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Biomedical subjects

J Colby

Publications and source records attributed to J Colby.

At least 19 recordsLinked to original sources

Special problems of children with myalgic encephalomyelitis/chronic fatigue syndrome and the enteroviral link.

Since 1997, it has been known that myalgic encephalomyelitis/chronic fatigue syndrome constitutes the biggest cause of long-term sickness leading to absence from school, in both staff and pupils. The scale of the problem in children is substantial, and the pattern of illness in schools suggests a prominent role for viral infection--for example, the clustering of cases. The Dowsett-Colby study of 1997, researching long-term sickness, reported on a school roll of 333,024 pupils and 27,327 staff, and found a prevalence of long-term sickness in 70 of 100,000 pupils and 500 of 100,000 staff; 39% of cases were in clusters of three or more. The peak age was 14-16 years. The illness is known to be potentially severe and chronic. In addition, the Tymes Trust has reported that many affected children struggle for recognition of their needs, and are bullied by medical and educational professionals. Children should have time to recover sufficiently before returning to school; sustainable, energy-efficient and often home-based education is important here to fulfil legal obligations. Research is needed on viruses that trigger childhood myalgic encephalomyelitis--for example, enteroviruses--and on the neurocognitive defects caused by myalgic encephalomyelitis. We should recognise the value of previous biological research and records of outbreaks, and I recommend that myalgic encephalomyelitis be made notifiable owing to the encephalitic nature of the effects commonly reported in this illness.

Adolescent↗

Association of calnexin with mutant peripheral myelin protein-22 ex vivo: a basis for "gain-of-function" ER diseases.

Schwann cell-derived peripheral myelin protein-22 (PMP-22) when mutated or overexpressed causes heritable neuropathies with a previously unexplained "gain-of-function" endoplasmic reticulum (ER) retention phenotype. In wild-type sciatic nerves, PMP-22 associates in a specific, transient (t(1/2 ) approximately equal to 11 min), and oligosaccharide processing-dependent manner with the lectin chaperone calnexin (CNX), but not calreticulin nor BiP. In Trembler-J (Tr-J) sciatic nerves, prolonged association of mutant PMP-22 with CNX is found (t(1/2) > 60 min). In 293A cells overexpressing PMP-22(Tr-J), CNX and PMP-22 colocalize in large intracellular structures identified at the electron microscopy level as myelin-like figures with CNX localization in the structures dependent on PMP-22 glucosylation. Similar intracellular myelin-like figures were also present in Schwann cells of sciatic nerves from homozygous Trembler-J mice with no detectable activation of the stress response pathway as deduced from BiP and CHOP expression. Sequestration of CNX in intracellular myelin-like figures may be relevant to the autosomal dominant Charcot-Marie-Tooth-related neuropathies.

Animals↗

Cloning, purification and characterization of the 6-phospho-3-hexulose isomerase YckF from Bacillus subtilis.

The enzyme 6-phospho-3-hexulose isomerase (YckF) from Bacillus subtilis has been prepared and crystallized in a form suitable for X-ray crystallographic analysis. Crystals were grown by the hanging-drop method at 291 K using polyethylene glycol 2000 monomethylether as precipitant. They diffract beyond 1.7 A using an in-house Cu Kalpha source and belong to either space group P6(5)22 or P6(1)22, with unit-cell parameters a = b = 72.4, c = 241.2 A, and have two molecules of YckF in the asymmetric unit.

Aldose-Ketose Isomerases↗

PMP22 carrying the trembler or trembler-J mutation is intracellularly retained in myelinating Schwann cells.

Missense mutations in the murine peripheral myelin protein-22 gene (Pmp22) underly the neuropathies in the trembler (Tr) and trembler-J (Tr-J) mice and in some humans with Charcot-Marie-Tooth disease. We have generated replication-defective adenoviruses containing epitope-tagged, wild-type-, Tr-, or Tr-J-PMP22 bicistronic with the Lac-Z reporter gene. These viruses were microinjected into the sciatic nerves of 10-day-old Sprague-Dawley rats and, later, analyzed by immunohistochemistry to determine the distribution of mutant protein in infected myelinating Schwann cells. We found that epitope-tagged, wild-type PMP22 is successfully transported to compact myelin, whereas the Tr and the Tr-J mutant proteins are retained in cytoplasmic compartment, colocalizing with the endoplasmic reticulum. These results provide in vivo evidence that the pathogenesis of the Tr and Tr-J mutations are most likely a function of abnormal retention within the endoplasmic reticulum of myelinating Schwann cells.

Adenoviridae↗

The anatomy and cell biology of peripheral myelin protein-22.

The gain of function phenotypes exhibited by the heterozygous Tr, Tr-J, and CMT1A mutations indicate that these mutations interfere with more than the function of a single PMP22 allele. The identification of proteins that interact with PMP22 and that are sensitive both to stoichiometry and the effects of the mutations could provide important leads to a unified hypothesis to explain the riddle of the PMP22-related neuropathies.

Animals↗

Florid angiogenesis in mucosa surrounding an ileal carcinoid tumor expressing transforming growth factor-alpha.

Carcinoid tumors of the gastrointestinal tract are known to be associated with fibrosis and vascular elastosis, either within the tumor or at distant sites. The current report describes prominent vascular proliferation in the villi extending 38 cm proximal and 15 cm distal to an ileal carcinoid tumor. These villi were expanded by vessels, producing a segmental carpet of multiple small polypoid protrusions around the tumor. Immunohistochemical analysis suggested that the major stromal components were of endothelial and myofibroblastic cell origin. The stroma of the tumor itself had minimal fibrosis and vascularity. To our knowledge, this is the first description of vascular proliferation in the vicinity but distinct from a carcinoid tumor. The demonstration of transforming growth factor-alpha (TGF-alpha) synthesis by tumor cells supports the possibility of a field effect by angiogenic factor(s) secreted by the tumor.

Actins↗

Breast carcinoma metastatic to the esophagus: clinicopathological and management features of four cases, and literature review.

Dysphagia due to esophageal metastases from primary breast carcinoma is an unusual entity. In this series of cases, we describe the clinical features of dysphagia due to metastatic esophageal lesions in four patients (with a primary diagnosis of breast cancer made 8-22 yr previously). We provide the first endoscopic ultrasound characterization of metastatic lesions to the esophagus from breast carcinoma. Endoscopic management of these strictures with both bougienage and balloon dilation techniques resulted in esophageal perforation in three of our four patients. We believe that endoscopic ultrasound is helpful in the diagnosis of metastatic breast cancer to the esophagus. However, endoscopic dilation of these strictures should be done gently and only after other treatment options have been carefully considered.

Aged↗

DNA sequence of the cut A, B and C genes, encoding the molybdenum containing hydroxylase carbon monoxide dehydrogenase, from Pseudomonas thermocarboxydovorans strain C2.

Pseudomonas thermocarboxydovorans strain C2 is capable of using carbon monoxide as the sole source of carbon and energy. The key enzyme for CO utilisation is the molybdenum containing iron-flavoprotein carbon monoxide dehydrogenase (CODH). This paper reports the DNA sequencing of a 4.7 kb region of the C2 genome which appears to encode the CODH enzyme. The genes for the three subunits of CODH, which we have named cut A, B and C, have been identified and they appear to form an operon. The predicted protein sequences of the three subunits have homology to the structurally related protein, xanthine dehydrogenase, from Drosophila melanogaster. By comparison with xanthine dehydrogenase it can be predicted that the molybdenum cofactor binds to the large subunit of CODH, the small subunit of CODH contains the iron-sulphur centers and the medium subunit binds FAD/NAD+.

Aldehyde Oxidoreductases↗

Cloning and expression of the carbon monoxide dehydrogenase genes from Pseudomonas thermocarboxydovorans strain C2.

Carbon monoxide dehydrogenase (CODH) from Pseudomonas thermocarboxydovorans strain C2 is composed of three non-identical subunits. A gene library of C2 DNA in lambda vector L47.1 was generated and screened using anti-CODH serum. Western blotting experiments revealed a protein which co-migrated with and had the same immunological reaction as the large subunit of CODH in some of the clones isolated from the library. The coding region was pinpointed to a 4 kb fragment which was subcloned into plasmid. Western blotting experiments showed that all three subunits of CODH were coded for by the subclone. However, no CODH activity was detected.

Aldehyde Oxidoreductases↗

Purification and characterization of D-2-haloacid dehalogenase from Pseudomonas putida strain AJ1/23.

A D-2-haloacid dehalogenase was isolated and purified to homogeneity from Pseudomonas putida strain AJ1/23. The enzyme catalysed the stereospecific dehalogenation of the D-isomer of 2-chloropropionate. Using a new ion-chromatograph assay, the enzyme was found to catalyse the dehalogenation of short-chain 2-halocarboxylic acids. Maximum enzyme activity occurred at pH 9.5 and 50 degrees C and the enzyme was insensitive to most -SH reagents. The enzyme has an Mr of about 135,000 and appears to be composed of four subunits of identical Mr.

Hydrocarbons, Chlorinated↗

CO oxidoreductase from Streptomyces strain G26 is a molybdenum hydroxylase.

CO oxidoreductase was purified to 95% homogeneity from crude mycelial extracts of Streptomyces G26. The purified preparation has a specific activity of 25.7 units/mg, a 13-fold improvement on crude soluble mycelial extracts. The native enzyme (Mr 282,000) is composed of non-identical subunits of Mr 110,000 and 33,000. It is a molybdenum hydroxylase containing 1.6 mol of FAD, 7.3 mol of Fe, 8.3 mol of acid-labile sulphide and 1.3 mol of Mo per mol of enzyme. Purified CO oxidoreductase catalyses the reduction of benzyl viologen, confirming the previously reported ability of this enzyme to interact with low-potential acceptors. Cytochrome c reduction cannot be accounted for entirely by non-enzymic reduction by superoxide radicals. NAD+ and NADP+ are not reduced, nor is clostridial ferredoxin.

Aldehyde Oxidoreductases↗

Biotechnological applications of carboxydotrophic bacteria.

Carbon monoxide (CO) is a widespread pollutant and a hazard to man because of its extremely toxic nature. It is a major component of some industrial gas mixtures and may be derived from coal. The carboxydotrophic bacteria obtain energy and carbon from the oxidation of CO. These organisms may be used to produce new metabolites, and the oxidases from them may be used to produce fuel cells and biosensors for CO.

Bacteria↗

A pharmacological investigation of the biphasic nature of the contractile response of rabbit and rat vas deferens to field stimulation.

It has been demonstrated previously with the vas deferens of the guinea-pig that the first and second phases of the contractile response to motor nerve stimulation are preferentially antagonized by the P2-purinoceptor antagonist arylazido aminopropionyl ATP (ANAPP3), and the alpha 1-adrenoceptor antagonist prazosin, respectively. We have now investigated the effect of the two antagonists on the biphasic contraction in the vas deferens of two other species; rabbit and rat. ANAPP3, in a concentration which antagonized responses to exogenously applied ATP but not those to exogenous norepinephrine, preferentially reduced the initial phasic response of the rabbit vas deferens to motor nerve stimulation without significantly reducing the secondary, tonic phase of the response. Prazosin had the opposite effect; antagonizing the response to norepinephrine but not to ATP and reducing the tonic response to motor nerve stimulation without significantly reducing the initial phasic response. Results obtained with the rat vas deferens were similar. The present results combined with previous findings suggest that ATP and norepinephrine act as cotransmitters in the vas deferens of several species.

Adenosine Triphosphate↗

Effect of intra-aortic balloon pumping on left ventricular function: evaluation by radionuclide ventriculography.

The purpose of this study was to evaluate the effect of intra-aortic balloon pumping (IABP) on left ventricular (LV) performance in ten patients (group I) with pump failure and in ten patients (group II) with angina pectoris. Left ventricular ejection fraction, regional ejection fraction, systolic chordal shortening and volumes were measured by first-pass radionuclide ventriculography using a computerized multicrystal gamma camera. Patients in group I had significantly lower ejection fractions, regional ejection fractions and systolic chordal shortening and larger end-diastolic and end-systolic volumes than patients in group II, both on (p greater than 0.0001) and off (p less than 0.004) IABP. With IABP, the ejection fraction increased by 0 +/- 0.5% in group I and 5.8 +/- 1.7% in group II (p = 0.004); the regional ejection fraction increased by 0.1 +/- 0.9% in group I and 10.3 +/- 2.1% in group II (p = 0.0004); the systolic chordal shortening increased by 1.1 +/- 0.6% in group I and 6.5 +/- 1.1% in group II (p = 0.0006); the end-diastolic volume decreased by -0.4 +/- 6% in group I and -14 +/- 4% in group II (p = 0.07); and the end-systolic volume decreased by -1 +/- 6% in group I and -21 +/- 5% in group II (p = 0.02). Thus, IABP results in improvement in left ventricular performance in patients with angina pectoris but not in patients with pump failure.

Aged↗

Similarity between women and men in manifestation of myocardial ischemia during exercise.

We assessed the effect of gender on the electrocardiographic changes and thallium-201 myocardial perfusion during exercise in patients with coronary artery disease. Eighty-nine patients with coronary artery disease (50% or greater diameter narrowing of one or more major coronary arteries) who had undergone exercise thallium scintigraphy were retrospectively studied. There were 29 women and 60 men. Fifty-six patients had one-vessel disease, 11 patients had two-vessel disease, and 22 patients had three-vessel disease or left main disease. The extent of coronary artery disease was assessed by the Gensini score. There was no difference between men and women in age, medications, number of diseased vessels and the coronary artery disease score. Exercise tolerance was lower, although insignificantly in women compared to men. However, exercise heart rate, double product, and the electrocardiographic response were similar in men and women. Also, both the presence and size of exercise-induced perfusion defects were similar in men and women. Thus, the electrocardiographic response to exercise is not influenced by gender in patients with similar extent of coronary artery disease and comparable manifestations of myocardial ischemia.

Cardiac Catheterization↗

Evidence for a contribution by purines to the neurogenic response of the guinea-pig urinary bladder.

In order to determine if ATP contributes as an excitatory transmitter in the guinea-pig bladder, experiments were conducted with ANAPP3, a photoaffinity analogue of ATP, which is an antagonist of adenine nucleotides in several other smooth muscles. With or without photoactivation with visible light, ANAPP3 antagonized contractile responses of in vitro strips of bladder to exogenous ATP. The antagonism was specific in that responses to acetylcholine and KCl were not affected by ANAPP3. Responses of strips of bladder to transmural electrical stimulation were not antagonized by ANAPP3 and were relatively insensitive to atropine. However, combined treatment with ANAPP3 and atropine produced a marked antagonism of the neurogenic response. In experiments with bladders obtained from animals pretreated with 6-hydroxydopamine, the ANAPP3-sensitive component of the neurogenic response was absent. These results suggest that acetylcholine, released from cholinergic nerves, and a purine, released from 6-hydroxy-dopamine-sensitive nerves, are both involved in motor transmission in this tissue.

Acetylcholine↗