Spontaneous osteomyelitis in an athlete: MR findings.
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Acute Disease↗
Biomedical subjects
C Helms
Publications and source records attributed to C Helms.
VNTR and microsatellite polymorphisms within the subtelomeric region of 7q.
The molecular basis of a highly polymorphic RFLP marker, HTY146c3 (D7S591), within the subtelomeric region of human chromosome 7q was determined by restriction-fragment and DNA sequence analysis. Two polymorphic systems were found--a simple base-substitution polymorphism and a GC-rich VNTR element with a core structure of C3AG2C2. In addition, a compound-imperfect CA dinucleotide-repeat element was identified approximately 10-20 kb from the telomeric sequence repeat (T2AG3), demonstrating that microsatellites can extend essentially to the ends of human chromosomes. The microsatellite marker, sAVH-6 (D7S594), is highly polymorphic, with 10 alleles and an observed heterozygosity of 84% found with the CEPH (Centre d'Etude du Polymorphisme Humain) reference pedigree collection. In combination with the RFLPs, the informativeness of the markers contained within 240 kb at the telomere approaches 100%. A unique genetic and physical STS marker, sAVH-6, defines the endpoint of the long arm of human chromosome 7.
Base Sequence↗
Identification of a second pseudoautosomal region near the Xq and Yq telomeres.
The telomeres of Xq and Yq have been observed to associate during meiosis, and in rare cases a short synaptonemal complex is present. Molecular cloning of loci from Xqter and Yqter has revealed that their sequence homology extends over 400 kilobases, which suggests the possibility of genetic exchange. This hypothesis was tested by the development of two highly informative microsatellite markers from yeast artificial chromosome clones that carried Xqter sequences and the following of their inheritance in a set of reference pedigrees from the Centre d'Etude du Polymorphisme Humain in Paris, France. From a total of 195 informative male meioses, four recombination events between these loci were observed. In three cases, paternal X alleles were inherited by male offspring, and in one case a female offspring inherited her father's Y allele. These data support the existence of genetic exchange at Xq-Yq, which defines a second pseudoautosomal region between the sex chromosomes.
Alleles↗
Chronically administered nicotine attenuates bradykinin-induced plasma extravasation and aggravates arthritis-induced joint injury in the rat.
We recently showed that acute administration of nicotine in the rat decreases bradykinin-induced plasma extravasation and that adrenal medullary-derived epinephrine, acting at a beta 2-adrenergic receptor, mediates the nicotine effect. Since agents which decrease bradykinin-induced plasma extravasation have been associated with increased joint injury in a rat model of chronic inflammation (experimental arthritis induced by subcutaneous injection of Mycobacterium butyricum) we examined the effect of chronic nicotine on both plasma extravasation and the severity of joint injury. In normal rats, bradykinin-induced plasma extravasation was decreased after nicotine administered both by repeated injection (10(-2) mg/kg, s.c., once per h for 4 h) and by continuous long-term infusion (subcutaneous mini-osmotic pump; 1.5 x 10(-3) mg/kg per h for 30 days). Nicotine-induced inhibition of bradykinin-induced plasma extravasation did not show tachyphylaxis. In rats with arthritis, chronic administration of nicotine also produced a decrease in bradykinin-induced plasma extravasation. This effect of chronic nicotine in the arthritic rats was antagonized by co-administration of hexamethonium (a nicotinic receptor antagonist), by surgical removal of the adrenal medulla, or by co-administration of ICI-118,551 (a beta 2-adrenoceptor antagonist). Chronic administration of nicotine decreased the latency to the onset of arthritis and, in a dose-dependent manner, led to an increase in the radiographic joint injury score.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Medulla↗
A 2-cM genetic linkage map of human chromosome 7p that includes 47 loci.
A new high-resolution genetic linkage map for human chromosome 7p has been constructed. The map is composed of 47 loci (54 polymorphic systems), 19 of which are uniquely placed with odds of at least 1000:1. Four genes are represented, including glucokinase (GCK, ATP:D-hexose-6-phosphotransferase, EC 2.7.1.2) which was mapped via a (CA)n dinucleotide repeat polymorphism. The sex-average map measures 94.4 cM and the male and female maps measure 73.2 and 116.1 cM, respectively. We believe that the genetic map extends nearly the full length of the short arm of chromosome 7 since a centromere marker has been incorporated, and the most distal marker, D7S21, has been cytogenetically localized by in situ hybridization to 7p22-pter. The average marker spacing is 2 cM, and the largest interval between uniquely placed markers is 13 cM (sex-average map). Overall, female recombination was observed to be about 1.5 times that of males, and a statistically significant sex-specific recombination frequency was found for a single interval. The map is based on genotypic data gathered from 40 CEPH reference pedigrees and was constructed using the CRI-MAP program package. The map presented here represents a combined and substantially expanded dataset compared to previously published chromosome 7 maps, and it will serve as a "baseline" genetic map that should prove useful for future efforts to develop a 1-cM map and for construction of a contiguous clone-based physical map for this chromosome.
Base Sequence↗
Closure of a genetic linkage map of human chromosome 7q with centromere and telomere polymorphisms.
We have constructed a 2.4-cM resolution genetic linkage map for chromosome 7q that is bounded by centromere and telomere polymorphisms and contains 66 loci (88 polymorphic systems), 38 of which are uniquely placed with odds for order of at least 1000:1. Ten genes are included in the map and 11 markers have heterozygosities of at least 70%. This map is the first to incorporate several highly informative markers derived from a telomere YAC clone HTY146 (locus D7S427), including HTY146c3 (HET 92%). The telomere locus markers span at least 200 kb of the 7q terminus and no crossovers within the physical confines of the locus were observed in approximately 240 jointly informative meioses. The sex-equal map length is 158 cM and the largest genetic interval between uniquely localized markers in this map is 11 cM. The female and male map lengths are 181 and 133 cM, respectively. The map is based on the CEPH reference pedigrees and includes over 4000 new genotypes, our previously reported data plus 29 allele systems from the published CEPH version 5 database, and was constructed using the program package CRI-MAP. This genetic linkage map can be considered a baseline map for 7q, and will be useful for defining the extent of chromosome deletions previously reported for breast and prostate cancers, for developing additional genetic maps such as index marker and 1-cM maps, and ultimately for developing a fully integrated genetic and physical map for this chromosome.
Centromere↗
Two chromosome 7 dinucleotide repeat polymorphisms at gene loci epidermal growth factor receptor (EGFR) and pro alpha 2 (I) collagen (COL1A2).
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Base Sequence↗
Software for analysis and manipulation of genetic linkage data.
We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes.
Alleles↗
Purinergic regulation of bradykinin-induced plasma extravasation and adjuvant-induced arthritis in the rat.
We assessed the contribution of ATP and adenosine (i) to a major sign of acute inflammation, plasma extravasation (PE), in the rat knee joint and (ii) to the severity of joint injury in adjuvant-induced experimental arthritis, a chronic inflammatory disease. PE induced by local infusion of bradykinin, which we have previously shown to depend on the sympathetic postganglionic neuron terminal, was markedly enhanced by coinfusion of either ATP or the adenosine A2-receptor agonist 2-[4-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine. Bradykinin-induced PE was inhibited by coinfusion of the ATP receptor antagonist adenosine 5'-[alpha,beta-methylene]triphosphate, the A2-receptor antagonist 3-(5H-thiozolo[2,3b]quinazolin-3-yl)phenol monohydrochloride, or the adenosine A1-receptor agonist N6-cyclopentyladenosine. The joint injury associated with experimental arthritis, which is reduced in severity in sympathectomized rats, was also markedly attenuated by daily administration of either ATP (40% reduction) or adenosine (55% reduction). These results demonstrate that the purines ATP and adenosine (acting at the A2 receptor), cotransmitters in the sympathetic postganglionic neuron terminal, enhance bradykinin-induced sympathetic postganglionic neuron terminal-dependent PE but inhibit the joint injury of arthritis. These opposing purinergic effects on PE and joint injury suggest that enhanced PE protects against joint injury.
Adenosine↗
High-dose epinephrine acts at alpha 2-adrenoceptors to suppress experimental arthritis.
This study assessed the receptor site at which high systemic doses of epinephrine act to reduce the severity of adjuvant-induced arthritis in the rat. To this end we examined the effect of selective adrenergic antagonists on the reduction of arthritis by epinephrine, and also assessed whether high doses of selective adrenergic agonists mimicked the effect of epinephrine. The decrease in arthritis induced by epinephrine (0.5 mg/kg in chronic implant injected every 3 days) was significantly antagonized by the selective alpha 2-adrenergic antagonist, yohimbine, but not by selective alpha 1 (prazosin), beta 1 (metoprolol) or beta 2 (butoxamine) antagonists. In addition, chronic infusion of the alpha 2-adrenergic agonist clonidine, but not selective alpha 1 (phenylephrine), beta 1/beta 2 (isoproterenol) or beta 2 (salbutamol) agonists, resulted in decreased arthritis severity. These data suggest that the suppressive effect of high-dose epinephrine on joint injury in experimental arthritis is mediated by action at the alpha 2-adrenergic receptor.
Adrenergic alpha-Agonists↗
Increasing sympathetic nerve terminal-dependent plasma extravasation correlates with decreased arthritic joint injury in rats.
This study compared the pharmacology of adrenergic agents that influence plasma extravasation in normal animals with those agents that influence tissue injury in an inflammatory disease model. Specifically we studied the effects of beta 2- and alpha 2-adrenergic receptor agonists and antagonists on bradykinin-induced plasma extravasation in normal Sprague-Dawley rats and on joint injury in rats with experimental arthritis. Plasma extravasation induced by infusion of bradykinin in the rat knee joint was attenuated by the beta 2-agonist salbutamol or by the alpha 2-antagonist yohimbine, and was enhanced by the beta 2-antagonist, ICI-118,551, or by the alpha 2-agonist, clonidine. In rats that had undergone chemical symphathectomy, bradykinin-induced plasma extravasation was markedly reduced, and there was no enhancement of bradykinin-induced plasma extravasation by either ICI-118,551 or clonidine. Although ICI-118,551 and clonidine enhanced bradykinin-induced plasma extravasation, these drugs significantly reduced joint injury in rats with adjuvant-induced arthritis. Neither salbutamol nor yohimbine, however, significantly increased joint injury in the arthritic rats, presumably because arthritis severity is already high in these animals. Consistent with this hypothesis, both salbutamol and yohimbine did significantly increase the joint injury associated with experimental arthritis in Wistar-Kyoto rats, a strain which develops a mild adjuvant arthritis. The fact that increased plasma extravasation is associated with decreased arthritis severity suggests that plasma extravasation, a major sign of acute inflammation, contributes to tissue reparative processes.
Animals↗
The CEPH consortium linkage map of human chromosome 1.
This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of human chromosome 1. The map contains 101 loci defined by genotypes generated from CEPH family DNAs with 146 different contributions from 11 laboratories. A total of 58 loci are uniquely placed on the map with likelihood support of at least 1000:1. The map extends from loci in the terminal bands of both chromosome arms (locus D1Z2 in 1p36.3 and D1S68 in 1q44) and is anchored at the centromere by the D1Z5 alpha-satellite polymorphism. With the exception of a single locus, the remaining loci are arrayed on the fixed map in short intervals and their possible locations are indicated. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 308, 478, and 390 cM, respectively. The sex-averaged map contains only four intervals greater than 15 cM, and the mean genetic distance between the 58 uniquely placed loci is 6.7 cM.
Chromosome Mapping↗
MRI in the evaluation of patients with suspected instability of the shoulder joint including a comparison with CT-arthrography.
Thirty-two patients with clinical suspicion of shoulder instability were the subject of this assessment of MRI (1.5 T G. E. Signa) and its comparison with CT-arthrography (GE8800 and GE9800) of the shoulder. Twenty-seven patients had a final diagnosis established by arthroscopy and five by arthrotomy. The imaging examinations were interpreted independently by three radiologists blinded against history, surgical diagnosis and results of the compared test. The statistical analysis included ROC-curves, sensitivity, specificity and accuracy as well as predictive values. The significance of the comparative results was assessed by the McNemar Sign test. MRI showed significantly better diagnostic results in the evaluation of labral structures (sensitivity 85%, specificity 90%, accuracy 88%) and humeral head impression fractures (75, 82, 78 %). None of the tests were of sufficient diagnostic value to identify capsular abnormalities. CT and MRI results regarding the biceps tendon and loose bodies were similar, however, statistically not significant. MRI proved to be of high diagnostic value in the assessment of the unstable shoulder and compared favorably with CT-A.
Adolescent↗
Automated percutaneous discectomy.
Automated percutaneous discectomy is a new, safe procedure for treating herniated lumbar discs still contained by the annulus or posterior longitudinal ligament. In 1985, one of the authors reported a percutaneous nucleus aspiration technique using a 2-mm aspiration probe. This small probe produced minimal tissue damage, allowing the procedure to be done on an outpatient. In this series, 518 patients were treated using this technique for an overall success rate of 85%. Compensation patients, elderly patients, and patients with previous surgery were treated successfully using percutaneous discectomy on an outpatient basis. No intraoperative or postoperative complications occurred.
Adult↗
Menstrually-related toxic shock syndrome.
Cases of suspect toxic shock syndrome reported to a state health department were studied. Retrospective examination of 53 definite and 29 probable cases of menstrually-related TSS revealed no significant differences in mean age, proportion with vaginal or cervical isolates of Staphylococcus aureus, proportion using tampons, proportion hospitalized and mortality.
Adult↗
Epinephrine exacerbates arthritis by an action at presynaptic B2-adrenoceptors.
Sympathetic efferents contribute to the severity of joint injury in experimental arthritis in the rat, [Levine J. D. et al. (1986) J. Neurosci. 6, 3423-3429] and beta 2-adrenergic receptor antagonists suppress the disease [Levine J. D. et al. (1988) Proc. natn. Acad. Sci. U.S.A. 85, 4553-4556]. The present study was directed at determining the endogenous ligand for, and target of, the beta 2-receptor contribution to arthritis. We report that adrenal medullectomy significantly reduced joint injury in experimental arthritis, but that severe joint injury was re-established in adrenal medullectomized rats chronically treated with epinephrine or the beta 2-agonist, salbutamol. The ability of these two drugs to enhance joint injury in adrenal medullectomized rats was blocked by sympathectomy. These data suggest that adrenal medulla-derived epinephrine acts at beta 2-adrenoceptors on sympathetic efferent nerve terminals, to contribute to the severity of experimental arthritis.
Adrenal Medulla↗
A continuing art and growing science.
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Curriculum↗
Automated percutaneous discectomy: a prospective multi-institutional study.
A prospective multi-institutional study was carried out to evaluate automated percutaneous discectomy in the treatment of lumbar disc herniations. Of the 327 patients who prospectively met the study criteria and were followed for longer than 1 year, 75.2% were successfully treated. When patients (n = 168) who prospectively did not meet the study criteria were treated, the success rate was 49.4%. One case of discitis was reported; otherwise, no other serious complications were noted, and specifically no vascular or nerve damage was encountered. This study indicates that automated percutaneous discectomy can be used successfully to treat lumbar disc herniations with minimal morbidity and emphasizes the need for proper patient selection.
Humans↗