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J Williams

Publications and source records attributed to J Williams.

At least 271 records · Page 15Linked to original sources
PubMed1999

Genetic variability at the amyloid-beta precursor protein locus may contribute to the risk of late-onset Alzheimer's disease.

In a series of sibpairs with late onset Alzheimer's disease, we have examined the segregation of the loci involved in the early onset, autosomal dominant form of the disorder by using flanking microsatellite repeat markers: thus we have used APP-PCR3 and D21S210 to examine the segregation of the amyloid-beta precursor protein (APP) gene, the markers DI 4S77 and D14S284 to examine the segregation of the presenilin 1 (PSI) gene and the markers D1S227, D1S249 and D1S419 to examine the segregation of presenilin 2 (PS2). We carried out our analyses on the whole dataset of 291 affected sibpairs, and on subsets comprising those sibpairs in which neither had an apolipoprotein E4 allele (65 affected sibpairs) and those in which both had an apolipoprotein E4 allele (165 affected sibpairs). We used the programs SPLINK to generate allele frequencies and MAPMAKER/SIBS to analyze our results. We examined the segregation of the markers D19S908 and D19S918 that are close to the apolipoprotein E (ApoE) gene as a positive control to assess whether the methods we are employing have the capability to identify known loci. The sibpair approach to the identification of genetic risk loci is relatively insensitive as indicated by the failure of the ApoE locus to reach statistical significance (P = 0.06). Nevertheless, these data suggest that neither the PS1 nor the PS2 gene is a major locus for late-onset AD, but that the APP gene cannot be ruled out as a risk locus in those sibships without an E4 allele (P = 0.014). The possibility that APP is indeed a locus for late onset disease will need confirmation in other series of familial cases.

Age of Onset↗
PubMed1999

p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter.

In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino acids (a.a.) 328 and 596 and a. a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP.

Binding Sites↗
PubMed1999

Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study.

OBJECTIVE: To compare the effect of unmodified cows' milk and iron supplemented formula milk on psychomotor development in infants from inner city areas when used as the main milk source. DESIGN: Double blind, randomised intervention trial. SETTING: Birmingham health centre. SUBJECTS: 100 infants, mean age 7.8 months (range 5.7 to 8.6 months), whose mothers had already elected to use unmodified cows' milk as their infant's milk source. INTERVENTION: Changing to an iron supplemented formula milk from enrolment to 18 months of age, or continuing with unmodified cows' milk. MAIN OUTCOME MEASURES: Developmental assessments using Griffiths scales at enrolment and at 18 and 24 months. RESULTS: 85 participants completed the trial. There were no significant differences in haemoglobin concentration between the two groups at enrolment, but by 18 months of age 33% of the unmodified cows' milk group, but only 2% of the iron supplemented group, were anaemic (P<0.001). The experimental groups had Griffiths general quotient scores that were not significantly different at enrolment, but the scores in both groups declined during the study. By 24 months the decrease in the mean scores in the unmodified cows' milk group was 14.7 whereas the decrease in the mean scores in the iron supplemented group was 9.3 (P<0.02, 95% confidence interval 0.4 to 10.4). Mean subquotient scores were considerably lower in the unmodified cows' milk group at 24 months; significantly so for personal and social scores (P<0.02, 1.2 to 16.8 [corrected]). CONCLUSION: Replacing unmodified cows' milk with an iron supplemented formula milk up to 18 months of age in infants from inner city areas prevents iron deficiency anaemia and reduces the decline in psychomotor development seen in such infants from the second half of the first year.

Anemia, Iron-Deficiency↗
PubMed1999

No association between the alpha-2 macroglobulin I1000V polymorphism and Alzheimer's disease.

Recent reports have suggested that variability in the alpha2-macroglobulin gene is a genetic risk factor for Alzheimer's disease. Here we have both tested a common polymorphism in the gene (I1000V) for association with the disease in a four-site case control study design, and tested the locus for linkage in a large series of sibpairs afflicted with late onset disease. Our results fail to show an association between this polymorphism and disease.

Age of Onset↗
PubMed1999

Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites.

Stem cells indigenous to the cancellous spaces of the bone bed in an acute injury provide an important source of pluripotent cells for cartilage repair. Insulin-like growth factor-I facilitates chondrogenesis of bone marrow-derived stem cells in long-term culture and may enhance chondrogenesis in healing cartilage lesions in vivo. This study examined the impact of insulin-like growth factor-I, gradually released from fibrin clots polymerized in situ, on the recruitable stem-cell pool in a full-thickness critical cartilage defect model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by an injection of autogenous fibrin containing 25 microg of human recombinant insulin-like growth factor-I or, in control joints, fibrin without the growth factor. All horses were killed at 6 months, and cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, types I and II collagen immunohistochemistry, types I and II collagen in situ hybridization, and matrix biochemical determinations. White tissue filled grafted and control lesions, with the growth factor-treated defects being more completely filled and securely attached to the subchondral bone. A moderately improved chondrocyte population, more columnar cellular organization, and better attachment to the underlying bone were evident on histological evaluation of growth factor-treated defects. Type-II procollagen mRNA was abundantly present in the deeper half of the treated sections compared with moderate message expression in control tissues. Immunolocalization of type-II collagen showed a preponderance of the collagen in growth factor-treated lesions, confirming translation of type-II message to protein. Composite histologic healing scores for treated defects were significantly improved over those for control defects. DNA content in the cartilage defects was similar in treated and control joints. Matrix proteoglycan content was similar in treated and control defects and lower in the defects than in the intact surrounding and remote cartilage of the treated and control joints. The proportion of type-II collagen significantly increased in growth factor-treated tissues. Fibrin polymers laden with insulin-like growth factor-I improved the histologic appearance and the proportion of type-II collagen in healing, full-thickness cartilage lesions. However, none of the biochemical or morphologic features were consistent with those of normal articular cartilage.

Animals↗
PubMed1999

Outcomes of a cardiovascular nutrition counseling program in African-Americans with elevated blood pressure or cholesterol level.

OBJECTIVE: To evaluate a cardiovascular nutrition education package designed for African-American adults with a wide range of literacy skills. DESIGN: Comparison of a self-help group and a full-instruction group; each group received nutrition counseling and clinical monitoring every 4 months. SUBJECTS: Three hundred thirty African-American adults, aged 40 to 70 years, with elevated cholesterol level or high blood pressure were randomly assigned to the self-help or full-instruction group; 255 completed the 12-month follow-up. INTERVENTIONS: Counseling to reduce intake of dietary fat, cholesterol, and sodium was based on Cardiovascular Dietary Education System (CARDES) materials, which included food-picture cards, a nutrition guide (self-help and full-instruction group), a video and audiotape series, and 4 classes (full-instruction group only). MAIN OUTCOME MEASURES: Changes in lipid levels and blood pressure after 12 months. STATISTICAL ANALYSES PERFORMED: Primary analyses consisted of repeated-measures analysis of variance to examine effects of time and randomization group on outcomes. RESULTS: Total cholesterol and low-density lipoprotein cholesterol level decreased by 7% to 8% in the self-help and full-instruction groups of men and women (P < .01). The ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) decreased in both groups of women and in the men in the full-instruction group (P < .01). In full-instruction and self-help participants with elevated blood pressure at baseline, systolic blood pressure decreased by 7 to 11 mm Hg and diastolic blood pressure decreased by 4 to 7 mm Hg (P < .01). Outcomes did not differ by literacy scores but were positively related to the reported initial frequency of using CARDES materials. APPLICATIONS/CONCLUSIONS: These results suggest that periodic nutrition counseling based on CARDES materials used for home study can enhance management of lipid levels and blood pressure in African-American outpatients.

Adult↗
PubMed1999

In vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration.

The present study provides in vivo trials of poly(L-lactic acid) (PLLA) as a porous biodegradable nerve conduit using a 10 mm sciatic nerve defect model in rats. The PLLA conduits, fabricated by an extrusion technique, had an inner diameter of 1.6 mm, an outer diameter of 3.2 mm, and a length of 12 mm. They were highly porous with an interconnected pore structure (of 83.5% porosity and 12.1 microm mean pore size). The conduits were interposed into the right sciatic nerve defect of Sprague Dawley rats using microsurgical techniques; nerve isografts served as controls. Walking track analysis was performed after conduit placement monthly through 16 weeks. At the conclusion of 6 and 16 weeks, sections from the isograft/conduit and distal nerve were harvested for histomorphometric analysis. The right gastrocnemius muscle was also harvested and its weight was determined. All conduits remained intact without breakage. Moreover, no conduit elongated during the 16 weeks of placement. Walking track analysis and gastrocnemius muscle weight demonstrated increasing regeneration over the 16 weeks in both the conduit and isograft control groups, with control values significantly greater. The nerve fiber density in the distal sciatic nerve for the PLLA conduits (0.16+/-0.07) was similar to that for the control isografts (0.19+/-0.05) at 16 weeks. The number of axons/mm2 in the distal sciatic nerve for the PLLA conduits was lower than that for the isografts (13 800+/-2500 vs. 10700+/-4700) at 16 weeks. The results for PLLA were significantly improved over those for 75:25 poly(DL-lactic-co-glycolic acid) of a previous study and suggest that PLLA porous conduits may serve as a scaffold for peripheral nerve regeneration.

Animals↗
PubMed1999

Functional status and quality of life in patients with heart failure undergoing coronary bypass surgery after assessment of myocardial viability.

OBJECTIVES: The aim of this study was to evaluate whether preoperative clinical and test data could be used to predict the effects of myocardial revascularization on functional status and quality of life in patients with heart failure and ischemic LV dysfunction. BACKGROUND: Revascularization of viable myocardial segments has been shown to improve regional and global LV function. The effects of revascularization on exercise capacity and quality of life (QOL) are not well defined. METHODS: Sixty three patients (51 men, age 66+/-9 years) with moderate or worse LV dysfunction (LVEF 0.28+/-0.07) and symptomatic heart failure were studied before and after coronary artery bypass surgery. All patients underwent preoperative positron emission tomography (PET) using FDG and Rb-82 before and after dipyridamole stress; the extent of viable myocardium by PET was defined by the number of segments with metabolism-perfusion mismatch or ischemia. Dobutamine echocardiography (DbE) was performed in 47 patients; viability was defined by augmentation at low dose or the development of new or worsening wall motion abnormalities. Functional class, exercise testing and a QOL score (Nottingham Health Profile) were obtained at baseline and follow-up. RESULTS: Patients had wall motion abnormalities in 83+/-18% of LV segments. A mismatch pattern was identified in 12+/-15% of LV segments, and PET evidence of viability was detected in 30+/-21% of the LV. Viability was reported in 43+/-18% of the LV by DbE. The difference between pre- and postoperative exercise capacity ranged from a reduction of 2.8 to an augmentation of 5.2 METS. The degree of improvement of exercise capacity correlated with the extent of viability by PET (r = 0.54, p = 0.0001) but not the extent of viable myocardium by DbE (r = 0.02, p = 0.92). The area under the ROC curve for PET (0.76) exceeded that for DbE (0.66). In a multiple linear regression, the extent of viability by PET and nitrate use were the only independent predictors of improvement of exercise capacity (model r = 0.63, p = 0.0001). Change in Functional Class correlated weakly with the change in exercise capacity (r = 0.25), extent of viable myocardium by PET (r = 0.23) and extent of viability by DbE (r = 0.31). Four components of the quality of life score (energy, pain, emotion and mobility status) significantly improved over follow-up, but no correlations could be identified between quality of life scores and the results of preoperative testing or changes in exercise capacity. CONCLUSIONS: In patients with LV dysfunction, improvement of exercise capacity correlates with the extent of viable myocardium. Quality of life improves in most patients undergoing revascularization. However, its measurement by this index does not correlate with changes in other parameters nor is it readily predictable.

Aged↗
PubMed1999

Localization of the cGMP-dependent protein kinases in relation to nitric oxide synthase in the brain.

The distributions of the type I and type II isoforms of cGMP-dependent protein kinase were determined in the rat brain using immunohistochemistry and in situ hybridization, and compared with the localization of NO synthase determined with NADPH-diaphorase histochemistry. The type I cGMP-dependent protein kinase was highly expressed in the Purkinje cells of the cerebellar cortex, where it was closely associated with the NO synthase containing granule and basket cells. This kinase was also found in neurons in the dorsomedial nucleus of the hypothalamus, where it may be regulated by NO or atriopeptides. The type I kinase was not detected in other central neurons. In contrast, the type II kinase was widely distributed in the brain. In particular, it was highly expressed in the olfactory bulb, cortex, septum, thalamus, tectum and various brainstem nuclei. Many regions expressing this kinase also contained, or received innervation from NO synthase positive neurons. These results indicate that type I cGMP-dependent protein kinase may act as a downstream effector for NO only in the cerebellar cortex and the dorsomedial hypothalamus. The type II cGMP-dependent protein kinase appears to be a major mediator of NO actions in the brain.

Animals↗
PubMed1999

Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism.

Here, we show that disruption of N-ethylmaleimide-sensitive fusion protein- (NSF-) GluR2 interaction by infusion into cultured hippocampal neurons of a blocking peptide (pep2m) caused a rapid decrease in the frequency but no change in the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). N-methyl-D-aspartate (NMDA) receptor-mediated mEPSCs were not changed. Viral expression of pep2m reduced the surface expression of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors, whereas NMDA receptor surface expression in the same living cells was unchanged. In permeabilized neurons, the total amount of GluR2 immunoreactivity was unchanged, and a punctate distribution of GluR2 was observed throughout the dendritic tree. These data suggest that the NSF-GluR2 interaction is required for the surface expression of GluR2-containing AMPA receptors and that disruption of the interaction leads to the functional elimination of AMPA receptors at synapses.

Adenoviridae↗
PubMed1999

Myocardial bradykinin production during coronary balloon angioplasty in humans.

BACKGROUND: Recent studies have implicated the peptide bradykinin as a potential trigger of ischaemic preconditioning, the phenomenon whereby a brief episode of myocardial ischaemia induces an increased tolerance to subsequent more prolonged ischaemia. Brief myocardial ischaemia occurring during percutaneous transluminal coronary balloon angioplasty in humans is reported to be capable of inducing preconditioning. DESIGN: We studied the intracardiac production of bradykinin in eight patients (seven men, mean age 53.5 years) undergoing elective percutaneous transluminal coronary angioplasty for a single left anterior descending coronary artery stenosis. Paired blood samples were obtained from the coronary sinus and the proximal aorta at baseline, immediately before balloon deflation after a 2-min inflation, and at 1, 3 and 5 min post deflation. Bradykinin levels were measured by radioimmunoassay. RESULTS: There was no significant change either in aortic or coronary sinus bradykinin levels at any time point. CONCLUSIONS: Intracardiac production of bradykinin is unlikely to be a trigger for ischaemic preconditioning after brief myocardial ischaemia in humans.

Adult↗
PubMed1999

Determinants of participation in an epidemiological study of preterm delivery.

We describe the study design and patterns of participation for a cohort study of preterm delivery, focused on genital tract infections, nutrition, tobacco use, illicit drugs and psychosocial stress. Women are recruited at 24-29 weeks' gestation from prenatal clinics at a teaching hospital and a county health department. We recruited 57% of the first 1843 eligible women; 29% refused and 8% could not be contacted. White women were somewhat more likely to participate than African-American women (61% vs. 54% respectively). More notable differences were found comparing teaching hospital and health department clinics (71% vs. 47% participation respectively), with the health department clinic having a greater proportion refuse (24% vs. 33%) and more women who could not be contacted (4% vs. 11%). Participation was affected only minimally by day or timing of recruitment, but inability to contact diminished substantially as the study continued (13-0%). Refusals were largely unrelated to patient attributes. Lower education predicted inability to contact. Risk of preterm delivery was 14% among recruited women, 10% among women who refused, and 15% among women whom we were not able to contact, demonstrating that, overall, risk status was not lower among recruited women.

Adolescent↗
PubMed1999

Stromal progenitor cells present within liposuction and reduction abdominoplasty fat for autologous transfer to aged skin.

BACKGROUND: Autologous fat is used for direct transfer to locally replace fat, as well as for use intradermally in the treatment of rhytids in aged skin. OBJECTIVE: To determine if the components of the autologous fat could be separated to produce a better agent for the treatment of rhytids. METHODS: Liposuction material from four patients and fat from abdominoplasty from five patients was processed by homogenization and centrifugation to separate mature lipocytes from other stromal cell populations in its associated extracellular matrix, and then to separate this from the blood and cellular debris. The cellular layer was evaluated histologically and with the immunohistochemical antibodies for CD34, SM-actin, S-100 protein, MIB-1, Bcl-2, and factor XIIIa. RESULTS: The cellular layer showed spindle cells, some small vascular structures, a small amount of mature fat, and extracellular matrix. CD34 showed diffuse staining of most spindle and endothelial cells in all sections, factor XIIIa showed only focal staining of spindle and dendritic cells, and Bcl-2 showed light to moderate staining in scattered cells within the cellular component. S-100 protein, SM-actin, and MIB-1 were negative. CONCLUSION: Processed liposuction and abdominoplasty processed fat may be ideal for the treatment of wrinkles in aged skin because it contains progenitor stromal cells that are known to be present within the fat and which may be concentrated by processing methods.

Abdomen↗