Biomedical subjects
Publications and source records attributed to J M Cox.
[reaction: see text] This Letter describes the synthesis of the hemibrevetoxin B tetracyclic ring system in 14 linear transformations from the Danishefsky-Kitahara diene.
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.
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.
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.
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.
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.
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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.
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.
BACKGROUND: The purpose of this study was to use the breath ethane test to determine if either maternal cigarette smoking, formula, and/or deficiency of the antioxidant nutrients vitamins A and E was associated with oxidant stress in newborn infants. The rationale for this study was: (1) our observation that cigarette smoking was a source of oxidant stress in pregnant women, suggesting that it could be a source of oxidant stress for infants exposed in utero; (2) formula was predicted to be prooxidant compared to colostrum, which contains several compounds with antioxidant activity in vitro; and (3) deficiencies of vitamins A and E have been shown to promote oxidant stress in experimental animals. METHODS: Breath ethane, a volatile alkane produced by peroxide of n-3 fatty acids, was utilized as an index of oxidant stress status. Forty-five healthy full-term infants of the women mentioned above were studied at 18-24 h of age, after four to six feedings of breast milk (colostrum) or caseinbased infant formula. Relationships between infant breath ethane, maternal smoking, mode of infant nutrition, and serum concentrations of the antioxidant vitamins A and E of infants were examined. RESULTS: The breath ethane of the entire group of infants whose mothers smoked (n = 19) was increased compared to values of infants whose mothers did not smoke (n = 26): 97 +/- 16 versus 43 +/- 9 pmol/kg/min, p < 0.03. When infants of mothers who smoked were eliminated from the analysis in order to study effects of nutrition alone, formula appeared to be prooxidant compared to breast milk. Breath ethane of formula-fed infants (n = 16) was 62 +/- 13 versus 13 +/- 4 pmol/kg/min for breast-fed infants (n = 10), p < 0.04. For the group as a whole, there was no correlation between infant breath ethane and serum concentrations of vitamins A and E. CONCLUSIONS: Exposure to maternal smoking in utero is prooxidant in newborn infants. Formula also has a prooxidant effect compared to colostrum in newborn infants not exposed to maternal smoking in utero. Further investigations will be necessary to explore the clinical consequences of these observations.
BACKGROUND: Increased lipid peroxidation caused by oxygen free radicals is thought to be one of the common pathogenetic mechanisms for the so-called oxygen radical diseases of prematurity. Since in vitro studies have shown that various forms of vitamin A can exert antioxidant effects that are more potent than those of vitamin E (treatment with which has been ineffective in these diseases), the purpose of this prospective, controlled study was to determine whether administration of supplemental vitamin A to premature infants deficient in this vitamin would have an antioxidant effect in vivo. METHODS: Fourteen infants (1181 +/- 35 g; gestational age 29 +/- 0.04 weeks) with a serum retinol concentration at 7 +/- 2 days of age in the deficient range, lower than 0.7 mumol/l (< 20 micrograms/dl), were enrolled in the study. Infants were randomized to receive the standard amount of vitamin A or standard plus supplemental (2.6 mumol/l [2500 IU] orally each day) vitamin A, beginning at 1 week of age. Antioxidant effects of supplementation were assessed by a decrease in lipid peroxidation, quantified by the ethane content of expired air. RESULTS: Three weeks after study enrollment, total daily vitamin A intake in the infants receiving supplements was 4.565 +/- 0.236 mumol (4354 +/- 225 IU) versus 1.879 +/- 0.317 mumol/l (1792 +/- 302 IU) in infants receiving standard amounts of the vitamin. In spite of the difference in intake of vitamin A, 3 weeks after study enrollment, serum retinol concentrations did not differ between the infants given supplements and those receiving standard amounts of vitamin A, 0.70 +/- 0.21 versus 0.66 +/- 0.07 mumol/l (20 +/- 6 micrograms/dl versus 19 +/- 2 micrograms/dl, respectively). In the infants receiving supplemental vitamin A, breath ethane values declined from baseline values. There was an inverse correlation between the number of weeks of supplementation and breath ethane values, whereas there was no significant correlation between the duration of the study and breath ethane values in the infants not given supplements. CONCLUSIONS: Our data suggest that supplementation with vitamin A in a small group of vitamin A-deficient preterm infants was associated with an antioxidant effect. Although no immediate clinical benefits were associated with supplementation, the data provide the rationale for future investigations of possible antioxidant effects of (larger amounts?) of vitamin A in higher risk premature infants born with subnormal serum retinol concentrations.
Seventy-three Australian isolates of Salmonella Enteritidis (SE) were analysed by multilocus enzyme electrophoresis (MEE) using a polyacrylamide gel system. Analysis of 11 enzyme loci identified eight electrophoretic types (ETs), with 61 of the isolates assigned to ET1, and 72 isolates considered to represent a clonal lineage. Representative isolates of each of the Australian ETs were then compared with isolates from England, Germany and the United States, using a starch gel system and 13 enzyme loci. The overseas isolates formed a single ET with representatives of the major Australian ET. It is concluded that Australian isolates of SE are closely related genetically to those from countries in which egg-borne transmission is common.
Susceptibility of 66 and 62 Australian isolates of Salmonella enteritidis to nitrofurantoin and furazolidone, respectively, was determined. Most isolates were susceptible to both antibiotics. Cross-resistance was low among all isolates, but higher among the subset of phage type 4 isolates. These results contrast directly with those of a previous study (Rampling, A., Upson, R. and Brown, D.F.J. (1990) J. Antimicrob. Chemother., 25: 285-290). Sensitivity among Australian isolates of S. enteritidis does to some extent, support the contention that furans may have played a role in the selection and enhanced colonisation of poultry by Salmonella enteritidis in Britain. Furthermore, nitrofurantoin should not be used as a selective agent in the isolation of Salmonella enteritidis.
Two Enteritidis PT4 isolates which differed in inherent tolerance to heat, acid, H2O2 and the ability to survive on surfaces were used to infect mice, day-old chicks or laying hens. The acid-, heat-, H2O2- and surface-tolerant isolate was more virulent in mice and more invasive in laying hens, particularly in reproductive tissue. However, no significant differences were observed in behaviour in chicks. Both PT4 isolates were able to infect chicks housed in the same room as infected birds, although the heat-tolerant isolate survived significantly better than the heat-sensitive one in aerosols.
BACKGROUND: HTLV-I Tax is believed to activate viral gene expression by binding bZIP proteins (such as CREB) and increasing their affinities for proviral TRE target sites. Each 21 bp TRE target site contains an imperfect copy of the intrinsically bent CRE target site (the TRE core) surrounded by highly conserved flanking sequences. These flanking sequences are essential for maximal increases in DNA affinity and transactivation, but they are not, apparently, contacted by protein. Here we employ non-denaturing gel electrophoresis to evaluate TRE conformation in the presence and absence of bZIP proteins, and to explore the role of DNA conformation in viral transactivation. RESULTS: Our results show that the TRE-1 flanking sequences modulate the structure and modestly increase the affinity of a CREB bZIP peptide for the TRE-1 core recognition sequence. These flanking sequences are also essential for a maximal increase in stability of the CREB-DNA complex in the presence of Tax. CONCLUSIONS: The CRE-like TRE core and the TRE flanking sequences are both essential for formation of stable CREB-TRE-1 and Tax-CREB-TRE-1 complexes. These two DNA segments may have co-evolved into a unique structure capable of recognizing Tax and a bZIP protein.
Using an in-well lysis technique, 73 Australian strains of Salmonella enteritidis were shown to possess a large plasmid, similar in size to that possessed by a reference phage type 4 strain. Restriction analysis of the large plasmid from nine strains using EcoRI, HindIII and PstI suggested that these plasmids are similar to or the same as the 38 MDa plasmid described in strains of this species from other parts of the world.
The world-wide clinical incidence of Salmonella Enteritidis has increased markedly. The increase is associated with the enhanced ability of the bacterium to systemically colonise layer chickens. Subsequent contamination and consumption of intact shell eggs from colonised layer hens, either directly or in foods containing raw or lightly cooked eggs, causes human disease. Despite investigation, no change in the biology of the bacterium has been correlated with increased colonisation in chickens. To date, no method of control at the production level has proven effective; consumer education is the best means of minimising the public health risk.
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