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J D Smith

Publications and source records attributed to J D Smith.

At least 163 records · Page 9Linked to original sources
PubMed1995

Common genetic variation in the promoter of the human apo CIII gene abolishes regulation by insulin and may contribute to hypertriglyceridemia.

Overexpression of plasma apolipoprotein CIII (apo CIII) causes hypertriglyceridemia in transgenic mice. A genetically variant form of the human apo CIII promoter, containing five single base pair changes, has been shown to be associated with severe hypertriglyceridemia in a patient population. In animals and in cultured cells the apo CIII gene is transcriptionally downregulated by insulin. In this study we demonstrate that, unlike the wild-type promoter, the variant promoter was defective in its response to insulin treatment, remaining constitutively active at all concentrations of insulin. The loss of insulin regulation was mapped to polymorphic sites at -482 and -455, which fall within a previously identified insulin response element. Loss of insulin regulation could result in overexpression of the apo CIII gene and contribute to the development of hypertriglyceridemia. The variant apo CIII promoter is common in the human population and may represent a major contributing factor to the development of hypertriglyceridemia.

Alleles↗
PubMed1995

Fibrous dysplasia: a case report.

Fibrous dysplasia is a benign fibro-osseous disorder that often affects both the maxilla and mandible. The dentist, therefore, is often the first person to identify and diagnose the disease. This article focuses on the pathology, diagnosis, clinical course, and treatment of this complex problem. A case report demonstrates the multidisciplinary approach to the management of this disease entity.

Adolescent↗
PubMed1994

The selective antiproliferative effects of alpha-tocopheryl hemisuccinate and cholesteryl hemisuccinate on murine leukemia cells result from the action of the intact compounds.

In the present study we have established that the antitumor activity of alpha-tocopheryl succinate (TS, vitamin E succinate) and cholesteryl succinate (CS) result from the action of the intact TS and CS compounds and not from the release of alpha-tocopherol, cholesterol, or succinate. We report that treatment of murine leukemia cell lines C1498 (myeloid) and L1210 (lymphocytic), with the tris salts of TS or CS, but not alpha-tocopherol and tris succinate or cholesterol and tris succinate, significantly inhibit the growth of these tumor cells and significantly enhance doxorubicin-induced tumor cell kill in a similar fashion. In contrast, the treatments mentioned above did not adversely affect the growth of murine normal bone marrow cells (colony-forming unit-granulocyte-macrophage). In fact, colony-forming unit granulocyte-macrophage cell growth was stimulated by exposure to CS and TS (as well as their ether analogues) at concentrations above 100 microM. Furthermore, pretreatment of colony-forming unit granulocyte-macrophage cells with TS or CS appears to protect these normal cells from the lethal effect of doxorubicin exposure. Selective inhibition of leukemia cell proliferation (identical to that noted for CS and TS) was also observed following the treatment of cells with the nonhydrolyzable ether forms of CS (cholesteryloxybutyric acid) and TS (alpha-tocopheryloxybutyric acid). These findings suggest that TS, alpha-tocopheryloxybutyric acid, CS, and cholesteryloxybutyric acid may prove clinically useful as selective antitumor agents when administered alone or in combination with doxorubicin by a route that ensures tissue accumulation of the intact compound.

Acute Disease↗
PubMed1994

Inhibition of cholinesterase activity by tetrahydroaminoacridine and the hemisuccinate esters of tocopherol and cholesterol.

The anticholinesterase properties of tetrahydroaminoacridine (THA, Tacrine), alpha-tocopheryl hemisuccinate (TS), and cholesteryl hemisuccinate (CS), given alone and in combination, were examined in vitro. Results from these studies indicate that: [1] THA is a potent inhibitor of acetylcholinesterase (AChE, IC50 of 0.40 microM) and butyrylcholinesterase (BChE, IC50 of 0.10 microM) with greatest inhibitory activity towards BChE; [2] TS and CS are weak inhibitors of BChE (IC50 of 100 microM and 168 microM, respectively) but potent inhibitors of ACHE (IC50 of 1.73 microM and 0.79 microM, respectively); [3] both TS and CS treatment in combination with THA significantly increased THA's anticholinesterase activity. The percentage AChE inhibition observed with this combination was often significantly greater than the sum of the individual values (synergistic). The addition of 0.5 microM CS or TS to an ACHE preparation reduced THA's IC50 value from 0.40 microM or 0.18 microM, respectively [4]; inhibition of AChE by THA, TS and CS are mixed non-competitive while THA inhibition of BChE is mixed non-competitive and TS and CS inhibition of BChE are simple non-competitive; and [5] inhibition of cholinesterases by TS and CS occurs immediately (50 to 75%), during the first 30 min of incubation (25 to 50%) and is dependent on the anionic charged portion of the molecule. In conclusion, our experimental data indicate that TS and CS are potent inhibitors of AChE activity and significantly potentiate the anticholinesterase activity of THA. Such potent and synergistic inhibition of AChE suggest that TS or CS, alone and in combination with THA, may prove beneficial in the treatment of organophosphate poisoning and Alzheimer's disease.

Acetylcholinesterase↗
PubMed1994

What child is this? What interval was that? Familiar tunes and music perception in novice listeners.

In the laboratory, musical novices often seem insensitive even to basic structural elements of music (octaves, intervals, etc.), undermining long-held theories of music perception, and threatening to leave current theories applicable only to experts. Consequently it is important to demonstrate novices' basic listening competence where possible. Two experiments examined the perception of musical intervals (minor thirds, major thirds and perfect fourths) by musical novices. Subjects received either standard instructions or familiar folk-tune labels to aid performance. The folk-tune labels greatly improved identification performance, producing expert-caliber performance by some musically inexperienced subjects. The effectiveness of the folk-tune manipulation was much more limited in a difficult discrimination task. The results suggest that novices do have some basic competence when assayed appropriately, and that familiar musical tokens may be a critical element in such assays. Larger implications of the role of familiarity in novices' competence are discussed, including those that relate to music cognition and aesthetics.

Adolescent↗
PubMed1994

Reactions of Ugandan antisera with peptides encoded by V3 loop epitopes of human immunodeficiency virus type 1.

The specificities of antibodies reacting with peptides encoded by V3 loop apical epitopes were determined for sera from 230 seropositive Ugandans, including asymptomatic persons and AIDS patients, sampled between 1986 and 1992. Most (71%) of the sera reacted with the peptide encoded by HIV-MN, 59% reacted with a peptide containing a consensus sequence for Ugandan variants of the HIV-1 global subtype A (referred to as the Uganda A consensus), 59% reacted with a peptide containing a consensus sequence for Ugandan variants of the global subtype D (the Uganda D consensus); 19% of the sera also reacted with peptides encoded by the divergent Ugandan variant U31. There was no obvious correlation between the specificities of antibody binding and the V3 loop sequence of the corresponding virus isolate or provirus. Competitive inhibition and antibody adsorption experiments indicated that the MN peptide, the Uganda A consensus peptide, the Uganda D consensus peptide, and the U31 peptide were recognized by different sets of antibodies. Eighteen percent of the sera from AIDS patients and 26% of the sera from asymptomatic persons were monospecific for one of the MN, Uganda A, or Uganda D peptides. Whereas all except one of the singly reactive AIDS sera were specific for MN, 39% of the singly reactive asymptomatic sera were specific for MN, 39% for the Uganda A peptide, and 21% for the Uganda D peptides. We conclude that analysis of the specificities of antibodies against the V3 loop epitopes in sera from asymptomatic persons could provide useful epidemiological data about the prevalence of viral subtypes within a population.

Adult↗
PubMed1994

Definition of TCR recognition sites on Ld-tum- complexes.

The P911 variant of the P815 mastocytoma was shown by Lurquin et al. (Cell 58:293, 1989) to elicit rapid tumor rejection in a syngeneic host. This rejection was mediated by Ld-restricted cytotoxic T lymphocytes (CTL) for which targets could be sensitized by the synthetic peptide designated tum- (P91A-.12-24). In a previous study, T cell clones specific for Ld-tum- complexes displayed very restricted TCR usage and a characteristic TCR motif in the V alpha CDR3 region, predicted to interact with peptide. However, in contrast to the majority of Ld peptide ligands that are nonamers, the tum- peptide is a 13-mer and its sequence does not fit the Ld binding motif. Thus, to define shorter versions of the tum- 13-mer and residues involved in TCR recognition, nonamer derivatives were synthesized and compared in several different binding and functional assays. From these comparisons, the peptide TQNHRALDL was found to be the optimal nonamer. CTL recognition of Ala-substituted analogues of this peptide indicated that the His and Arg residues at positions 4 and 5 are important for TCR contact. We propose that these basic residues of the tum- peptide interact with the previously defined acidic residues in the CDR3 region of several TCR known to recognize Ld-tum- complexes.

Amino Acid Sequence↗
PubMed1994

Physical activity patterns among adults in Georgia: results from the 1990 Behavioral Risk Factor Surveillance System.

Regular physical activity increases a person's ability to perform daily activities more efficiently, reduces the risk of specific chronic diseases, including coronary artery disease, and lowers death rates in general. The Healthy People 2000 Physical Activity and Fitness Objectives underscored the importance of monitoring and tracking the prevalence of physical activity and fitness in the United States population for the purpose of planning, implementing, and evaluating efforts to improve the public's physical activity habits. This report examines the prevalence of self-reported leisure-time physical activity (LTPA) among southeastern adults aged 18 years and older living in the state of Georgia. Using data from the 1990 Behavioral Risk Factor Surveillance System (BRFSS) surveys from Georgia, we describe the LTPA patterns of Georgia adults aged 18 years and older. A total of 1,723 adults were interviewed during 1990. Results show the following: women are less active than men, blacks are less active than whites, persons of lower socioeconomic status (SES) are less active than those of higher SES, and older adults are less active than younger adults. These results suggest that a more concerted effort needs to be made in promoting physical activity for women, persons of lower SES, and older adults.

Adolescent↗
PubMed1994

Overexpression of apolipoprotein CII causes hypertriglyceridemia in transgenic mice.

We have generated transgenic mice expressing the human apolipoprotein CII (apoCII) gene under the transcriptional control of the human cytochrome P-450 IA1 (CYPIA1) promoter. Human apoCII transgenic (HuCIITg) mice exhibited significant basal expression of the transgene (plasma apoCII level = 26.1 +/- 4 mg/dl) and showed further induction of transgene expression after treatment with beta-naphthoflavone. Unexpectedly, HuCIITg mice were hypertriglyceridemic and human apoCII levels correlated strongly to triglyceride levels (R = 0.89, P < 0.0001). Triglyceride levels (mg/dl +/- SEM) were elevated compared to controls in both the fed (804 +/- 113 vs 146 +/- 18, P < 0.001) and fasted (273 +/- 39 vs 61 +/- 4, P < 0.001) states. HuCIITg mice accumulated triglyceride-rich very low density lipoproteins (VLDL) with an increased apoC/apoE ratio. Tracer kinetic studies indicated delayed clearance of VLDL-triglyceride, and studies using Triton inhibition of VLDL clearance showed no increase in VLDL production. Plasma from these mice activated mouse lipoprotein lipase normally and radiolabeled VLDL were normally hydrolyzed. However, HuCIITg VLDL showed markedly decreased binding to heparin-Sepharose, suggesting that apoCII-rich, apoE-poor lipoprotein may be less accessible to cell surface lipases or receptors within their glycosaminoglycan matrices. HuCIITg mice are a promising model of hypertriglyceridemia that suggests a more complex role for apoCII in the metabolism of plasma triglycerides.

Animals↗
PubMed1994

Fatal carbon dioxide embolism complicating attempted laparoscopic cholecystectomy--case report and literature review.

Laparoscopic cholecystectomy has become the surgical procedure of choice for individuals with symptomatic gallbladder disease. The procedure has gained popularity among surgeons and patients because of inconspicuous abdominal incisions/scars, less postoperative pain, shorter hospitalization, and reduced medical costs. Bile duct, vascular, and gastrointestinal iatrogenic injuries are major complications. We describe the case of a 50-year-old woman who died of CO2 embolism during elective laparoscopic cholecystectomy for symptomatic cholelithiasis. With the patient under general anesthesia, a 1.5 cm incision was made just below the umbilicus, and a pneumoperitoneum was created by CO2 insufflation with a pneumoperitoneum (modified Veress) needle. Immediately, she experienced a cardiopulmonary arrest and could not be resuscitated. At autopsy, air bubbles were admixed with blood in the epicardial veins and leptomeningeal blood vessels. A triangular 0.1 cm perforation in the left common iliac vein had been created by the pneumoperitoneum needle. A pneumoperitoneum is required for laparoscopy and CO2 is the most commonly used gas. Carbon dioxide is highly soluble in blood and fairly innocuous to the peritoneum. Small amounts absorbed into the circulation cause slight increases in arterial and alveolar CO2 and in central venous pressure. When CO2 enters the venous circulation through iatrogenically opened vascular channels, catastrophic and potentially fatal hemodynamic and respiratory compromise may result.

Carbon Dioxide↗
PubMed1994

Correcting torsional deformities with Ilizarov's apparatus.

Patients undergoing limb lengthening with circular fixators often have rotational deformities requiring correction as well. At the end of lengthening, special rotation constructs are added to the Ilizarov frame to correct the rotational deformity. Unfortunately, the bone is usually eccentrically positioned in the rings, leading to secondary translational deformities after derotation. A trigonometric equation can predict the amount of inadvertent translation (t) that occurs with a given amount of derotation. Factors in this equation include the distance from the center of the ring to the outer edge of bone (r) and the amount of planned derotation (theta): t = (r sin theta)/sin (90 -theta/2). This sinusoidal function for derotation angles of less than 45 degrees can be approximated as a simple equation: t = 0.017 theta r. Armed with this information, the surgeon may calculate how much translation will be induced by the derotation maneuver. If the amount of predicted translation is deemed significant, then a more complex derotation frame with outriggers can be constructed to change the center of rotation to the middle of the eccentric bone. Alternatively, the translation induced by rotation can later be corrected with a translation construct.

Bone Lengthening↗
PubMed1994

Retransplantation in heart-lung recipients with obliterative bronchiolitis.

Obliterative bronchiolitis remains the leading cause of morbidity and mortality in long-term survivors after heart-lung transplantation. Despite enhanced immunosuppressive therapy, a significant number of patients progress to end-stage respiratory failure, leaving retransplantation as the only potential therapeutic option. Between October 1986 and August 1990, 25 heart-lung recipients (mean age 22 +/- 2 years) underwent repeat heart-lung transplantation at an average of 21 months after their first procedure. Twenty-one patients (83%) were ventilator dependent at the time of retransplantation. The Kaplan-Meier survival at 1, 6, 12, and 24 months was 52%, 33%, 25%, and 25%, respectively. Postoperative complications included bleeding, multisystem organ failure, and infection. Obliterative bronchiolitis resulted in death or graft failure in three patients between 12 and 36 months after the second transplantation. Five patients were currently alive at the time this article was written, with a median follow-up of 54 months. Three were in New York Heart Association class I, and two had obliterative bronchiolitis with class III symptoms. Recently, we investigated the role of single lung retransplantation in nine heart-lung recipients (mean age 23 +/- 3 years). The mean interval between procedures was 36 months, and eight patients (88%) were ventilator dependent. The Kaplan-Meier survival at 1, 6, 12, and 24 months was 89%, 67%, 67%, and 50%, respectively. We observed significantly less perioperative morbidity in this group. Five patients were alive (median follow-up 20 months); four were in New York Heart Association class I or II, and one was in New York Heart Association class III with recurrent obliterative bronchiolitis. We did not have enough patients to perform multivariate survival analysis. Survival curve comparisons with the use of the Wilcoxon test did show that the absence of performed antibodies in the recipient (panel reactive antibody frequency less than 10%) was associated with significantly improved survival after retransplantation. We also noted trends for improved survival in patients who had retransplantation at least 18 months after their original transplantation and in patients with negative preoperative sputum cultures. Retransplantation is a high-risk procedure that can result in rehabilitation in otherwise incapacitated patients. Single lung retransplantation appears to be the preferred option in carefully selected patients.

Adolescent↗
PubMed1993

Model for the in vivo assembly of nascent Ld class I molecules and for the expression of unfolded Ld molecules at the cell surface.

To characterize the process of class I assembly and maturation, we have studied the Ld molecule of the mouse. Previous studies have shown that a significant proportion of intracellular and surface Ld molecules can be detected in an alternative conformation designated Ldalt1. Nascent Ldalt molecules are non-peptide ligand associated and are weakly associated with beta 2-microglobulin (beta 2m). Unexpectedly, when monoclonal antibodies were added directly to the lysis buffer, significant amounts of Ldalt/beta 2m heterodimer were detected, suggesting that beta 2m association is not necessarily sufficient to induce Ld conformation. By contrast, addition of peptide to cell lysates rapidly induced the folding of beta 2m-associated Ldalt to conformed Ld. Furthermore, the time course and dynamics of this conversion correlated precisely with peptide binding to Ld. The precursor-product relationship of Ldalt and conformed Ld was also visualized in vivo by pulse-chase analysis of BALB/c splenocytes. To investigate the factors that regulate intracellular transport of class I molecules, expression of Ld was studied in the peptide transport-deficient cell line, RMA.S-Ld, and in beta 2m-/- splenocytes. In contrast to wild-type cell lines, both Ldalt and conformed Ld are poorly expressed at the cell surface of RMA.S-Ld and beta 2m-/- splenocytes. Therefore, surface expression of Ldalt is dependent upon the concomitant expression of conformed Ld molecules. To determine whether surface Ldalt molecules can result from melting of conformed Ld molecules, surface Ld molecules were loaded with several different known Ld peptide ligands. Complexes of Ld with different ligands were found to have dramatically disparate surface half-lives. Importantly, the Ld peptide complexes that turned over the most rapidly resulted in the most gain in surface Ldalt, implying that peptide dissociation can induce the accumulation of nonconformed Ld heavy chains at the cell surface.

Amino Acid Sequence↗
PubMed1993

Binding of peptides lacking consensus anchor residue alters H-2Ld serologic recognition.

CTL recognize class I MHC/peptide complexes on the surface of target cells. Crystallographic and serologic data have indicated that peptide ligands can influence the conformation of class I molecules and hence T cell recognition. How the binding of peptides with disparate sequence motifs affects the conformation of distinct regions within a class I molecule remains unknown. A series of site-directed mutants of the murine class I molecule H-2Ld was studied to address this question. These mutants were generated by in vitro mutagenesis and used to map the serologic epitopes recognized by a panel of Ld-reactive mAb. The influence of six different ligands on serologic recognition by these mAb was then examined. Of 12 mAb tested, only one, B22/249, was found to be significantly influenced by the bound peptide. Peptide discrimination by B22/249 was observed at the cell surface and in immunoprecipitates of Ld after incubation with two of the six ligands. The two peptides that caused suboptimal B22/249 recognition of Ld/peptide lack a proline at position 2, which is present in the other four peptides and has previously been defined as an anchor residue for Ld ligands. The epitope on Ld detected by mAb B22/249 includes residues 63 to 70 on the alpha 1 domain helix. Two of these residues are in pocket B, which computer modeling predicts to be in contact with the second residue of Ld-binding peptides. Therefore, these data imply that a mAb to a class I molecule can distinguish peptides with different motifs, possibly reflecting peptide-dependent conformational changes in the class I molecule.

Amino Acid Sequence↗