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Biomedical subjects

J M Cox

Publications and source records attributed to J M Cox.

At least 19 recordsLinked to original sources

The growth, properties and interactions of yeasts and bacteria associated with the maturation of Camembert and blue-veined cheeses.

The growth of yeasts and bacteria were monitored during the maturation of Camembert and blue-veined cheese produced in Australia. Yeasts were prominent throughout maturation, growing to 10(5)-10(9)/g, depending on the manufacturer. Debaryomyces hansenii predominated, but there were lesser, inconsistent contributions from Yarrowia lipolytica. Of the non-lactic acid bacteria, Acinetobacter species were significant during the maturation of Camembert but not blue-veined cheeses, and grew to 10(6)-10(8) cfu/g. Staphylococcus and Micrococcus species were consistently isolated from the cheeses with Staphylococcus xylosus growing to 10(5)-10(9) cfu/g, depending on the product. Lactic acid bacteria (10(7)-10(9) cfu/g) were present throughout maturation but were not identified. Interactions between the various yeasts and bacterial isolates were examined. Several strains of D. hansenii exhibited killer activity but not against Y. lipolytica. None of the yeasts were antagonistic towards the bacteria but some strains of D. hansenii enhanced the growth of Y. lipolytica and S. xylosus. The yeast and bacterial isolates exhibited various degrees of extracellular proteolytic and lipolytic activities.

Bacteria↗

C-glycosides to fused polycyclic ethers. A formal synthesis of (+/-)-hemibrevetoxin B.

This paper describes a formal total synthesis of the marine ladder toxin hemibrevetoxin B from Danishefsky's dienes. This approach couples the generation of C-glycosides from cyclic enol ethers with metathesis or acid-mediated annulation reactions. The result is a highly efficient synthesis of the tetracyclic ring system of hemibrevetoxin B.

Ethers↗

Fluorescent detection of Zn(2+)-rich vesicles with Zinquin: mechanism of action in lipid environments.

High concentrations of free Zn2+ ions are found in certain glutamatergic synaptic vesicles in the mammalian brain. These terminals can be visualized histochemically with quinoline sulfonamide compounds that form fluorescent complexes with Zn2+. The present study was undertaken to examine the interaction of the water-soluble quinoline sulfonamide probe, Zinquin (2-methyl-8-(toluene-p-sulfonamido)-6-quinolyloxyacetic acid) with the complex heterogeneous cellular environment. Experiments on rat hippocampal and neocortical slices gave indications that Zinquin in its free acid form was able to diffuse across the plasma and synaptic vesicle membranes. Further experiments were undertaken on unilamellar liposomes to study the interaction of Zinquin and its metal complexes in membranes. These experiments confirmed that Zinquin is able to diffuse across lipid bilayers. Steady-state and time-resolved fluorimetric studies showed that Zinquin in aqueous solution mainly forms a 1:2 (metal:ligand) complex with small amounts of a 1:1 complex. Formation of the 1:1 complex was favored by the presence of lipid, suggesting that it partitions into membranes. Evidence is presented that Zinquin can act as a Zn(2+)-ionophore, exchanging Zn2+ for two protons. The presence of a pH gradient across vesicles traps the Zn(2+)-probe complex within the vesicles. Zinquin is useful as a qualitative probe for detecting the presence of vesicular Zn2+; however, its tendency to partition into membranes and to serve as an ionophore should be borne in mind.

Animals↗

Applications of nylon membrane arrays to gene expression analysis.

Gene expression analyses by hybridization of probes derived from mRNA to cDNA targets arrayed on a nylon membranes have been performed with increasing frequency and success over the last decade. While the initial costs of generating arrays are moderately high, they are now available commercially as complete packages which include the membranes and associated image analysis software for acquisition and processing of the data. Arrays can be used to generate information concerning the expression of mRNA from cells treated with various agents or from different tissues, e.g. comparing diseased with normal controls. To date, many groups, including immunologists, have used this technology to examine gene expression within their area of biological interest. The main characteristic of these systems is the large amount of data generated, since the expression of many thousands of genes are measured in parallel. The main practical issues are sensitivity of detection, reproducibility, comparability with other systems (e.g. Northern blots) and processing of data. Some of the significant applications of nylon array technology to date are reviewed in this chapter, and with these issues in mind, we include a discussion of our own experiences in this area.

Arthritis, Rheumatoid↗

Dynamic two-dimensional fluorescence correlation spectroscopy. Generalized correlation and experimental factors.

Dynamic two-dimensional fluorescence correlation spectroscopy (2D FCS) is presented in the general form. Dynamic 2D FCS evaluates the time correlation function between two wavelength axes when an external perturbation is applied to the sample. It displays the vibronic features with similar time response functions in the synchronous correlation spectrum and the features with different time responses in the asynchronous correlation spectrum. The correlation analysis allows detailed assignments of the vibronic spectra of multicomponent samples. The emission-emission 2D FCS has proven to be able to resolve spectra with substantial overlaps, of species in equilibrium with each other, and of reacting species whose kinetic constants are linked and multiexponential. Similarly, the correlation analysis between excitation wavelengths allows the assignment of the excitation bands to fluorescent components. When a sinusoidal light source is used to excite the sample, the excitation-emission correlation requires the collection of only four spectra, two in-phase and two quadrature. The two-dimensional excitation-emission correlation analysis uncovers the association between the excitation and the emission vibronic features, enabling the complete assignment of the component spectra. The band associations and spectral assignments are facilitated by the two-dimensional phase map that is constructed from the synchronous and asynchronous correlation spectra. Spectral resolution can be optimized by varying the frequency of excitation and is not influenced by the detector phase angle used to collect the spectra. The resolution power of the 2D FCS is demonstrated with the retrieval of the anthracene emission spectrum from a pyrene-anthracene mixture when it contributes only 4% to the total fluorescence intensity.

Anthracenes↗

Schwannoma: challenging diagnosis.

OBJECTIVE: To discuss the presentation of a schwannoma in a 30-year-old man and to discuss the clincial features of this tumor. CLINICAL FEATURES: The patient had lower right back and abdominal pain that was made worse by any jarring motion. Magnetic resonance imaging showed an intradural extramedullary mass of the thoracic spine behind the T10 vertebral body, which was found to be a schwannoma. INTERVENTION AND OUTCOME: A full laminectomy of T10 and partial laminectomies of T9 and T11 allowed removal of the tumor. CONCLUSION: When undiagnosed abdominal pain is present, spinal tumor should be considered one possible diagnosis.

Abdominal Pain↗

cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes.

Helicobacter pylori strains containing the cag pathogenicity island (PAI) induce NF-kappaB activation and interleukin-8 secretion in gastric epithelial cells. The aim of this study was to investigate changes in epithelial gene expression induced by cag PAI-positive and -negative strains of H. pylori using high-density cDNA array hybridization technology. Radio-labeled cDNA prepared from H. pylori-infected Kato 3 gastric epithelial cells was hybridized to high-density cDNA arrays to identify changes in epithelial gene expression compared to noninfected controls. In vivo expression of selected, differentially expressed genes was examined by reverse transcription-PCR analysis of H. pylori-positive and -negative gastric mucosa. Screening of ca. 57,800 cDNAs identified 208 known genes and 48 novel genes and/or expressed sequence tags of unknown function to be differentially expressed in Kato 3 cells following H. pylori infection. Marked differences in gene expression profiles were observed following cag PAI-positive and cag PAI-negative infection with 15 novel cDNAs and 92 known genes being differentially expressed. H. pylori was found to change the expression of genes encoding growth factors and cytokine/chemokines and their receptors, apoptosis proteins, transcription factors and metalloprotease-disintegrin proteins (ADAMs), and tissue inhibitors of metalloproteinases. Gastric differential expression of selected known genes (amphiregulin and ADAM 10) and a novel gene (HPYR1) was confirmed in vivo in patients with H. pylori infection. Confirmation of the in vivo expression of selected genes demonstrates the usefulness of this approach for investigating pathogen-induced changes in host gene expression.

ADAM Proteins↗

Evaluation of the use of a skills acquisition manual within the common foundation programme for pre-registration nursing.

A skills acquisition manual had been developed for use in the common foundation programme. This article describes an evaluative study of the use of this manual by two cohorts within the pre-registration programme. Information was gained by analysis of the skills acquisition manual and interviewing a sample of participants from both the student cohorts, clinical staff and lecturers involved with the programme. Findings identify a number of issues of interest and demonstrate that the range of clinical opportunities within the common foundation programme enable students to achieve a wide range of transferable skills within a programme that reflects all aspects of nursing.

Clinical Competence↗

Assessment of practice in pre-registration nurse education and the development of a skills acquisition manual.

It has been suggested that Project 2000 training has not taken account of the need to assess the development of specific nursing skills. This could result in nurses who may be in a vulnerable position upon qualification regarding the expectations of their skills performance. A new initiative has been developed at the University of Luton, which enables specific skills to be assessed for pre-registration students during the Common Foundation Programme. This document is discussed here and is the precursor to a wider research study proposed to be undertaken upon completion of the evaluation.

Clinical Competence↗

Preinitation complex assembly: potentially a bumpy path.

During 1996 and 1997, several chemical issues that arise in the early stages of preinitiation complex (PIC) formation were resolved. Kinetics experiments indicated that both TBP dimerization and DNA bending influence the rate of TBP-TATA box assembly. Affinity cleavage experiments indicated that TBP lacks the specificity to nucleate assembly of a properly oriented PIC. Finally, high-resolution structures provided the atomic detail of early intermediates in PIC formation.

DNA↗

Phage types of Australian isolates of Salmonella enterica subsp. enterica serovar Virchow.

Australian isolates (79) of Salmonella enterica subsp. enterica serovar Virchow (Salmonella Virchow) were characterized by phage typing. Thirteen phage types were identified, of which phage type (PT) 8, representing 54 of 79 isolates, was predominant, as it had been in England and Wales up to 1994 when it was replaced by PT26. Other phage types identified in Australia were distinct from those observed in England and Wales. This suggests that PT8 may be a global phage type, while others may be distinct to particular geographical regions.

Animals↗

Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer.

OBJECTIVE: To define preliminary guidelines for the use of lymphatic mapping techniques in patients with breast cancer. SUMMARY BACKGROUND DATA: Lymphatic mapping techniques have the potential of changing the standard of surgical care of patients with breast cancer. METHODS: Four hundred sixty-six consecutive patients with newly diagnosed breast cancer underwent a prospective trial of intraoperative lymphatic mapping using a combination of vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine hematoxylin and eosin (H&E) stains and immunohistochemical stains for cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined cluster of positive-staining cells that could be confirmed histologically on H&E sections. RESULTS: Fine-needle aspiration (FNA) or stereotactic core biopsy was used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422 patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients who failed lymphatic mappings, a complete axillary dissection was performed, and metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26 patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core biopsy. Of interest, there was only one skip metastasis (defined as a negative SLN with higher nodes in the chain being positive) in a patient with prior excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844 (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive SLNs was found in patients who had invasive tumors of increasing size: 18 of 112 patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs. However, a significantly greater percentage of patients (43 of 131 [32.8%] with tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and 5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a positive SLN (p < 0.001). CONCLUSIONS: This study demonstrates that accurate SLN identification was obtained when all blue and hot lymph nodes were harvested as SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a combination of vital blue dye and radiolabeled sulfur colloid is used. Furthermore, these data demonstrate that patients with ductal carcinoma in situ or small tumors exhibit a low but significant incidence of metastatic disease to the axillary lymph nodes and may benefit most from selective lymphadenectomy, avoiding the unnecessary complications of a complete axillary lymph node dissection.

Biopsy↗

Lymphatic mapping in the treatment of breast cancer.

Developed initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested sentinel lymph nodes are evaluated more thoroughly by detailed pathologic examination using serial sectioning, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. This allows for the detection of smaller tumor volumes and leads to more accurate staging. Lymphatic mapping has a 68% to 98% success rate in identifying the sentinel lymph node. The false-negative rate (defined as a negative sentinel lymph node while a higher node or nodes in the axilla are positive) is between 0% and 2%. The morbidity associated with this procedure is minimal. We believe that lymphatic mapping and sentinel lymph node biopsy will ultimately lead to more conservative treatment of patients with breast cancer. This article describes the historical background and technical aspects of the procedure. This is followed by updated, prospectively collected outcomes data from 466 consecutive breast cancer patients who underwent lymphatic mapping at the H. Lee Moffitt Cancer Center, as well as an up-to-date review of the literature.

Biopsy↗

Bidirectional binding of the TATA box binding protein to the TATA box.

By selective attachment of a DNA cleavage agent to specific residues in the yeast TATA box binding protein (yTBP), we demonstrate that, in solution, yTBP binds to the TATA boxes of both the adenovirus major late promoter and the yeast CYC1 promoter with only a modest preference in orientation and binds well to several overlapping binding sites. The general factors TFIIA and TFIIB each increase the rotational and translational selectivity of yTBP but are not sufficient, at least individually, to confer a unique polarity to the preinitiation complex. We conclude that TBP alone cannot define the productive orientation of general factor assembly on a promoter.

Adenoviridae↗