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J Chapman

Publications and source records attributed to J Chapman.

At least 163 records · Page 9Linked to original sources
PubMed1999

The promoter of human tissue factor pathway inhibitor gene: identification of potential regulatory elements.

Tissue factor pathway inhibitor is the major potent physiologic inhibitor of tissue factor-induced coagulation. Several potential binding sites for transcription factors have been described in the 750 bp of the 5' flanking region of the human tissue factor pathway inhibitor gene reported earlier. To identify elements that regulate the expression of tissue factor pathway inhibitor in endothelial, hepatocyte, and monocyte cells, the sequence of an additional 770 bp of tissue factor pathway inhibitor was determined. Comparison of this new sequence as well as that reported earlier with consensus sequences for transcription factor binding sites provided matches for GATA-2, SP1, and c-Myc sequences. Moreover, plasmids containing deletion mutants of the 5' tissue factor pathway inhibitor promoter region and the luciferase reporter gene were transfected into HepG2, ECV304, and THP1 cells. Three negative regulatory elements were localized between -548 to -390, - 390 to -75, and -1158 to -796 relative to the transcriptional start, respectively, in HepG2, ECV304 and THP-1 cells.

Base Sequence↗
PubMed1999

Antibodies to prothrombin in patients with Sneddon's syndrome.

Antiprothrombin antibodies (aPT), a new serologic marker of antiphospholipid syndrome, were studied in 46 patients randomly selected from 73 with Sneddon's syndrome and 20 matched normal controls. aPT were elevated in 26 patients (57%) and were not found in any of the controls. The addition of aPT data increased the proportion of Sneddon's syndrome patients with at least one type of antiphospholipid syndrome marker from 65 to 78%. The finding that aPT are common in Sneddon's syndrome supports the hypothesis that Sneddon's syndrome is a form of antiphospholipid syndrome.

Adolescent↗
PubMed1999

[Prevalence of APO e4 allele in Israeli ethnic groups].

The 4 allele of the APOE gene, coding for apo-lipoprotein E, is the most common genetic risk factor for Alzheimer's disease and a significant risk factor for coronary atherosclerosis. There is therefore much interest in studying its frequency in different ethnic groups. We examined its frequency in Jews originating from Libya, Buchara and Ethiopia and in Jews of Sepharadi and Ashkenazi origins. Its frequency among Ethiopian immigrants was 0.27, significantly higher than in the other groups, in which the frequency was between 0.067 and 0.10. These differences in allele frequency may serve as a basis for future studies in Israel to assess the relative contributions of genetic and environmental factors to the incidence of dementia.

Africa↗
PubMed1999

Intermittent rhythmic delta activity (IRDA) morphology cannot distinguish between focal and diffuse brain disturbances.

IRDA (intermittent rhythmic delta activity) is an abnormal generalized EEG pattern that is not specific to any single etiology and can occur with diffuse or focal cerebral disturbances. To determine whether different electrographic features of IRDA and associated EEG findings can differentiate underlying focal from diffuse brain disturbances, we performed a blind analysis of 58 consecutive EEGs with an IRDA pattern, recorded from 1993 until 1996, in which we evaluated posterior background activity, focal slowing and IRDA characteristics (frequency, distribution, duration, symmetry and abundance). The clinical diagnosis, state of consciousness and CT brain findings were retrieved from the patients' hospital records. There were 58 patients (33 females; mean age, 58+/-21 years). Twelve (21%) had only focal brain lesions, while 46 (79%) had diffuse brain abnormalities, (15 diffuse structural, 19 metabolic abnormalities, 12 postictal). Normal consciousness and focal EEG slowing were more frequent in patients with focal abnormalities, however, this was not statistically significant. Of the patients with focal abnormality, 11 (92%) had normal posterior background activity either bilaterally (n=4) or contralateral to the focal lesion (n=7). Bilaterally normal posterior background activity was observed in about 30% in both groups. Bilaterally abnormal posterior background activity was apparent in one patient (8%) with focal brain lesion and in 31 patients (67%) with diffuse brain abnormalities (P<0.0001). There were no significant differences in IRDA electrographic features between the focal group and the group with diffuse brain disturbances. We conclude that IRDA morphology cannot distinguish between focal and diffuse brain abnormalities.

Adolescent↗
PubMed1999

Microphase separation in low density lipoproteins. Evidence for a fluid triglyceride core below the lipid melting transition.

The structural organization of the neutral lipid core in human low density lipoproteins (LDL) was investigated in physicochemically defined, distinct human LDL subspecies in the density range of 1. 0244-1.0435 g/ml by evaluation of the core lipid transition temperature, chemical composition, and the behavior of spin-labeled core lipids. Calorimetric studies were performed on more than 60 LDL preparations, and the transition temperature, which varied between 19 and 32 degreesC, was correlated to the chemical composition and revealed a discontinuity at a critical cholesteryl ester to triglyceride ratio of approximately 7:1. For electron spin resonance studies, several LDL preparations were probed with spin-labeled cholesteryl esters and triglycerides, respectively. In LDL with a high triglyceride content, both labels exhibited similar mobility behavior. In contrast, in LDL with only small concentrations of triglycerides, the behavior of labeled cholesteryl esters and labeled triglycerides differed distinctly. The cholesteryl esters were strongly immobilized below the transition temperature, whereas the triglycerides remained fluid throughout the measured temperatures. These results suggest that the critical cholesteryl ester to triglyceride mass ratio of 7:1 corresponds to two concentric compartments with a radial ratio of 2:1, where the liquid triglycerides occupy the core, and the cholesteryl esters form the frozen shell. At higher triglyceride contents, the triglyceride molecules insert into the cholesteryl ester shell and depress the peak transition temperature of the LDL core, whereas at lower triglyceride contents, excess cholesteryl esters are dissolved in the core.

Calorimetry, Differential Scanning↗
PubMed1999

Preliminary observations on APOE epsilon4 allele and progression of disability in multiple sclerosis.

BACKGROUND: Apolipoprotein E expression is increased in regenerating neural tissue and the APOE epsilon4 allele is associated with impaired neuronal repair. Since repair is essential for the restoration of central nervous system function following multiple sclerosis (MS) relapses, APOE genotype may influence clinical progression of the disease. OBJECTIVE: To examine the association of the APOE genotype with disease susceptibility and progression in MS. PATIENTS AND METHODS: APOE genotyping was determined by polymerase chain reaction and restriction enzyme digestion in 47 patients with MS who had been followed up every 3 months for 2 years as part of an open-label clinical trial with glatiramer acetate. The Expanded Disability Status Scale (EDSS) was used to assess clinical progression. RESULTS: Nine patients were heterozygous and 1 patient was homozygous for the APOE epsilon4 allele, for a frequency of 12% (11/94), which is similar to that of the general Israeli population. The APOE epsilon4 carriers had a mean +/- SE EDSS score of 3.10+/-0.45 at entry, which was not significantly different from the remaining 37 patients (2.62+/-0.25). During the observation period, the EDSS score of the APOE epsilon4 carriers deteriorated to 4.00+/-0.63 while the other patients remained stable with an EDSS score of 2.74+/-0.31. The interaction of genotype with disability over time was significant (P = .02 by repeated-measures analysis of variance). There were no differences in the number of relapses occurring in the 2 groups. CONCLUSIONS: These preliminary observations suggest that APOE genotype may influence disease progression in MS. The APOE epsilon4 allele was not associated with an increased risk of MS or relapses.

Adult↗
PubMed1999

Altered expression of CD44 and variant isoforms in human adenocarcinoma of the endocervix during progression.

OBJECTIVE: Altered expression of the CD44 family of cell adhesion molecules has been associated with tumor progression and metastasis. The aim of this study was to investigate the expression of the gene products of CD44 standard (CD44s) and several alternatively spliced variants (CD44v4, v6, v7, and v9) in adenocarcinoma of the endocervix and to correlate the degree of their expression with disease progression. METHODS: Immunohistochemical staining for CD44s and CD44v4, v6, v7, and v9 was performed on formalin-fixed, paraffin-embedded endocervical specimens. Seventeen cases of adenocarcinoma in situ (AIS) and 22 cases of invasive adenocarcinoma of the endocervix were included in this study, and the immunoreactivity was compared with that of normal endocervical epithelium. RESULTS: (1) In the normal endocervical mucosa, immunoreactivity for CD44s and the splice variants was lacking or was confined to only the basal portion of the glandular epithelium along the basement membrane; (2) CD44s was diffusely expressed along the entire cytoplasmic membrane, including the luminal surface of the tumorous glands in 94% of AIS and 95% of invasive adenocarcinomas; (3) a significantly stronger expression of CD44s was observed in invasive adenocarcinomas than in AIS; (4) in contrast to all other splice variants, CD44v9 demonstrated an increased expression in nearly all in situ and invasive lesions compared to the normal tissue; (5) CD44v4 and v6 were expressed only in a small proportion of invasive adenocarcinomas and were near totally absent in the in situ lesions; and (6) CD44 v7 was totally absent in all normal, in situ, and invasive lesions studied. CONCLUSIONS: It appears that neoplastic transformation of endocervical epithelium is associated with qualitative and quantitative changes in the expression of CD44 standard molecule and some CD44 splice variants.

Adenocarcinoma↗
PubMed1999

Sequence polymorphisms in the apolipoprotein(a) gene and their association with lipoprotein(a) levels and myocardial infarction. The ECTIM Study.

Lp(a) concentrations are largely determined by apo(a) isoform size, but several studies have shown that apo(a) isoforms could not entirely explain the increase of Lp(a) levels observed in patients with coronary heart disease (CHD). Since up to 90% of the variance in Lp(a) levels has been suggested to be attributable to the apo(a) locus, the hypothesis that polymorphisms of the apo(a) gene other than size could contribute to the increase of Lp(a) levels in CHD patients must be considered. This hypothesis was tested in the ECTIM Study comparing 594 patients with myocardial infarction and 682 control subjects in Northern Ireland and France. In addition to apo(a) phenotyping, five previously described polymorphisms of the apo(a) gene were genotyped: a (TTTTA)n repeat at position -1400 from the ATG, a G/A at -914, a C/T at -49, a G/A at -21 and a Met/Thr affecting amino acid 4168. As reported earlier [Parra HJ, Evans AE, Cambou JP, Amouyel P, Bingham A, McMaster D, Schaffer P, Douste-Blazy P, Luc G, Richard JL, Ducimetiere P, Fruchart JC, Cambien F. A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM study. Arterioscler Thromb 1992; 12:701-707], mean Lp(a) levels were higher in cases than in controls (20.7 vs 14.6 mg/dl in Belfast, 17.2 vs 8.9 mg/dl in France, P < 0.001 for case-control and population differences). In the present study, mean apo(a) isoform size differed significantly between cases and controls (25.7 vs 26.6 kr in Belfast, 25.9 vs 27.4 kr in France, P < 0.001 for case-control and P = 0.13 for population difference). After adjustment for apo(a) isoforms, Lp(a) levels remained significantly higher in cases than in controls (difference, 4.6 mg/dl; P < 0.001). Genotype and allele frequencies did not differ significantly between cases and controls for any of the five polymorphisms studied. The five polymorphisms were in strong linkage disequilibrium and had a combined heterozygosity of 0.83. In multivariate regression analysis adjusted for apo(a) isoforms, only the (TTTTA)n polymorphism was significantly associated with Lp(a) levels; it explained 4.5% of Lp(a) variability in cases and 3.1% in controls. The Lp(a) case/control difference was not reduced after taking into account the (TTTTA)n effect. We conclude that the increase of Lp(a) levels observed in MI cases, and which was not directly attributable to apo(a) size variation, was not related to the five polymorphisms of the apo(a) gene considered.

Adult↗
PubMed1999

Loading technique comparison in permanent 125I prostate implants.

Treatment of prostate cancer utilizing iodine 125 (125I) interstitial seed implants has become an accepted and widely used modality. Numerous variations in 125I seed implant loading distribution techniques have developed as a result of the preferences of individual institutions implementing the modality. No particular universal standard is currently used for 1251 seed implants. A major concern with 125I seed implants is coverage of the prostate with the desired dose and the minimization of dose to the urethra. A variation of seed distribution per individual anatomy is desirable. Historically, brachytherapy relied on dosimetry systems, such as the Paris, Quimby, and Manchester systems to achieve the desired dose distribution. Use of various peripherally loaded 125I seed implant distributions to accommodate anatomic variations within the same institution prompted the interest of how the results compare to the Manchester system.

Brachytherapy↗
PubMed1999

Is surveillance for stage 1 germ cell tumours of the testis appropriate outside a specialist centre?

OBJECTIVE: To assess the results of treatment for stage 1 germ cell tumours of the testis, outside a specialist centre. PATIENTS AND METHODS: From May 1984 until March 1996, 123 patients with stage 1 disease were treated at our institution. Sixty patients with seminoma and 31 with teratoma were treated with orchidectomy only and surveillance; 32 patients with stage 1 seminoma elected for orchidectomy and adjuvant radiotherapy. The mean ages were 40, 31 and 35 years, and the median follow-up 52, 47 and 49 months, respectively. RESULTS: There were no disease- or treatment-related deaths. However, 18 (30%) patients with seminoma treated by orchidectomy only relapsed (median time 8 months, range 3-19); 14 of these responded to radiotherapy, three to radiotherapy and chemotherapy for second relapses outside the irradiated fields, and one to chemotherapy initially, for large-volume relapse. Fifteen (48%) patients with teratoma relapsed (median time 3 months, range 1-12); all responded to 4-6 courses of bleomycin/etoposide/cisplatin chemotherapy. One patient had a second relapse and is currently disease-free 3 years after surgical excision of a lung metastasis. CONCLUSION: These results show that stage 1 testis tumours can be managed successfully in a district general hospital. However, we are concerned about the high relapse rates and are now attempting to identify patients at greater risk of recurrence, to consider adjuvant therapy in this group.

Adult↗
PubMed1999

Effects of methylene blue-treated plasma on red cells and stored platelet concentrates.

BACKGROUND: Photochemical methods can effectively inactivate extracellular viruses and bacteria found in blood components. Treatment of plasma with methylene blue (MB), a phenothiazine dye, and visible light inactivates enveloped viruses including HIV-1. The effects of MB-treated plasma on cellular components stored in vitro have not been well characterized. STUDY DESIGN AND METHODS: MB-treated plasma (83 microg MB/250 mL plasma) was added to single-donor platelets, stored AS-1 red cells (RBCs), irradiated RBCs, and frozen-deglycerolized RBCs. In vitro platelet assays performed after 1 and 5 days of storage in MB-treated plasma included pH, pO2, pCO2, HCO3, platelet number, lactate dehydrogenase, glucose, osmotic recovery, and CD62 expression. RBC components were examined at specific intervals for leakage of potassium, plasma hemoglobin level, and percentage of hemolysis. Direct antiglobulin tests, osmotic fragilities, and RBC antigen stability tests were also performed on RBCs stored in MB-treated plasma. Components stored with autologous plasma or nontreated allogeneic plasma served as controls. RESULTS: Similar storage-induced changes in pH, glucose, and platelet numbers, as well as increases in lactate dehydrogenase, CD62 expression, and lactate were seen in single-donor platelets stored with MB-treated and control plasma. Platelet morphology scores and osmotic recoveries were not altered. Plasma hemoglobin and potassium and percentage of hemolysis increased equally in the various RBC components stored with MB-treated or nontreated plasma. Osmotic fragility and RBC antigen stability were not appreciably altered by MB-treated plasma. CONCLUSION: Plasma treated by MB photoinactivation can be used for in vitro resuspension and storage of platelets or RBCs, because of the lack of influence of MB-treated plasma on a variety of in vitro platelet and RBC assays.

Blood Platelets↗
PubMed1999

Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) belongs to a group of prion diseases that may be infectious, sporadic, or hereditary. The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide. Prevalence of the 200K variant of familial CJD is especially high in Slovakia, Chile, and Italy, and among populations of Libyan and Tunisian Jews. To study ancestral origins of the 200K mutation-associated chromosomes, we selected microsatellite markers flanking the PRNP gene on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at the PRNP codon 129. Haplotypes were constructed for 62 CJD families originating from 11 world populations. The results show that Libyan, Tunisian, Italian, Chilean, and Spanish families share a major haplotype, suggesting that the 200K mutation may have originated from a single mutational event, perhaps in Spain, and spread to all these populations with Sephardic migrants expelled from Spain in the Middle Ages. Slovakian families and a family of Polish origin show another unique haplotype. The haplotypes in families from Germany, Sicily, Austria, and Japan are different from the Mediterranean or eastern European haplotypes. On the basis of this study, we conclude that founder effect and independent mutational events are responsible for the current geographic distribution of hereditary CJD associated with the 200K mutation.

Amyloid↗
PubMed1999

Impaired cholera toxin relaxation with age in rat aorta.

Beta-adrenergic-mediated vasorelaxation declines with maturation and aging. Available data suggest that impaired stimulatory G-protein function could explain this deficit. We have previously found a loss of cholera toxin (CT)-stimulated adenosine diphosphate (ADP) ribosylation with age in rat aortic membrane preparations, without evidence for loss of the stimulatory alpha subunit of G protein (Gsalpha) by immunoblotting. The purpose of this investigation was to determine if cholera toxin-mediated vasorelaxation was also impaired with age. Aortic ring segments from 6 weeks, 6 months, 12 months, and 24 months old male F-344 rats were used. Contraction to KCl and phenylephrine was assessed along with relaxation to cholera toxin (azide-free), isoproterenol and forskolin. There were no age-related changes to KCl or phenylephrine contraction. There was a significant decrease with age in relaxation to isoproterenol. This loss with age was significantly greater with KCl-preconstricted vessels than phenylephrine-preconstricted vessels. There were no age-related changes in the relaxation to forskolin. There was a significant decrease with age in the maximal relaxation to cholera toxin as well as a rightward shift in the dose-response curve. Cholera toxin-stimulated adenosine 3', 5'-cyclic phosphate (cAMP) levels were measured and there was no increase in cAMP levels surrounding the time period associated with relaxation induced by cholera toxin. These data suggest that different preconstricting agents markedly affect the age-related changes in beta-adrenergic-mediated vasorelaxation. Furthermore, they suggest that the mechanism of cholera toxin-mediated vasorelaxation may not be mediated through increases in cAMP concentration.

Adenosine Diphosphate↗
PubMed1999

Validity and usefulness of the Wisconsin Manual for Assessing Psychotic-like Experiences.

The Wisconsin Manual for Assessing Psychotic-like Experiences is an interview-based assessment system for rating psychotic and psychotic-like symptoms on a continuum of deviancy from normal to grossly psychotic. The original manual contained six scales, assessing thought transmission, passivity experiences, thought withdrawal, auditory experiences, personally relevant aberrant beliefs, and visual experiences. A seventh scale assessing deviant olfactory experiences was subsequently added. The rating scales have good interrater reliability when used by trained raters. Cross-sectional studies indicated that the frequency and deviancy of psychotic-like experiences are elevated among college students who were identified, hypothetically, as psychosis prone by other criteria. Psychotic-like experiences of moderate deviancy in college students successfully predicted the development of psychotic illness and poorer overall adjustment 10 years later. The manual is useful for identifying psychosis-prone individuals and is recommended for use in linkage and treatment outcome studies. The present article provides an interview schedule for collecting information required for rating psychotic-like experiences.

Delusions↗
PubMed1999

The A677V methylenetetrahydrofolate reductase gene polymorphism and carotid atherosclerosis.

BACKGROUND AND PURPOSE: The alanine/valine (A/V) polymorphism at codon 677 of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene correlates with elevated levels of plasma homocysteine and with an increased risk of atherosclerotic cardiovascular disease. Our study was designed to assess the frequency of the A and V alleles in patients with asymptomatic severe carotid artery stenosis (CAS) assessed by extracranial duplex examination in comparison with age- and sex-matched subjects without carotid atherosclerosis. METHODS: Consecutive patients (n=48; 28 men, mean+/-SD age 67.1+/-11. 4 years) with asymptomatic severe (>75%) CAS were compared with subjects without CAS (n=26; 15 men, aged 61.2+/-11.5). The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. The chi(2) analysis and t test were used to compare the groups. RESULTS: The frequency of V alleles was significantly higher in the CAS group (0.47) compared with control subjects (0.27, chi(2) test; OR 2.4 [95% CI 1.1 to 5.3]; P<0.02). CONCLUSIONS: Our results indicate that the MTHFR A677V allele is significantly associated with severe CAS.

Aged↗
PubMed1999

Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel.

A strong association exists between multiple sclerosis (MS) and the DRB1*1501 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DRB1*1501 positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB1*1501 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1501 effect of HLA on susceptibility for MS. MS multiplex families and healthy controls were molecularly typed for six highly polymorphic markers located within the MHC region: DRB1, DQA1 and DQB1, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient group with both healthy relative, and healthy control groups (b) a transmission test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and parametric LOD score analyses using the GENEHUNTER program. The DRB1*1303 allele was significantly more frequent among the MS patients. There was a trend towards transmission disequilibrium of DRB1*1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRB1*1303 observed in our family patients provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patients. Thus, DRB1*1303 may serve as genetic risk factor for MS. Our study exemplifies the genetic heterogeneity in MS as there is a genetic effect of HLA on MS susceptibility in our low frequency DRB1*1501 patients.

Alleles↗