An argument for outsourcing.
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Contract Services↗
Biomedical subjects
J Wood
Publications and source records attributed to J Wood.
Hormone replacement therapy is associated with lower risk of adenomatous polyps of the large bowel: the Minnesota Cancer Prevention Research Unit Case-Control Study.
Evidence of a role for steroid hormones and reproduction in colon neoplasia remains tantalizing but unclear. Hormone replacement therapy (HRT) has been reported in a number of recent studies to be associated with a reduced risk of colon cancer. A case-control study was undertaken to establish whether HRT is associated with lower risk of adenomatous polyps. This case-control study was undertaken as a project of the Minnesota Cancer Prevention Research Unit. Cases (n = 219) were women, ages 30-74 years with colonoscopy-proven, pathology-confirmed, adenomatous polyps of colon and rectum recruited at Digestive Healthcare PA (Minneapolis, MN). Two control groups were selected: women without polyps at colonoscopy (n = 438) at Digestive Healthcare and age- and zip code-matched women selected from the general community (n = 247). Response rates were 68% among those colonoscoped and 65% among community controls. Parity, age at first live birth, and oral contraceptive use did not distinguish cases from either control group. Multivariate adjusted odds ratios and 95% confidence limits for use of HRT for less than 5 years (compared with never use) among postmenopausal women were 0.52 (0.32-0.85) versus colonoscopy-negative controls and 0.74 (0.44-1.26) versus community controls. For 5 years of use or greater, the corresponding figures were 0.39 (0.23-0.67) and 0.61 (0.34-1.07). These results were not materially different when stratified on body mass index, oophorectomy, hysterectomy, aspirin use, or family history. There is no marked increase in risk even 5 years after cessation of HRT use. HRT appears to lower risk of colorectal adenomatous polyps, suggesting that it acts quite early in the neoplastic process. Mechanisms remain unclear. Reduction of risk of colorectal neoplasia is an additional benefit of postmenopausal HRT.
Adenocarcinoma↗
The effect of kainate on protein kinase C, GABA, and the uptake of serotonin in the rabbit retina in vivo.
The purpose of this study was to investigate the effect of kainate on protein kinase C (PKC), gamma-aminobutyrate (GABA) and serotonin uptake in the rabbit retina. Kainate when injected into the vitreous humour produces a change in the GABA immunoreactivity within 6 hours. After 3 days, remnants of the normal GABA immunoreactivity still persist and additionally astrocyte and microglia-like elements "stain" positively for GABA. After 7 days exposure to kainate none of the normal GABA immunoreactivity is apparent, instead a number of round-shaped elements which may be reactive astrocytes and/or microglia stain positively for GABA. During these stages kainate does not affect the alpha PKC immunoreactivity associated with the on-bipolar cells. Six hours following kainate treatment the ability of certain GABA amacrine cells to take up exogenous serotonin is unaffected. After three days only a few of these cells can still take up exogenous serotonin and then not avidly. After seven days the GABA/serotonin amacrine cells cannot take up exogenous serotonin suggesting that all of these neurons are irreversibly damaged. One hour after treatment with kainate both calcium-dependent and -independent PKC species are translocated from the cytosolic to membrane compartments. After 5 hours and 7 days there was also evidence from the enzyme assay experiments that kainate caused the calcium-dependent and -independent PKC enzymes to be translocated but because the total enzyme activity was reduced due perhaps to down-regulation of the enzyme this was difficult to assess precisely.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The influence of experimental ischaemia on protein kinase C and the GABAergic system in the rabbit retina.
Pressure-induced ocular ischaemia followed by 25-28 hr of reperfusion to the rabbit retina drastically reduces or eliminates the b-wave of the electroretinogram and results in all the GABA from the amacrine cells being released, as judged by immunohistochemistry. Some of these GABA cells have the capacity to take-up exogenous serotonin and these GABA/serotonin cells have kainate/AMPA receptors. Previous studies have shown that an ischaemic insult causes these receptors to be stimulated to produce a release of the cells' GABA. The majority of the GABA/serotonin cells are also incapable of taking-up exogenous serotonin after ischaemia, which suggests that they are irreversibly damaged. However, there was still a minority of the cells which accumulated serotonin, which shows that neurones containing kainate/AMPA receptors are not irreversibly damaged at the same rate by ischaemia. The "staining" patterns for GABAA-receptor and GABA immunoreactivities in the rabbit retina are very similar and following ischaemia the GABAA-receptor immunoreactivity was reduced in intensity and became patchy in nature. It is not known whether this result reflects a down-regulation of the GABAA-receptors caused by the released GABA or a destruction of cells containing the GABAA-receptors. The ischaemic conditions used caused patchy, irregular and inconsistent signs of histological damage to the retina, even in areas of similar eccentricity, suggesting this parameter should be used with caution when judging the severity of an ischaemic insult. alpha-Protein kinase C (alpha PKC) present in the on-bipolar cells which have glutamate metabotropic APB receptors is both reduced or down-regulated and translocated by ischaemia. This is also the case for delta PKC which is absent from the on-bipolar cells. These data were established by a combination of immunohistochemistry and electrophoresis/blotting experiments. Enzyme analysis also showed that all PKC calcium-dependent and -independent isoenzymes, are translocated and reduced by ischaemia making it difficult to judge whether PKC inhibitors may be appropriate anti-ischaemic agents.
Animals↗
The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat.
Using a highly purified recombinant protein, mMOG, we demonstrated that autoimmune responses to the N-terminal domain (a.a 1-125) of the myelin oligodendrocyte glycoprotein (MOG) induce an acute demyelinating variant of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Immunisation with 100 micrograms of mMOG in adjuvant at the base of the tail induced mild clinical disease in 9 of 11 animals (mean clinical score 1.1). The disease was characterised histopathologically by the presence of inflammation and focal demyelinating lesions in the central nervous system (CNS). Adoptive transfer experiments suggest that this inflammatory demyelinating pathology is mediated by synergy between a weakly encephalitogenic, MOG-specific T cell response and a demyelinating, MOG-specific autoantibody response. Using in vitro selected mMOG-reactive T cell lines, the encephalitogenic T cell response to this domain of MOG was found to recognise two distinct epitopes, MOG1-20 and MOG35-55; whereas ELISA demonstrated that the immunodominant B cell epitope was located within the amino acid sequence MOG1-25. However although active immunisation with synthetic peptides corresponding to the T cell epitopes, MOG1-20 or MOG35-55, induced an inflammatory response in the CNS, this was not associated with demyelination indicating that the demyelinating antibody response recognises other, possibly conformation dependent epitopes. This study unequivocally demonstrates that MOG-specific autoimmune responses are alone sufficient to induce a demyelinating disease of the CNS and supports the proposal that MOG may play an important role in the immunopathogenesis of multiple sclerosis.
Amino Acid Sequence↗
Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation.
OBJECTIVES: To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. METHODS: Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response. RESULTS: Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy. CONCLUSIONS: Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered for a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.
Administration, Intravesical↗
Characterising the Huntington's disease gene product.
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Animals↗
Age effects on lingual pressure generation as a risk factor for dysphagia.
BACKGROUND: Tongue activity plays a crucial role in both oral and pharyngeal phases of swallowing. In this study, maximum lingual isometric and swallowing pressures were quantified in two groups of healthy men to investigate possible age effects on performance. Magnetic resonance images of the brain were also obtained to examine the relationship between age-related anatomical changes and swallowing function. METHODS: Pressures were recorded at three lingual sites (tip, blade, and dorsum) during a maximal isometric task and during saliva swallows. Task order was randomized, and subjects performed three trails per placement site. Additionally, t2-weighted MRIs were obtained on 9 of the 10 young subjects (mean age = 25 years) and all 15 older subjects (mean age = 75 years). RESULTS: Maximal isometric pressures were significantly greater for younger subjects at the tongue blade site (p = .002), whereas peak swallowing pressures remained similar across both age groups. Within-subject comparisons of maximum isometric to swallowing pressures, a measure of reserve capacity, revealed reduced difference scores at the tongue blade in the older group (p = .02). Older subjects exhibited significantly more cerebral atrophy (p = .001) and greater incidence of periventricular white matter lesions (p = .0001) than did younger subjects. CONCLUSIONS: While swallowing pressures remain similar across the life span, overall pressure reserve declines with age. The implications are: (a) older people may be working harder to produce adequate swallowing pressures, and (b) age-related illness may put geriatric patients at higher risk for dysphagia, thus further complicating recovery.
Adult↗
Sensitizing nurses for a changing environmental health role.
This paper traces the evolution of a broader environmental health role for nursing by focusing on the health effects of exposure to environmental pollutants and of global environmental change. This evolving role is reviewed through the examination of selected community health nursing texts published during the last several decades. Key role strategies based on this expanded and evolving environmental role are proposed. Finally, a survey is described that is intended to heighten awareness of personal and professional attitudes and behaviors related to the environment.
Adult↗
High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graft-versus-host disease.
Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.
Chromatography, High Pressure Liquid↗
The challenge of individual rights. Mental health review tribunals.
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Humans↗
Scarborough's Palliative 'At-home' Care Team (PACT): a model for a suburban physician palliative care team.
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Family Practice↗
Microfluctuations of steady-state accommodation and the cardiopulmonary system.
The relationship between variations in steady-state accommodation (microfluctuations) and rhythmic cycles in cardiopulmonary system was investigated. As previously reported, vascular pulse frequency was consistently correlated with the high frequency component of steady-state accommodation microfluctuations. In a new finding, respiration rate and an associated cycle in the instantaneous pulse rate also showed a correlation with a low frequency component of the accommodation power spectra. This apparent coherence between respiration frequency and an accommodation low frequency component was maintained during rapid breathing and was evident at the expected frequency during regulated breathing patterns. This association may reflect the direct influence of the autonomic nervous system upon the ciliary muscle or may be caused by the modulation of intraocular pulse by the autonomic nervous system.
Accommodation, Ocular↗
The occurrence of three calcium-independent protein kinase C subspecies (delta, epsilon and zeta) in retina of different species.
The localisation and immunochemical identification of three different forms of calcium-independent protein kinase C (PKC-epsilon, PKC-delta and PKC-zeta) in retinas of different species were analysed by immunohistochemistry and SDS-PAGE/Western blotting, respectively. More than one component of different molecular weights reacted with the polyclonal antibodies in all retinal samples though in all instances a component of molecular weight corresponding to the individual PKCs was recognised and could be eliminated or reduced by preincubating the primary antibodies with the peptides used to generate the antibodies. PKC-zeta immunoreactivity was exclusively associated with the inner segments of the photoreceptors in both mammalian (guinea-pig, rabbit, rat) and non-mammalian (goldfish, chick) retinas. PKC-epsilon immunoreactivity is present in bipolar cells, particularly in their terminals of mammalian and goldfish retinas. In the chick retina immunoreactivity for this enzyme and for PKC-delta was with the inner segments of the photoreceptors. The Müller cells in mammalian retinas and a sub-population of ganglion cells in the goldfish retina exhibited positive immunoreactivity for PKC-delta. The immunoreactivities for all the PKC isoenzymes were eliminated or drastically reduced when the primary antibodies were first preincubated with the peptides used to generate the antibodies.
Amino Acid Sequence↗
Models of the diffusional spread of nitric oxide: implications for neural nitric oxide signalling and its pharmacological properties.
Nitric oxide (NO) functions as a diffusible messenger molecule in many different tissues, including the brain. To create a conceptual framework for understanding the behaviour of NO in a biological (particularly neurobiological) scenario, we have developed theoretical models describing the kinetic and concentration profiles for NO generated from single or multiple sources. It is predicted that the physiological sphere of influence of a single point source of NO that emits for 1-10 sec has a diameter of about 200 microns corresponding to a volume of brain enclosing 2 million synapses. Inactivation of NO (imposed as a half-life of 0.5-5 sec) has only relatively minor effects because diffusion is so fast. When there are multiple simultaneously-active NO sources within a tissue volume, and in the absence of decay of NO or of a time-dependent reduction in source strength, the concentration of NO simply rises linearly with time, indicating the likely importance of negative feedback by NO on NO synthesis. Distant sources (200-500 microns away) make significant contributions to the steady-state NO concentrations in this situation even when the half-life of NO is short (0.5-5 sec). The models predict the results of several pharmacological experiments that were interpreted to suggest that a NO-containing molecule, rather than NO itself, is the endogenous messenger. Accordingly, invoking the presence of a hypothetical "NO carrier" on the basis of these experimental results is unnecessary.
Diffusion↗
Antigenicity and immunogenicity of experimental equine influenza ISCOM vaccines.
A comparison of the antigenicity and immunogenicity of ISCOM vaccines prepared from equine influenza viruses H3N8 and H7N7 was made with inactivated whole-virus vaccines containing equivalent amounts of virus haemagglutinin. ISCOMs stimulated superior antibody responses in terms of both amount and duration. As with conventional whole-virus vaccines, the levels of antibody to virus haemagglutinin induced by ISCOMs correlated with protection.
Animals↗
Interferon (IFN)-alpha 2 genotype analysis of Chinese chronic hepatitis B patients undergoing recombinant IFN-alpha 2a therapy.
Sixteen Chinese chronic hepatitis B virus (HBV)-infected patients were treated with recombinant interferon-alpha 2a (rIFN-alpha 2a). Of these, 8 made a response to IFN, with titers of neutralizing antibody of 141-4525 as determined by an antiviral neutralization bioassay. To determine whether the immunogenicity of the IFN was directly linked to the patients' genotype, their genomic DNA was analyzed for the presence of the human IFN-alpha 2a gene. None of the patients possessed the gene for IFN-alpha 2a, but only 50% developed neutralizing antibodies. The hypothesis, therefore, of a direct link between antibody formation and genotype cannot be sustained. Alternative explanations of the immunogenicity of IFN-alpha 2a must be sought.
Adult↗
Rapid immune response to influenza vaccination.
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Adult↗