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Biomedical subjects

J S Wilson

Publications and source records attributed to J S Wilson.

At least 91 records · Page 5Linked to original sources

Intracellular response of caudate neurons to variable frequency stimulation of motor cortical areas in dog.

The intracellular response to electrical stimulation of motor cortex was studied in 77 neurons recorded in the head of the caudate (Cd) nucleus of dog. Single pulse stimulation of either medial, intermediate or lateral precruciate cortex produced a response in 69 neurons, 59% of which responded to more than one cortical area. Most intracellular responses were complex potentials consisting of an initial depolarization (E) followed by a longer duration hyperpolarization (I) or E-I response complex. When stimulated with trains of low frequency pulses (10 Hz), the stimulus-generated I potentials reduced the absolute amplitude of the evoked E's, often to a level below resting potential. However, at higher frequencies (50 Hz), the I potentials were attenuated and the E potentials summated into a prolonged depolarization lasting the duration of the stimulus train. A computer model of the response to multiple stimuli was generated assuming that the E-I response to each stimulus pulse in the train should temporally summate with previous responses. As the frequency of stimulation was increased, this model consistently predicted greater summation of the I potentials than was experimentally observed. These data suggest that inhibition of Cd neurons is input frequency dependent such that as the frequency of cortical input increases there is a decrease of input-generated inhibition of Cd neurons. Thus, inhibition may modulate the response of Cd neurons such that cortical input must reach a critical firing frequency before being relayed through the Cd nucleus.

Animals↗

The action of MPTP on synaptic transmission is affected by changes in Ca2+ concentrations.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a disruption of nigrostriatal dopaminergic function which resembles parkinsonism. On the cellular level, the disruption involves a Ca2+ independent release of dopamine, depletion of nigral and striatal dopamine, and the death of dopaminergic neurons. We have previously reported that MPTP can cause a non-reversible inhibition of neostriatal synaptic transmission. In this study we investigated the effect of altering Ca2+ concentration on MPTP's actions in the mouse nigrostriatal brain slice. We report finding that the MPTP induced non-reversible decrease in N-2 amplitude did not occur if synaptic transmission had been blocked using a low Ca2(+)-high Mg2+ artificial cerebrospinal fluid (ACSF) during MPTP application. Low Ca2(+)-high Mg2+ ACSF did not however alter the decrease in slice dopamine content caused by MPTP. These data provide initial support for the hypothesis that MPTP's ability to alter functional synaptic transmission is Ca2+ dependent whereas its releasing action on dopamine is Ca2+ independent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Side effects from amiodarone.

Amiodarone causes many side effects involving all organ systems. Although most of the side effects are mild and do not limit the use of the drug, there are several that are serious. Since many of these toxic reactions develop only after a prolonged period of therapy, careful follow-up on a regular basis is essential.

Age Factors↗

Mechanisms of the inotropic actions of MPTP and MPP+ on isolated atria of rat.

Besides having toxic actions, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (1-methyl-4-phenyl-pyridinium ion) produce the release of catecholamines in the peripheral and central nervous systems. This paper reports on the effects of MPTP and MPP+ on isolated left atria of rats and their mechanisms. MPP+ and MPTP produced a concentration-dependent positive inotropic effect. This action was blocked by propranolol and nomifensine; however, inhibition of monoamine oxidase had no effect on the response. In atria from reserpinized rats, the positive inotropic effect of MPTP was also blocked and a negative inotropic effect was unmasked which continued to increase in magnitude during wash. The negative inotropic effect was markedly reduced by superoxide dismutase and catalase. These results indicate that MPTP and MPP+ produce a catecholamine-mediated positive inotropic effect that is not MAO-dependent, unlike the toxic actions of MPTP. These results also suggest that MPTP may directly damage cardiac muscle by generating free radicals which might explain why high doses of MPTP are lethal to animals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis.

Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis.

Acute Disease↗

Cruel and unusual punishment: the health care of women in prison.

Nationally, the number of female prison inmates--although small compared with the number of male inmates--is on the upswing. Since correctional facilities are legally mandated under the eighth amendment to provide inmates with their constitutional right to health care, innovative methods of delivering that care will have to be devised within a current system that is neither funded nor prepared to design and dispense such programs. The most frequent medical problems among incarcerated women are drug/alcohol addiction, gynecological diseases, and exacerbation of chronic health problems, particularly hypertension, diabetes and epilepsy. The prison health care system is also being faced with management of an increasing number of pregnant and postpartal inmates. Health needs of this group include basic health care, teaching, counseling and supportive care--services that can be appropriately provided by nurse practitioners and other health care providers.

Child↗

Effects of MPTP on the fine structure of neurons in substantia nigra of dogs.

This study evaluates fine structural changes in neurons from pars compacta of substantia nigra in dogs 1 and 4 days after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The toxin induced a disruption and high amplitude swelling of mitochondria, and dispersion of rough endoplasmic reticulum at 4 days. Mitochondria in dendrites were less damaged than those in the soma. Swelling of myelinated axons in the nigrostriatal pathway was evident at 1 and 4 days after injection. Similar morphologic changes are produced by axotomy and inhibitors of mitochondrial function.

Animals↗

Separation and characterization of basal and secretory cells from the rat trachea by flow cytometry.

Basal and secretory cells have been separated as highly enriched viable populations from single-cell suspensions of rat tracheal epithelial cells. Isolation of the populations was achieved by preparation of a cell suspension and separation by flow cytometry using contour maps generated from 2 degrees and 90 degrees light scatter signals. Flow cytometric analysis of cells showed 10% of the whole preparation were cells in SG2M phase of the cell cycle. The secretory cells accounted for 86% of these cycling cells; the remainder were accounted for by the basal cells. Culture of sorted populations of basal and secretory cells in serum free defined medium showed that basal cells had a lower (0.6%) colony-forming efficiency than secretory cells (3.4%). Significant differences in blue auto-fluorescence, Hoechst 33342 uptake, and lectin staining were apparent between basal and secretory cells. These results suggest that the secretory cell rather than the basal cell is primarily the cell type involved in maintenance of the normal tracheal epithelium. Secretory cells are greater in number, have a higher proliferative potential, and greater metabolic capability. Because of these traits they may be a critical cell at risk from damage by environmental agents.

Animals↗

Interactive effects of dietary protein and ethanol on rat pancreas. Protein synthesis and enzyme secretion.

Nutritional factors, especially the protein and fat content of the diet, may alter the likelihood of pancreatic injury after a number of insults, including chronic ethanol intake. This issue was studied experimentally by match-feeding rats liquid diets of varying protein content with and without ethanol. Protein synthesis and enzyme secretion were investigated, because these parameters are believed to increase the capacity for pancreatic autodigestion. Protein synthesis was assessed by determining the incorporation of tritiated phenylalanine into trichloroacetic acid precipitated protein 10 minutes after IP injection and then corrected for the size of the precursor pool. Enzyme secretion was studied using pancreatic acini, which were prepared using clostripain-poor collagenase. Chronic ethanol feeding stimulated protein synthesis and lipase secretion and content in rats receiving adequate amounts of protein. These stimulatory effects of ethanol were markedly attenuated in rats administered protein poor diets. Protein deficiency per se significantly decreased the weight, protein, and enzyme content of the rat pancreas as well as increased the percentage release of lipase from acini. Although extrapolation from animal studies may be tenuous, the present findings may explain the link between nutrition and the occurrence of alcoholic pancreatitis.

Animals↗

The conductance of cultured epithelial cell monolayers: oxidants, adenosine triphosphate, and phorbol dibutyrate.

Oxidants are one class of inflammatory molecules that may contribute to an increase in epithelial permeability to water and solutes that commonly occurs during acute inflammation. We and others have observed that oxidants reversibly alter the paracellular conductance of Madin Darby canine kidney epithelial (MDCK) cell monolayers. The mechanism by which oxidants reversibly alter MDCK monolayer conductance is not yet fully understood. Some investigators have suggested that oxidants might alter MDCK monolayer paracellular conductance by depleting adenosine triphosphate (ATP) in the cells. When we exposed MDCK cells to doses of oxidants that increased monolayer paracellular conductance in earlier studies, ATP was depleted within 10 min. However, when ATP was depleted to similar levels with an inhibitor of glycolytic ATP production, 2-deoxy-D-glucose (DOG), monolayer paracellular conductance was not increased. Severe ATP depletion with DOG and the mitochondrial metabolic inhibitor, antimycin A (AA), had very limited, ATP-independent effects on paracellular conductance. As an alternative explanation for the effects of oxidants on MDCK monolayer paracellular conductance, we had reported that oxidants increased production of inositol phosphates and diglycerides in MDCK cells. Synthetic diglyceride and phorbol dibutyrate (PDBU) increased MDCK monolayer conductance to ions and mannitol in earlier studies. When MDCK cell ATP was depleted with DOG (to the level caused by oxidants), the increase in conductance following PDBU was not different from that observed in control cells. More severe ATP depletion, with DOG and AA, prevented the increase in conductance following PDBU.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Both ethanol consumption and protein deficiency increase the fragility of pancreatic lysosomes.

Both ethanol abuse and protein deficiency result in pancreatic injury. Moreover, these two variables frequently coexist. As lysosomal enzymes may play a role in the initiation of pancreatic injury, the aim of this study was to determine the effects of ethanol consumption and protein deficiency on pancreatic lysosomal stability. For 3 weeks, male Sprague-Dawley rats were match-fed (in groups of four) isocaloric amounts of one of the following liquid diets: (1) protein-sufficient diet, (2) protein-sufficient diet containing ethanol as 36% of the total energy, (3) protein-deficient diet, and (4) protein-deficient diet containing ethanol as 36% of energy. Pancreatic lysosomal stability was assessed by determining (a) latency, as indicated by the percentage increase in lysosomal enzyme activity in pancreatic homogenate induced by Triton X-100, and (b) by the percentage of lysosomal enzyme remaining in the supernatant after sedimentation of the lysosomal pellet from the pancreatic homogenate. Protein deficiency was associated with a decrease in latency and an increase in supernatant enzyme. Ethanol administration was associated with a decreased latency. Both protein-deficient and ethanol-fed animals exhibited higher pancreatic activities of cathepsin B, a lysosomal protease capable of activating trypsinogen. In addition, protein-deficient animals exhibited higher pancreatic activities of acid phosphatase, N-acetyl-glucosaminidase, and beta-glucuronidase. As lysosomal enzymes are postulated to play a role in the initiation of pancreatitis, these results suggest that ethanol consumption and protein deficiency may at least partly exert their toxic effects on the pancreas by altering pancreatic lysosomal stability and increasing the glandular content of cathepsin B.

Acetylglucosaminidase↗

Abdominal reduction following jejunoileal bypass for morbid obesity.

We present six patients who underwent abdominal reduction after successfully losing weight following jejunoileal bypass. Three patients needed more than one operation to achieve a good cosmetic result. There were no serious complications. After reviewing these patients and the few previously reported cases we make the following suggestions: 2 years should elapse after a stable weight is attained before surgery. Preoperative metabolic screening is essential. Preoperative marking of the lines of excision, prophylactic antibiotics and drainage of the wounds are strongly recommended. Lower abdominal aprons may be safely removed by a low transverse incision extended laterally up to the iliac crests and superiorly as far as the umbilicus. The umbilicus can be resited without risk of necrosis. High abdominal aprons should be excised as a transverse or vertical "melon-slice" ellipse without undermining.

Abdomen↗

Alcohol-induced pancreatic injury (Part I). Unexplained features and ductular theories of pathogenesis.

The pathogenesis of alcoholic pancreatitis continues to be a puzzle. Classical theories of pathogenesis tend to overlook the dual nature of the disease, i.e., symptomatic acute attacks and chronic progressive parenchymal destruction. Furthermore, it is unknown why only a small minority of alcoholics develop clinical pancreatic injury. In addition, there is a lack of basic data concerning the natural history of the condition after cessation of alcohol consumption. The most widely accepted theory of pathogenesis postulates the deposition of protein plugs in peripheral pancreatic ducts as the initial lesion. However, it has not been established that these plugs are the cause rather than a result of pancreatic injury. The so-called "Big Duct" theories of pathogenesis (biliary-pancreatic reflux, duodeno-pancreatic reflux, and obstruction-hypersecretion) are confounded by a lack of agreement concerning the effect of alcohol on the sphincter of Oddi. Nutritional factors and heredity may be responsible for the selectivity of alcohol in this condition; in this regard, a number of dietary and HLA studies have been performed, but these have generally been inadequately controlled. Subcellular pancreatic injury (fat droplets, autophagic vacuoles, and mitochondrial lesions) has been observed in alcoholics without pancreatitis and in animals fed alcohol. In addition, ethanol feeding in animals has been shown to affect pancreatic cholesterol, phospholipid, and fatty acid metabolism as well as pancreatic content of digestive enzymes. Research is hampered by the lack of a suitable animal model of the disease.

Alcohol Drinking↗