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C Barnes

Publications and source records attributed to C Barnes.

At least 73 records · Page 4Linked to original sources
PubMed2000

Recent developments in the encoding and deconvolution of combinatorial libraries.

The value of molecular libraries generated by combinatorial methods is largely dependent on the ease and ability to deconvolute or decode the structure of compounds of interest after screening the library. Following the introduction of promising concepts in the early 1990s, there has been considerable progress in the development and refinement of methodologies to address this issue.

Combinatorial Chemistry Techniques↗
PubMed2000

Induction of immune tolerance and suppression of anaphylaxis in a child with haemophilia B by simple plasmapheresis and antigen exposure.

Anaphylaxis to factor IX (FIX) in patients with haemophilia B is a rare and life-threatening complication that has been reported to occur in association with the development of inhibitors to FIX. Management of these patients is difficult. This report presents an 18-month-old boy with a frame-shift mutation of the FIX gene and FIX coagulant level of <1% who developed anaphylactoid reactions to low and high purity plasma-derived FIX concentration infusions and an inhibitor measuring 1.0 BU mL(-1). The patient was managed with simple plasmapheresis, a short course of corticosteroids and high-dose antigen exposure, which successfully induced long-lasting immune tolerance to FIX concentrates.

Anaphylaxis↗
PubMed2000

Paraganglioma of the external auditory canal: an unusual case.

Primary paraganglioma of the external auditory canal is a rare otological finding. To date, only three cases have been reported in the world-wide literature. Such a tumour is now described in a 42-year-old female. The clinical and histopathological features of the case are discussed. The role of immunocytochemistry in defining diagnosis, from a large list of differentials, is illustrated. We present the first magnetic resonance images of this rare tumour and highlight the benefit of intra-operative frozen section in limiting surgery to canal excision.

Adult↗
PubMed1999

Ocular adnexal lymphoma-comparison of MALT lymphoma with other histological types.

AIMS: To correlate histological features of ocular adnexal lymphoma using the revised European American lymphoma classification (REAL), with stage of disease at presentation, treatment modalities, and patient outcome. MALT lymphoma defines an extranodal marginal zone B cell lymphoma as outlined in the REAL classification. Comparison groups of patients included those with primary ocular adnexal MALT lymphoma versus primary ocular adnexal lymphomas of other types, MALT lymphoma versus non-MALT lymphomas (primary and secondary), and primary ocular adnexal lymphoma (MALT lymphomas and other types) versus secondary ocular adnexal lymphomas. METHODS: A retrospective review of the National Ophthalmic Pathology Laboratory records identified 20 cases of ocular adnexal lymphoma over a 10 year period which were reclassified using appropriate immunohistochemical stains. Patients' medical records were examined for data including stage of the disease at presentation, mode of treatment, and patient outcome. RESULTS: Among the 20 cases identified 14 had primary ocular adnexal lymphomas. 10 of the primary lymphomas had histological features of MALT lymphoma. One case was a primary ocular adnexal T cell lymphoma, one a follicular centre, follicular B cell lymphoma, and two were large cell B cell lymphomas. Six cases had systemic disease, four large B cell, one follicular centre, follicular B cell, and one mantle cell. A significantly higher proportion of patients with MALT lymphomas had early disease (p = 0.005), initially required local treatment (p = 0.005) and were alive at last follow up (p = 0.001) than those without. Two patients with MALT lymphoma had recurrence of lymphoma which responded to further treatment. CONCLUSIONS: Patients with primary ocular adnexal MALT lymphomas present with localised disease requiring local treatment and have a better outcome compared with patients with other types. As a small percentage of these tumours recur, patients should be followed up indefinitely.

Adult↗
PubMed1999

Infant pulmonary hemorrhage in a suburban home with water damage and mold (Stachybotrys atra).

The American Academy of Pediatrics recently issued guidelines regarding the potential toxic effect of indoor molds. We now report another case of an infant with pulmonary hemorrhage whose residential environmental assessment revealed the presence of the toxigenic mold Stachybotrys atra. We used a questionnaire to identify environmental factors that could predispose the home to fungal contamination. We collected air samples from multiple locations in the home that we felt would reflect areas of relevant exposure. Surface samples were collected with a piece of transparent tape for semiquantitative measurement of spores present. We classified spores into their respective genera based on shape, size, and color. We also measured mycotoxin levels. Air sampling revealed significantly elevated total spore counts in the patient's bedroom and in the attic. Aspergillus/Penicillium species were predominant. Stachybotrys spores were found in the air sampled in the patient's bedroom, as well as from surfaces sampled in the patient's closet and the attic ceiling. Additionally, a small patch of Stachybotrys-contaminated area in the closet ceiling was sent for mycotoxin analysis. This material proved to be highly toxigenic. As the link between the presence of Stachybotrys in the home and pulmonary hemorrhage in infants increases, further efforts should be made to educate physicians, health care providers, and new parents about the potential toxic effects of this mold.

Air Pollution, Indoor↗
PubMed1998

Monoclonal antibodies raised to paraffin wax embedded archival tissue; feasibility study of their potential to detect novel antigenic markers.

A study to determine the feasibility of using archival paraffin wax embedded tissue to generate monoclonal antibodies is described. Specifically, monoclonal antibodies were raised to paraffin wax embedded normal human kidney tissue to test the possibility of producing antibodies to such tissue samples prior to attempting generation of antibodies to valuable archival tissue. Multiple sections (10 x 5 microm) were pooled and dewaxed as for immunohistochemical procedures and combined with Freund's adjuvant for immunization of BALB/c mice in vivo. Immunized spleen cells were fused with SP2 myeloma cells and subsequent clones screened on paraffin wax embedded normal human kidney sections, a range of cell lines and normal mouse tissue. Supernatants from 11 wells (from a total of 90 wells screened) showed different staining patterns on sections of paraffin wax embedded kidney. One clone, 1/11C, (isotype IgG1) which exhibited strong staining on all kidney tubules by immunohistochemical studies (glomeruli interstitium and vessels were unstained) and identified a band at 52 kDa on immunoblots of dewaxed kidney tissue (as used for immunogen) was chosen for further characterization. Immunoblotting of five mammalian cell lines showed differential expression of this 52 kDa band (distinct expression on 3/5, weak expression on 2/5 cell lines) whereas, all cell lines displayed a band at 44 kDa and a third band at 70 kDa was observed on 2/5 cell lines. In mouse tissue extracts, the 52 kDa band was identified in kidney tissue only (not in the lung, liver or spleen) with the 44 kDa and 70 kDa bands weakly expressed in all tissues. This preliminary investigation of a novel approach to identifying possible new antigenic markers or producing monoclonal antibodies which react better to known antigens on sections of paraffin wax embedded tissue showed that this method is feasible. The need to have a comprehensive screening system in place and the ability to identify potentially useful clones after the initial screening is paramount due to the relative scarcity of screening material (archival tissue sections) and the tedious nature of the screening method.

Animals↗
PubMed1998

Simplified method for purification of colostrum to obtain secretory component of immunoglobulin A, using secretory component as a reference protein in tracheal aspirate fluid.

Many studies employ bronchoalveolar lavage fluid for assessment of biologically active substances secreted from the lung. However, investigators continue to search for a useful reference standard to correct for the inevitable but variable degree of dilution of this fluid. The glycoprotein, soluble secretory component of IgA, may serve as a valid reference protein. We report a simplified method for the purification of secretory component from colostrum. Soluble secretory component was isolated from human colostrum using serial centrifugation, size-exclusion fractionation and ion-exchange chromatography. Secretory component rich fractions were assayed by enzyme immunoassay. They were also evaluated for total amino acid content and distribution and sequence determination with satisfactory agreement with published results. We then demonstrated that soluble secretory component concentration in tracheal aspirate fluid did not correlate with either albumin or with total protein measured in the same samples. Therefore, we conclude that the secretory component of IgA serves as a useful reference marker because its use may avoid errors resulting from leakage of plasma proteins into epithelial lining fluid. Advantages of this method for establishing a standard for secretory component include ready availability of soluble secretory component, simplicity of the method and relative rapidity of the techniques.

Chemical Fractionation↗
PubMed1998

Cytotoxicity of substituted alkyl-3,4-bis(4-methoxyphenyl)pyrrole-2-carboxylates in L1210 lymphoid leukemia cells.

Two alkyl-3,4-bis(4-methoxyphenyl)pyrrole-2-carboxylates proved to be potent cytotoxic agents in the murine L1210 lymphoid leukemia screen. DNA synthesis was preferentially inhibited with the major target of the agents being de novo purine biosynthesis at the regulatory enzyme sites of PRPP-amido transferase and IMP dehydrogenase. Other enzymatic activities which were suppressed by the drugs were DNA polymerase alpha, RNA polymerases, ribonucleoside reductase and dihydrofolate reductase. The d[NTP] pools, nucleoside kinase and the pyrimidine pathway were not affected by the presence of drugs. The DNA molecule itself was not the target of the agents, i.e. no alkylation of nucleotide bases, intercalation between bases or cross-linking of DNA strands occurred. The agents did cause L1210 DNA fragmentation after 24 h incubation at 100 microM.

Animals↗
PubMed1998

Eight-epi-PGF2alpha: a possible marker of lipid peroxidation in term infants with severe pulmonary disease.

A prostaglandin F2-like compound, 8-epi-PGF2alpha, formed from oxidation of arachidonate, has been proposed as an indicator of lipid peroxidation. We determined whether tracheal aspirate or urinary 8-epi-PGF2alpha levels would differ over time or between infants in a control group and infants with severe respiratory failure. We correlated tracheal aspirate 8-epi-PGF2alpha levels with the fraction of inspired oxygen and with mean airway pressures at 24 and 48 hours of life. Levels in tracheal aspirates were in the range of 0 to 36 pg/microg of fSC of IgA and were higher in infants with severe pulmonary disorders compared with those in infants in the control group (p < 0.02). Urinary concentrations did not discriminate between sick infants and infants in the control group.

Biomarkers↗
PubMed1998

MDR1 expression is associated with adverse survival in melanoma of the uveal tract.

Metastatic uveal melanoma is profoundly chemoresistant and has a very poor outcome. We have previously shown that the MDR1 gene and its gene product P-glycoprotein (P-gp), which are known to cause drug resistance in cancer cells, are expressed in ocular melanoma. Overexpression of MDR1 has been associated with a poor survival in some tumor types treated by chemotherapy and in some untreated tumours. To assess whether MDR1 expression is of prognostic value in uveal melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108 cases. Three semiquantitative grades were used to evaluate positive staining. We detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade II staining; and 22%, grade III staining. There was a statistically significant association (P=.004) between MDR1 expression by tumor cells and shorter survival times (n=96), which was most striking at grade III levels of expression. Multivariate analysis showed that MDR1 expression is an independent prognostic indicator of poor survival. We conclude that (1) MDR1 may be involved in chemoresistance and tumor propagation in primary uveal melanoma, and (2) increasing levels of expression are prognostically significant and may prove a useful marker of tumor invasiveness, independent of established prognostic factors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Northern blot identification of mRNA containing sequence for protein allergen, Alt a1, in eight strains of Alternaria alternata.

BACKGROUND: Concentrations of Alt a1, a major allergen from Alternaria alternata extracts, exhibit significant batch-to-batch variability. This variability may result from basic strain-related genetic differences or from environmental influences such as growth conditions or extraction methods. OBJECTIVE: The objective of this work is to determine if strain-to-strain allergen variability in Alternaria alternata, Alt a1 allergen occurs at the nucleic acid level. METHODS: We compared the content of mRNA for a segment known to contain sequence coding for the reported N-termini of this allergen in eight strains of Alternaria obtained from three individual sources grown under identical conditions. RNA was extracted from rapidly growing mycelia and analyzed by northern blot analysis for the content of a specific segment containing sequence for the Alt a1 allergen. Blots were also analyzed for the content of a specific 5.8S rRNA segment. RESULTS: The size of the mRNA for this protein was about 700 bases. Sequence for the specific segment was found in all of the eight strains tested. When normalized for extraction variabilities using the content of 5.8S rRNA, the calculated concentrations of Alt a1 mRNA of seven of the eight strains were similar. CONCLUSIONS: The results of these experiments suggest that this Alt a1 related allergen sequence is found in many strains of Alternaria and that variabilities in allergen protein content noted previously result from posttranslational events.

Allergens↗
PubMed1998

Monoclonal antibody-based assay for Alt a1, a major Alternaria allergen.

BACKGROUND: Allergenic materials from Alternaria are significant causes of human disease. One 31-kD glycoprotein, designated Alt a1, has been described previously as being a significant allergen. OBJECTIVES: The purpose of this study is to characterize purified Alt a1 and to provide a method for measuring it in laboratory and environmental samples. METHODS: Monoclonal antibodies directed to the purified allergen were produced and used to construct a double monoclonal assay for Alt a1. The purified allergen detected by this assay was tested for IgE binding in vitro and in vivo. RESULTS: Purified allergen detected by this assay was shown to bind IgE from patients sensitive to Alternaria and gave a positive skin test in 15 of 16 patients skin test reactive to commercial Alternaria extracts. The assay is sensitive to Alt a1 concentrations as low as 0.2 microg/nmL and is very specific for the allergen. The three commercial Alternaria extracts assayed contained measurable quantities of the allergen varying from 12 to 84 microg/mL. CONCLUSIONS: Alt a1 is a significant Alternaria allergen. The ability to measure this allergen may assist in standardizing Alternaria extracts and lead to an understanding of the significance of exposure to this allergen.

Allergens↗
PubMed1998

Semi-quantitation of urokinase plasminogen activator and its receptor in breast carcinomas by immunocytochemistry.

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA acts in vivo by binding to a membrane receptor known as uPAR. In this study, uPA and uPAR levels were semiquantitated by immunocytochemistry in 36 primary breast carcinomas. Using monoclonal antibody HD-UK 1, uPA was detected both in stromal and in malignant cells. However, the predominant location was in the stromal cells. Using double-staining, cells containing uPA were also found to coexpress either cytokeratin (an epithelial cell marker) or more frequently KP1 (a macrophage/monocyte cell marker). With monoclonal antibody HD-uPAR 13.1, uPAR was localized principally to spindle- or macrophage-like stromal cells, especially when these cells surrounded invasive breast cancer. In contrast, uPAR was only rarely detected in cancer cells and was not detected in normal epithelia surrounding tumour or in areas of adenosis. uPA levels in both stromal and epithelial cells were significantly correlated with those for uPAR. We conclude that both uPA and its receptor are mostly present in stromal cells in invasive breast carcinomas. These results suggest that stromal cells collaborate with malignant cells to mediate metastasis.

Antibodies, Monoclonal↗
PubMed1998

Recommendations for education and training of genetic nurses and counsellors in the United Kingdom.

Genetic nurses and counsellors work as part of the professional team providing clinical genetic services from regional centres in the United Kingdom. The education and training needs of genetic nurses and counsellors have not previously been formally identified. The guidelines presented have been devised to equip practitioners to fulfil their professional role as defined in a previous study, by identifying objectives, educational pathways, and means of assessment. While academic courses provide an essential framework, experiential learning in a clinical setting is also considered a vital component of the preparation for practice.

Education, Graduate↗
PubMed1998

Connected and separate selves: development of an inventory and initial validation.

We describe the development and validation of the Relationship Self Inventory (RSI), which assesses 2 general self-orientations, (a) the Separate Self (SS) and (b) the Connected Self (CS), as well as two manifestations of connection, (a) Primacy of Other Care and (b) Self and Other Care. The CS reflects the importance of interconnectedness with others and a "voice of caring," whereas the SS reflects autonomy, independence, and a "voice of justice." Adequate reliability was demonstrated for the RSI on samples consisting of 927 women and 218 men ranging in age from 26 to 78. Construct validity of the RSI was also explored in a subsample (n = 604) by comparing its scales with measures of personality, temperament, and psychological adjustment. Although mean scores of men and women differed minimally on the CS and SS scales, gender differences in patterns of correlation with validity measures suggested that the meanings of the scales differed for men and women. The RSI appears to be an adequate survey tool for assessing these self-orientations.

Adaptation, Psychological↗
PubMed1997

Effects of antidepressant treatment on corticotropin-induced cortisol responses in patients with melancholic depression.

To date, there appears to be no consensus of opinion as to whether the adrenal glands are hyperresponsive during depression and, if so, whether this a state-dependent phenomenon. We aimed to determine the effects of antidepressant treatment on ACTH-induced cortisol responses in patients with melancholic depression. Seven female patients with DSM-III-R major depressive disorder, non-psychotic, melancholic subtype, were evaluated using the following rating scales: the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale and the Newcastle Endogenicity Scale. All subjects were then given an intravenous bolus dose (250 micrograms) of tetracosactrin, a potent stimulus of adrenocortical hormone secretion. Plasma levels of cortisol were measured at times 0, + 30, + 60, + 90, + 120 and + 180 min. Patients were then randomised to receive either 50 mg of sertraline or 20 mg of paroxetine (both of which are selective serotonin re-uptake inhibitors) and were re-tested while medication-free. Treatment resulted in a significant decrease in delta (the difference between the baseline values and the maximum increase post-ACTH administration) cortisol values of 1633.3 +/- 378.5 nmol/l vs. 595.1 +/- 207.7 nmol/l. Successful pharmacological treatment of major depressive disorder appears to be associated with a reduction in ACTH-induced cortisol release in drug-free patients.

Adult↗