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Biomedical subjects

S Mahoney

Publications and source records attributed to S Mahoney.

17 recordsLinked to original sources
PubMed2000

Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity.

The neuropeptide galanin is expressed developmentally in the dorsal root ganglion (DRG) and is rapidly up-regulated 120-fold after peripheral nerve section in the adult. Here we report that adult mice carrying a loss-of-function mutation in the galanin gene have a 13% reduction in the number of cells in the DRG associated with a 24% decrease in the percentage of neurons that express substance P. These deficits are associated with a 2.8- and 2.6-fold increase in the number of apoptotic cells in the DRG at postnatal days 3 and 4, respectively. After crush injury to the sciatic nerve, the rate of peripheral nerve regeneration is reduced by 35% with associated long-term functional deficits. Cultured DRG neurons from adult mutant mice demonstrate similar deficits in neurite number and length. These results identify a critical role for galanin in the development and regeneration of sensory neurons.

Animals↗
PubMed2000

Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons.

The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents. Chronic intracerebroventricular infusion of nerve growth factor induces a 3- to 4-fold increase in galanin gene expression in these neurons. Here we report the loss of a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene. These deficits are associated with a 2-fold increase in the number of apoptotic cells in the forebrain at postnatal day seven. This loss is associated with marked age-dependent deficits in stimulated acetylcholine release, performance in the Morris water maze, and induction of long-term potentiation in the CA1 region of the hippocampus. These data provide unexpected evidence that galanin plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergic neurons.

Animals↗
PubMed1999

Synechococcus mutants resistant to an enamine mechanism inhibitor of glutamate-1-semialdehyde aminotransferase.

An enamine mechanism-based inactivator of mammalian delta-aminobutyric acid aminotransferase, 4-amino 5-fluoropentanoic acid is a potent inhibitor of cell growth and pigment formation in the cyanobacterium Synechococcus PCC 6301. It was demonstrated that 4-amino 5-fluoropentanoic acid inhibits the aminolaevulinate synthesis at glutamate 1-semialdehyde aminotransferase and that in the mutant obtained by exposing cells to 40 microM 4-amino 5-fluoropentanoic acid, this enzyme was insensitive to the inhibitor. The specific activity of glutamate 1-semialdehyde aminotransferase in cell extracts was lower in the mutant, although the cell growth rate was unaffected. The decrease in sensitivity to 4-amino 5-fluoropentanoic acid in the mutant is due to a structural gene mutation, a single base change in the hemL gene resulting in a S162T substitution in the gene product.

Aminolevulinic Acid↗
PubMed1999

A simple objective method of adjusting sling tension.

PURPOSE: Pubovaginal sling is gaining widespread acceptance as a primary form of treatment for types II and III stress urinary incontinence. However, a major drawback is postoperative obstructed voiding due to excessive force placed on the suspension suture. We describe a simple objective method for intraoperative adjustment of sling tension that can be performed by a single surgeon during pubovaginal sling surgery. MATERIALS AND METHODS: A cotton swab is inserted into the urethra and placed at the urethrovesical junction after the sling is fixed suburethrally and the vaginal mucosa is closed. The suspension sutures are tied down directly onto the rectus fascia with enough tension to keep the cotton swab angle between 0 and 10 degrees to the horizontal plane. A total of 29 patients with an average age of 62 years underwent pubovaginal sling surgery with rectus and cadaveric fascia using this technique for tension adjustment. Of the patients 21 were diagnosed with types II and III, 5 had type II only and 3 had type III only incontinence. Preoperative evaluation revealed detrusor instability in 5 patients. Mean postoperative indwelling catheterization period was 6.2 days. Average followup was 15.6 months. RESULTS: To date no permanent urinary retention has occurred. Of the patients 15 voided without difficulty after catheter removal, 13 had urinary difficulty requiring intermittent catheterization for 1 week or less and 1 had retention requiring intermittent catheterization for 10 weeks. Preoperative symptoms of detrusor instability resolved in all cases. De novo detrusor instability in 3 cases was controlled with anticholinergics. CONCLUSIONS: Overzealous sling tension adjustment has been recognized as a cause of treatment failure leading to urethral obstruction. Our technique is effective in preventing over adjustment of tension, is reproducible and can be performed by 1 surgeon.

Adult↗
PubMed1998

A prospective randomized trial of an urban general practice attachment for medical students.

A randomized controlled trial was undertaken to evaluate the effectiveness of a new model for providing urban general practice attachments for final-year medical students at the Flinders University of South Australia. All the student groups in that year were randomized prospectively to either the standard student attachment, as run by the university, or to an attachment organized by a project team from a local network of general practitioners. Students in the intervention group had their personal learning goals assessed and matched with their general practice preceptors, and the students were set a task that developed their contact with other health resources in the community. Results from an evaluation questionnaire completed by the students at the end of their terms showed that the students in the intervention group rated their general practice preceptors more highly, had more contact with allied health and community organizations, felt that they had met their own learning goals to a greater extent, and enjoyed their term more. Student examination results showed that the students in the intervention group did not perform as well in one of the four areas of their end of term examination as did the students in the standard attachment. The additional cost of providing the intervention was estimated to be A$340 per student. We conclude that long-term decisions about adopting this new model of organizing general practice attachments on a wider scale will need to balance the apparent benefits against the increased resources required.

Education, Medical, Undergraduate↗
PubMed1996

Characterization of charge change super-repressor mutants of trp repressor: effects on oligomerization conformation, ligation and stability.

We have carried out a physical characterization of mutant repressor proteins of the trp repressor system of Escherichia coli by circular dichroism, chemical denaturation, and 8-anilino-1-naphthalenesulfonate binding. We have also probed the protein-protein interactions via fluorescence anisotropy and lifetime measurements and measured the thermodynamics of ligand (L-tryptophan) binding by isothermal titration calorimetry. Here, we present investigations of four charge change super-repressor mutants: EK13, EK18, DN46 and EK49, and compare these results with those previously obtained for wild-type trp repressor and the AV77 super-repressor mutant. These studies demonstrate that super-repressor phenotypes may result from changes in operator affinity (DN46, EK49), protein-protein interactions (EK18), as well as the coupling of folding to ligand binding (AV77, EK13, EK18). Correlations between the oligomerization behavior and cooperativity of DNA binding for some of these mutants indicate that coupling of oligomerization to DNA binding modulates operator site occupation giving rise to the super-repressor phenotype. The present results underscore the complex interplay between the multiple equilibria in this system. Moreover, they provide insights into the structural basis for the mutational perturbation of the energetics of this classical allosterically controlled transcriptional regulator.

Anilino Naphthalenesulfonates↗
PubMed1995

Nutritional and treatment-related characteristics of pediatric oncology patients referred or not referred for nutritional support.

Nutritional problems often result from malignancies and aggressive multimodal treatment. Early identification of reliable risk factors associated with malnutrition and need for nutritional support is necessary for development of preventative approaches. Nutritional and treatment-related characteristics were examined for 173 pediatric oncology patients referred for nutritional support and a comparison sample of 43 patients matched on treatment protocol and/or diagnosis who had never been referred for nutritional support. Abnormally low serum albumin levels, poor oral intake, mucositis, prior radiation therapy, and increased gastrointestinal toxicity were significantly more frequent among referred than non-referred patients. A discriminant function analysis indicated that poor oral intake was the single best predictor of need for nutritional support. Patients with solid tumors were more nutritionally depleted at the time of referral; all bone marrow transplant patients received nutritional support. Patients with central nervous system (CNS) tumors required nutritional support for longer time periods. We conclude that routine documentation of poor oral intake (i.e., observation of change in a child's eating patterns) is the most reliable indicator of children who eventually require nutritional support and who may benefit from interventions that could delay or prevent nutritional problems. Prophylactic interventions should be tailored to meet the specific needs of individual diagnostic groups.

Adolescent↗
PubMed1995

Insulin autoimmune syndrome as a cause of spontaneous hypoglycemia in alcoholic cirrhosis.

Hypoglycemia in fulminant hepatic failure and hyperinsulinemia in cirrhosis are well-described phenomena. A patient with alcoholic cirrhosis who developed fasting hypoglycemia with an extremely high immunoreactive insulin level and a mildly elevated C-peptide level is reported. An insulinoma was excluded by detailed radiological imaging of the pancreas and by endoscopic ultrasonography. Detection of very high levels of insulin autoantibodies with no prior exposure to exogenous insulin confirmed the diagnosis of insulin autoimmune syndrome. During his hospital course, the patient developed another rare syndrome, acquired inhibitors to factor V, which led to the fatal coagulopathy that resulted in his death. Insulin autoimmune syndrome is the third leading cause of spontaneous hypoglycemia in Japan, where it has been associated with a variety of diseases and drugs. Outside of Japan, only approximately 20 cases have been reported and usually have been found in the context of an underlying autoimmune disorder or prior exposure to sulfhydryl drugs. It is believed that this is the first case reported outside Japan occurring in association with alcoholic liver disease, and the first in the world with coexisting acquired inhibitors to factor V.

Autoimmune Diseases↗
PubMed1991

Improved detection of in situ hybridization by laser scanning confocal microscopy.

Laser scanning confocal microscopy (LSCM) offers a significant improvement over conventional bright-field and dark-field light microscopy for producing images of silver grains in autoradiograms of specimens prepared by in situ hybridization. The out-of-focus image of the background silver grains present in the emulsion is eliminated from the in-focus image of the radioactive probe associated with the cells by optical sectioning with the LSCM operated in a reflected light mode. The improved images produced by the LSCM provide a significant increase in the sensitivity of detecting positively labeled cells and tissues prepared by in situ hybridization. The power of this detection method is demonstrated using samples of HIV-infected human peripheral blood cells, tissue sections of human placenta and human skin. It is anticipated that the method can be universally applied to samples prepared by in situ hybridization techniques.

Cell Line↗
PubMed1991

Syphilis superinfection activates expression of human immunodeficiency virus I in latently infected rabbits.

Superinfection of latently human immunodeficiency virus (HIV)-infected rabbits with either Treponema pallidum or Shope fibroma virus (SFV) activates HIV expression. In addition, HIV-infected rabbits demonstrate prolonged cutaneous lesions (chancres) after intracutaneous challenge with T. pallidum, the causative agent of syphilis. Rabbits were infected by intravenous inoculation of 3 x 10(7) human T-cell lymphotrophic virus type III (HTLV-III)/B10 (HIV-1)-infected H9 (human) cells. Five weeks after initial infection, integrated HIV-1-specific DNA sequences were detected in the DNA of the peripheral blood lymphocytes of only one of eight rabbits using polymerase chain reactions (PCR); human DNA could not be detected at this time. Furthermore HIV infection could not be demonstrated by either seroconversion or PCR during the next 6 months. All HIV-infected rabbits remained clinically healthy and had normal white blood cell counts. Six months after HIV infection, four HIV-infected and two noninfected controls were superinfected with 10(6) T. pallidum in eight skin sites in the shaved skin of the back, and four infected and two control animals were challenged with an intradermal injection with SFV. After infection with either syphilis or SFV, the DNA from the white blood cells of all eight HIV-infected rabbits contained HIV sequences, and HIV sequences were demonstrated in dermal mononuclear cells of the syphilitic lesions by in situ hybridization. The SFV-induced tumors were rejected normally in the HIV-infected rabbits, but four of the four rabbits challenged with T. pallidum had delayed development of cutaneous lesions and three of four demonstrated larger and more prolonged lesions. White blood counts, mitogen responses, and interleukin-2 production remained within normal limits, and seroconversion for HIV was not detected. Three of four rabbits in a second group, challenged with T. pallidum 4 months after HIV-inoculation, also had delayed healing of syphilitic lesions. These results indicate that latent HIV-infection of rabbits may be activated by immunostimulation and that latently HIV-infected rabbits have impaired delayed hypersensitivity reactions. It is hypothesized that true latent HIV-infection in the rabbits is in monocytes and postulated that further immunostimulation may produce infection of lymphocytes and activation of disease.

Animals↗
PubMed1984

Incidental fetal hydronephrosis: clinical implication.

Maternal ultrasonography performed after twenty weeks of gestation is able accurately to identify and diagnose fetal hydronephrosis. We believe this finding should serve to alert the obstetrician as well as the pediatrician to potential complications which may arise at the time of delivery or immediately thereafter. Urologic evaluation and definitive surgical repair may then be performed when indicated.

Adult↗
PubMed1983

A blinded prospective study comparing four current noninvasive approaches in the differential diagnosis of medical versus surgical jaundice.

A prospective study was undertaken to compare the diagnostic accuracy of clinical evaluation, ultrasound, computed tomography, and technetium 99m-HIDA or -PIPIDA biliary scans in distinguishing between intrahepatic and extrahepatic jaundice. A final diagnosis was established in each of the 50 patients who completed the study, among whom 29 had intrahepatic cholestasis and 21 had extrahepatic obstruction. In the diagnosis of extrahepatic obstruction, the sensitivities of clinical evaluation, ultrasound, computed tomography, and nuclear medicine biliary scan were 95%, 55%, 63%, and 41%, respectively; the specificities were 76%, 93%, 93%, and 88%; and the overall accuracies were 84%, 78%, 81%, and 68%. These data support the conclusion that when the clinical evaluation is carefully performed, it is the single most effective noninvasive means of detecting extrahepatic biliary obstruction in a jaundiced patient. Although ultrasound, computed tomography, and radionuclide biliary scan are less sensitive, they are highly reliable if they indicate that extrahepatic obstruction is present. A flow chart of invasive and noninvasive approaches for evaluation of the jaundiced patient is presented.

Adult↗
PubMed1978

A circadian susceptibility/resistance rhythm for potassium cyanide in male BALB/cCr mice.

Circadian rhythms in mortality and/or survival time following a single intraperitoneal injection of a LD50 of potassium cyanide were studied. In two investigations, different but comparable subgroups of inbred male BALB/cCr mice were treated at 4-h intervals (under conditions standardized for chronobiologic study) during 24-h spans. Mice were observed for exact time-to-death during the first hour after treatment as well as overall mortality during the entire 24-h post-injection span following each KCN treatment timepoint. In both studies, mortality from KCN exhibited a 24-h rhythm. Highest mortality occurred in mice injected at 1600 (80% mortality) in Experiment 1 and 2000 (100% mortality) in Experiment II. Lowest mortality occurred at 0400 (40% mortality) in Experiment I and 0800 (30% mortality) in Experiment II. The need to consider the circadian organization of physiologic function when bioassaying toxicity is discussed.

Animals↗