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Christopher Jones

Publications and source records attributed to Christopher Jones.

At least 37 records · Page 2Linked to original sources
PubMed2004

The 11q terminal deletion disorder: a prospective study of 110 cases.

We performed a prospective study of 110 patients (75 not previously published) with the 11q terminal deletion disorder (previously called Jacobsen syndrome), diagnosed by karyotype. All the patients have multiple dysmorphic features. Nearly all the patients (94%) have Paris-Trousseau syndrome characterized by thrombocytopenia and platelet dysfunction. In total, 56% of the patients have serious congenital heart defects. Cognitive function ranged from normal intelligence to moderate mental retardation. Nearly half of the patients have mild mental retardation with a characteristic neuropsychiatric profile demonstrating near normal receptive language ability, but mild to moderate impairment in expressive language. Ophthalmologic, gastrointestinal, and genitourinary problems were common, as were gross and fine motor delays. Infections of the upper respiratory system were common, but no life-threatening infections were reported. We include a molecular analysis of the deletion breakpoints in 65 patients, from which genetic "critical regions" for 14 clinical phenotypes are defined, as well as for the neuropsychiatric profiles. Based on these findings, we provide a comprehensive set of recommendations for the clinical management of patients with the 11q terminal deletion disorder.

Adolescent↗
PubMed2004

Endocrine abnormalities in patients with Jacobsen (11q-) syndrome.

Jacobsen syndrome (JS), a rare disorder with multiple dysmorphic features, is caused by the terminal deletion of chromosome 11q. Short stature has been reported in this syndrome, however very few of these patients have undergone endocrine evaluation. Serum insulin-like growth factor-1 (IGF-1) levels are an indirect indicator of growth hormone activity and are a useful initial screening tool in the assessment of an individual's growth hormone axis. We studied nine children with JS, eight of whom had short stature. Four out of eight children with short stature (50%) had low IGF-1 values, with three low for age and one low for Tanner stage. Four out of six males (67%) had cryptorchidism, a potential sign of hypogonadism. We conclude that low IGF-1 is common in patients with JS and short stature, and that growth hormone status and possibly hypothalamic-pituitary function should be evaluated in this patient population.

Adolescent↗
PubMed2004

Direct evidence from siRNA-directed "knock down" that p16(INK4a) is required for human fibroblast senescence and for limiting ras-induced epithelial cell proliferation.

The selective pressure for disruption of the cyclin-dependent kinase inhibitor p16(INK4a) in human cancer has been postulated to reflect its role in mediating growth arrest, both in response to telomere erosion (replicative senescence) and to oncogene-induced and other "stress" signals. Given the known species-specific differences in regulation of senescence, we have tested this hypothesis in human, as opposed to rodent, cells by designing a small interfering RNA (siRNA) to knock down p16(INK4a) expression. Transfection of this siRNA into late-passage normal human diploid fibroblasts allowed at least temporary escape from entry into replicative senescence. Furthermore, in our in vitro model of early-stage, RAS-induced thyroid tumorigenesis, sequential transfections with this siRNA allowed outgrowth of small clusters of proliferating epithelial cells, consistent with escape from the spontaneous "senescence", which normally curtails their proliferative response to mutant RAS. These data provide the first direct evidence that p16(INK4a) is necessary for the initiation of both telomere-dependent and telomere-independent senescence in human cells.

Cell Division↗
PubMed2004

Detection of O-acetylated Vi polysaccharide of Salmonella enterica subspecies typhi by enzyme immunoassay.

Immunisation with capsular Vi polysaccharide (Vi PS) of Salmonella enterica serovar Typhi (S. typhi) protects against typhoid. This protection depends on the presence of O-acetyl groups on the Vi PS, which form an immunodominant epitope. An antiserum raised against conjugated Vi PS was used as the basis for an indirect Enzyme Immunoassay (EIA). The antiserum did not react with lipopolysaccharide of five gram negative bacteria including S. typhi. Vi PS from three different sources was tested, and all but one of 18 native Vi PS preparations had EIA values comparable to a standard Vi PS preparation. The sensitivity of the EIA for the detection of O-acetyl groups on Vi PS was compared to an NMR spectroscopy assay (Biologicals 28 (2000) 17-24). The EIA distinguished between O-acetylated and de-O-acetylated Vi PS preparations. However, significantly lower EIA reactivity was observed only for samples which had O-acetylation levels of 25% or less. This assay should facilitate batch control of Vi vaccines.

Acetylation↗
PubMed2004

Ocular findings in Jacobsen syndrome.

PURPOSE: To discuss the ophthalmic findings and their clinical significance in 10 new cases of Jacobsen syndrome (mental retardation, craniofacial anomalies, congenital heart defects, and blood dyscrasias) and to review the ophthalmic findings in all previously reported cases in the literature. METHODS: Ten new cases of Jacobsen syndrome were collected and studied prospectively for detection of abnormal ophthalmologic examination findings. A total of 63 previously reported cases were identified from Medline and analyzed for ophthalmologic abnormalities. RESULTS: The most common ophthalmologic findings in the new cases of Jacobsen syndrome included strabismus (90.0%), refractive error (90.0%), and ptosis (70.0%). Facial dysmorphism was also common and included hypertelorism, epicanthal folds, and down-slanting palpebral fissures. Uncommon ophthalmic findings included 5 patients with retinal vascular tortuosity, 1 with glaucoma, and 3 with amblyopia. In 63 cases reviewed, 36 reported ophthalmologic abnormalities. The most common findings included facial anomalies and ptosis. Only 5 of the 63 patients had evidence of strabismus, and none were reported to have retinal vascular tortuosity. CONCLUSIONS: To prevent unnecessary vision loss in children with Jacobsen syndrome, proper screening for amblyogenic factors is imperative. We recommend a baseline complete ophthalmologic examination with subsequent follow-up examinations depending on the particular findings noted during the initial screening visit.

Adult↗
PubMed2004

Glycoinositolphospholipid from Trypanosoma cruzi: structure, biosynthesis and immunobiology.

The pathogenic protozoan parasite Trypanosoma cruzi expresses on its surface an unusual family of glycoinositolphospholipids (GIPLs) closely related to glycosylphosphatidylinositol (GPI) anchors. Different parasite isolates express distinct GIPLs which fall into two series, depending on the substitution of the third mannosyl residue in the conserved glycan sequence Man4-(AEP)-GlcN-InsPO4 by ethanolamine phosphate or beta-galactofuranose. Although the exact role of these molecules in the cell biology and pathogenicity of T. cruzi remains unknown, the lipid and glycan moieties impart distinct responses to host T and B lymphocytes and phagocytes, overall favouring an immune response permissive to the parasite. The biosynsthesis of GIPLs follows a pathway similar to that observed for GPI anchors. However, a more detailed understanding might enable the development of specific inhibitors of parasite-specific enzymes and lead to novel drugs to ameliorate Chagas disease.

Animals↗
PubMed2004

Control and lot release of meningococcal group C conjugate vaccines.

Meningococcal group C conjugate vaccines were first introduced to the UK in 1999. To date, the vaccines have been demonstrated to have an efficacy of approximately 90% and have since been adopted by other countries worldwide. The development of control tests used for lot release of meningococcal group C vaccines has been based on those used for Haemophilus influenzae type b conjugates, the key criteria being measurement of free saccharide and conjugate integrity by physicochemical means. In future, meningococcal group C vaccines are likely to be replaced by multivalent formulations containing different components in combination. This will present a new challenge for regulatory authorities and more extensive testing will be required to ensure vaccine safety and efficacy.

Aluminum Compounds↗
PubMed2003

Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia.

Autosomal recessive hypercholesterolemia (ARH) is a genetic form of hypercholesterolemia that clinically resembles familial hypercholesterolemia (FH). As in FH, the rate of clearance of circulating low density lipoprotein (LDL) by the LDL receptor (LDLR) in the liver is markedly reduced in ARH. Unlike FH, LDL uptake in cultured fibroblasts from ARH patients is normal or only slightly impaired. The gene defective in ARH encodes a putative adaptor protein that has been implicated in linking the LDLR to the endocytic machinery. To determine the role of ARH in the liver, ARH-deficient mice were developed. Plasma levels of LDL-cholesterol were elevated in the chow-fed Arh-/- mice (83 +/- 8 mg/dl versus 68 +/- 8 mg/dl) but were lower than those of mice expressing no LDLR (Ldlr-/-) (197 +/- 8 mg/dl). Cholesterol feeding elevated plasma cholesterol levels in both strains. The fractional clearance rate of radiolabeled LDL was reduced to similar levels in the Arh-/- and Ldlr-/- mice, whereas the rate of removal of alpha2-macroglobulin by the LDLR-related protein, which also interacts with ARH, was unchanged. Immunolocalization studies revealed that a much greater proportion of immunodetectable LDLR, but not LDLR-related protein, was present on the sinusoidal surface of hepatocytes in the Arh-/- mice. Taken together, these results are consistent with ARH playing a critical and specific role in LDLR endocytosis in the liver.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Structural analysis of the Lactobacillus rhamnosus strain KL37C exopolysaccharide.

The exopolysaccharide from the lactic acid bacterium Lactobacillus rhamnosus strain KL37C isolated from human intestinal flora was prepared by sonication of bacterial cell mass suspended in water followed by centrifugation and cold ethanol precipitation of the supernatant. The polysaccharide material was purified by gel permeation chromatography on an TSK HW-50 column and characterised using chemical and enzymatic methods. On the basis of sugar and methylation analysis and 1H, 13C, 1D and 2D NMR spectroscopy the exopolysaccharide was shown to be composed of the following pentasaccharide repeating unit:-->3)-alpha-D-Glcp-(1-->2)-beta-D-Galf-(1-->6)-alpha-D-Galp-(1-->6)-alpha-D-Glcp-(1-->3)-beta-D-Galf-(1-->

Carbohydrate Sequence↗
PubMed2003

Can medical hypnosis accelerate post-surgical wound healing? Results of a clinical trial.

Although medical hypnosis has a long history of myriad functional applications (pain reduction, procedural preparation etc.), it has been little tested for site-specific effects on physical healing per se. In this randomized controlled trial, we compared the relative efficacy of an adjunctive hypnotic intervention, supportive attention, and usual care only on early post-surgical wound healing. Eighteen healthy women presenting consecutively for medically recommended reduction mammaplasty at an ambulatory surgery practice underwent the same surgical protocol and postoperative care following preoperative randomization (n = 6 each) to one of the three treatment conditions: usual care, 8 adjunctive supportive attention sessions, or 8 adjunctive hypnosis sessions targeting accelerated wound healing. The primary outcome data of interest were objective, observational measures of incision healing made at 1,7 weeks postoperatively by medical staff blind to the participants' group assignments. Data included clinical exams and digitized photographs that were scored using a wound assessment inventory (WAI). Secondary outcome measures included the participants' subjectively rated pain, perceived incision healing (VAS Scales), and baseline and post-surgical functional health status (SF-36). Analysis of variance showed the hypnosis group's objectively observed wound healing to be significantly greater than the other two groups', p < .001, through 7 postoperative weeks; standard care controls showed the smallest degree of healing. In addition, at both the 1 and 7 week post-surgical observation intervals, one-way analyses showed the hypnosis group to be significantly more healed than the usual care controls, p < 0.02. The mean scores of the subjective assessments of postoperative pain, incision healing and functional recovery trended similarly. Results of this preliminary trial indicate that use of a targeted hypnotic intervention can accelerate postoperative wound healing and suggest that further tests of using hypnosis to augment physical healing are warranted.

Adult↗
PubMed2003

The mediating effects of effort upon the relationship between head injury severity and cognitive functioning.

PRIMARY OBJECTIVE: Given that poor effort may have a profound impact upon the results of neuropsychological assessment, it is of critical importance that assessment of effort is incorporated into the interpretation of a patient's neuropsychological profile. The current study examines the relationship between head injury severity (as measured by length of post-traumatic amnesia) and level of cognitive functioning in patients passing or failing a test of effort (Test of Malingered Memory). RESEARCH DESIGN: A cross-sectional correlational design was employed in a consecutive cohort of 78 persons with ongoing compensation claims. METHODS AND PROCEDURES: Head injury severity was assessed by duration of post-traumatic amnesia. All participants received a clinical interview followed by neuropsychological assessment. MAIN OUTCOMES AND RESULTS: A systematic and interpretable negative correlation between head injury severity and intellectual and memory functioning was demonstrated in persons passing the test of effort. However, in persons failing the test of effort no such relationships were demonstrated. CONCLUSIONS: The implications for the interpretation of neuropsychological test data are discussed. It is strongly recommend that valid interpretation of neuropsychological assessment data should include consideration of at least one test of effort.

Adolescent↗
PubMed2003

Paris-Trousseau syndrome : clinical, hematological, molecular data of ten new cases.

Paris-Trousseau syndrome (PTS) is an inherited disorder characterized by mild hemorragic tendency associated with 11q chromosome deletion. Here we report ten new patients (5 boys, 5 girls) with complete clinical history, biological data, ultra-structural and molecular investigations. Thrombocytopenia is chronic in all the patients except two boys in whom it disappeared during the two first years of life. On Romanovsky stained peripheral blood smears, abnormal platelets with giant granules were detected in all the children and confirmed by electron microscopy (EM). On bone marrow smears, dysmegakaryopoiesis with many micromegakaryocytes was constantly observed. Abnormal alpha-granules were virtually absent from bone marrow and cultured megakaryocytes, while EM detected numerous images of granule fusion within blood platelets. Molecular analyses evidenced that the fli-1 gene is deleted in all the patients except one confirming the crucial role of the transcription factor FLI-1 in megakaryopoiesis. In summary, this study documents ten new cases of PTS with characteristic alpha-granule abnormalities, and shows the putative pathogenic role of fli-1 gene in the pathophysiology of this syndrome.

Blood Platelet Disorders↗