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Biomedical subjects

J Hurst

Publications and source records attributed to J Hurst.

At least 19 recordsLinked to original sources
PubMed2005

MRI and neurological findings in macrocephaly-cutis marmorata telangiectatica congenita syndrome: report of ten cases and review of the literature.

MRI and neurological findings in macrocephaly-cutis marmorata telangiectatica congenita syndrome: report of ten cases and review of the literature: We describe the clinical history and magnetic resonance imaging (MRI) findings in 10 children with the Macrocephaly-Cutis Marmorata Telangiectatica Congenita syndrome (M-CMTC--MIM 602501). This syndrome has recently been delineated within the general group of patients with Cutis Marmorata Telangiectatica (CMTC) as a distinct and easily recognisable entity. In contrast to most children with CMTC, patients with M-CMTC syndrome have a high risk of neurological abnormalities, such as hydrocephalus, megalencephaly, developmental delay and mental retardation. An MRI scan showed structural cerebral abnormalities in all of our patients, including megalencephaly, asymmetry of the cerebral hemispheres and abnormally increased signal of white matter. Seven patients also had Chiari type I malformation. Reviewing all reported cases, we propose appropriate surveillance for known complications.

Abnormalities, Multiple↗
PubMed2004

Variation in the helminth community structure in spiny mice (Acomys dimidiatus) from four montane wadis in the St Katherine region of the Sinai Peninsula in Egypt.

We compared helminth communities in spiny mice (Acomys dimidiatus) from 4 wadis in the arid montane region of the southern Sinai in Egypt, in a 4-week period in late summer. Total helminth species richness was 14 (8 nematodes, 5 cestodes and 1 acanthocephalan) with 94% of mice carrying at least 1 species and an overall mean species richness of 1.85. The most prevalent parasites were Protospirura muricola (47.8 %) and Dentostomella kuntzi (46.3%). One larval cestode, Joyeuxiella rossicum, represents a new host record. The helminth community was dominated by intestinal nematodes (88.7%) of which 58.2% were arthropod-transmitted heteroxenic species. At the component community level, 70% of the worms were recovered from mice in just two wadis (Gharaba and Tlah) and 48.6 % of intestinal nematodes were from Wadi Gharaba. Although only 7 species of helminths were recorded from Wadi Gharaba, this site gave the highest Berger-Parker dominance index because of P. muricola. P. muricola was also dominant in Wadi El Arbaein whilst Syphacia minuta was the dominant species in Wadis Gebal and Tlah. At the infracommunity level, mean species richness and Brillouin's index of diversity were highest in Wadi Tlah and lowest in Wadi Gebal, and the former was age dependent. Whilst mice from different wadis differed in the nematodes that were most common, those from Wadi Gharaba carried the highest mean number of worms/mouse. The abundance of P. muricola in particular varied markedly between sites: Wadi Gharaba was distinct as the site showing the highest mean worm burden whereas mice from Wadi Gebal were uninfected. None of the directly transmitted oxyuroid nematodes showed significant variation in abundance between wadis, or host sex or age classes. Overall, the single extrinsic factor in the study, site of capture, was more important than the intrinsic factors in explaining variation in helminth communities in the region. We conclude that in the high mountains of southern Sinai, each wadi is distinct in terms of its rodent parasites, and hence we expect spatially different coevolutionary pressures on their hosts, with resultant variation in life-histories.

Age Factors↗
PubMed2001

Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia.

We have previously shown that familial septo-optic dysplasia (SOD), a syndromic form of congenital hypopituitarism involving optic nerve hypoplasia and agenesis of midline brain structures, is associated with homozygosity for an inactivating mutation in the homeobox gene HESX1/Hesx1 in man and mouse. However, as most SOD/congenital hypopituitarism occurs sporadically, the possible contribution of HESX1 mutations to the aetiology of these cases is presently unclear. Interestingly, a small proportion of mice heterozygous for the Hesx1 null allele show a milder SOD phenocopy, implying that heterozygous mutations in human HESX1 could underlie some cases of congenital pituitary hypoplasia with or without midline defects. Accordingly, we have now scanned for HESX1 mutations in 228 patients with a broad spectrum of congenital pituitary defects, ranging in severity from isolated growth hormone deficiency to SOD with panhypopituitarism. Three different heterozygous missense mutations were detected in individuals with relatively mild pituitary hypoplasia or SOD, which display incomplete penetrance and variable phenotype amongst heterozygous family members. Gel shift analysis of the HESX1-S170L mutant protein, which is encoded by the C509T mutated allele, indicated that a significant reduction in relative DNA binding activity results from this mutation. Segregation analysis of a haplotype spanning 6.1 cM, which contains the HESX1 locus, indicated that only one HESX1 mutation was present in the families containing the C509T and A541G mutations. These results demonstrate that some sporadic cases of the more common mild forms of pituitary hypoplasia have a genetic basis, resulting from heterozygous mutation of the HESX1 gene.

Alleles↗
PubMed2001

Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America.

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis of OA1 and for the establishment of any mutation detection program for this disorder.

Albinism, Ocular↗
PubMed2000

A refined physical and transcriptional map of the SPG9 locus on 10q23.3-q24.2.

Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disorder characterised by progressive spasticity of the lower limbs. Beside 'pure' forms of HSP, 'complicated' forms are reported, where spasticity occurs associated with additional symptoms. We recently described an Italian family with a complicated dominant form of HSP (SPG9) and we mapped the gene responsible to 10q23.3-q24.2, in a 12cM interval between markers D10S564 and D10S603. The phenotypic manifestations in our family are reminiscent of those already described in a smaller British pedigree. We typed individuals from this British family using markers located in the SPG9 critical interval and haplotype reconstruction showed the disorder co-segregating with SPG9. To characterise the SPG9 region better, we constructed a contig of 22 YACs, assigned it to 18 polymorphic markers and positioned 54 ESTs. Furthermore, we searched for ESTs containing a trinucleotide repeat sequence, since anticipation of symptoms was reported in both families. Finally, analysis of a muscle biopsy specimen from one patient was normal, suggesting that, contrary to SPG7, mitochondrial disturbance could not be a primary feature of SPG9.

Biopsy↗
PubMed2000

Challenges for health systems in member countries of the Organisation for Economic Co-operation and Development.

For reasons of equity most OECD countries have chosen to base their funding of health care mainly on public sources. There is an almost universal problem of affordability in the health systems of these countries, arising from the tension between the willingness of populations to pay taxes and the eagerness of patients to use health services where these are free or heavily subsidized at the point of use. These tensions are likely to be exacerbated by a surge of new medical technologies adding to demands for health care. Some observers have predicted the breakdown of publicly funded systems of health care under new spending pressures. However, governments can deploy a range of policies for handling new demands. They can also take comfort from the fact that many of them have already coped with successive waves of technological change in health care without abandoning their core commitment to the public funding of health systems. Furthermore, if standards of living continue to rise, public and private insurers should find it easier to obtain the revenues needed to pay for the improved health care expected by consumers.

Delivery of Health Care↗
PubMed1999

PAF binding to a single receptor in corneal epithelium plasma membrane.

PURPOSE: To study the binding characteristics and the expression of platelet-activating factor receptors (PAF-R) in corneal epithelium to elucidate the site of action of PAF. METHODS: Binding of [3H]PAF was investigated in subcellular fractions of the epithelia of bovine corneas and in membranes from cultured rabbit corneal epithelial cells. Dose-response inhibition curves of [3H]PAF-specific binding were generated using increasing concentrations of several PAF-R antagonists. RNA from rabbit corneal epithelial cells was probed for PAF-R expression by reverse transcription-polymerase chain reaction (RT-PCR) with specifically designed degenerated primers. RESULTS: Scatchard analysis showed a high-affinity binding site in bovine and rabbit corneal epithelium. The dissociation constant (Kd) and the maximum binding sites (Bmax) in a bovine membrane preparation and similar rabbit fraction were 0.77+/-0.03 nM and 180+/-21 femtomoles/mg protein and 4.3 nM and 1.3 picomoles/mg protein, respectively. Specific PAF-binding sites were found in bovine preparations enriched in plasma membranes with a Kd = 69.6 pM and Bmax = 80 femtomoles/mg protein; no specific binding was found in nuclei or microsomal fractions. RT-PCR of rabbit corneal epithelium generated a single product of the predicted size (478 bp). The deduced amino acid sequence of the purified PCR product was 87% homologous to human PAF-R. The hetrazepines BN 50727 and BN 50730 and the PAF structural analogues CV 3988 and CV 6209 competitively inhibited [3H]PAF binding to corneal epithelium with similar potency. WEB 2086 BS was two orders of magnitude less active in antagonizing PAF binding. CONCLUSIONS: Corneal epithelium contains a single population of receptors localized in the plasma membrane. PAF antagonists exert their actions by blocking this PAF-R. The partial sequence deduced in rabbit corneal PAF-R show a higher homology to the human PAF-R.

Amino Acid Sequence↗
PubMed1999

Expression of mdm-2 oncoprotein in the primary and metastatic sites of mammary tumor (GI-101) implanted athymic nude mice.

The expression of mdm-2 oncoprotein (p90) was determined in a human breast tumor xenograft line (GI-101) that was derived from a 57 year old female cancer patient with recurrent, infiltrating ductal adenocarcinoma (Stage IIIa, T3N2MX). Immunoprecipitation coupled western blot analysis of the primary tumors that have been obtained from xenograft implanted athymic nude mice, using mdm-2 (Ab-1) mouse monoclonal antibody, primarily revealed high level expression of a 90 kD full length mdm-2 protein. In the GI-101 tumor the level of full length mdm-2 (p90) protein expression increased with the increase in the size of the tumor (100 to 2,000 mm(3)) and a maximum expression was detected in 2,000 mm(3) size tumors. In addition to the expression in the primary site, a significantly high level expression of mdm-2 protein (p90) was detected in the lung and liver tissues also, which are the known metastatic sites for GI-101 xenograft tumors. However, the level of mdm-2 protein expression was undetectable in the lung and liver tissues obtained from control mice. A cell line (GI-101A) derived from the GI-101 xenograft tumor also showed a high level expression of mdm-2 protein after several generations of cell passage. When the GI-101A cells were treated with DES (Diethylstilbestrol) the mdm-2 protein expression increased after 10 min treatment and reached a peak level at 40 min. Interestingly, DES (10 and 20 microM) treatment increased the total cell number also after 96 hr treatment compared to the non-treated cells. It appears that mdm-2 (p90) may have a significant role in supporting the tumor cell growth as well as the metastatic process of the GI-101A cells.

Animals↗
PubMed1998

Are physicians' office laboratory results of comparable quality to those produced in other laboratory settings?

CONTEXT: In 1995, California adopted a bill that brought laboratory laws in line with the 1988 Clinical Laboratory Improvement Amendments' standards for clinical laboratories and mandated a study comparing results in physicians' office laboratories (POLs) with other settings. OBJECTIVE: To determine whether persons conducting tests in POLs produce accurate and reliable test results comparable to those produced by non-POLs. DESIGN: Survey of clinical laboratories using proficiency testing data. SETTING: All California clinical laboratories participating in the American Association of Bioanalysts proficiency testing program in 1996 (n=1110). MAIN OUTCOME MEASURES: "Unsatisfactory" (single testing event failure) and "unsuccessful" (repeated testing event failure) on proficiency testing samples. RESULTS: The unsatisfactory failure rate for POLs was nearly 3 times (21.5% vs 8.1%) the rate for the non-POLs and about 1.5 times (21.5% vs 14.0%) for POLs that used laboratory professionals as testing or supervisory personnel (P<.001). The POL unsuccessful rate was more than 4 times (4.4% vs 0.9%) the rate for non-POLs and more than twice (4.4% vs 1.8%) the rate for the POLs using laboratory professionals (P<.001). CONCLUSIONS: Significant differences exist among POLs, POLs using licensed clinical laboratory scientists (medical technologists), and non-POLs. Testing personnel in many POLs might lack the necessary education, training, and oversight common to larger facilities. We must better understand the contributing factors that result in the poorer results of POLs relative to non-POLs. In the meantime, patients should be aware that preliminary findings suggest that differences in quality of laboratory tests based on testing site may exist. Laboratory directors at all testing sites must ensure that they understand laboratory practice sufficiently to minimize errors and maximize accuracy and reliability. Directors must understand their obligation when they elect to oversee those assigned testing responsibility. Legislators may wish to reconsider the wisdom of further easing restrictions on those to whom we entrust our laboratory specimens.

California↗
PubMed1998

Efficient 3'-end formation of human beta-globin mRNA in vivo requires sequences within the last intron but occurs independently of the splicing reaction.

The second intron (betaIVS-II) of the human beta-globin gene is essential for the accumulation of stable cytoplasmic mRNA and is implicated in promoting efficient 3'-end formation. This report presents quantitative comparisons between betaIVS-II mutants at physiological levels of expression from within a natural chromatin context in vivo which further defines it's function. In marked contrast to a beta-globin gene lacking a second intron, two mutants defective in splicing (small size or a splice donor mutation), still undergo essentially normal levels of 3'-end formation and in the absence of exon skipping. Therefore, 3' cleavage of beta-globin transcripts requires the presence of betaIVS-II sequences, but not the splicing reaction. The placement of betaIVS-II in the IVS-I position did not reduce the efficiency of 3' cleavage indicating that the distance between the necessary element(s) in this intron and the polyadenylation recognition site is not a crucial factor. Subsequent placement of betaIVS-I in the intron II position, reduced the efficiency of 3'-end formation to only 16% of normal. A direct replacement of intron II by the heterologous introns betaIVS-I or alpha-globin IVS-II, only partially substitute (16 and 30% respectively) for betaIVS-II. Hybrid introns show that efficient 3'-end formation is strongly enhanced by the presence of the terminal 60 nt of betaIVS-II. These data imply that the last intervening sequence of multiple intron containing genes is a principal determinant of the efficiency of 3'-end formation and may act as a post-transcriptional regulatory step in gene expression.

Animals↗
PubMed1998

The impact of health economics on health policy in England, and the impact of health policy on health economics, 1972-1997.

This paper contains a review of the impact of health economics on health policy in England during the past 25 years. Some health economists have expressed disappointment with the scale of the impact that health economics has had on policy but the record set out below suggests that there is modest cause for celebration. That is not to say that there is cause for complacency. There is still a long way to go before all important health policies are based on sound economics reasoning and evidence. The paper begins with some definitions and background; it covers nine areas of health policy, and health policy making, where past impacts of health economics have been postulated; it covers briefly the reciprocal impact of health policy on health economics; and it concludes with a discussion about the findings.

Economics, Medical↗
PubMed1998

An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa.

Elastin is the protein responsible for the characteristic elastic properties of many tissues including the skin, lungs and large blood vessels. Loss-of-function mutations in the elastin gene are known to cause the heart defect supravalvular aortic stenosis (SVAS). We and others have identified deletions, nonsense mutations and splice site mutations in SVAS patients that abolish the function of one elastin gene. We have now identified an elastin mutation in a patient with a completely different phenotype, the rare autosomal dominant condition cutis laxa. A frameshift mutation in exon 32 of the elastin gene is predicted to replace 37 amino acids at the C-terminus of elastin by a novel sequence of 62 amino acids. mRNA and immunoprecipitation studies show that the mutant allele is expressed. Electron microscopy of skin sections shows abnormal branching and fragmentation in the amorphous elastin component, and immunocytochemistry shows reduced elastin deposition in the elastic fibres and fewer microfibrils in the dermis. These findings suggest that the mutant tropoelastin protein is synthesized, secreted and incorporated into the elastic matrix, where it alters the architecture of elastic fibres. Interference with cross-linking would reduce elastic recoil in affected tissues and explain the cutis laxa phenotype.

Adult↗
PubMed1998

Dynamic positron emission tomography with F-18 fluorodeoxyglucose imaging in differentiation of benign from malignant lung/mediastinal lesions.

PURPOSE: This study was done to evaluate the diagnostic utility of dynamic positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) imaging in patients with suspected malignant pulmonary lesions. We wanted to test the hypothesis that the rate of FDG uptake (FDG influx constant values) would differentiate malignant from benign lung or mediastinal lesions. MATERIALS AND METHODS: We performed segmental dynamic PET imaging studies following administration of FDG in 19 patients with indeterminate pulmonary lesions based on chest radiograph and/or CT scans. Patlak analysis was done to compute Ki (FDG influx constant) values and compared with FDG standardized uptake values (SUVs) and histology. RESULTS: FDG Ki values (mean+/-SD) were significantly greater (p < 0.01) in all 12 malignant lesions (0.029+/-0.02) as compared with 7 benign lesions (0.0024+/-0.0011) with good correlation to the SUV values. Distinct time activity curve patterns were identified in malignant and benign lesions with continued uptake in malignant lesions. CONCLUSION: Dynamic PET-FDG imaging accurately differentiates malignant from benign pulmonary lesions. In certain cases with equivocal findings on visual analysis and SUV values, dynamic imaging may be further helpful in differentiating benign and malignant lesions.

Adenocarcinoma↗
PubMed1997

Aluminablasting of human tooth enamel.

As part of a programme aimed at enhancing the degree of bonding that can be developed between dental polymer and human tooth enamel, the enamel has been subjected to two types of pretreatment, namely, aluminablasting (a mechanical etching) and aluminablasting followed by surface etching with orthophosphoric acid. Analysis of the surfaces so prepared by scanning electron microscopy has shown that enamel patterns with different degrees of retention ability have been obtained, and that the surfaces should be capable of bonding with dental polymer.

Journal Article↗
PubMed1997

Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis.

We describe the complete exon-intron structure of the human elastin (ELN) gene located at chromosome 7q11.23. There are 34 exons occupying approximately 47 kb of genomic DNA. All exons are in-frame, allowing exon skipping without disrupting the reading frame. Microsatellites are located in introns 17 and 18. Deletions of all or large parts of the ELN gene have been previously reported in two patients with supravalvular aortic stenosis (SVAS), and SVAS is also a frequent feature of Williams syndrome, where patients are hemizygous for ELN. We list primer pairs for amplifying each exon, with flanking intron, from genomic DNA to allow detection of point mutations in the ELN gene. We show that some patients with isolated SVAS have point mutations that are predicted to lead to premature chain termination. Knowledge of the genomic structure will allow more extensive mutation screening in genomic DNA of patients with SVAS and other conditions.

Amino Acid Sequence↗
PubMed1997

Impact of the in-house trauma surgeon on initial patient care, outcome, and cost.

BACKGROUND: The purpose of this study is to evaluate the effect of having attending trauma surgeons with added qualifications in surgical critical care present for the initial resuscitation at a regional trauma center. METHODS: This study is a retrospective review of patients admitted between August of 1994 and December of 1995 from our trauma registry. The patients were categorized by the call preference of the admitting physician as in-house (IH) or call-back from home (CB), day of admission (weekend vs. weekday), time of admission (AM VS. PM), and a value of the injury severity scale < or = 15 or > 15. Demographics, admission vital signs, Injury Severity Scale, Glasgow Coma Score, and elapsed time to diagnostic, therapeutic, and/or operative interventions were studied. The effect on intensive care unit length of stay, mortality, and hospital cost for resuscitation were also studied. RESULTS: The study population consisted of 1,043 patients. The IH and CB groups each included two attending surgeons. IH significantly reduced the average time to completion of diagnostic peritoneal lavage (22 vs. 34 minutes; p < 0.05), therapeutic intervention (21 vs 38 minutes; p < 0.05), and transport to the operating room (206 vs. 312 minutes; p < 0.05) during the AM compared with CB. There was no difference in these times for the PM admissions. There was no significant difference in intensive care unit length of stay. Among patients with severe head and thoracoabdominal injury (Abbreviated Injury Score > 4 and 3, respectively) there was no difference in mortality. Analysis of cost for emergency room resuscitation in severely injured patients (Injury Severity Score > or = 15), seen during weekdays, was significantly less when evaluated by IH (IH = $5,097 vs. CB = $6,779; p < 0.05). CONCLUSIONS: During the initial resuscitation of patients with severely injured during the weekdays, IH significantly reduced the cost, and elapsed time to diagnostic testing, therapeutic intervention, and to the operating room, respectively. IH reduced fatalities compared with CB.

Adult↗