrophotometric method (Smith, L., Davies, H.C. and Nava, M.E. (1976) Biochemistry 15, 5827-5831), in the polarographic assays the membrane-bound oxidase reacts with about equal rapidity with exogenous bovine and P. denitrificans cytochromes c. The reaction of the oxidase with the endogenous cytochrome c proceeds at high rates and preferentially to that with exogenous cytochrome c; the reaction with the latter, but not the former is inhibited by positively charged poly(L-lysine). The cytochrome c and the oxidase appear to be very closely associated on the membrane.

Animals↗

Intracisternal A-particle genes as movable elements in the mouse genome.

We analyzed two functionally defective mouse kappa light chain gene variants previously shown to contain novel insertions of repetitive DNA in their intervening sequences [Hawley, R. G., Shulman, M. J., Murialdo, H., Gibson, D. M. & Hozumi, N. (1982) Proc. Natl. Acad. Sci. USA 79, 7425-7429]. Heteroduplex analysis of the cloned genes shows that the insertions consist of intracisternal A-particle (IAP) genetic elements. Each insertion includes an IAP 5' long terminal repeat (LTR) sequence and extends to a characteristic IAP internal BamHI site where the IAP sequence is interrupted because the mutant genes were cloned from complete BamHI digests of the cellular DNAs. Restriction enzyme mapping indicates that the 5' LTR boundaries of the inserted IAP elements correspond closely to the previously determined rearrangement sites in the mutant genes. The IAP insertions in the two mutants can be distinguished by restriction-site differences and by the fact that one of them contains a deletion that is absent in the other. Nucleotide sequence data are presented for the LTRs of one full-length IAP gene copy randomly selected from a mouse genomic DNA library. These LTRs show many features typical of known integrated retroviral terminal repeat units, and the entire gene is bracketed by short direct repeats within the adjacent cellular DNA. Thus, the findings show that IAP genetic elements can appear in new locations in mouse cellular DNA and suggest that this may occur through a process of proviral insertion.

Animals↗

A conceptual model of families incorporating an adolescent mother and child into the household.

This study explores the normative course of family development in families incorporating a teenage mother and her child into the household during the infant's first year. An exploratory, factor-isolating design was used to generate this conceptual model. A developmental framework of family life cycle theory provides the conceptual orientation for the study. Qualitative family data were collected and analyzed according to the constant comparative method. Implications for research and theory development, particularly with regard to clinical practice, are identified.

Adaptation, Psychological↗

Pre-operative localisation of parathyroid tumours using neck vein catheterisation and radioimmunoassay for parathyroid hormone: the Glasgow experience.

Reliable pre-operative localisation of parathyroid tumours can be of value in surgery for primary hyperparathyroidism, and particularly so where re-exploration of the neck is required. Neck vein catheterisation and parathyroid hormone radioimmunoassay have been suggested as a sensitive means of tumour localisation, and we report our experience of the technique over the last five years. A total of 46 patients with primary hyperparathyroidism had 50 studies performed with positive localisation and a pre-operative prediction made on 38 occasions (76%). Forty-two operations were carried out and a parathyroid tumour confirmed in 39 cases for a localisation efficiency of 69 per cent. No negative neck exploration followed a positive localisation. Twelve studies were performed in patients with renal osteodystrophy and localisation to a single site was achieved on only three occasions. It is concluded that neck vein catheterisation and parathyroid hormone assay can correctly localise parathyroid tumours in most cases of primary hyperparathyroidism, but it is suggested that its use be restricted to selected cases such as those subjects with previous negative neck exploration or patients for whom prolonged or repeated surgery may be a particular hazard.

Adenoma↗

The localisation of parathyroid tumours--a comparison of computed tomography with cervical vein hormone assay.

Computed tomography has been employed for the localisation of parathyroid tissue in 26 patients with primary hyperparathyroidism. In 14 of these selective venous catheter studies with parathyroid hormone assay were also undertaken. Computed tomography proved unreliable, identifying only 39 per cent whereas the cervical venous hormone assay studies localised 69 per cent of lesions correctly--a figure which is in agreement with several other groups. On balance our results suggest that neither technique should be routinely employed pre-operatively but that, following unsuccessful parathyroid surgery, the most useful localisation technique remains venous hormone assay.

Adenoma↗

Metabolism of benzo(a)pyrene and 1-naphthol in cultured human tumorous and nontumorous colon.

The oxidative metabolism of benzo(a)pyrene and the conjugative metabolism of 1-naphthol by explant cultures of normal human colon and colonic tumor tissue, obtained at surgery, have been studied. After 24 hr in culture, the explants were exposed to either [1-14C]-1-naphthol (20 to 100 microM) or [3H]-benzo(a) pyrene (1.5 microM) for a further 1.5 to 24 hr. Both normal-appearing tissue and tumor tissue metabolized benzo(a)pyrene to a wide variety of organic solvent-soluble metabolites, including monohydroxybenzo(a)pyrenes, dihydrodiols, and tetrols. 1-Naphthol was metabolized by cultured human colonic mucosa and tumor tissue to both its glucuronic acid and sulfate ester conjugates. In the normal tissues, with naphthol (20 microM), sulfate ester conjugation predominated. However, with the tumor tissue, sulfate ester conjugation decreased; thus, the percentage of glucuronic acid conjugates, expressed as a percentage of total metabolites formed, was increased significantly compared to normal tissue. The relationship, if any, of these changes to neoplastic transformation is unclear. The technique of explant culture described in this study may be of use for the study of other facets of the pathobiology of solid tumors.

Adenocarcinoma↗

Prognostic factors at the time of renal retransplantation.

One hundred and eighty-two patients with a second cadaver (CD) transplant performed during 1969-80 showed similar patient and graft survival to that of 535 recipients of first CD grafts. Loss of the first graft after 12 months resulted in a significantly higher second graft survival (GS II) than loss in early acute rejection within three months, 71 per cent vs 34 per cent at one year (p less than 0.01). A high frequency of presensitised patients was observed (53%) which negatively influenced the GS II, at one year 55 per cent vs 40 per cent for patients without and with antibodies (p less than 0.01). A good HLA-A, B match and absence of antibodies positively influenced GS II. Blood transfusions prior to the first transplantation did not influence survival of the second graft.

Adult↗

Dysrhythmias following the Senning operation for dextro-transposition of the great arteries.

Twenty-nine patients have undergone the Senning operation for repair of dextro-transposition of the great arteries (TGA) since 1979 at St. Louis Children's Hospital. The early mortality has been comparable to that reported for the Mustard operation (10%). Electrocardiograms (ECGs) following the Senning operation reveal abnormalities similar to those noted after the Mustard operation; 63% of survivors were in normal sinus rhythm 1 week postoperatively, and 86% demonstrated normal sinus rhythm at a mean of 15 months after operation. Twenty-four hour ambulatory monitoring revealed normal sinus rhythm in 35% and occasional premature atrial or ventricular contractions in another 30%. No cases of sudden unexpected death have been noted, and no pacemakers have been inserted. Possible mechanisms for rhythm disturbances following venous transposition operations are discussed.

Arrhythmias, Cardiac↗

Neutrophils and zinc in infection-prone children with sickle cell disease.

Neutrophils can be distinguished as EA negative (EA-N) or EA positive (EA+N), according to rosette formation with sheep erythrocytes. EA- neutrophils show a bactericidal activity 50% to 70% lower than EA+ neutrophils. Thirty children with sickle cell disease were studied during steady state and crises/infections, together with matched control children. EA+ and EA- neutrophils, zinc levels in the body, and frequency of previous bacterial infection were evaluated. Sixty percent of the patients (18/30) had zinc deficiency (zinc less than 8.5 micrograms/10(10) RBC): of this group, more than three fourths (14/18) had a high frequency of infections (greater than or equal to 3/yr) and most of those (11/14) also had an increased percentage of EA- neutrophils (80% to 85% v 35% to 45% in control subjects). Only 4/18 of patients with zinc deficiency had a low frequency of infections, and only one of these four had a higher percentage of EA- neutrophils. In patients with normal zinc levels (12/30 or 40%), only three had frequent infections, but only one of these had an increased percentage of EA- neutrophils. The number of EA+ neutrophils increased after stimulation with epinephrine or during crises/infections. In six patients with more pronounced zinc deficiency and more severe crisis/infection, a delay in the increase of EA+ neutrophils occurred and was corrected by treatment. These findings suggest that a higher percentage of neutrophils with less bactericidal activity in many children with sickle cell disease and zinc deficiency may be a factor in the higher incidence of infections noted in these patients, and zinc might play a role in the formation, release, and activity of neutrophils.

Adolescent↗

Transfilter studies on the mechanism of epitheliomesenchymal interaction leading to chondrogenic differentiation of neural crest cells.

Interaction with an epithelium is a prerequisite for avian cranial neural crest (NC) cells to differentiate into cartilage and bone (Bee & Thorogood, 1980). In order to investigate the causal mechanism we have selected one such interaction - that between mesencephalic NC and retinal pigmented epithelium (RPE) for further study. Premigratory NC cells were grown transfilter to RPE explants of different developmental ages and on Nuclepore filters of different pore size which either allowed or prevented penetration by cell processes. Initial scanning electron microscopy (SEM) observations established that pores of 0.8 microns allowed the passage of cell processes through the filter whereas 0.2 microns pores did not. The transfilter experiments demonstrated that chondrogenic differentiation of NC cells will occur only if the Nuclepore filters have a pore size large enough to permit the passage of cell processes. Furthermore SEM observations established that cell processes do traverse the Nuclepore filter when NC and RPE are grown in transfilter combination. The results indicate that the mechanism is not mediated by diffusable factors but rather is mediated either by direct contact between NC cells and non-diffusable matrix closely associated with RPE or by direct plasmalemmal contact between RPE and NC cells through discontinuities in the basement membrane. The results of these experiments also demonstrate that younger (stage 17) RPE is more effective at eliciting chondrogenesis from premigratory NC cells than older (stage 24) RPE and that the interaction between RPE and NC cells is a prolonged one, taking place over days rather than within hours. Both of these in vitro observations are compatible with the timing of events leading to scleral cartilage formation in vivo.

Animals↗

Increases in cytochrome p-450 in cultured hepatocytes mediated by 3- and 4-carbon alcohols.

The amount of cytochrome P-450 was increased to different extents after treatment of cultured chick embryo hepatocytes with n-propanol, isopropanol, n-butanol, or isobutanol. These increases were associated with increases in benzphetamine demethylase activity, a cytochrome P-450-catalyzed oxidation, and glucuronidation of phenol red, catalyzed by UDP-glucuronyl transferase. The responses were similar to those obtained with ethanol or propylisopropylacetamide, which the phenobarbital-like inducers. Pretreatment of cells with cycloheximide prevented the increases in both cytochrome P-450 and glucuronidation of phenol red, indicating that protein synthesis was required for these responses.

Alcohols↗

The reaction of the trifluoromethylphenylcarbamylated lysine-13 derivative of horse cytochrome c with cytochrome oxidase.

The kinetics of oxidation of horse cytochrome c and the trifluoromethylphenylcarbamylated lysine-13 derivative by cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, EC 1.9.3.1) were compared using both spectrophotometric and polarographic methods under different experimental conditions. The rate constants measured spectrophotometrically in 0.025 M tris-cacodylate buffers were similar with the two cytochrome at pH 7.8, but those with the derivative were slightly higher at pH 6. Rates measured with polarographic assays in these buffers were the same with the horse and the derivative cytochromes c at pH 6, but at pH 7.8 the rates with the derivative were less at cytochrome c concentrations between 0.05 and 0.5 micro M and were greater at higher concentrations. The pH optima in the polarographic assays of the derivative and the native pigments were different in 0.025 M Tris-cacodylate buffers; in spectrophotometric assays at pH 7.8 the trifluoromethylphenylcarbamylated lysine-13 cytochrome c showed a greater sensitivity to changes in ionic strength than did the native cytochrome. The variations in apparent Km and V values calculated from spectrophotometric and polarographic assays with the two cytochromes cannot be explained as due to changes in binding of cytochrome c to cytochrome oxidase. The large excess of O2 uptake seen in polarographic assays with horse cytochrome c over that expected from spectrophotometric measurements was not apparent with the trifluoromethylphenylcarbamylated lysine-13 derivative. Thus, the derivative seems to have decreased ability to form the combination of cytochrome c with the oxidase giving high turnover rates.

Animals↗

Effect of wheat germ agglutinin on the viscoelastic properties of erythrocyte membrane.

The elasticity and viscosity of the human erythrocyte membrane were measured as a function of the concentration of wheat germ agglutinin (WGA) in a suspending solution containing 1 mg/ml albumin, approximately 5 X 10(5) cells/ml and between 0.0 and 0.2 microgram/ml WGA. Membrane elasticity was characterized by the elastic shear modulus, which provided a measure of the resistance of the membrane to constant-area elastic deformations that occurred in the membrane plane. The elastic shear modulus was determined by aspirating a portion of the membrane into a micropipette and measuring the extension of the membrane into the pipette as a function of the suction pressure. The results indicated no significant change in shear modulus for concentrations of WGA between 0.0 and 0.2 microgram/ml. Membrane viscosity was characterized by the coefficient of surface viscosity, which, in effect, was a measure of the membrane's resistance to rates of deformation. This coefficient was determined from the time required for an erythrocyte to recover its undeformed shape after it had been elongated by the application of an equal and opposite force applied at diametrically opposite points on the erythrocyte rim. The value for the coefficient of surface viscosity was found to increase by a factor of almost three when the WGA concentration was increased from 0.0 to 0.2 microgram/ml. These results indicated that, in the presence of albumin, WGA can increase membrane dissipation (viscosity) without altering the structural rigidity (elasticity) of the membrane.

Erythrocyte Membrane↗