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Biomedical subjects

D R Wilson

Publications and source records attributed to D R Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1993

Uniparental disomy for chromosome 16 in humans.

The association between chromosomal mosaicism observed on chorionic villus sampling (CVS) and poor pregnancy outcome has been well documented. CVS mosaicism usually represents abnormal cell lines confined to the placenta and often involves chromosomal trisomy. Such confined placental mosaicism (CPM) may occur when there is complete dichotomy between a trisomic karyotype in the placenta and a normal diploid fetus or when both diploid and trisomic components are present within the placenta. Gestations involving pure or significant trisomy in placental lineages associated with a diploid fetal karyotype probably result from a trisomic zygote which has lost one copy of the trisomic chromosome in the embryonic progenitor cells during cleavage. Uniparental disomy would be expected to occur in one-third of such cases. Trisomy of chromosome 7, 9, 15, or 16 is most common among the gestations with these dichotomic CPMs. Nine pregnancies with trisomy 16 confined to the placenta were prenatally diagnosed. Pregnancy outcome, levels of trisomic cells in term placentas, and fetal uniparental disomy were studied. Intrauterine growth retardation (IUGR), low birthweight, or fetal death was observed in six of these pregnancies and correlated with high levels of trisomic cells in the term placentas. Four of the five cases of IUGR or fetal death showed fetal uniparental disomy for chromosome 16. One of the infants with maternal uniparental disomy 16 had a significant malformation (imperforate anus). All infants with normal intrauterine growth showed term placentas with low levels of trisomic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Salary structure, promotion, and tenure policies in nurturing the young academician.

With respect to salary structure, promotion, and tenure for academic clinical faculty, and based on the issues I have described, we must consider the following five priorities: 1. To provide salary support which is appropriate for responsibilities in teaching, research, and clinical administration, and not dependent on clinical earnings, 2. To maintain flexible salary arrangements which may include a component of clinical fee-for-service earnings, and partial salary support for defined clinical teaching or administration, 3. To design a more integrated management system for these new funding arrangements which brings together medical schools and teaching hospitals and is accountable to the appropriate government agencies. 4. To improve performance review and promotion procedures, based on agreed job descriptions and recognizing the importance of teaching, research, clinical administration, and service, and 5. To review critically the role of tenure for academic clinicians and examine alternatives such as renewable term appointments There is a growing momentum to address these issues and priorities among all of those involved. This will be critical in the continued career development of Canadian academic physicians.

Canada↗
PubMed1991

A portable, easily performed muscle power test and its association with falls by elderly persoms.

This study developed and evaluated a simple, inexpensive, and safe screening test for assessment of falling risk in elderly persons. Subjects sat in chairs (hips and knees at 90 degrees) with their feet over a force transducer and stood as forcefully as possible. After standing for five seconds, they sat as fast as possible. The rate of change in force (dF/dT) for standing and sitting were calculated from data collected by computer. A group of nonfallers (n = 23, age = 23 to 72 years) and a group of fallers (n = 22, age = 63 to 92 years) were studied. Nonfallers' dF/dT for standing decreased linearly from 4kg.sec-1.kg-1 to 2.5kg.sec-1.kg-1. Values in fallers decreased linearly from 3kg.sec-1.kg-1 to 0.1kg.sec-1.kg-1. The dF/dT for sitting was not dependent on age in either group. Fallers had lower dF/dT than nonfallers (1.3 +/- .6kg.sec-1.kg-1 and 2.3 +/- .01kg.sec-1.kg-1, respectively). Seventeen of 22 fallers were identified by a reduced dF/dT and reduced overshoot force (kg).

Accidental Falls↗
PubMed1991

Evaluation of relative promoter strength in primary hepatocytes using optimized lipofection.

For most genetic deficiencies manifested in the liver, maximization of gene expression in hepatocytes will be an important factor in achieving successful gene therapy. A rapid, highly efficient, and nontoxic method for transfecting DNA into hepatocytes was used to compare directly promoter strengths of various cellular and viral promoters. Conditions are described here for transfecting 5-10% of primary hepatocytes using the positively charged liposomes, Lipofectin. Cells are not damaged by this method as they continue to transcribe genes controlled by liver specific promoters and can survive for over 2 weeks in culture. We find that the cytomegalovirus, SR alpha, and beta-actin promoters are more active than the SV40, RSV, RNA polymerase II, albumin, alpha 1-antitrypsin, or phosphoenolpyruvate carboxykinase promoters. A simple TK promoter and a TK promoter with the polyoma enhancer (MCI) were almost completely inactive. This information will be useful in the construction of vectors designed to express genes efficiently in primary hepatocytes for purposes of gene therapy, although the stability of expression from these promoters will need to be demonstrated in hepatocytes in vivo.

Animals↗
PubMed1991

The effect of isoproterenol on fluid and electrolyte transport in the inner medullary collecting duct.

In the late distal and cortical collecting tubule, which is the principal regulatory site for potassium (K) excretion, vasopressin stimulates, and epinephrine via beta-adrenergic action, inhibits K secretion. In the inner medullary collecting duct (IMCD) we have shown that vasopressin also stimulates K secretion. The present experiments were designed to determine whether the beta-adrenergic agonist, isoproterenol, would induce K reabsorption in the IMCD, and (or) prevent a secretory response to acute KCl infusion. Two groups of rats, with or without isoproterenol administration (3 micrograms/h), were subjected to retrograde microcatheterization of the IMCD before and during infusion of 0.83 mol/h KCl. Isoproterenol reduced plasma K concentration and urinary K excretion, but the response to acute KCl infusion was qualitatively similar to control. Isoproterenol decreased delivery of potassium, chloride, and fluid to the IMCD, there was no net transport of K along the duct in either group, and KCl infusion did not result in K secretion in either group. The results indicate that isoproterenol may inhibit K secretion in the late distal or cortical collecting tubule. However, there was no statistically significant difference in K transport along the IMCD between isoproterenol and control groups. Reduced sodium excretion, which was found during isoproterenol administration both before and after KCl infusion, was associated with no change in sodium delivery but with increased sodium reabsorption in the IMCD. This increased sodium reabsorption may be a direct effect of isoproterenol, or may be due to reflex cardiovascular adjustments associated with systemic actions of the drug.

Animals↗
PubMed1990

Demonstration of Epstein-Barr virus in primary central nervous system lymphomas by the polymerase chain reaction and in situ hybridization.

Primary lymphomas of the central nervous system (CNS) account for 0.3% to 1.5% of all intracranial neoplasms. Several reports have noted a coincidence between this neoplasm and serologic evidence of Epstein-Barr virus (EBV) infection, but in only a few instances has the EBV genome been demonstrated in these tumors. To further evaluate the frequency of this occurrence, we analyzed primary CNS lymphomas using nucleic acid hybridization methods and the polymerase chain reaction (PCR). In situ hybridization was used in selected cases. Sequences of EBV were found in two of nine cases by PCR and in situ hybridization. Southern blot hybridization of genomic DNA from these samples was negative for EBV. Both tumors arose in patients with conditions shown to produce secondary immunodeficiency, namely, chronic alcohol abuse and diabetes mellitus. We conclude that the association of EBV and CNS lymphoma is not restricted to patients with severe primary immune deficiency, and that PCR can be applied successfully to paraffin-embedded tissue for the detection of low-abundance viral sequences.

Central Nervous System Diseases↗
PubMed1990

The relationship between pKa and skin irritation for a series of basic penetrants in man.

For a series of bases, which penetrate through human skin in vitro at similar rates (0.056-0.49 microM/cm2/hr), penetrant pKa is shown to correlate with erythema, edema, and color meter readings. As estimates of irritation, erythema, edema, and redness measurements are highly linearly correlated. For the selected series, irritation becomes significant for bases with a pKa greater than 8. The irritation potential of acids with pKa less than or equal to 4 has been previously reported; pKa appears highly predictive of acute skin irritation for acids and bases in man.

Adult↗
PubMed1990

A 58-base-pair region of the human C3 gene confers synergistic inducibility by interleukin-1 and interleukin-6.

We have cloned the promoter for the human third component of complement (C3) gene and have identified sequences involved in its regulation during the acute-phase response. A construct linking 199 bp of the C3 promoter to the firefly luciferase gene was found to be very responsive to interleukin-1 (IL-1) and modestly responsive to interleukin-6 (IL-6) by transfection analysis in the human hepatoma line Hep3B2. Simultaneous treatment with the two cytokines showed a strong synergy between the actions of the two molecules. A 58-bp fragment (-127 to -70 bp) was shown by 5' and 3' deletional mutagenesis to contain cis-acting elements that mediated both the IL-1 response and the IL-1-plus-IL-6 synergistic response of this promoter. When coupled to a heterologous promoter, this fragment enabled the synergistic induction by IL-1 plus IL-6. Sequences homologous to the palindrome ACATTGCACAATCT, which mediates the induction of the IL-6 gene by IL-1 (S. Akira, H. Isshiki, T. Sugita, O. Tanabe, S. Kinoshita, Y. Nishio, T. Nakajima, T. Hirano, and T. Kishimoto, EMBO J. 9:1897-1906, 1990), and the core sequence of the IL-6-responsive element of the rat alpha 2-macroglobulin gene (CTGGGA; M. Hattori, L. J. Abraham, W. Northemann, and G. H. Fey, Proc. Natl. Acad. Sci. USA 87:2364-2368, 1990) are contained within this fragment in immediate juxtaposition and partially overlapping. Site-directed mutagenesis within this homology region drastically reduced the inducibility of the C3 promoter by either cytokine. DNase I footprinting analysis defined a binding site for the transcription factor CCAAT/enhancer-binding protein (C/EBP), which included the IL-1-responsive element-like sequence. No differences were seen between the footprints generated by using extracts from unstimulated and IL-1-stimulated Hep3B2 cells. However, gel retardation analyses revealed two IL-1-specific bands. The data suggest that the induction by IL-1 is mediated by a factor belonging to the family of C/EBP-related proteins.

Animals↗
PubMed1990

Effects of increased perfusion pressure on medullary collecting duct function.

The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 +/- 4.1 to 51 +/- 9.3% (p less than 0.01) and from 65.7 +/- 6.0 to 42.7 +/- 9.1% (p less than 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.

Animals↗
PubMed1990

In vivo microperfusion of inner medullary collecting duct in rats: effect of amiloride and ANF.

A method is described that allows perfusion of the inner medullary collecting duct (IMCD) of the rat kidney in situ and in vivo. Fine polyethylene catheters connected to a microperfusion pump were inserted into collecting ducts via the openings at the exposed papilla tip. Perfusate contained 22Na as well as [3H]inulin. During perfusion at 30 nl/min, urine was simultaneously collected. A decrease in the Na-to-inulin concentration ratio in the urinary sample, compared with the perfusate, was taken as indicating unidirectional efflux of Na from the perfused duct system. The effects of luminal amiloride (2 X 10(-4) M) or atrial natriuretic factor (ANF, 10(-8) M) were studied. Compared with control perfusions, both agonists reduced Na efflux from the IMCD to approximately 50%, indicating luminal sites of action. Combination of amiloride and ANF at their respective concentrations had no further effect. The lack of statistically significant additivity suggests, but does not prove, that ANF, administered from the luminal side, is able to block amiloride-sensitive Na channels in the apical membrane of IMCD cells.

Amiloride↗
PubMed1990

Fostering interdisciplinary research in a faculty of medicine: an integrated model.

Modern biomedical research spans a variety of clinical and basic medical sciences and may not fit the departmental structure of a traditional medical school, which is determined by patient care and teaching responsibilities. Interdisciplinary research has therefore often been developed in research institutes with limited relationship to regular university departments. This paper outlines the important organizational initiatives which contribute to an integrated model of interdisciplinary research more closely linked with the medical school. The establishment of close working relationships among Department Chairs is essential for the integration of interdisciplinary research with existing clinical and basic medical science departments. Department of Chairs must see the development of interdisciplinary research groups as a means of enhancing research related to their disciplines. It is important to identify priority research areas using broad-based interdisciplinary committees (for example in neuroscience), and to establish guidelines for recruitment of selected research groups which include both Ph.D. and M.D. scientists who maintain appointments in a regular department for teaching and other academic functions. Physical proximity for the group may require reorganization of departmental research space which is maintained under the overall control of the Dean. The ability to maintain and renew interdisciplinary research groups, or to phase them out if necessary, can also be strengthened by using this integrated model.

Research↗
PubMed1989

N-myc amplification and neuronal differentiation in human primitive neuroectodermal tumors of the central nervous system.

Despite the phenotypic similarities between primitive neuroectodermal tumors of the central nervous system, childhood neuroblastoma, and peripheral neuroepithelioma, a histogenetic relationship among these neoplasms has not been shown. High levels of N-myc expression occur selectively in developing brain and in some embryonic tumors of neural origin. N-myc amplification and high levels of N-myc expression in childhood neuroblastoma have been correlated with disease stage and prognosis. To determine whether the copy number of the N-myc gene in primitive neuroectodermal tumors of the central nervous system is altered, we examined 20 primitive neuroectodermal tumors by Southern and/or slot blot hybridization to a 1-kilobase N-myc genomic DNA sequence and a 492-base pair N-myc-specific subclone as well as to a 1.1-kilobase albumin complementary DNA sequence as a control for gene copy number. Amplification of the N-myc gene was detected in two cerebellar tumors both of which exhibited neuronal differentiation by light microscopy. These tumors had not been treated previously. Of the remaining 18 tumors, eight were undifferentiated, three showed early neuroblastic, and seven focal glial differentiation. These findings suggest a possible relationship between N-myc amplification and neuronal differentiation.

Brain Neoplasms↗
PubMed1989

Effects of chronic hypokalaemia and adrenalectomy on potassium transport by the medullary collecting duct of the rat.

1. The purpose of this study was to evaluate the roles of chronic hypokalaemia and of aldosterone in K+ transport in the medullary collecting duct. Renal clearance and duct transport measurements were made before and after KCl infusion in three groups of animals: normal rats on a regular K+ diet (group I), and sham-operated (II) or adrenalectomized rats (group III), both on a low K+ diet. 2. Only the sham-operated animals on the low K+ diet became hypokalaemic. They also had the lowest rate of K+ excretion at the time of study. Adrenalectomized rats were normokalaemic, and had an intermediate rate of K+ excretion. After the acute KCl infusion, kaliuresis remained significantly depressed in the rats which were previously hypokalaemic. In contrast, K+ excretion rates in response to K+ infusion were high and not significantly different in both previously normokalaemic groups, independent of the presence of the adrenal glands. 3. In the medullary collecting duct, before the KCl infusion there was no net K+ transport in either normokalaemic group (I and III). However, after the KCl infusion there was significant K+ secretion in both of these groups (32% and 22% of total urinary excretion, respectively). In contrast, the sham-operated hypokalaemic rats on the low K+ diet had a small absolute, but large fractional K+ reabsorption (64% of delivered load) in the medullary collecting duct. With KCl infusion in this group, K+ delivery to the medullary duct increased, but absolute reabsorption along the duct was maintained, resulting in a fractional reabsorption of 28% of delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗