Search PubMed⌕ Search

Biomedical subjects

J Green

Publications and source records attributed to J Green.

At least 181 records · Page 10Linked to original sources
PubMed1999

Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor-beta2.

The transforming growth factor-betas (TGF-betas) are potent fibrogenic factors implicated in numerous central nervous system (CNS) pathologies in which fibrosis and neural dysfunction are causally associated. In this study, we aim to limit the fibrogenic process in a model of CNS scarring using a recombinant human monoclonal antibody, derived from phage display libraries and specific to the active form of the TGF-beta2 isoform. The implicit inference of the work was that, as such antibodies are potential pharmacological agents for the treatment of human CNS fibrotic diseases, validation of efficacy in a mammalian animal model is a first step towards this end. Treatment of cerebral wounds with the anti-TGF-beta2 antibody led to a marked attenuation of all aspects of CNS scarring, including matrix deposition, formation of an accessory glial-limiting membrane, inflammation and angiogenesis. For example, in the wound, levels of: (i) the connective tissue components fibronectin, laminin and chondroitin sulphate proteoglycan; and (ii) wound-responsive cells including astrocytes and macrophages/microglia, were markedly reduced. Our findings suggest that such synthetic anti-fibrotic TGF-beta antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.

Animals↗
PubMed1999

Gli1 protein is expressed in basal cell carcinomas, outer root sheath keratinocytes and a subpopulation of mesenchymal cells in normal human skin.

Genetic studies of patients with the nevoid basal cell carcinoma syndrome have led to the recognition of the importance of the hedgehog signaling pathway in the development of basal cell carcinomas of the skin. Although hedgehog signaling is known to be important in hair follicle development, the function of this pathway in adult skin and the mechanism by which activation of this pathway leads to basal cell carcinoma development remain to be established. The Gli1 family of transcription factors mediates hedgehog signaling in mammalian cells and we have shown in previous studies that Gli1 mRNA is differentially expressed in basal cell carcinomas. Using antibodies to epitopes on the N and C terminal regions of Gli1 we show now that Gli1 protein is present in basal cell carcinomas and that the protein is mainly localized to the cytoplasmic compartment. Focal nuclear staining was seen in a small number of basal cell carcinomas with the C terminal antibody which suggest that nuclear localization is not dependent on loss of the C terminus of Gli1 due to proteolysis. Strong Gli1 immunostaining was seen in the outer root sheath keratinocytes of some hair follicles, a subpopulation of mesenchymal cells in the vicinity of the bulge region of adult hair follicles and the dermal sheath cells of developing hair follicles. Quantitation of Gli1 mRNA in basal cell carcinomas using northern blot analysis indicates that Gli1 is highly expressed in basal cell carcinomas. This suggests that the lower intensity of Gli1 immunostaining in basal cell carcinoma islands relative to outer root sheath keratinocytes is not simply a reflection of differences in gene expression. The continued expression of Gli1 in adult hair follicles and in the mesenchyme of adult human skin suggest that Hh signaling may play a part in hair cycling and in epidermal mesenchymal interactions important in normal skin maintenance.

Basal Cell Carcinoma↗
PubMed1999

Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats.

In these studies, we examined the neuroprotective effects of the potent antiinflammatory cytokine interleukin-10 (IL-10) following spinal cord injury (SCI). Neuroprotection was assessed by using behavioral and morphological end points. We hypothesized that injury-induced inflammation contributes to the resulting neuropathology and subsequent loss of function. Therefore, by attenuating injury-induced inflammation, we should promote functional recovery. The New York University device was used to induce moderate SCI and study the resulting inflammatory response and functional consequences of inhibiting this response in rats. We determined that SCI induces the expression of tumor necrosis factor-alpha (TNF-alpha) in the spinal cord and by SCI-activated monocytes isolated from the peripheral circulation. IL-10 (5.0 microg) administered 30 minutes after-injury significantly reduced the expression of TNF-alpha protein in the spinal cord and in vitro by SCI-activated monocytes. Next, we investigated whether IL-10 would improve functional recovery after SCI. Randomized, double-blinded studies demonstrated that a single injection of IL-10 significantly improves hind limb motor function 2 months after injury, as determined by the Basso, Beattie and Bresnahan (BBB) open-field behavioral test. IL-10-treated animals had a mean BBB score of 18.0+/-0.5 (SEM, n = 9) compared with a score of 12.9+/-0.6 (SEM, n = 9) for the saline-treated controls. Morphological analysis demonstrated that IL-10 reduces lesion volume by approximately 49% 2 months after injury. These data suggest that acute administration of IL-10 reduces TNF-alpha synthesis in the spinal cord and by activated macrophages, is neuroprotective, and promotes functional recovery following SCI.

Animals↗
PubMed1999

Altered vascular reactivity following partial nephrectomy in the rat: a possible mechanism of the blood-pressure-lowering effect of heparin.

BACKGROUND: This study was designed to assess whether the antihypertensive effect of heparin in rats after renal mass reduction (RMR) is related to changes in nitric oxide activity, and to study in vitro the altered behaviour of resistance-sized arteries induced by chronic administration of heparin. METHODS: Male Wistar rats were assigned to one of two experimental protocols. In the first protocol, RMR rats received heparin (250 units/day s.c.) and tail systolic blood pressure (SBP) was measured weekly for 4 weeks. In a subgroup, urinary nitrate excretion (UNO3) and in vitro vascular reactivity of isolated perfused mesenteric arterial beds were measured 2 weeks after RMR. The second protocol assessed whether inhibition of NO synthesis with L-NAME (70 mg/l added to the drinking water) prevents the blood-pressure-lowering effect of heparin. RESULTS: In untreated RMR rats SBP increased from 111+/-3 mmHg to 127+/-5 mmHg at 2 weeks and 139+/-5 mmHg at 4 weeks. In contrast, in RMR rats treated with heparin, SBP was 114 +/-3 mmHg at 2 weeks and 115+/-4 mmHg at 4 weeks (P<0.05 for both). Treatment with L-NAME increased SBP both in untreated and heparin-treated RMR groups. Two weeks after nephrectomy daily urinary nitrate increased significantly more in RMR rats treated with heparin than in untreated RMR rats (22+/-2 vs 14.2+/-2.3 micromol/day, P<0.05). In vitro studies performed at 2 weeks showed that vessels of untreated RMR rats had a blunted vasodilator response to acetylcholine that was restored to levels similar to that of controls in the heparin-treated group. CONCLUSIONS: These results suggest that, in rats after renal ablation, heparin may exert its antihypertensive effect, at least in part, by affecting the altered behaviour of resistance vessels during the development phase of hypertension. Increased NO production may contribute to this effect.

Animals↗
PubMed1999

Role of thromboxane in the altered vascular reactivity of pregnant rats with adriamycin nephropathy.

BACKGROUND: Pregnant rats with adriamycin nephropathy (ADRP rats) develop hypertension and have an increased vascular reactivity to noradrenaline in the isolated mesenteric bed in vitro. We have shown previously that the administration of daltroban, a specific thromboxane receptor antagonist, prevented hypertension in ADRP rats. METHODS: We measured the effect of daltroban (10(-5) mol/l) on the vasoconstrictory response to noradrenaline (1-10 micromol/l) in the isolated mesenteric bed of ADRP rats at the end of pregnancy, as compared with normal pregnant and adriamycin-treated virgin rats. In further experiments, we measured the changes of flow induced by increasing concentrations of the thromboxane analogue, U46619 (10(-7)-10(-6) mol/l). Finally, changes of flow were assessed in arteries maximally constricted with U46619 (10(-6) mol/l), during perfusion in the presence of increasing concentrations of daltroban (10(-7)-10(-5) mol/l). RESULTS: Daltroban diminished the response to noradrenaline in all groups, shifting the concentration-effect curve to the right. However, at maximal concentrations of noradrenaline, daltroban was ineffective in all rats, except in ADRP animals. The vasoconstrictory response to U46619 was significantly reduced in all pregnant rats, both normal and adriamycin-treated. Daltroban progressively released the vasoconstriction induced by U46619 in all groups. However, this vasodilator response was attenuated in the adriamycin-treated rats, the slopes of their curves being smaller than those of the respective untreated groups (0.038 +/- 0.006 in virgin rats vs 0.063 +/- 0.011 in controls, P < 0.05; and 0.015 +/- 0.005 in ADRP vs 0.028 +/- 0.008 in normal pregnancy, P < 0.05). CONCLUSIONS: The findings could be explained by enhanced occupancy of thromboxane receptors by an endogenous agonist, possibly PGH2, as a consequence of either increased levels of the autacoid or increased number of affinity receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Towards a secure evidence base for health promotion.

The importance of a sound evidence base for health promotion is recognized. Criteria for establishing evidence have, in the past, been heavily influenced by the bio-medical agenda. The problems in using experimental and quasi-experimental approaches and their limited relevance for evaluating health promotion interventions are examined. The multifactorial nature of the health promotion enterprise in relation to both inputs and outputs is recognized and a range of direct, indirect and process indicators are identified. The relevance of combining quantitative and qualitative methods for data collection is discussed and the paper concludes by advocating a 'judicial principle' for assessing evidence.

Data Collection↗
PubMed1999

Use of isobutyl cyanoacrylate tissue adhesive to stabilize mucous membrane grafts in total socket reconstruction.

PURPOSE: To describe a technique to secure a mucous membrane graft to a custom conformer during reconstruction of the conjunctival fornices and socket. METHODS: A cyanoacrylate-based tissue glue was used instead of sutures to secure the mucous membrane graft to the conformer. RESULTS: The adhesion between the graft and the conformer weakens over time, permitting easy removal of the conformer from the socket 6 to 12 weeks postoperatively. No complications were encountered in six patients in whom this technique was used. CONCLUSION: Using a cyanoacrylate-based tissue glue is simpler and quicker than suturing a mucous membrane graft.

Bucrylate↗
PubMed1999

Tau pathology in a family with dementia and a P301L mutation in tau.

Familial forms of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) have recently been associated with coding region and intronic mutations in the tau gene. Here we report our findings on 2 affected siblings from a family with early-onset dementia, characterized by extensive tau pathology and a Pro to Leu mutation at codon 301 of tau. The proband, a 55-year-old woman, and her 63-year-old brother died after a progressive dementing illness clinically diagnosed as Alzheimer disease. Their mother, 2 sisters, maternal aunt and uncle, and several cousins were also affected. Autopsy in both cases revealed frontotemporal atrophy and degeneration of basal ganglia and substantia nigra. Sequencing of exon 10 of the tau gene revealed a C to T transition at codon 301, resulting in a Pro to Leu substitution. Widespread neuronal and glial inclusions, neuropil threads, and astrocytic plaques similar to those seen in corticobasal degeneration were labeled with a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes spanning the entire tau sequence. Isolated tau filaments had the morphology of narrow twisted ribbons. Sarkosyl-insoluble tau exhibited 2 major bands of 64 and 68 kDa and a minor 72 kDa band, similar to the pattern seen in a familial tauopathy associated with an intronic tau mutation. These pathological tau bands predominantly contained the subset of tau isoforms with 4 microtubule-binding repeats selectively affected by the P301L missense mutation. Our findings emphasize the phenotypic and genetic heterogeneity of tauopathies and highlight intriguing links between FTDP-17 and other neurodegenerative diseases.

Atrophy↗
PubMed1999

Use of prescribed drugs among older people in Japan: association with not having a regular physician.

OBJECTIVES: Minimizing the overuse of prescribed drugs among older people is a goal of geriatricians and healthcare policy makers. Indirect evidence indicates that use of prescribed drugs is more common in Japan than in some Western countries, but the actual situation in Japan is unknown. The first aim of this study was to clarify the use of prescribed drugs among older people in Japan. We also tested the hypothesis that using five or more prescribed drugs is associated with a situation that is modifiable and is relatively common in Japan: not having a regular physician. DESIGN: A cross-sectional survey. PARTICIPANTS: Subjects representing the Japanese general population aged 65 years and older were selected by two-stage stratified sampling; 617 persons were eligible for the study. MEASUREMENTS: Each subject was given a self-report questionnaire about current medications, sociodemographic characteristics, current state of health, health-related quality of life, and whether they had a regular physician. Among users of prescribed drugs, the association between using five or more prescribed drugs and not having a regular physician was assessed by univariate analysis and by stepwise logistic regression. RESULTS: The questionnaire was returned by 491 (80%) of the eligible subjects, 299 (61%) of whom were taking at least one prescribed drug. Nearly 30% of those subjects were taking at least five prescribed drugs. The distribution of the number of prescribed drugs being taken was positively skewed; the minimum was one and the maximum was 17, the middle 50% of the values ranged from two to five, and the median was three. About half of those who were taking at least five prescribed drugs did not have a regular physician. Compared with those who had a regular physician, those who did not were 2.5 times more likely to be taking at least five prescribed drugs (95% confidence interval, 1.4 - 4.6). CONCLUSIONS: Older people in Japan are less likely to be taking many prescribed drugs if they have the continuity of care provided by a regular physician.

Aged↗
PubMed1999

Expression and self-assembly of Grimsby virus: antigenic distinction from Norwalk and Mexico viruses.

A cDNA obtained from Grimsby virus (GRV), a Norwalk-like virus, purified from a stool sample of a symptomatic adult associated with a gastroenteritis outbreak in the United Kingdom, was used to obtain the complete nucleotide sequence of the second open reading frame (ORF2). The ORF2 sequence of GRV predicts a capsid of 539 amino acids (aa) which exhibits aa identities of 96% to Lordsdale virus, 67% to Mexico virus (MXV), and 43% to Norwalk virus (NV). The GRV capsid protein was expressed in insects cells by using a recombinant baculovirus, and the resulting virus-like particles (VLPs) possessed a protein with an apparent molecular weight of 58,000. Hyperimmune antisera raised against purified GRV, MXV, and NV VLPs were tested in an indirect enzyme-linked immunosorbent assay (ELISA) against GRV, NV, and MXV VLPs, revealing that GRV is antigenically distinct from both NV and MXV. The antigenic specificity of the GRV-hyperimmune antiserum was confirmed in an antigen capture ELISA using GRV-, NV-, or MXV-containing fecal specimens. The expression of the GRV capsid protein has, for the first time, allowed the antigenic comparison of three distinct recombinant Norwalk-like viruses.

Adult↗
PubMed1999

Molecular epidemiology of outbreaks of gastroenteritis associated with small round-structured viruses in East Anglia, United Kingdom, during the 1996-1997 season.

During the winter season from November 1996 to May 1997, 550 fecal specimens were submitted from 94 outbreaks of gastroenteritis occurring in East Anglia, United Kingdom. These specimens were tested for the presence of small round-structured viruses (SRSVs) by electron microscopy, reverse transcriptase PCR, or both methods. SRSVs were shown to be associated with 64 of 94 (68%) of these outbreaks, of which 16 (25%) outbreaks occurred at a single location (Southend) within the region. Twenty-four specimens from 13 of the 16 SRSV-positive outbreaks occurring in Southend were available for genomic analysis, in which divergence within the RNA polymerase region of the SRSV genome was investigated. A further 27 specimens from 17 other SRSV-associated outbreaks, occurring at different locations within East Anglia but at the same time as those at Southend, were also studied. Fifty of the total of 51 (98%) specimens studied were shown to belong to genogroup II, and within this genogroup, 49 of 50 (98%) specimens were shown to be Grimsby-like viruses, with only one Mexico-like strain. Furthermore, phylogenetic analysis of the Grimsby-like viruses indicated clusterings according to the geographical location of the outbreak. One specimen contained a virus belonging to genogroup I, and this had the greatest sequence identity (83%) with Southampton virus.

Base Sequence↗
PubMed1999

Language development in children implanted with the CLARION cochlear implant.

This study examined the development of language skills in 23 prelingually, profoundly deaf children following implantation with the CLARION Multi-Strategy Cochlear Implant. Language skills were assessed with the Reynell Developmental Language Scales (RDLS) preoperatively with hearing aids, and compared to postoperative performance after 6 months of Clarion use. The RDLS was administered in each child's preferred mode of communication, either spoken English alone or simultaneous spoken and signed English. Significant improvements were observed in average age-equivalent scores over time, both for receptive and expressive skills, although the absolute language levels of the implanted children remained delayed relative to those of hearing peers of the same chronological age. The children's rate of language growth in the first 6 months of implant use also was calculated. The results from this analysis showed that the Clarion children, on average, progressed at a rate that exceeded that of normal-hearing children of the same language age. There was no significant difference between the language performance of children who used oral versus total communication.

Aging↗
PubMed1999

A common MSH2 mutation in English and North American HNPCC families: origin, phenotypic expression, and sex specific differences in colorectal cancer.

The frequency, origin, and phenotypic expression of a germline MSH2 gene mutation previously identified in seven kindreds with hereditary non-polyposis cancer syndrome (HNPCC) was investigated. The mutation (A-->T at nt943+3) disrupts the 3' splice site of exon 5 leading to the deletion of this exon from MSH2 mRNA and represents the only frequent MSH2 mutation so far reported. Although this mutation was initially detected in four of 33 colorectal cancer families analysed from eastern England, more extensive analysis has reduced the frequency to four of 52 (8%) English HNPCC kindreds analysed. In contrast, the MSH2 mutation was identified in 10 of 20 (50%) separately identified colorectal families from Newfoundland. To investigate the origin of this mutation in colorectal cancer families from England (n=4), Newfoundland (n=10), and the United States (n=3), haplotype analysis using microsatellite markers linked to MSH2 was performed. Within the English and US families there was little evidence for a recent common origin of the MSH2 splice site mutation in most families. In contrast, a common haplotype was identified at the two flanking markers (CA5 and D2S288) in eight of the Newfoundland families. These findings suggested a founder effect within Newfoundland similar to that reported by others for two MLH1 mutations in Finnish HNPCC families. We calculated age related risks of all, colorectal, endometrial, and ovarian cancers in nt943+3 A-->T MSH2 mutation carriers (n=76) for all patients and for men and women separately. For both sexes combined, the penetrances at age 60 years for all cancers and for colorectal cancer were 0.86 and 0.57, respectively. The risk of colorectal cancer was significantly higher (p<0.01) in males than females (0.63 v 0.30 and 0.84 v 0.44 at ages 50 and 60 years, respectively). For females there was a high risk of endometrial cancer (0.5 at age 60 years) and premenopausal ovarian cancer (0.2 at 50 years). These intersex differences in colorectal cancer risks have implications for screening programmes and for attempts to identify colorectal cancer susceptibility modifiers.

Age Factors↗
PubMed1999

Managing intractable pain with an intrathecal catheter and injection port: technique and guidelines.

The objective of our study was to describe an effective technique for the management of chronic intractable pain in patients with intermediate life expectancy or as a long-term screening device prior to implantable pump therapy. In the study, an InDura intraspinal catheter is connected to a BardPort, which is accessed transdermally. We describe our surgical technique, recommended dosage calculations, cost comparison to an implantable infusion pump, and our experience with 13 cases. In our series of 13 patients, there was one seroma and one dural leak. There were no infections, and all were functioning well in the 12 cancer patients until their deaths. One case was converted to an implantable pump. There were no malfunctions or infections of the intrathecal infusion system in the 12 cancer patients. This intrathecal drug infusion system should be considered in the treatment armamentarium for chronic intractable pain and cancer pain.

Adult↗
PubMed1998

Co-regulation of lipoamide dehydrogenase and 2-oxoglutarate dehydrogenase synthesis in Escherichia coli: characterisation of an ArcA binding site in the lpd promoter.

The lipoamide dehydrogenase gene (lpdA) encoding the E3 subunits of both the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes of Escherichia coli, is expressed from the upstream pdh and internal lpd promoters of the pdh operon (pdhR-aceEF-lpdA). Under aerobic conditions, the specific components of the 2-oxoglutarate dehydrogenase complex encoded by the sucAB genes in the sdhCDAB-sucABCD operon are expressed from the sdh promoter. The provision of lipoamide dehydrogenase subunits for assembly into the 2-oxoglutarate dehydrogenase complex could thus be controlled by co-regulation of the lpd promoter with the sdh promoter. Here, the transcription start point of the lpd promoter was defined by primer extension analysis, and an ArcA binding site, TGTTAACAAT, overlapping the lpd promoter and matching the consensus at 8 out of 10 positions, was identified by in vitro footprint analysis. PdhR was not bound to the lpd promoter nor was ArcA bound specifically to the pdh promoter. These results support the view that co-regulation of the lpd and sdh promoters is mediated primarily by ArcA.

Aerobiosis↗
PubMed1998

Theory and Experiment on the Measurement of Kinetic Rate Constants for Surfactant Exchange at an Air/Water Interface.

The paper focuses on the measurement of the rate constants for the kinetic steps of adsorption and desorption of surfactant between an air/water surface and the aqueous bulk sublayer adjacent to the surface. Kinetic constants are determined in nonequilibrium experiments in which either a clean surface is contacted with a bulk solution and surfactant diffuses toward and adsorbs onto the interface, or the area of an established monolayer in equilibrium with an underlying solution is changed, and surfactant exchanges between the surface and bulk. The dynamic tension change due to the surfactant exchange is measured, and compared to predictions of kinetic-diffusive transport models in order to infer the kinetic coefficients as well the diffusion coefficients. Model comparisons for highly surface active surfactants have resolved only the diffusion coefficient as the transport was found to be diffusion controlled; kinetic constants have only been established for less active materials such as alcohols or bolaform surfactants. In this study, we demonstrate that kinetics can be differentiated from diffusion in clean interface adsorption and re-equilibration if high bulk concentrations of the surfactant are used, or in re-equilibration, if the surface is compressed sufficiently. We first establish theoretically that mass transfer shifts from diffusion-limited to mixed as the bulk concentration increases in clean interface adsorption, or the surface compression is increased in re-equilibration. We then experimentally verify this idea by using the polyethoxylated surfactant C12E6 (C12H25 (OCH2CH2)6-OH) and by measuring dynamic surface tensions in clean interface adsorption and re-equilibration, respectively by the shape analysis of pendant bubbles. We find values of 6 x 10(-10) m2/s for the diffusion coefficient, and 1.4 x 10(-5) m/sec and 1.4 x 10(-4) s-1 for the adsorption and desorption rate constants, respectively, in a Frumkin kinetic formulation. While the adsorption constant is comparable to previously measured values for the less surface active surfactants, the desorption rate constant is a few orders of magnitude smaller. This indicates that the more surface active materials may have much smaller desorption rate constants than had been previously anticipated based on the studies of the less surface active materials. Copyright 1998 Academic Press.

Journal Article↗