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J C Webb

Publications and source records attributed to J C Webb.

At least 19 recordsLinked to original sources
PubMed2001

Observation of polarization in bottomonium production at square root of s = 38.8 GeV.

We present a measurement of the polarization observed for bottomonium states produced in p-Cu collisions at square root of s = 38.8 GeV. The angular distribution of the decay dimuons of the Upsilon(1S) state shows no polarization at small values of the fractional longitudinal momentum x(F) and transverse momentum p(T) but significant positive transverse production polarization for either p(T)>1.8 GeV/c or for x(F)>0.35. The Upsilon(2S+3S) (unresolved) states show a large transverse production polarization at all values of x(F) and p(T) measured. These observations challenge NRQCD calculations of the polarization expected in the hadronic production of bottomonium states.

Journal Article↗
PubMed2001

Population-based study of microinvasive adenocarcinoma of the uterine cervix.

OBJECTIVE: To analyze lymph node status and survival rates of women with microinvasive cervical adenocarcinoma (International Federation of Gynecology and Obstetrics stages IA(1) and IA(2)). METHODS: The Surveillance, Epidemiology, and End Results (SEER) Public-Use Database was used to identify cases of microinvasive cervical adenocarcinoma diagnosed between 1988 and 1997. Variables analyzed included stage, extent of surgery, lymph node status, radiation therapy, and age. Statistics included analysis of trends, analysis of variance, log-rank test, one-sided binomial confidence interval estimation, and power analysis. RESULTS: Among 301 reported cases, 131 had stage IA(1) and 170 IA(2) disease. Simple hysterectomies were done in 54 women with IA(1) and 64 with IA(2) disease and radical hysterectomies were done in 50 and 83 women, respectively. Only one of 140 women who had lymphadenectomy had a single positive lymph node. There were four tumor-related deaths (one with IA(1), and three with IA(2) disease). There were no deaths among 96 women (47, IA(1); 49, IA(2)) treated by simple hysterectomy alone. The mean follow-up was 46.5 months (range 1--119). The censored survival rate was 98.7% overall (99.2% IA(1), 98.2% IA(2)). Power analysis estimated that 720 patients would be required in each group to detect a 2% difference in survival. Using one-sided 95% confidence interval estimations, the risk-adverse events rate for IA(1) was no more than 3.57%, and 4.50% for IA(2) disease. CONCLUSION: Prognosis is excellent for microinvasive adenocarcinoma of the uterine cervix. In 96 cases (31.9%), simple hysterectomy alone proved adequate.

Adenocarcinoma↗
PubMed1999

Loss of heterozygosity and microsatellite instability at the MLL locus are common in childhood acute leukemia, but not in infant acute leukemia.

Rearrangements involving the MLL gene at chromosome 11q23 are associated with leukemia and are present in up to 70% of infant leukemias. Loss of heterozygosity (LOH) has been shown for anonymous polymorphic markers at 11q23 in adult leukemias. To study LOH at the MLL locus, we have identified two new polymorphic microsatellite markers: a GAA repeat (mllGAAn) in intron 6 of the MLL gene and a GA (mllGAn) repeat in the 5' flanking region of the gene, approximately 2 kb upstream of the translation initiation codon. The heterozygosity index of mllGAAn is 0.54, which renders it useful for analyzing LOH. We screened two groups of leukemia patients to study LOH at the mllGAAn marker. Group A (n = 18) was selected on the basis of presentation before 18 months. Cytogenetic and reverse transcription-polymerase chain reaction analysis showed that 9 of these 18 children had translocations involving MLL. No LOH was observed. Group B (n = 36) were randomly selected children who had presented with leukemia between 1993 and 1994. Cytogenetic analysis of this group showed a variety of different chromosomal abnormalities. LOH was shown in 9 of 20 individuals (45%) who were informative. Microsatellite instability (MSI) was demonstrated in 1 of 18 individuals in group A and 5 of 36 individuals (13.9%) in group B. MSI and LOH were observed simultaneously in three individuals. Loss of an allele was confirmed in one individual by fluorescence in situ hybridization. Individuals with MSI or LOH at mllGAAn were selected for analysis at anonymous polymorphic markers D11S1364 and D11S1356, which flank the MLL gene. No LOH or MSI was observed at these markers in those individuals who were informative. These results show that LOH at the MLL gene locus is a common event during leukemogenesis. Furthermore, the presence of MSI at this locus suggests that the region is a hotspot for genetic instability.

Acute Disease↗
PubMed1997

Pregnancy complicated by primary aldosteronism.

Pregnancy is rarely complicated by aldosteronism. We report the case of a 32-year-old woman who became pregnant soon after primary aldosteronism was diagnosed. Only antihypertensive medication and oral potassium supplementation were required in addition to routine prenatal care. A healthy female infant was delivered at term. In this case, no adrenal adenoma was identified. We discuss management of aldosteronism in pregnancy and review the literature.

Adult↗
PubMed1996

Hematosalpinx with pelvic pain after endometrial ablation confirms the postablation-tubal sterilization syndrome.

Complications after endometrial ablation are uncommon, and published series show that the majority of women who are treated by this technique remain symptom free in the postoperative period. A 39-year-old woman with previous tubal ligation underwent laparoscopic-assisted vaginal hysterectomy for debilitating pelvic pain 1 year after endometrial ablation. Pathologic assessment of the surgical specimen showed bilateral hematosalpinges from continued cyclic occult bleeding. The symptoms and findings in this case confirm the postablation-tubal sterilization syndrome.

Adult↗
PubMed1996

Genetic variation at a splicing branch point in intron 9 of the low density lipoprotein (LDL)-receptor gene: a rare mutation that disrupts mRNA splicing in a patient with familial hypercholesterolaemia and a common polymorphism.

Mutations in the coding sequence, splice junctions or promoter of the gene for the low density lipoprotein (LDL) receptor are known to be the underlying cause of familial hypercholesterolaemia (FH), but mutations of this type cannot be identified in all patients with a clinical diagnosis of FH. We show here that minor sequence changes elsewhere in introns can be deleterious. A minor rearrangement 30 bp upstream from the junction of intron 9 with exon 10 was detected as a heteroduplex in amplified genomic DNA from one out of 300 heterozygous FH patients. The mutation destroys the only consensus sequence for a splicing branch point in intron 9 and analysis of mRNA from cells from the patient showed that it causes retention of intron 9 or, more rarely, in the use of cryptic splice sites in exon 10. The effect of the mutation on mRNA splicing was confirmed by analysis of mRNA in cells transfected with LDL-receptor mini-gene constructs expressing exons 9 and 10, together with the normal or mutant intron 9. A common C/T polymorphism within this branch point in intron 9 of the LDL-receptor gene does not affect mRNA splicing in vitro and is not associated with significant differences in mean plasma cholesterol concentration in a healthy population.

Adult↗
PubMed1996

Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom.

Mutations in the gene for the low density lipoprotein (LDL) receptor have been identified in 15 patients with homozygous familial hypercholesterolemia (FH). Five patients are homozygous at the LDL-receptor locus; their mutant alleles include Glu387Lys and Pro664Leu in patients of Asian-Indian descent, Cys292Stop in a Greek Cypriot, Cys281Trp in a Turkish patient, and Gln 540Stop in a West Indian. The other 10 patients (9 of apparently British ancestry) are compound heterozygotes. Mutations have been identified in 18 of 20 possible alleles, including Glu80Lys (2 patients), Pro664Leu (3 patients), Asp69Gly, Cys176Arg, Cys227Tyr, Ser265Arg, Asp280Ala, Asp283Glu, Arg329Pro, Asp461Asn, Leu578Ser, a single bp deletion in exon 15, a 21 bp duplication of codons 200-206 and two large deletions. The seven mutations underlined above have not been described previously. The two uncharacterized mutant alleles fail to produce detectable amounts of mRNA. LDL-receptor activity in cultured cells from 13 of the 15 homozygous patients varied from undetectable to about 30% of normal, but there was no correlation between LDL-receptor activity and the untreated plasma cholesterol concentration in these patients. When genomic DNA from 295 patients with a clinical diagnosis of FH was screened for 29 mutations found in these and other FH patients of British ancestry, most were identified in only one or a few individuals. Four patients heterozygous for the Asp461Asn allele showed a wide range of clinical manifestations. These observations confirm the striking heterogeneity underlying FH in most populations and demonstrate the variability in phenotype between patients with the same mutation.

Adolescent↗
PubMed1994

Adult onset immunodeficiency caused by inherited adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency is identified here as a cause of adult onset immunodeficiency. Two sisters who noted recurrent, predominantly chest infections in their twenties were found in their thirties to have CD4+ lymphopenia and lymphocyte ADA activity of approximately 5% of the lower limit of normal. Immune function, measured by proliferation of PBMCs in vitro to mitogens and specific Ags, was impaired. Inheritance of a polymorphic marker showed that both patients were heterozygous at the ADA locus. In the paternal allele there was a deletion resulting from homologous recombination between two alu elements that normally flank the first exon and the polymorphic marker. The recombination site was distinct from that in similar deletions described in two infants having severe combined immunodeficiency. This allele is predicted to result in a null phenotype. In the mutant allele inherited from the mother, a C to T transition in a CpG dinucleotide changed the codon for arginine 211, which lies in a conserved sequence close to the active site, to that for cysteine. This mutation has been observed previously in a child in whom the other allele was also a null mutation, but who was diagnosed as having partial ADA deficiency because immune function was apparently normal. The late onset of immunodeficiency in our patients suggests that immune function in children with partial ADA deficiency may deteriorate with time and that ADA deficiency should be regarded as a possible cause of adult onset immune dysfunction of unknown etiology.

Adenosine Deaminase↗
PubMed1994

Characterization and tissue-specific expression of the human 'very low density lipoprotein (VLDL) receptor' mRNA.

A cDNA has been isolated from human heart that is homologous to a member of the low density lipoprotein (LDL) receptor gene family recently identified in rabbit. It was named the very low density lipoprotein (VLDL) receptor, although its physiological function is not yet known. The predicted human protein shows 97.4% sequence homology to the rabbit protein, much more than the approximately 75% observed between their LDL receptor proteins. The sequence is also highly conserved in the hamster and the African green monkey. The mRNA was identified as a 3.9 kb transcript by Northern blotting in Hep G2 cells, cultured arterial smooth muscle cells and human skin fibroblasts, where its level was unaffected by sterols. The mRNA was not detected in EBV-lymphoblasts or in monocyte-macrophages by Northern blotting or by RT-PCR. In human tissues in vivo, the mRNA was expressed predominantly in heart and skeletal muscle, and also in ovary and kidney, but not in the liver. Although the 3.9 kb mRNA was the major transcript, a larger variant of 5.2 kb was also detectable and was predominant in skeletal muscle. Amplification of the mRNA from cultured human cells also revealed a potential splice variant that lacked 84 bp coding for a region equivalent to the O-linked sugars domain of the LDL receptor. It was a minor component in most cell types, but was predominant in Hep G2 cells.

Amino Acid Sequence↗
PubMed1994

Familial hypercholesterolemia in China. Identification of mutations in the LDL-receptor gene that result in a receptor-negative phenotype.

Familial hypercholesterolemia (FH), caused by many different mutations in the low-density lipoprotein (LDL)-receptor gene, invariably leads to severe premature coronary heart disease (CHD) in homozygous individuals. Heterozygous FH patients are less severely affected but are still at increased risk of CHD in most populations. Although FH homozygotes in China are affected similarly to those elsewhere, heterozygotes are not detected in the general population and obligate heterozygotes are often not hypercholesterolemic by Western standards. Mutations in the LDL-receptor genes of 10 homozygous FH patients from the Jiang-su province of China and their heterozygous parents were analyzed. These include one large and two minor deletions and eight point mutations: four are predicted to introduce a premature stop codon, five to result in a single amino acid substitution or deletion, and one to produce a protein with an abnormal cytoplasmic tail. Expression of the mutant LDL-receptor cDNAs in vitro confirmed that these mutations impaired LDL-receptor function and that several would cause a receptor-negative phenotype. Thus, the lack of clinical expression in obligate FH heterozygotes is not due to unusually "mild" mutations in the LDL-receptor gene, and other genetic or environmental factors must therefore be important in determining phenotypic expression.

Adolescent↗
PubMed1994

Co-expression of renin-angiotensin system component genes in human atrial tissue.

OBJECTIVES: To detect co-expression of genes coding for components of the renin-angiotensin system and investigate the potential for variation in the level of angiotensin converting enzyme (ACE) gene expression in the right atrial appendage of patients undergoing heart surgery. DESIGN: The right atrial appendage was collected at the time of surgery from 30 randomly chosen patients and was rapidly frozen in liquid nitrogen prior to extraction of messenger (m)RNA. Surgical samples of heart valve (n = 6) and papillary muscle (n = 3) were also examined. METHODS: Aliquots of purified mRNA were reverse-transcribed for analysis of gene expression by a polymerase chain reaction amplification assay. Primers specific for angiotensinogen, renin, ACE, cardiac chymase, atrial natriuretic peptide, glyceraldehyde-3-phosphate dehydrogenase, adenosine deaminase and the transferrin receptor were used for a qualitative analysis of co-expression of these genes within the same sample. In a subgroup of eight patients, a quantitative comparison of the relative levels of ACE gene expression was performed using a competitive polymerase chain reaction. RESULTS: Angiotensinogen and ACE expression were detected in all atrial, valve and ventricular samples examined, at levels similar to those of 'housekeeping' genes such as the transferrin receptor. Atrial renin and chymase expression were more difficult to detect, being demonstrable in only 70 and 63% of the samples, respectively. Higher levels of chymase were detected in ventricular samples than in atrial tissues. A quantitative analysis of ACE expression in eight atrial samples provided evidence of interindividual variation in the relative level of atrial ACE expression. CONCLUSIONS: The essential components of the renin-angiotensin system are co-expressed at a low level in the right atrial appendage and are detectable in other regions of the human heart. Renin and chymase genes are expressed at a lower level than the angiotensinogen and ACE genes and exhibit regional differences in expression. Interindividual variation in the relative level of ACE expression can be detected by a competitive polymerase chain reaction.

Angiotensinogen↗
PubMed1993

Correlation between p53 mutations and antibody staining in breast carcinoma.

Abnormalities of the p53 gene and protein were examined in 81 primary breast carcinoma samples. Using a polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis, mutations in p53 exons 5-8 were identified in 13 of 81 tumours (16 per cent) and confirmed by DNA sequencing. Positive staining for p53 protein was detected in ten of 77 (13 per cent) of these tumours using polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR-SSCP analysis were more common in grade III tumours (P = 0.015), but no correlation was found with tumour size, node status or level of epidermal growth factor receptor expression. A p53 mutation was associated with positive antibody staining in only two patients. Positive immunohistochemical staining using a p53 antibody may detect p53 protein expression, but this may not correlate directly with an underlying mutation in the hot spot region examined.

Adult↗
PubMed1993

Cholesterol-lowering drug therapy in a patient with receptor-negative homozygous familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is caused by mutations in the gene for the low density lipoprotein (LDL) receptor. It is generally believed that homozygous FH patients do not respond well to lipid-lowering drug therapy with inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase because they cannot respond to an increased demand for hepatic cholesterol by up-regulation of LDL-receptor activity. In this paper we show that serum cholesterol in a homozygous FH patient with a receptor-negative LDL-receptor phenotype was reduced by 30% after treatment with simvastatin alone and by a further 11% with simvastatin in combination with probucol and nicotinic acid. The patient was a true homozygote, with two identical alleles of the LDL receptor gene in which a previously undescribed point mutation in exon 11 introduces a premature termination codon at residue 540 in the protein; the mutant protein is predicted to be truncated in the domain with homology to the epidermal growth factor precursor. Cultured cells from the patient were unable to bind, internalise or degrade LDL by the receptor pathway and there was no immunodetectable LDL receptor protein in the cells. Thus the lipid lowering effect of simvastatin in this individual must involve mechanisms other than stimulation of LDL receptors.

Adolescent↗
PubMed1992

Characterization of deletions in the LDL receptor gene in patients with familial hypercholesterolemia in the United Kingdom.

A sample of 200 patients with a clinical diagnosis of heterozygous (189) or homozygous (11) familial hypercholesterolemia (FH) attending lipid clinics in the London area have been screened for the presence of major gene defects in the low density lipoprotein (LDL) receptor gene by Southern blotting of genomic DNA with specific probes. This study is part of a project to determine the frequency of known mutations in the LDL receptor gene in this population. A new polymorphism for the enzyme Bgl II was identified by hybridization with a probe specific for the promoter plus exon 1 of the LDL receptor gene. The observed frequency of the rare allele, characterized by a Bgl II fragment of 13 kb compared with 10 kb for the common allele, was 0.08 in this group of FH patients. Several individuals who were heterozygous for the rare allele were also heterozygous for a mutation elsewhere in the LDL receptor gene that is known to cause FH. Eight different mutations, seven deletions and one duplication, were detected in a total of nine patients, accounting for 4.5% of the mutant alleles in this group. Three of the mutations are apparently identical to deletions that have been described previously in FH patients of British or European origin, while the remaining five have not been described. Two of these were in patients of Polish and Asian Indian origin, while the other three were in patients of apparently British ancestry.

Alleles↗
PubMed1992

Characterization of two new point mutations in the low density lipoprotein receptor genes of an English patient with homozygous familial hypercholesterolemia.

Two new point mutations have been detected in the low density lipoprotein (LDL) receptor gene of a patient with a clinical diagnosis of homozygous familial hypercholesterolemia (FH). The patient is a compound heterozygote, in whom the mutant allele inherited from his English father has a single base substitution of A for G in exon 3, changing the codon for residue 80 in the mature protein from glutamic acid to lysine. The mutant allele inherited from his mother, who is of Irish origin, has a single base pair deletion in the codon for residue 743 in exon 15 that causes a frameshift and introduces a new stop codon in the adjacent position. The glu80 to lys mutation results in a transport-defective phenotype and a mature protein that migrates abnormally slowly on nonreduced SDS-PAGE, but normally under reducing conditions; this was confirmed by site-directed mutagenesis and expression in vitro. The deletion in exon 15 results in a null phenotype in which the putative truncated receptor protein cannot be detected in cultured skin fibroblasts and the amount of mRNA derived from the allele is reduced. The glu80 to lys mutation was found in a further five unrelated individuals in a sample of 200 FH patients from the London area and in 11 from a sample of 77 FH patients from Manchester. Haplotype analysis suggested that all the patients had inherited this allele from a common ancestor. The deletion in exon 15 was not found in the London sample, nor in any unrelated individuals in the Manchester sample.

Alleles↗