Biomedical subjects

J Vaughan

Publications and source records attributed to J Vaughan.

At least 55 records · Page 3Linked to original sources

PubMed1998

The alpha-synuclein Ala53Thr mutation is not a common cause of familial Parkinson's disease: a study of 230 European cases. European Consortium on Genetic Susceptibility in Parkinson's Disease.

We report the results of a screen of 230 European familial index cases of Parkinson's disease for the recently described Ala53Thr mutation in the alpha-synuclein gene in an autosomal dominant Parkinson's disease kindred. No mutations were found from this broad white population, and we therefore conclude that although of great interest, this mutation is a very rare cause of familial Parkinson's disease.

Adult↗

PubMed1998

The effect of short-term fasting, phenobarbital and refeeding on apoptotic loss, cell replication and gene expression in rat liver during the promotion stage.

Previous work from this laboratory has reported on the effects of two sequential 5 day periods of fasting and subsequent refeeding on tumor promotion in multistage hepatocarcinogenesis in the rat (Carcinogenesis, 18, 159-166, 1997). In the present extension of the earlier study, the sequential fasting-refeeding regimen was begun at later time points (28 and 54 days post-initiation) than the first study. This was done to determine whether larger-sized altered hepatic foci (AHF) exhibited a depletion similar to that of the relatively small AHF in the published experiment and to study concomitant molecular changes during the fasting periods. Groups of animals were fasted in the presence and absence of 0.05% phenobarbital (PB) in the drinking water. During the fasting periods, both body and liver weights decreased dramatically, less in the fast begun at 54 days. This change was accompanied by a significant decrease in the bromodeoxyuridine (BrdU) labeling indices of hepatocytes within AHF. Apoptotic bodies increased dramatically in the non-focal (surrounding the AHF) hepatocytes during the fasting periods. These parameters were slightly lower in hepatocytes of rats administered PB during the fasting periods, most notably during the 54-66 day period. With the nick end-labeling method, the proportion of hepatocytes undergoing apoptosis was significantly higher in cells within AHF at the end of each of the fasting periods in all but one group. Concomitantly, the number of AHF and percentage of liver volume occupied by AHF decreased dramatically during the fasting periods. Refeeding caused a marked increase in BrdU labeling in hepatocytes within and surrounding AHF during the first week or two, most notably in animals not receiving PB during the fasting period. Both the number and volume percentage of liver AHF returned to control values within approximately 2 weeks of the refeeding regimen. Assays of nuclear DNA fragmentation with samples of whole liver indicated that a 'laddering' effect was most noticeable in livers of animals subjected to the fasting-refeeding regimen when phenobarbital was not present during the fasting period. Studies of the levels of mRNA of several genes in the total liver revealed that the expression of c-myc increased 3- to 9-fold during the fasting periods but rapidly returned to normal levels after refeeding. Levels of albumin and insulin-like growth factor I mRNAs decreased significantly during the fasting period, but rapidly reappeared on refeeding. These results indicate that the extensive loss of AHF during the short-term fasting periods occurs even when the number and volume of AHF are 10- to 50-fold greater at the beginning of the fast than the values published previously. Both the decrease in insulin growth factor I and the elevation of c-myc expression during the fasting period may indicate the role of these genes in the transcriptional regulation of hepatocyte apoptosis in both normal and preneoplastic hepatocytes in the rat.

Actins↗

PubMed1997

Association of slow acetylator genotype for N-acetyltransferase 2 with familial Parkinson's disease.

BACKGROUND: Epidemiological studies have identified positive family history and exposure to environmental toxins as risk factors for Parkinson's disease (PD). An inherited defect of xenobiotic metabolism could result in increased susceptibility to such toxins. We investigated the frequency of functionally relevant polymorphisms in six detoxification enzymes among patients with PD to elucidate the relation between these polymorphisms and the disease. METHODS: We obtained brain-tissue samples from 100 patients with apparently sporadic PD and blood samples from 100 living patients with familial PD. For the control group, we extracted DNA from the tissue of 100 pathologically normal brains. The six enzymes analysed in these three groups were: CYP2D6, CYP2E1, NAD(P)H-menadione reductase, glutathione transferases M1 and T1, and N-acetyltransferase 2. We also investigated N-acetyltransferase 2 in 100 blood samples from patients with genetically proven Huntington's disease. We used PCR-based methods and restriction-enzyme analysis to detect polymorphisms. FINDINGS: The slow acetylator genotype for N-acetyltransferase 2 was more common in the familial PD group (69%) than in all controls (37%). Even after correction for multiple comparisons, this result remained highly significant (p = 0.002) for familial PD compared with normal controls (odds ratio 3.79 [95% CI 2.08-6.90]) and compared with Huntington's disease (2.45 [1.37-4.38], p = 0.004). The slow acetylator frequency for N-acetyltransferase 2 for sporadic PD was between that for Huntington's disease and familial PD. The frequencies of all the other polymorphisms were similar in the two study groups and the normal control group. INTERPRETATION: We found an association between the slow acetylator genotype for N-acetyltransferase 2 and familial PD. Further studies are needed to investigate the biological relevance of these findings, but slow acetylation could lead to impaired ability of patients with familial PD to handle neurotoxic substances.

Acetylation↗

PubMed1997

Speed and sequential effects in reaching.

To investigate the impact of future task demands on reaching, participants performed repetitive sagittal-plane reaches at low and high speeds. In a control condition, they reached from a start location to a target and back. In the experimental conditions, they reached from the start to the target, then to a second target (the location of which varied between trials), then back to the first target, and finally back to the start. Contributions of the hip, shoulder, and elbow to reaches made to the first target depended on the second target's location, on movement speed, and on repetition. Participants combined sustained and transient postural adjustments to minimize effort. The results support the knowledge model of movement selection (D. A. Rosenbaum, L. D. Loukopoulos, R. G. M. Meulenbroek, J. Vaughan, & S. E. Engelbrecht, 1995) but also call for its elaboration. Variants of the model are explored through simulations of the above study.

Adult↗

PubMed1997

The effect of two periods of short-term fasting during the promotion stage of hepatocarcinogenesis in rats: the role of apoptosis and cell proliferation.

The loss of body and liver weight caused by chronic caloric restriction and its effects on carcinogenesis are well known; however, the effects of acute fasting on carcinogenesis have not been intensively investigated. We have studied some parameters of rat liver during short-term fasting and its effect on the stage of promotion in hepatocarcinogenesis in rats. During two fasting periods, body and liver weight decreased remarkably. Bromodeoxyuridine (BrdU) labeling indices (LI) decreased, and cell density increased prominently in liver sections. Hematoxylin and eosin-stained and nick end labeling (TUNEL)-stained sections showed an increase of apoptotic bodies in the absence of necrosis during the fasting period. Moreover, gel electrophoresis of DNA isolated from whole liver revealed ladder formation indicative of nucleosomal DNA cleavage. At the beginning of the fasting period livers exhibited a small but definite number of altered hepatic foci (AHF) expressing glutathione S-transferase, placental form (GST-P), but at the end of the fasting period no AHF were discernible in all livers of animals subjected to the fasting period. After refeeding, cell density and the incidence of apoptotic bodies decreased prior to a transient increase of BrdU LI. The percentage volume of liver occupied by AHF of fasted rats was significantly greater than that of control rats at 140 days after initiation. These results suggest that both the liver weight loss and the complete loss of discernible AHF from short-term fasting was caused by (i) decrease of cell volume, (ii) cell loss by apoptosis, and (iii) a decrease of hepatocyte proliferation. Furthermore, this relatively transient liver weight loss enhanced the promotion of hepatocarcinogenesis, possibly by enhanced cell proliferation compensatory to the fasting cycles.

Animals↗

PubMed1997

Cardiac inotropic actions of urocortin in conscious sheep.

Urocortin (Ucn) is a recently isolated peptide related to the corticotropin-releasing factor (CRF) family, which can produce hemodynamic and hormonal actions in conscious rats. This study examined in detail the cardiovascular actions of Ucn and CRF after intravenous injection in chronically instrumented, conscious sheep. Injection of Ucn produced dose-dependent changes in cardiac contractility [rate of increase of aortic flow (dF/dt)], maximum aortic flow (Fmax), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and coronary blood flow (CF). Ucn injected at 100 micrograms produced a potent increase in dF/dt, from 909 +/- 44 to a maximum of 1,849 +/- 901.min-1.s-1, and in Fmax, from 25.5 +/- 0.8 to 36.6 +/- 1.4 l/min. Cardiac contractility increased within 30 min of injection and remained significantly elevated for up to 24 h. MAP increased from 78 +/- 2 to 90 +/- 3 mmHg, and HR increased from 73 +/- 4 to 103 +/- 9 beats/min. CO rose from 5.0 +/- 0.1 to 5.8 +/- 0.2 l/min, whereas central venous pressure, total peripheral conductance, and stroke volume were unchanged. All Ucn-induced cardiovascular effects were inhibited by prior treatment with the CRF antagonist alpha-helical CRF-(9-41). Equimolar doses of CRF produced little change in any hemodynamic parameter. Both peptides increased plasma levels of adrenocorticotropin and cortisol, with Ucn having a more potent effect than CRF. We have shown for the first time that Ucn can produce potent and long-lasting actions to elevate cardiac contractility in conscious animals.

Adrenocorticotropic Hormone↗

PubMed1997

Is there really racism in nursing?

Nurses have long been aware of the array of cultural differences within society and how those differences impact health care delivery. One of the corporate buzz-words of the decade is diversity. Does nursing with all of its experience in managing various ethnic variances truly embrace this concept as a professional value? Or does the sociological trend of white female domination of the profession lend a hand to racism? Could there really be racism in nursing? Racism in nursing is examined from a historical, professional, and personal perspective to analyze the relevance of this timely issue to educators within the profession.

Cultural Diversity↗

PubMed1996

Adaptation of a reaching model to handwriting: how different effectors can produce the same written output, and other results.

This report shows how a model initially developed for the control of reaching can be adapted for the control of handwriting. The main problem addressed by the model is how people can produce essentially the same written output with different effectors (e.g., the preferred or nonpreferred hand, the foot, or even the mouth). The model is based on the assumption that writers strive for invariant graphic outputs when they write with different effectors, when they write on surfaces with different orientations, or when they write large or small script; such output invariance is an essential requirement for later recognition of the written result. Given this assumption, the question is how the motor system enables the relevant effectors to generate the necessary pen strokes. The adapted model provides one possible answer to this question. It is first fully working model of multijoint activity underlying writing and related graphic tasks. We describe how the model differs from other models developed in the past, and we review the model's strengths and weaknesses.

Female↗

PubMed1996

Cooperative selection of movements: the optimal selection model.

How one selects a movement when faced with alternative ways of doing a task is a central problem in human motor control. Moving the fingertip a short distance can be achieved with any of an infinite number of combinations of knuckle, wrist, elbow, shoulder, and hip movements. The question therefore arises: how is a unique combination chosen? In our model, choice is achieved by consideration of the similarity between the task requirements and the optimal biomechanical performance of each limb segment. Two variants of the model account for the movements that are selected when subjects freely oscillate the fingertip and when they tap against an obstacle. An important feature of both is that the impulse of collision with an obstacle (as in drumming with the hand or tapping with the finger) is assumed to be controlled in part by aiming for a point beyond the surface being struck. Thus, a force-related control variable may be represented and controlled spatially.

Arm↗

PubMed1996

The effect of tamoxifen and two of its non-isomerizable fixed-ring analogs on multistage rat hepatocarcinogenesis.

Long-term treatment of breast cancer patients with tamoxifen has prompted concern over potential toxicity of this drug with chronic administration. Since tamoxifen has estrogenic action in the rat liver and estrogenic agents can increase hepatoma incidence in rats, tamoxifen and two non-isomerizable, fixed-ring analogs (FRT1 and FRT2) were evaluated as promoting agents in a two-stage model of hepatocarcinogenesis in female Fischer F344 rats. The rats were subjected to 70% partial hepatectomy and half of the animals were administered the initiating agent, diethylnitrosamine (DEN; 10 mg/kg body wt), while the other half were not initiated. Groups of initiated and uninitiated animals were allowed to recover for 2 weeks and were then administered tamoxifen or one of the fixed-ring analogs admixed into AIN-76A diet at 25, 100 or 250 mg/kg diet. After 6 months of anti-estrogen administration the rats were sacrificed and uterine weights, blood levels of anti-estrogen, and liver histopathology were assessed. Uterine weights were decreased 2- to 3-fold by each of the agents, consistent with an anti-estrogenic action in the rat. The serum levels in rats administered 250 mg anti-estrogen/kg diet for 6 months were 320+/-20 ng/ml for tamoxifen, 320+/-10 for FRT1 and 350+/-20 for FRT2. The liver levels after a 6 month administration of 250 mg anti-estrogen/kg diet were 13 870+/-860 ng/g for tamoxifen, 13 300 +/-860 for FRT1 and 26 900+/-1900 for FRT2. A dose-dependent increase in serum and liver level of each compound was noted when measured at the 6 month time period. The number and percentage of the liver occupied by altered hepatic foci (AHF) were determined by quantitative stereology. A dose-dependent increase above initiated controls was observed in the initiated, tamoxifen-treated rats. Both fixed-ring analogs also increased the number and size of AHF compared with initiated controls, but were less potent than tamoxifen, suggesting that tamoxifen has an intrinsic promoting action in the liver that is independent of its ability to isomerize to more potent estrogenic compounds. In addition, the fixed-ring analogs have a weaker promoting activity in the rat liver than does tamoxifen. This may be due to pharmacokinetic differences at the lower two doses, but it is independent of achieved serum level at the highest dose and hence may reflect differences in intrinsic activity of these compounds. Thus tamoxifen and the two fixed-ring analogs promote the development of rat hepatocarcinogenesis.

Animals↗

PubMed1996

Human placenta and fetal membranes express human urocortin mRNA and peptide.

Recently a new member of the corticotropin-releasing factor (CRF) family has been cloned and named urocortin. It has been localized in rat brain and to human chromosome 2. The present study investigated whether human placenta and related tissues express mRNA and immunoreactive urocortin. Using specific oligonucleotide primers, reverse transcriptase-polymerase chain reaction experiments were performed on total RNA isolated from human placenta and decidua collected both at early stage of gestation (8-11 weeks) and at term (39-40 weeks). In addition, experiments were also done on specimens of amnion and chorion collected at term. Independently from the gestational age, placental and decidual cells expressed urocortin mRNA, with a 145 bp DNA band corresponding to the expected length. The expression of urocortin mRNA was also found in amnion and chorion. Using specific antiserum and an immunoperoxidase technique, immunoreactive urocortin was then localized in syncytiotrophoblast cells and in some extent in cytotrophoblast cells of placental villi at term, as well as in fetal membranes and maternal decidua. The present findings revealed that human placenta and gestational related tissues express human urocortin gene and localize immunoreactive urocortin, supporting the concept that these tissues are capable of expressing a large number of neuroendocrine peptides.

Amnion↗

PubMed1996

How to choose the right capitalization option.

Physician group practices and networks must have ready access to capital to finance their working capital needs, capital equipment acquisitions, and real estate purchases, as well as to fund the acquisition of additional practices. At least three options for capitalization are available to group practices and networks: debt financing, equity financing, or a combination of the two. The best option for physician group practices and networks depends on the costs of capital and the impact the strategy will have on decision making and governance.

Capital Financing↗

PubMed1995

Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor.

Corticotropin-releasing factor (CRF), a peptide first isolated from mammalian brain, is critical in the regulation of the pituitary-adrenal axis, and in complementary stress-related endocrine, autonomic and behavioural responses. Fish urotensin I and amphibian sauvagine were considered to be homologues of CRF until peptides even more closely related to CRF were identified in these same vertebrate classes. We have characterized another mammalian member of the CRF family and have localized its urotensin-like immunoreactivity to, and cloned related complementary DNAs from, a discrete rat midbrain region. The deduced protein encodes a peptide that we name urocortin, which is related to urotensin (63% sequence identity) and CRF (45% sequence identity). Synthetic urocortin evokes secretion of adrenocorticotropic hormone (ACTH) both in vitro and in vivo and binds and activates transfected type-1 CRF receptors, the subtype expressed by pituitary corticotropes. The coincidence of urotensin-like immunoreactivity with type-2 CRF receptors in brain, and our observation that urocortin is more potent than CRF at binding and activating type-2 CRF receptors, as well as at inducing c-Fos (an index of cellular activation) in regions enriched in type-2 CRF receptors, indicate that this new peptide could be an endogenous ligand for type-2 CRF receptors.

Adrenocorticotropic Hormone↗

PubMed1995

Planning reaches by evaluating stored postures.

This article describes a theory of the computations underlying the selection of coordinated motion patterns, especially in reaching tasks. The central idea is that when a spatial target is selected as an object to be reached, stored postures are evaluated for the contributions they can make to the task. Weights are assigned to the stored postures, and a single target posture is found by taking a weighted sum of the stored postures. Movement is achieved by reducing the distance between the starting angle and target angle of each joint. The model explains compensation for reduced joint mobility, tool use, practice effects, performance errors, and aspects of movement kinematics. Extensions of the model can account for anticipation and coarticulation effects, movement through via points, and hierarchical control of series of movements.

Biomechanical Phenomena↗

PubMed1995

Comparison of the effects of tamoxifen and toremifene on liver and kidney tumor promotion in female rats.

Female rats were subjected to a 70% partial hepatectomy and administered either diethylnitrosamine (10 mg/kg) or the solvent, trioctanoin. After a 2 day recovery from the surgery, the rats were placed on basal diet alone or containing phenobarbital (500 mg/kg diet), mestranol (0.2 mg/kg diet), tamoxifen (250 or 500 mg/kg diet) or toremifene (250, 500 or 750 mg/kg diet) for 6 or 18 months prior to killing. The liver and kidneys were prepared for pathological diagnoses. In addition, sections of liver from the 6 month killing were frozen and serially sectioned. The sections were stained for expression of the placental isozyme of glutathione S-transferase (GST), gamma glutamyl transpeptidase (GGT), canalicular ATPase (ATP) and glucose 6-phosphatase (G6P) and scored by quantitative stereology for number and volume fraction of liver occupied by altered hepatic foci (AHF) with alterations in these markers individually and combined (ANY). Each of the agents increased the volume fraction of liver occupied by AHF when the ANY category was used. Statistical increases in both the GGT-positive and G6P-deficient AHF populations were observed in the spontaneously as well as DEN-initiated groups treated with tamoxifen or toremifene. After 18 months of administration, the highest concentration of tamoxifen increased the incidence of malignant hepatic neoplasms in non-DEN-initiated rats. Toremifene, at the highest tested dose, increased the incidence of hepatocellular carcinomas in the DEN-initiated groups to a level one-third that observed with tamoxifen administration to DEN-initiated rats. Both tamoxifen and toremifene increased the incidence of hypernephromas in previously DEN-initiated rats. While both tamoxifen and toremifene are effective promoting agents for DEN-initiated lesions, tamoxifen is more potent than toremifene in the induction of rat hepatocarcinogenesis.

Adenosine Triphosphatases↗

PubMed1995

Symptomatic acute mucositis can be minimized or prophylaxed by the combination of sucralfate and fluconazole.

Mucositis is a common and often serious acute morbidity when radiation is delivered to portals encompassing the oral cavity, pharynx, or esophagus. In an effort to minimize this side effect, the combination of sucralfate and fluconazole was prescribed to 40 patients. Half were given sucralfate, 1 g in suspension q.i.d. from the first week to the completion of radiation with fluconazole 100 mg., q.d. for 14 days initiated during the fourth week. The remaining individuals were placed on the same dosages of the two drugs dispensed simultaneously after symptoms appeared. For both cohorts the combination of sucralfate and fluconazole was effective in diminishing oral discomfort and pain associated with radiation and chemotherapy. When medication was delivered from the first week of therapy, all patients could achieve the prescribed radiation dose without treatment interruption and be maintained on a regular diet. The combination of drugs was also effective in minimizing symptoms once they appeared.

Drug Therapy, Combination↗

PubMed1995

Proliferation-associated differences in the spatial and temporal expression of gap junction genes in rat liver.

After a 70% partial hepatectomy (PH), the steady-state levels of Connexin (Cx)32, Cx26, and Cx43 messenger RNA (mRNA) transcripts each displayed unique patterns of temporal expression. Within 1 hour after surgical resection, increased expression of all three Cx mRNAs was observed. Subsequently, the level of Cx32 mRNA transcripts transiently decreased to a nadir at 12 hours. Comparisons of the spatial changes with previously reported hepatocyte proliferation kinetics induced by PH demonstrated that hepatocytes before S-phase "remodel" their GJs. Within 1 to 5 hours post-PH, midzonal hepatocytes exhibited diffuse membrane staining different from the normal punctate distribution. Subsequently, midzonal hepatocytes expressed colocalized punctate Cx32 and Cx26 immunostaining. Because the changes occurred in midzonal hepatocytes before 24 hours post-PH, near the peak of hepatocyte DNA synthesis, these findings indicate that Cx26 is enhanced in hepatocytes before the onset of S-phase. In contrast to the restricted expression of Cx43 in Glisson's capsule in adult liver, Cx43 protein and mRNA were enhanced specifically in proliferating bile duct and perisinusoidal cells post-PH. PH performed during continuous administration of 2-acetylaminofluorene (AAF) prevented changes in Cx32 and Cx26 staining observed in the absence of AAF. Proliferating oval cells were found to express diffuse Cx43 immunoreactivity. On day 11 post-PH and AAF, basophilic hepatocytes displayed both punctate Cx32 and Cx26 staining, whereas bile ducts and perisinusoidal cells expressed Cx43. These findings indicate that alterations in Cx32 and Cx26 expression occur rapidly in hepatocytes stimulated to proliferate and that several nonparenchymal liver cell types upregulate Cx43 expression when induced to proliferate. Differentiation of oval cells into basophilic hepatocytes resulted in their expression of Cx32 and Cx26.

Animals↗

PubMed1994

Characterization of a basic serine proteinase (pI approximately 9.5) secreted by virulent strains of Dichelobacter nodosus and identification of a distinct, but closely related, proteinase secreted by benign strains.

An extracellular serine proteinase with a PI approximately 9.5 (referred to as 'basic proteinase') was purified to homogeneity, from strains of Dichelobacter nodosus that cause virulent foot-rot, by gel filtration of concentrated culture supernatant on Sephadex G-100 and chromatography on sulphopropyl-Sephadex C-25 at pH 8.6 D. nodosus strains that cause benign foot-rot do not secrete a corresponding basic proteinase with a pI of approximately 9.5. Benign strains secrete a closely related, but distinct, proteinase which has the same molecular mass and N-terminal sequences as the 'virulent' basic proteinase, but a lower pI of approximately 8.6. The basic proteinases from both strains appear to interact with other proteins present in the culture medium, which results in anomalous behavior on gel filtration. Pure D. nodosus 'virulent' basic proteinase has a molecular mass of 36 kDa and showed a low solubility at I < 0.05 precipitating quantitatively from solution as microcrystals. The proteinase shows optimal activity at pH 8.0 and is stable to heating to 55 degrees C for 30 min, but at higher temperatures activity is rapidly lost. Bivalent-metal ions (e.g. Ca2+) are required to maintain the structural integrity and stability of the proteinase; in the presence of EDTA or conditions that cause protein unfolding, the proteinase undergoes rapid and complete autolysis. Cleavage of oxidized insulin A- and B-chain showed that the basic proteinase has a broad specificity, including cleavage at lysine and arginine bonds.

Amino Acid Sequence↗