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Biomedical subjects

D Bailey

Publications and source records attributed to D Bailey.

At least 37 records · Page 2Linked to original sources

Metastatic neuroendocrine tumor presenting as spinal cord compression--a case report and brief comment.

Gastrointestinal neuroendocrine tumors are derived from the diffuse neuroendocrine system of the gastrointestinal tract which is composed of amine and acid producing cells with different hormonal profiles, depending on the site of origin. The tumors they produce can be divided into carcinoid tumors and pancreatic endocrine tumors. We believe this to be only the fourth case in the literature of a patient presenting with cord compression as a result of a metastatic neuroendocrine tumor (MEDLINE 1966-2000).

Aged↗

Association of beta 1 integrin with focal adhesion kinase and paxillin in differentiating Schwann cells.

Schwann cells (SCs) differentiate into a myelinating cell when simultaneously adhering to an axon destined for myelination and basal lamina. We are interested in defining the signaling pathway activated by basal lamina. Using SC/sensory neuron (N) cocultures, we identified beta1 integrin and F-actin as components of a pathway leading to myelin gene expression and myelination (Fernandez-Valle et al., 1994, 1997). Here, we show that focal adhesion kinase (FAK) and paxillin are constitutively expressed by SCs contacting axons in the absence of basal lamina. Tyrosine phosphorylation of FAK and paxillin increases as SCs form basal lamina and differentiate. FAK and paxillin specifically coimmunoprecipitate with beta1 integrin in differentiating SC/N cocultures but not SC-only cultures. Paxillin coimmunoprecipitates with FAK and fyn kinase in differentiating SC/N cocultures. A subset of tyrosine-phosphorylated beta1 integrin, FAK, and paxillin molecules reside in the insoluble, F-actin-rich fraction of differentiating cocultures. Cytochalasin D, an actin depolymerizing agent, decreases tyrosine phosphorylation of FAK and paxillin and their association with beta1 integrin and causes a dose-dependent increase in the abundance of insoluble FAK and paxillin complexes. Collectively, our work indicates that beta1 integrin, FAK, paxillin, and fyn kinase form an actin-associated complex in SCs adhering to basal lamina in the presence of axons. This complex may be important for initiating the process of SC differentiation into a myelinating cell.

Animals↗

Conformational studies of the glycopeptide Ac-Tyr-[Man5GlcNAc-beta-(1-->4)GlcNAc-beta-(1-->Ndelta)]-Asn-Leu-Thr-Se r-OBz and the constituent peptide and oligosaccharide.

Glycopeptides of desired structure can be conveniently prepared by the coupling of reducing oligosaccharides to aspartic acid of peptides via their glycosylamines formed in the presence of saturated aqueous ammonium hydrogen carbonate. The resulting oligosaccharide chains are N-linked to asparagine as in natural glycoproteins, allowing different peptide oligosaccharide combinations to be analysed for conformational effects. In the present paper, a pentapeptide of ovalbumin was coupled to Man5GlcNAc2 oligosaccharide and the glycopeptide and the two parent compounds compared by NMR ROESY experiments and molecular dynamics simulations. Despite the small size of the peptide, conformational effects were observed suggestive of the oligosaccharide stabilising the peptide in solution and of the peptide influencing oligosaccharide conformation. These effects are relevant to the function of glycosylation and the enzymic processing of oligosaccharide chains.

Carbohydrate Conformation↗

Performance and standards for the process of head and neck cancer care: South and West audit of head and neck cancer 1996-1997 (SWAHN I). South and West Regional Cancer Organisation Tumour Panel for Head and Neck Cancer.

Evidence suggests wide variation in cancer care between different hospitals in the UK. To establish bench-marking data, we designed a prospective, 1 year regional study comparing key performance measures with established standards for the 28 hospital Trusts in the South and West of England involved in head and neck cancer care. 566 sequential patients with a newly-diagnosed head and neck cancer were included. Numbers referred and treated per hospital Trust were 1-58 and 1-65 respectively. 59% of patients received a pretreatment chest X-ray (standard 95%). 45% of patients were seen in a multidisciplinary clinic pretreatment (standard 95%), and this was proportional to the frequency of clinics held (P<0.0001). Median number of cases treated per surgeon was 4 (1-26), and by radiotherapist was 10 (1-51). Times between parts of the process of oral cancer care were closer to the standards than those for laryngeal cancer. Two patients were entered into a clinical trial. One had a quality-of-life score. Thus, in 1996-1997, in the South and West of England, there were major discrepancies between actual performance and established standards in many fundamental aspects of head and neck cancer care. Re-audit is essential to determine if the implementation of the Calman-Hine report has resulted in improvements.

Female↗

Real-time transmission of full-motion echocardiography over a high-speed data network: impact of data rate and network quality of service.

UNLABELLED: With high-resolution network transmission required for telemedicine, education, and guided-image acquisition, the impact of errors and transmission rates on image quality needs evaluation. METHODS: We transmitted clinical echocardiograms from 2 National Aeronautics and Space Administration (NASA) research centers with the use of Motion Picture Expert Group-2 (MPEG-2) encoding and asynchronous transmission mode (ATM) network protocol over the NASA Research and Education Network. Data rates and network quality (cell losses [CLR], errors [CER], and delay variability [CVD]) were altered and image quality was judged. RESULTS: At speeds of 3 to 5 megabits per second (Mbps), digital images were superior to those on videotape; at 2 Mbps, images were equivalent. Increasing CLR caused occasional, brief pauses. Extreme CER and CDV increases still yielded high-quality images. CONCLUSIONS: Real-time echocardiographic acquisition, guidance, and transmission is feasible with the use of MPEG-2 and ATM with broadcast quality seen above 3 Mbps, even with severe network quality degradation. These techniques can be applied to telemedicine and used for planned echocardiography aboard the International Space Station.

Artifacts↗

Glycosylation of immunoglobulin light chains associated with amyloidosis.

AL amyloidosis is a fatal disease caused by deposition of immunoglobulin light chains in a fibrillarforin (AL) in various organs. By searching the Kabat database of immunoglobulin sequences using the KabatMan software, we have shown that there is a preponderance of the consensus glycosylation sequon (AsnXxxSer/Thr) in the framework regions of amyloid light chains. We have characterised by computer graphics simulations, NMR spectroscopy and carbohydrate biochemistry the structure and conformation of the oligosaccharide from amyloid protein AL MS (lamba1) and from the amyloid associated Bence Jones protein of patient MH (kappa1). These proteins have glycosylation in the hypervariable complementarity-determining region versus framework region, respectively. Both contained a 2-6 sialylated core fucosylated biantennary chain mostly with bisecting GIcNAc. Together our results suggest that light chain glycosylation may be one of several modifications which may render the protein more prone to amyloid formation.

Amino Acid Sequence↗

Patterns of shaker family gene expression in single identified neurons of the American lobster, Homarus americanus.

The patterns of expression of voltage gated potassium channel genes of the Shaker family have been mapped in identified neurons of the lobster (Homarus americanus) ventral nerve cord using a single cell reverse transcriptase polymerase chain reaction procedure. Using specific oligonucleotides derived from the sequences of the shaker, shab, and shaw genes of the spiny lobster, Panulirus interruptus, we detected the corresponding potassium channel DNA fragments from Homarus americanus. The Homarus DNA fragments are 87-98% identical at the nucleotide level to the Panulirus DNA fragments. We used the Panulirus primers to measure the complement of RNAs for shaker, shab, and shaw in single identified cells that use GABA, glutamate, octopamine or serotonin as chemical messengers. Shaker and shaw RNAs were found in all four identified neuron types but shab RNA was not detected in serotonin cells under the present experimental conditions. All cells expressed alpha-tubulin RNA, which serves as an internal control suggesting that cells are intact after dissection. In glial cells that surround the neuronal cell bodies, the potassium channel genes are expressed at low to non-detectable levels.

Animals↗

Cushing's syndrome associated with a chemodectoma and a carcinoid tumour.

We present a case of Cushing's syndrome where 111In-octreotide scanning provided evidence for the presence of two neuroendocrine tumours. Uptake in the right neck corresponded to a chemodectoma, but there was no change in the clinical condition or fall in ACTH levels following surgical resection. Uptake in the left chest was assumed to relate to a bronchial carcinoid, but a tumour could not initially be localized on magnetic resonance imaging (MRI), spiral CT scanning or on selective venous sampling. A 1 cm bronchial carcinoid tumour was identified post-mortem which immunostained for ACTH. This case demonstrates that 111ln-octreotide scanning is a useful technique for identifying the source of ectopic ACTH production in difficult cases of Cushing's syndrome. Reliance should not be placed solely on standard imaging techniques to localize the tumour prior to surgery. Although rare, the possibility of a non-ACTH secreting neuroendocrine tumour should also be considered in patients with ectopic ACTH syndrome, who have positive 111In-octreotide scans.

Adult↗

Dorsal thoracic cord compression from a spinal angiolipoma: case report and brief comment.

Angiolipomas are benign tumors usually found in the forearms of young adults. To the best of our knowledge only 63 cases of spinal angiolipomas have been reported in the literature up until 1999 (MEDLINE 1966-1999). We report a case of a spinal angiolipoma causing dorsal cord compression in a 44-year-old woman presenting with subacute lower limb paresthesias, in the absence of sensory or motor findings, which mimicked multiple sclerosis by history. Operative intervention was curative.

Adult↗

A tyrosine-phosphorylated protein that binds to an important regulatory region on the cool family of p21-activated kinase-binding proteins.

The p21-activated kinases (Pak) are major targets of the small GTPases Cdc42 and Rac. We, and others, recently identified a family of proteins termed Cool/Pix, which interact with Pak3. In cells, p50(Cool-1) suppresses Pak activation by upstream activators; p85(Cool-1) has a permissive effect on Pak activation, and we now show that the closely related Cool-2 stimulates Pak kinase activity. To understand the differential regulation of Pak by Cool proteins, we screened for Cool-interacting proteins by affinity purification and microsequencing. This has led to the identification of two closely related proteins called Cat (Cool-associated, tyrosine phosphorylated), which contain a zinc finger followed by three ankyrin repeats. Cat-1 is identical to the recently identified binding partner for the beta-adrenergic receptor kinase (betaARK or GRK-2), which was shown to have Arf-GAP activity. Cat-1 and Cat-2 both bind to the COOH-terminal region of p85(Cool-1) and p85(Cool-2) but do not bind to p50(Cool-1). Cat-1 is tyrosine-phosphorylated in growing NIH 3T3 fibroblasts, and its tyrosine phosphorylation is increased following cell spreading on fibronectin, decreased in cells arrested in mitosis, and increased in the ensuing G(1) phase. Cat proteins are tyrosine-phosphorylated when co-expressed in cells with the focal adhesion kinase Fak and Src. These findings suggest that in addition to playing a role in Cool/Pak interactions, Cat proteins may serve as points of convergence between G protein-coupled receptors, integrins, Arf GTPases, cell cycle regulators, and Cdc42/Rac/Pak signaling pathways.

Adaptor Proteins, Signal Transducing↗

Chromosomal deletions occur in restricted regions of 5q in testicular germ cell cancer.

Since the biologic behavior and molecular genetic changes observed in testicular germ cell cancer differ from those seen in more common epithelial tumors, it is likely that hitherto uncharacterized genes play a role in the development of germ cell tumors. Our previous work on testicular germ cell cancer suggested that chromosome 5q might contain one or more novel tumor suppressor genes that play a role in this malignancy. In this study, we performed a high resolution loss of heterozygosity (LOH) study of testicular cancer using 37 informative markers on chromosome 5. We detected allelic losses in 20/48 (42%) specimens and identified three common sites of loss on chromosome 5q14, 5q21 and 5q34-qter, defined respectively by minimal regions of deletion of < or = 1 cM, 10 cM and approximately 20 (cM). Using an overlapping series of YACs and radiation hybrid mapping, we have constructed a physical map of the 5q14 deletion that should aid in the isolation and characterization of the putative tumor suppressor gene located therein.

Chromosome Deletion↗

Needle-in-a-haystack detection and identification of base substitution mutations in human tissues.

Background and induced germline mutagenesis and other genotoxicity studies have been hampered by the lack of a sufficiently sensitive technique for detecting mutations in a small cluster of cells or a single cell in a tissue sample composed of millions of cells. The most frequent type of genetic alteration is intragenic. The vast majority of oncogenic mutations in human and mammalian cancer involves only single base substitutions. We have developed universally applicable techniques that not only provide the necessary sensitivity and specificity for site specific mutagenesis studies, but also identify the point mutation. The exponential amplification procedures of polymerase chain reaction (PCR) and ligase chain reaction (LCR) have been combined with restriction endonuclease (RE) digestion to enable the selective enrichment and detection of single base substitution mutations in human oncogenic loci at a sensitivity of one mutant in more than 10(7) wild type alleles. These PCR/RE/LCR procedures have been successfully designed and used for codons 12 and 248 of the Ha-ras and p53 genes, respectively, both of which contain a natural MspI restriction endonuclease recognition sequence. These procedures have also been adapted for the detection and identification of mutations in oncogenic loci that do not contain a natural restriction endonuclease recognition sequence. Using PCR techniques, a HphI site was incorporated into the codons 12/13 region of the human N-ras gene, which was then used for the selective enrichment of mutants at this oncogenic locus. These PCR/RE/LCR procedures for base substitution mutations in codon 12 of the N-ras gene were found to have the sensitivity of detection of at least one mutant allele in the presence of the DNA equivalent of 10(6) wild type cells. Only one peripheral blood leukocyte DNA specimen out of nine normal individuals displayed an observable Ha-ras mutation that was present at frequency between 10(-5) and 10(-6). These PCR/RE/LCR techniques for detecting and identifying base substitution mutations are universally applicable to almost any locus or base site within the human or animal genome. With the added advantage of the adjustability of both the amount of DNA (number of genomes) to be tested and the sensitivity (10(-2) to 10(-7)) of the assay selection or enrichment procedures, these PCR/RE/LCR techniques will be useful in addressing a broad range of important questions in mutagenesis and carcinogenesis.

Base Sequence↗

Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours.

M2A antigen is an oncofetal antigen associated with germ cell neoplasia, present in testis on fetal gonocytes and re-expressed on carcinoma in situ (CIS) and germ cell tumours. We developed a panel of monoclonal antibodies (mAb), M2A (IgG2a), D1-26 (IgG2b) and D2-40 (IgG1), to this antigen in order to characterize its structure and study its distribution among germ cell tumours. M2A antigen was purified by sequential lectin and antibody affinity chromatography and characterized as a monomeric M, 40 000 surface sialoglycoprotein, extensively glycosylated with O-linked carbohydrate structures, but devoid of N-linked sugars. Terminal sialic acid residues were required for reactivity with mAb M2A and D1-26, but not D2-40. Sections of 69 testicular germ cell tumours, fixed in formalin and embedded in paraffin, were stained with mAb D2-40 to examine the distribution of M2A antigen. Uniform membrane staining was observed in seminomas, and focal staining in 69% of embryonal carcinomas, 29% of teratomas and 25% of yolk sac tumours. CIS in the vicinity of all germ cell tumours also displayed uniform membrane staining. The characterization of M2A antigen, and the development of mAb which react with it in conventionally preserved archival specimens, provide important initiatives to study the origin and progression of germ cell neoplasia.

Animals↗

Reversion of the differentiated phenotype and maturation block in Sertoli cells in pathological human testis.

To study the relationship between abnormal Sertoli cell differentiation and spermatogenic impairment, we examined the expression of Sertoli cell markers normally lost at puberty, cytokeratin 18 (CK18), anti-Müllerian hormone (AMH) and M2A antigen, in three children (aged 1-2 years), 50 adults (aged 19-45 years) with obstructive or non-obstructive azoospermia or oligozoospermia, and six patients (aged 1-18 years) with 5 alpha-reductase deficiency. There was CK18 and/or AMH expression, but never M2A antigen expression, associated with spermatogonial arrest or Sertoli cell-only (SCO) syndrome in infertile men. Loss of M2A antigen suggests the transition of Sertoli cells to an adult phenotype, while CK18 and/or AMH expression may be a manifestation of de-differentiation of Sertoli cells. In 5 alpha-reductase deficiency, there was a sequential loss of CK18, M2A antigen and AMH around puberty, associated with partial spermatogenesis. The persistence of immature Sertoli cells expressing M2A antigen was associated with prepubertal seminiferous cords and SCO syndrome. Therefore, 5 alpha-reductase deficiency may prevent the maturation of Sertoli cells, resulting in impairment of spermatogenesis, and loss of M2A antigen expression coincides with a critical step in the Sertoli cell maturation. High follicle stimulating hormone concentrations due to failure of normal Sertoli cell differentiation indicate a normal development pattern of the hypothalamic-pituitary-gonadal axis.

Adolescent↗

Ischemic colitis associated with pseudoephedrine: four cases.

OBJECTIVE: There is one previously reported case linking ischemic colitis and orally administered nasal decongestants containing pseudoephedrine (MEDLINE 1974-1998). We aimed to document an association between pseudoephedrine ingestion and ischemic colitis. METHODS: We reviewed the cases of four women (ages, 37-50 yr) who presented with the sudden onset of colicky abdominal pain followed by hematochezia. Three patients had used medicine containing pseudoephedrine daily for approximately 1 wk before admission. The fourth patient had used pseudoephedrine chronically for 6 months. Two patients had no significant past medical history. One woman had presented 6 months earlier with ischemic colitis while taking both pseudoephedrine and hormone replacement therapy. This time she presented with ischemic colitis while not taking hormone replacement therapy, but still taking decongestants. Another woman had a history of ulcerative colitis, which had been quiescent for 10 yr. One patient had been a smoker; however, like the other patients she had no evidence of systemic vascular disease. On colonoscopy, all four patients had colitis, primarily affecting the splenic flexure in the anatomical watershed area. Other causes of segmental colitis, including infectious colitides, pseudomembranous colitis, and Crohn's disease, were not evident. Colonoscopic biopsies were consistent with ischemic injury. RESULTS: All cases responded to abstinence from pseudoephedrine and medical supportive therapy. None has had a relapse since discontinuing the pseudoephedrine (8-12 months). CONCLUSIONS: The vasoconstrictive action of pseudoephedrine may predispose susceptible patients to develop ischemic colitis in the watershed area of the splenic flexure. Perimenopausal women may be especially susceptible because of irregular ovulation. This may result in relative vasoconstriction when estrogen levels are low or a hypercoagulable state when estrogen levels are excessive.

Adult↗

Identification of the cerebral loci processing human swallowing with H2(15)O PET activation.

Lesional and electrophysiological data implicate a role for the cerebral cortex in the initiation and modulation of human swallowing, and yet its functional neuroanatomy remains undefined. We therefore conducted a functional study of the cerebral loci processing human volitional swallowing with 15O-labeled water positron emission tomography (PET) activation imaging. Regional cerebral activation was investigated in 8 healthy right handed male volunteers with a randomized 12-scan paradigm of rest and water swallows (5 ml/bolus, continuous infusion) at increasing frequencies of 0.1, 0.2, and 0.3 Hz, which were visually cued and monitored with submental electromyogram (EMG). Group and individual linear covariate analyses were performed with SPM96. In five of eight subjects, the cortical motor representation of pharynx was subsequently mapped with transcranial magnetic stimulation (TMS) in a posthoc manner to substantiate findings of hemispheric differences in sensorimotor cortex activation seen with PET. During swallowing, group PET analysis identified increased regional cerebral blood flow (rCBF) (P < 0.001) within bilateral caudolateral sensorimotor cortex [Brodmann's area (BA) 3, 4, and 6], right anterior insula (BA 16), right orbitofrontal and temporopolar cortex (BA 11 and 38), left mesial premotor cortex (BA 6 and 24), left temporopolar cortex and amygdala (BA 38 and 34), left superiomedial cerebellum, and dorsal brain stem. Decreased rCBF (P < 0.001) was also observed within bilateral posterior parietal cortex (BA 7), right anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right prefrontal cortex (BA 9), and bilateral superiomedial temporal cortex (BA 41 and 42). Individual PET analysis revealed asymmetric representation within sensorimotor cortex in six of eight subjects, four lateralizing to right hemisphere and two to left hemisphere. TMS mapping in the five subjects identified condordant interhemisphere asymmetries in the motor representation for pharynx, consistent with the PET findings. We conclude that volitional swallowing recruits multiple cerebral regions, in particular sensorimotor cortex, insula, temporopolar cortex, cerebellum, and brain stem, the sensorimotor cortex displaying strong degrees of interhemispheric asymmetry, further substantiated with TMS. Such findings may help explain the variable nature of swallowing disorders after stroke and other focal lesions to the cerebral cortex.

Adult↗