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Biomedical subjects

J J Smith

Publications and source records attributed to J J Smith.

At least 109 records · Page 6Linked to original sources
PubMed1997

Acute and long-term effects of the angiotensin-converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction.

Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of Left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 1 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular ejection fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy.

Aged↗
PubMed1997

Conservative surgery for ureteral tumor associated with horseshoe kidney.

PURPOSE: We demonstrate the successful conservative management of a ureteral tumor in a horseshoe kidney. MATERIALS AND METHODS: A patient with low grade transitional cell carcinoma of the left lower ureter had asymptomatic horseshoe kidney. Biopsy specimen revealed low grade tumor in the lower urinary tract that was associated with a congenital abnormality. The patient underwent total ureterectomy with bladder cuff excision and ileal ureteral interposition. RESULTS: With this technique renal function was preserved without resection through the isthmus of the kidney. The patient has no evidence of recurrent disease after 20-month followup by cytology, computerized tomography, excretory urogram and cystoscopy. CONCLUSIONS: Organ preserving surgery is an alternative to total nephroureterectomy in lower ureteral tumors in select patients.

Carcinoma, Transitional Cell↗
PubMed1997

Augmentation cystoplasty.

The past 15 years have been witness to an explosion in the number of reconstructive procedures using bowel in the urinary tract. As with many concepts in medicine, one must rely on clinical experience while laboratory models and other advancements develop. This article attempts to address bladder reconstruction by enterocystoplasty, as well as the indications for augmentation, types of procedures available, and the early and late complications.

Anastomosis, Surgical↗
PubMed1997

Ileal ureter.

Ureteral replacement with ileal bowel segments has become common in the armamentarium of the reconstructive urologist. The use of ileal bowel substitution, whether total or segmental, has provided yet another surgical alternative for renal preservation. The indications, surgical technique, and results with the ileal ureter are reviewed.

Humans↗
PubMed1997

The role of nitric oxide in the cerebrovascular response to hypercapnia.

Laser Doppler flowmetry was used to further investigate the role of nitric oxide (NO) in CO2-induced cerebrocortical hyperemia in rats. A second objective was to elucidate the source(s) of the NO involved in the response to hypercapnia. We used the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase (NOS) and 7-nitroindazole (7-NI) to selectively inhibit brain or nonendothelial NOS. Rats were anesthetized with a single dose of intraperitoneal (IP) pentobarbital (65 mg/kg) for surgery; 60-90 min later they were ventilated with 1.0% halothane in 30% O2 for 1 h to achieve a steady state. The animals were assigned to one of five groups. A control group (n = 9) was infused with 1 mL of saline. The second group (n = 10) received 20 mg/kg of L-NAME intravenously (IV). A third group (n = 9) also received L-NAME; in addition, cerebrocortical laser Doppler flow (LDF) and mean arterial pressure (MAP) were restored to baseline using the NO donor sodium nitroprusside (SNP). In a fourth group (n = 9), MAP was increased to the level usually seen after L-NAME with an infusion of phenylephrine (0.5-5 micrograms.kg-1.min-1). A fifth group (n = 11) received 7-NI at 40 mg/kg IP. The hypercapnic response of LDF was tested in all groups by adding 5% CO2 to the inspired gas at 30-45 min posttreatment; all changes in LDF were significant. In the control group, hypercapnia induced a 70% +/- 24% increase in LDF. In the L-NAME-treated group, the response was decreased to 36% +/- 22% at a posttreatment LDF that was 25% +/- 13% lower than the pre-L-NAME level. In the group where baseline LDF and MAP were restored with SNP, the CO2 response was 56% +/- 15% (not significant versus control). In the group in which MAP was increased with phenylephrine, the response to hypercapnia was 48% +/- 22% at a posttreatment LDF unchanged from pretreatment. These data suggest that increased vascular tone or the absence of basal NO after NOS inhibition influenced the vasodilator response to hypercapnia. In the 7-NI-treated group the response to hypercapnia was 38% +/- 3%, significantly attenuated at a posttreatment flow only 14% +/- 7% lower than pre-7-NI. We conclude that 1) endothelial NO does not mediate the response to hypercapnia but may have a permissive role in the response and 2) that brain NO may have an important role in response to hypercapnia.

Animals↗
PubMed1997

The peroxin Pex17p of the yeast Yarrowia lipolytica is associated peripherally with the peroxisomal membrane and is required for the import of a subset of matrix proteins.

PEX genes encode peroxins, which are required for the biogenesis of peroxisomes. The Yarrowia lipolytica PEX17 gene encodes the peroxin Pex17p, which is 671 amino acids in length and has a predicted molecular mass of 75,588 Da. Pex17p is peripherally associated with the peroxisomal membrane. The carboxyl-terminal tripeptide, Gly-Thr-Leu, of Pex17p is not necessary for its targeting to peroxisomes. Synthesis of Pex17p is low in cells grown in glucose-containing medium and increases after the cells are shifted to oleic acid-containing medium. Cells of the pex17-1 mutant, the original mutant strain, and the pex17-KA mutant, a strain in which most of the PEX17 gene is deleted, fail to form normal peroxisomes but instead contain numerous large, multimembraned structures. The import of peroxisomal matrix proteins in these mutants is selectively impaired. This selective import is not a function of the nature of the peroxisomal targeting signal. We suggest a regulatory role for Pex17p in the import of a subset of matrix proteins into peroxisomes.

Amino Acid Sequence↗
PubMed1997

A new PhD training track: a proposal to improve basic science teaching.

There has been increasing criticism of medical basic science teaching; much of this has focused on overcrowding of the curriculum, inadequate application to clinical medicine, and the limited commitment of the faculty to teach. We have analyzed some of the factors that may contribute to these complaints, such as the fragmentation of physiology and the conflicting roles of the medical basic scientist. We have also reviewed some previous suggestions for improving basic science teaching. We suggest that a basic scientist with a background of integrative physiology, pharmacology, anatomy, and pathology, with a special emphasis on pathophysiology, would be well qualified to assume an important role in the medical education of the future. Because there is at present no established training program of this type, we have proposed a PhD training track with this objective and have listed some of the advantages and disadvantages of such a program.

Curriculum↗
PubMed1997

Phospholipase A2 inhibition results in sequestration of plasma membrane into electronlucent vesicles during IgG-mediated phagocytosis.

Arachidonic acid is essential for antibody-mediated phagocytosis but its role in this process has not been defined. The phospholipase A2 inhibitor bromoenol lactone decreases arachidonic acid release and arrests phagocytosis; this effect is bypassed by the addition of arachidonic acid to bromoenol lactone-treated cells. In this morphological study, monocytes treated with bromoenol lactone accumulate electronlucent vesicles in the cytoplasm underlying bound targets. The vesicles are not contiguous with the plasma membrane as they are not labeled with cationized ferritin and are not connected to the plasma membrane as determined by high voltage electron microscopy imaging. However, if the plasma membrane is decorated with wheat germ agglutinin-gold prior to vesicle formation, virtually all vesicles contain the gold marker, indicating that they are plasma membrane-derived. The number of vesicles decreases dramatically upon addition of arachidonic acid to phospholipase A2-inhibited monocytes and phagocytosis is restored. Time course studies reveal electronlucent regions surrounding targets at early timepoints and a morphology consistent with fusion of electronlucent vesicles into the developing phagosome. These results are consistent with the following model: during the early stages of antibody-mediated phagocytosis, plasma membrane is sequestered in intracellular vesicles that provide membrane for the forming phagosome via fusion events that require arachidonic acid.

Animals↗
PubMed1997

Mammary growth in Holstein cows during the dry period: quantification of nucleic acids and histology.

Influence of the dry period on mammary growth was studied using multiparous Holstein cows. Sixty days before expected parturition, 13 cows were dried off, and another 13 cows were milked throughout the prepartum period. Lactating cows and dry cows were slaughtered at 53, 35, 20, and 7 d prepartum. Total mammary parenchymal DNA increased twofold from 53 to 7 d prepartum without influence of lactation status. However, overall rate of [3H]thymidine incorporation by mammary tissue was 80% greater in dry cows than in lactating cows, indicating that replacement of mammary cells was greater in dry cows. Of the mammary cells labeled with [3H]thymidine, the percentage of epithelial cells in dry cows was greater than that in lactating cows (96% vs. 86%). By 7 d prepartum, epithelial calls accounted for a greater percentage of total mammary cells in dry cows than in lactating cows (83% vs. 74%). Tissue area occupied by alveolar or ductular lumina decreased by 25 d into the dry period (35 d prepartum) and then increased to a maximum by 7 d prepartum. None of the mammary epithelial cells in dry cows were classified as secretory at 35 d prepartum, but 98% of the epithelial cells of dry cows were classified as secretory at 7 d prepartum. Results indicated that mammary involution did not occur during a typical dry period of dairy cows. Data suggest that a dry period is important for replacing senescent mammary epithelial cells and increasing the epithelial component of the gland prior to the next lactation.

Animals↗
PubMed1996

The Yarrowia lipolytica gene PAY5 encodes a peroxisomal integral membrane protein homologous to the mammalian peroxisome assembly factor PAF-1.

Pay mutants of the yeast Yarrowia lipolytica fail to assemble functional peroxisomes. One mutant strain, pay5-1, lacks normal peroxisomes and instead contains irregular vesicular structures surrounded by multiple unit membranes. The pay5-1 mutant is not totally deficient in peroxisomal matrix protein targeting, as a subset of matrix proteins continues to localize to a subcellular fraction enriched for peroxisomes. The functionally complementing gene PAY5 encodes a protein, Pay5p, of 380 amino acids (41,720 Da). Pay5p is a peroxisomal integral membrane protein homologous to mammalian PAF-1 proteins, which are essential for peroxisome assembly and whose mutation in humans results in Zellweger syndrome. Pay5p is targeted to mammalian peroxisomes, demonstrating the evolutionary conservation of the targeting mechanism for peroxisomal membrane proteins. Our results suggest that in pay5 mutants, normal peroxisome assembly is blocked, which leads to the accumulation of the membranous vesicular structures observed.

Amino Acid Sequence↗
PubMed1996

Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid.

Despite an increased understanding of the cellular and molecular biology of the CFTR Cl- channel, it is not known how defective Cl- transport across airway epithelia causes chronic bacterial infections in cystic fibrosis (CF) airways. Here, we show that common CF pathogens were killed when added to the apical surface of normal airway epithelia. In contrast, these bacteria multiplied on CF epithelia. We found that bactericidal activity was present in airway surface fluid of both normal and CF epithelia. However, because bacterial killing required a low NaCl concentration and because CF surface fluid has a high NaCl concentration, CF epithelia failed to kill bacteria. This defect was corrected by reducing the NaCl concentration on CF epithelia. These data explain how the loss of CFTR Cl- channels may lead to lung disease and suggest new approaches to therapy.

Bacteriocins↗
PubMed1996

Intraoperative force-setting did not improve the mechanical properties of an augmented bone-tendon-bone anterior cruciate ligament graft in a goat model.

It has been hypothesized that load affects the mechanical properties of an anterior cruciate ligament graft while it remodels. The goal of this study was to use an existing goat model to evaluate the effect of intraoperative set force on the postoperative mechanical properties of an autograft that had been augmented with a synthetic segment. The following questions were addressed. Do augmented autografts set with a high force intraoperatively have improved structural and material graft properties and lower anterior-posterior knee laxity at 3 months after surgery, compared with autografts set with a low intraoperative force? How do the structural and material properties of these implanted autografts compare with the mechanical properties of an intact anterior cruciate ligament or an unimplanted control autograft? The anterior cruciate ligament was reconstructed in seven goats with use of a composite graft consisting of a bone-patellar tendon-bone autograft and a synthetic augmentation device. A force-setting technique was used intraoperatively to establish the load-sharing between the autograft and augmentation segments such that the autograft carried either a high (16.5 N in four animals) or low (1.5 N in three animals) level of force, while the total force in the composite graft remained constant. Tensile testing was performed at 3 months after surgery to determine the material and structural properties of the autograft, the intact anterior cruciate ligament from the normal contralateral knee, and a control bone-patellar tendon-bone graft of similar size that was harvested from the contralateral knee at the time of necropsy and had never been implanted in the joint. The structural and material properties of the autografts initially set to high or low loads at surgery were not significantly different after 3 months of implantation. The strength and stiffness of the implanted tendons were an average of 24 and 20% of the strength and stiffness of the normal anterior cruciate ligament and 31 and 62% of the control tendons, respectively. Intraoperative set force in an augmented anterior cruciate ligament graft at the levels chosen in this study did not significantly affect weakening of the autograft at 3 months.

Animals↗
PubMed1996

Calcium channel blockers in heart failure: help or hindrance?

Since their development, calcium channel blocking agents have stimulated interest in their potential benefit for a variety of cardiovascular disorders, including heart failure. The rationale for the potential benefit of calcium channel blockers in heart failure is multi-factorial, including vasodilation, correction of perturbed diastolic relaxation, anti-ischemic action, and potential for inhibiting myocyte hypertrophy and injury. Despite these potential benefits, the degree of salutary influence has remained controversial, and a number of studies have suggested potential adverse action in patients with heart failure, perhaps linked to either negative inotropic action or to reflex neurohormonal activation. Diversity among different agents, particularly with regard to tissue selectivity and pharmacokinetics may imply substantial differences in the relative benefits and risks in various subgroups of patients with heart failure. One trial with the newer dihydropyridine agent, amlodipine, indicates benefit to survival in patients with moderate to severe heart failure and reduced ejection fraction. The reproducibility of this finding and the mechanism for this benefit deserves further investigation.

Calcium Channel Blockers↗
PubMed1996

A phospholipase A2-like pseudogene retaining the highly conserved introns of Mojave toxin and other snake venom group II PLA2s, but having different exons.

Mojave toxin is a neurotoxic, heterodimeric phospholipase A2 (PLA2) from the venom of the Mojave rattlesnake (Crotalus scutulatus scutulatus) and is characteristic of all rattlesnake presynaptic neurotoxins. Here, we describe a phospholipase A2 pseudogene (psi-Mtx) located 2,000 nucleotides upstream, and on the opposite DNA strand, from a gene for Mojave toxin acidic subunit (Mtx-a). The pseudogene lacks the first exon and a few segments of noncoding DNA found in functional snake venom PLA2 genes, but does have the coding information for a complete PLA2 protein. psi-Mtx retains the unusual gene sequence similarity pattern found in functional viperid PLA2 genes. When compared to genes from C. s. scutulatus and the Hahn snake (Trimeresurus flavoviridus), psi-Mtx shows strong conservation of nocoding regions and variable protein-coding regions. Although the nocoding regions of psi-Mtx are conserved with respect to other viperid PLA2 genes, the three exons code for a unique PLA2-like protein similar in sequence to ammodytoxin b found in the venom of the western sand viper (Vipera ammodytes ammodytes). The structure of these genes suggests a common ancestor for all viperid PLA2 genes. Phylogenetic analysis of psi-Mtx, Mtx-a, Mtx-b, pgPLA 1a, and pgPLA 1b suggest that psi-Mtx diverged from an ancestral sequence before the presumed gene duplication event leading to Mtx-a and Mtx-b. However, analysis of the basis of coding regions alone gives a conflicting result.

Amino Acid Sequence↗