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Biomedical subjects

P Dowling

Publications and source records attributed to P Dowling.

At least 19 recordsLinked to original sources
PubMed2006

The effects of ageing on the distribution of vesicular acetylcholine transporter immunoreactive inputs to pelvic motoneurons of male Wistar rats.

Age-related changes in the number and size of large cholinergic terminals immunoreactive for vesicular acetylcholine transporter (VAChT), were documented for the dorsolateral nucleus (DLN), retrodorsolateral nucleus (RDLN) and spinal nucleus of the bulbospongiosus (SNB) of the lumbosacral spinal cord of male rats. The most significant changes were a large increase in the number and size of cholinergic terminals within the DLN of aged animals, together with a small decrease in terminal number within the RDLN. No significant age-associated differences in VAChT labeling were seen within the SNB. In both age groups, SNB motoneurons projecting to the levator ani muscle received about 9 to 10 contacts from large cholinergic terminals. Ultrastructural examination of the terminals revealed structures likely to be postsynaptic subsurface cisterns that are characteristic of type C terminal boutons. Since both the DLN and SNB contain motoneurons innervating pelvic muscles and sphincters, these findings provide further evidence for a central cholinergic influence on micturition and sexual reflexes and suggest that this may remain robust in the face of ageing.

Aging↗
PubMed2004

Pharmacokinetics of florfenicol in North American elk (Cervus elaphus).

Florfenicol pharmacokinetics after administration of a single subcutaneous (s.c.) dose of 40 mg/kg of body weight in adult elk (Cervus elaphus) was investigated. Serum florfenicol concentrations were determined by a sensitive high-performance liquid chromatographic method with limit of quantification of 0.03 microg/mL. Florfenicol pharmacokinetic parameters in elk were estimated using a noncompartmental approach. After a single s.c. injection, florfenicol concentrations remained above 1 microg/mL for approximately 36 h and above 0.5 microg/mL for approximately 72 h. Following s.c. injection, florfenicol was absorbed rapidly with a mean maximum concentration (C(max)) of 3.7 microg/mL achieved at 4.2 h (T(max)). The C(max) value in elk is similar to values reported in cattle at the same dose, suggesting that the 40 mg/kg s.c. dose achieves therapeutic concentrations in elk. A mean elimination half-life (t(1/2)) of 44 h is shorter than that reported in cattle. The more rapid elimination half-life in elk suggests that elk may require a multiple dose regimen for therapeutic success with s.c. Nuflor. We recommend s.c. Nuflor be administered subcutaneously to elk every 24 h at a dose level of 40 mg/kg.

Animals↗
PubMed2003

A meta-analysis review of the effects of recombinant bovine somatotropin. 1. Methodology and effects on production.

This manuscript presents the results of a review of the effects of recombinant bovine somatotropin (rBST) on milk production, milk composition, dry matter intake, and body condition score that was carried out by an expert panel established by the Canadian Veterinary Medical Association (CVMA). The panel was established by the CVMA in response to a request from Health Canada in 1998 and their report was made public in 1999. A series of meta-analyses was used to combine data on production and nutrition related parameters that were extracted from all randomized clinical trials, which had been published in peer-reviewed journals or which were provided by Health Canada, from the submission by Monsanto for registration of rBST in Canada. A companion paper will present the results of the effects of the drug on measures of health, reproductive performance, and culling parameters. Recombinant bovine somatotropin was found to increase milk production by 11.3% in primiparous cows and 15.6% in multiparous cows; although there was considerable variation from study to study. While some statistically significant effects on milk composition (% butterfat, protein, and lactose) were found, they were all very small. Treatment increased dry matter intake by an average 1.5 kg/day during the treatment period and dry matter intake remained elevated on into the first 60 days of the subsequent lactation. Despite the increase in dry matter intake, treated animals had lower body condition scores at the end of the treatment period, and the reduced scores persisted through until the start of the subsequent lactation.

Animals↗
PubMed2003

A meta-analysis review of the effects of recombinant bovine somatotropin. 2. Effects on animal health, reproductive performance, and culling.

This manuscript presents the results of a review of the effects of recombinant bovine somatotropin (rBST) on dairy cattle health, reproductive performance, and culling, that was carried out by an expert panel established by the Canadian Veterinary Medical Association (CVMA). The panel was established by the CVMA in response to a request from Health Canada in 1998 and their report was made public in 1999. A series of meta-analyses was used to combine data on health-related parameters that were extracted from all randomized clinical trials that had been published in peer-reviewed journals or which were provided by Health Canada from the submission by Monsanto for registration of rBST in Canada. A companion paper (1) presents the estimates of the effect of the drug on production parameters. Recombinant bovine somatotropin was found to increase the risk of clinical mastitis by approximately 25% during the treatment period but there was insufficient data to draw firm conclusions about the effects of the drug on the prevalence of subclinical intra-mammary infections. Use of rBST increased the risk of a cow failing to conceive by approximately 40%. For cows which did conceive, there was no effect on services per conception and only a small increase in average days open (5 days). Use of the drug had no effect on gestation length, but the information about a possible effect on the risk of twinning was equivocal. Cows treated with rBST had an estimated 55% increase in the risk of developing clinical signs of lameness. Few studies reported data on culling, but based on those that did, there appeared to be an increase risk of culling evident in multiparous cows. Use of the drug in 1 lactation period appeared to reduce the risk of metabolic diseases (particularly ketosis) in the early period of the subsequent lactation.

Animals↗
PubMed2001

Proliferating oligodendrocytes are present in both active and chronic inactive multiple sclerosis plaques.

The proliferation marker Ki-67 labels cell nuclei in the G(1), S, M, and G(2) phases of the cell cycle. We used Ki-67 immunohistochemistry to quantify proliferating glial cells in brain tissue sections from twenty-four patients, comprised of multiple sclerosis, normal brains, and other neurological disease controls. Glial proliferation was greatly increased in MS lesions when compared with control brain white matter. Both actively demyelinating/early remyelinating plaques and chronic inactive plaques of long standing often displayed large numbers of glial cells in the proliferative cycle. The bulk of these proliferating cells were of oligodendroglial lineage in the MS plaques. Ki-67 positive macrophage/microglial lineage cells were largely restricted to acute lesions. The finding of increased numbers of proliferating oligodendroglia in most MS plaques, regardless of disease duration or activity state, indicates that the MS brain is capable of recruiting unexpectedly large numbers of new oligodendrocytes over long periods of time. The factors within the MS plaque microenvironment that provoke new oligodendrocyte generation and their subsequent loss still need to be identified.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2001

Brain dystrophin-glycoprotein complex: persistent expression of beta-dystroglycan, impaired oligomerization of Dp71 and up-regulation of utrophins in animal models of muscular dystrophy.

BACKGROUND: Aside from muscle, brain is also a major expression site for dystrophin, the protein whose abnormal expression is responsible for Duchenne muscular dystrophy. Cognitive impairments are frequently associated with this genetic disease, we therefore studied the fate of brain and skeletal muscle dystrophins and dystroglycans in dystrophic animal models. RESULTS: All dystrophin-associated glycoproteins investigated were reduced in dystrophic muscle fibres. In Dp427-deficient mdx brain and Dp71-deficient mdx-3cv brain, the expression of alpha-dystroglycan and laminin was reduced, utrophin isoforms were up-regulated and beta-dystroglycan was not affected. Immunofluorescence localization of beta-dystroglycan in comparison with glial, endothelial and neuronal cell markers revealed co-localization of von Willebrand factor with beta-dystroglycan. Its expression at the endothelial-glial interface was preserved in dystrophin isoform-deficient brain from mdx and mdx-3cv mice. In addition, chemical crosslinking revealed that the Dp71 isoform exists in mdx brain predominantly as a monomer. CONCLUSIONS: This suggests an association of beta-dystroglycan with membranes at the vascular-glial interface in the forebrain. In contrast to dystrophic skeletal muscle fibres, dystrophin deficiency does not trigger a reduction of all dystroglycans in the brain, and utrophins may partially compensate for the lack of brain dystrophins. Abnormal oligomerization of the dystrophin isoform Dp71 might be involved in the pathophysiological mechanisms underlying abnormal brain functions.

Animals↗
PubMed2001

Platelet-derived growth factor-alpha receptor-positive oligodendroglia are frequent in multiple sclerosis lesions.

Platelet-derived growth factor (PDGF) ligand is a potent glial cell mitogen. When its cognate receptor (PDGF-alphaR) is expressed on oligodendroglial lineage cells, such cells are considered capable of division, and the receptor thus serves as a phenotypic marker for oligodendrocyte precursor cells. Here we identify using immunohistochemistry a considerably enlarged, PDGF-alphaR-expressing oligodendrocyte cell population within multiple sclerosis (MS) white matter lesions compared to control brains. Numerous PDGF-alphaR-positive oligodendroglia also colabel heavily with the nuclear cell proliferation marker antibody Ki-67. Our finding of large numbers of proliferating oligodendroglia in MS brains expressing up-regulated PDGF-alphaR suggests that these progenitor-like cells represent an important source of regenerating cells for the healing MS lesion.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2000

Latino physician supply in California: sources, locations, and projections.

PURPOSE: To determine the number of Latino physicians in California, identify the schools and countries where they were educated, determine the percentage located in Latino areas, and project the supply of Latino physicians to 2020. METHOD: From a 1999 list of 74,345 licensed physicians, the authors identified Latino U.S. medical graduates (USMGs) by "heavily Hispanic" surnames and Latino international medical graduates (IMGs) by country and school of graduation. The 1999 license addresses of all physicians in Los Angeles County were analyzed against 1998 Latino-population data by zip code. A baseline projection of the supply of Latino physicians was based on the ten-year (1986 to 1995) average annual production of Latino physicians educated in California, out of state, and in Latin America. A worst-case projection assumed the continuation of recent trends: a 32% decrease in California-educated Latino USMGs, a 19% decrease in out-of-state Latino USMGs, and a reduction of Latino IMGs to five per year. RESULTS: In 1999, 3,578 Latino physicians comprised 4.8% of all Californian physicians. In contrast, Latinos made up 30.4% of the state's population. Latino physicians were more likely than non-Latinos to have addresses in a heavily Latino zip code. In the baseline projection, while the overall supply of Latino physicians will increase by nearly 30% by 2020, that growth will be dwarfed by the 74% growth in the Latino population over the same time. In the worst-case projection, the actual number of Latino physicians will decrease from the 1999 figure of 3,578 to 3,448 by 2020, while the Latino population continues to grow. CONCLUSIONS: (1) The Latino USMG supply must be markedly increased in the number of first-year matriculants in both California and out-of-state schools. (2) The issue of Latino IMGs requires special attention, and may provide a temporary solution to the Latino physician shortfall. (3) Non-Latino physicians need to be prepared to be culturally effective with a large and growing Latino patient population.

California↗
PubMed1999

Up-regulated p75NTR neurotrophin receptor on glial cells in MS plaques.

OBJECTIVE: To investigate the expression of the neurotrophin receptor p75NTR on glial cells within MS plaques. BACKGROUND: In recent studies on the pathogenesis of MS white matter plaques, we found large populations of inflammatory and resident glial cells, including oligodendrocytes undergoing cell death, and identified increased expression of Fas receptor and ligand death pathway signaling molecules on the same glial cell types. In another study, the p75NTR was shown to induce apoptotic death of maturing oligodendrocytes when exposed to NGF in vitro. METHODS: We used immunohistochemistry and in situ reverse-transcription PCR to detect p75NTR expression on inflammatory and resident glial cells in MS plaques and used TUNEL staining for fragmented DNA to detect cell death. RESULTS: Up-regulated p75NTR messenger RNA and protein were demonstrated in both oligodendrocytes and microglia/macrophages in MS plaques but not in control white matter. However, only a fraction of p75NTR expressing oligodendrocytes was also stained by TUNEL. CONCLUSIONS: Glial cell expression of p75NTR receptor is up-regulated during MS plaque formation. The exact role of this receptor in glial cell death and/or survival in MS remains to be elucidated.

Antigens↗
PubMed1999

Deletion of the pseudoautosomal region in a male with a unique Y;13 translocation and short stature.

Short stature is a common finding in patients with Ullrich-Turner syndrome. Structural abnormalities involving the terminal short arms of the X and Y chromosomes have been shown to lead to short stature. A putative locus affecting height called PHOG/SHOX has been localized to a 170-kb critical region within the pseudoautosomal region (PAR). It contains a homeodomain and functions as a transcription factor. We have studied a 10-year-old boy with idiopathic short stature who was found to have a unique Y;13 translocation. Southern blot analysis using cDNA probes indicated that most of the PAR, including PHOG/SHOX, was lost as a result of this translocation. We conclude that haploinsufficiency for this gene is responsible for the growth failure in our patient. Treatment with recombinant growth hormone has resulted in greatly improved growth velocity.

Body Height↗
PubMed1999

Simultaneous occurrence of two supernumerary autosomal ring chromosomes r(1) and r(16) in twins.

Ring chromosomes are estimated to occur in 3/10000 newborns and the simultaneous occurrence of two autosomal rings must be a very rare event. Recently, the characterisation of these markers using fluorescence in situ hybridisation (FISH) has greatly enhanced cytogenetic-phenotypic correlations in patients with these marker chromosomes. This kind of analysis enabled us to clarify a unique karyotype containing a r(1) and a r(16) in identical twins born after a 26 week gestation with minimal somatic abnormalities. The origin of the rings was identified using a satellite and whole chromosome painting probes. FISH analysis showed the same abnormal female karyotype in both twins, 48,XX,+r(1)(p13q21),+r(16)(p11q11).ish r(1) (D1Z5+,wcpl+), r(16)(D16Z2+,wcp16+) in about two thirds of the cells. Each also had minor clones with a normal female karyotype or with one or the other supernumerary ring. Half of the r(1) contained CBG band negative material and the r(16) appeared to be totally CBG band positive. These twins represent the second report of the simultaneous occurrence of multiple autosomal rings. Their description may help to delineate a new chromosome disorder and shows the usefulness of FISH analysis.

Chromosomes, Human, Pair 1↗
PubMed1997

The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.

We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.

Adult↗
PubMed1997

Modified total lymphoid irradiation and low dose corticosteroids in progressive multiple sclerosis.

In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.

Adult↗