Search PubMed⌕ Search

Biomedical subjects

L Jones

Publications and source records attributed to L Jones.

At least 163 records · Page 9Linked to original sources
PubMed1997

The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Bacillus subtilis↗
PubMed1997

Light chain usage in anti-double-stranded DNA B cell subsets: role in cell fate determination.

Two major mechanisms for the regulation of autoreactive B cells that arise in the bone marrow are functional silencing (anergy) and deletion. Studies to date suggest that low avidity interactions between B cells and autoantigen lead to B cell silencing, whereas high avidity interactions lead to deletion. Anti-double stranded (ds) DNA antibodies represent a pathogenic autospecificity in Systemic Lupus Erythematosus (SLE). An understanding of their regulation is critical to an understanding of SLE. We now demonstrate in a transgenic model in which mice express the heavy chain of a potentially pathogenic anti-DNA antibody that antibody affinity for dsDNA does not alone determine the fate of anti-dsDNA B cells. B cells making antibodies with similar affinities for dsDNA are regulated differently, depending on light chain usage. A major implication of this observation is that dsDNA may not be the self antigen responsible for cell fate determinations of anti-dsDNA B cells. Light chain usage may determine antigenic cross-reactivity, and cross-reactive antigens may regulate B cells that also bind dsDNA.

Amino Acid Sequence↗
PubMed1997

Mastication and swallowing in patients with postirradiation xerostomia.

PURPOSE: Very little objective data has been reported on mastication and swallowing in xerostomic patients, which would substantiate presumed causal relationships between xerostomia and patient complaints. The purpose was to elucidate which components of mastication and swallowing were abnormal, and most directly related to xerostomia, and which appeared unaffected. METHODS AND MATERIALS: A retrospective analysis of timing events in mastication and swallowing was done using videofluoroscopic data for 15 cancer patients with xerostomia, and 20 normal controls. Scintigraphy was also used to determine oropharyngeal residue after a water swallow. Cancer treatment modalities included radiation therapy or chemoradiation therapy. RESULTS: For barium liquid and paste substances, timing measures were equivalent for controls and patients. Xerostomic patients took 46% longer to masticate a shortbread cookie, and timing for the initiation of swallowing was shorter, but duration of swallowing appeared unaffected. Oral and pharyngeal residues following the swallow were greater in the patient group. CONCLUSIONS: Xerostomia primarily affected mastication and oral manipulation of a dry, absorbent food material. Increased oral and pharyngeal residues after a water swallow are ambiguously related to xerostomia. The initiation and duration of the pharyngeal swallow was not abnormal.

Aged↗
PubMed1997

Regulation of the rat cardiac troponin I gene by the transcription factor GATA-4.

Troponin I is a thin-filament contractile protein expressed in striated muscle. There are three known troponin I genes which are expressed in a muscle-fibre-type-specific manner in mature animals. Although the slow skeletal troponin I isoform is expressed in fetal and neonatal heart, the cardiac isoform is restricted in its expression to the myocardium at all developmental stages. To study the regulation of this cardiac-specific and developmentally regulated gene in vitro, the rat cardiac troponin I gene was cloned. Transient transfection assays were performed with troponin I-luciferase fusion plasmids to characterize the regulatory regions of the gene. Proximal regions of the upstream sequence were sufficient to support high levels of expression of the reporter gene in cardiocytes and relatively low levels in other cell types. The highest luciferase activity in the cardiocytes was noted with a plasmid that included the region spanning -896 to +45 of the troponin I genomic sequence. Co-transfection of GATA-4, a recently identified cardiac transcription factor, with troponin I-luciferase constructs permitted high levels of luciferase expression in non-cardiac cells. Electrophoretic mobility-shift assays demonstrated specific binding of GATA-4 to oligonucleotides representative of multiple sites of the troponin I sequence. Mutation of a proximal GATA-4 DNA-binding site decreased transcriptional activation in transfected cardiocytes. These results indicate that the proximal cardiac troponin I sequence is sufficient to support high levels of cardiac-specific gene expression and that the GATA-4 transcription factor regulates troponin I-luciferase expression in vitro.

3T3 Cells↗
PubMed1997

Studies on the structure, regulation, and pathogenic potential of anti-dsDNA antibodies.

Studies of anti-double-stranded (anti-ds)DNA antibodies have provided insights into how and why these antibodies arise in systemic lupus erythematosus. In this review we discuss the experimental approaches that have been used by our laboratory to study these autoantibodies. Structure/function analyses including site-directed mutagenesis have helped characterize the molecular genetics of anti-dsDNA antibodies, and more recently peptide libraries have been used to define molecular motifs that these antibodies bind. Most of the pathogenic anti-dsDNA antibodies observed in lupus are somatically mutated. We demonstrated in vitro and in vivo that anti-bacterial antibodies can mutate to acquire specificity for dsDNA. Furthermore, using a fusion partner constitutively expressing bcl-2, NSO(bcl-2), we have shown the existence of anergic or preapoptotic B cells making antibodies that cross-react with both bacterial antigen and dsDNA. Whether defects in the regulation of these antibodies might contribute to serum expression of anti-dsDNA antibodies in some individuals remains unknown. A major emphasis of this review is the regulation of anti-dsDNA antibodies in a transgenic mouse model harboring the gene for the heavy chain of a pathogenic anti-dsDNA antibody. Nonautoimmune transgenic mice effectively regulate autoreactive B cells by anergy and deletion, while their autoimmune counterparts do not. The vast majority of anergic B cells expressing high-affinity transgenic anti-dsDNA antibody fail to display allelic exclusion of the heavy chain. We postulate that this may be one mechanism that allows them to escape deletion. Comparative studies on light chain usage in both the autoimmune and the nonautoimmune transgenic mouse strains have demonstrated that within the autoreactive B-cell population, there are subsets that are differentially regulated. Ultimately transgenic animals making pathogenic autoantibodies may provide us with a system for testing novel therapies for autoimmune disease.

Animals↗
PubMed1997

Cocaine administration in pregnant rabbits alters cortical structure and function in their progeny in the absence of maternal seizures.

Previous studies have reported that cocaine exposure in utero results in structural and functional alterations in the development of the anterior cingulate cortex (ACC). In the present study, the effects of maternal cocaine dosage and of cocaine-elicited maternal seizures on the progeny were studied. The incidence of maternal generalized tonic clonic seizures (GTCSs) elicited by cocaine was recorded. No GTCSs were elicited in pregnant rabbits by doses of 2 or 3 mg/kg of cocaine, but GTCSs were sometimes elicited by the highest dose (4 mg/kg per injection). We analyzed the offspring of cocaine-exposed and control animals using three assays of ACC development: (i) the structure of apical dendrites of pyramidal neurons, (ii) the distribution of a calcium binding protein (parvalbumin) in the dendrites of GABAergic neurons, and (iii) coupling of D1-like receptors and their G proteins. In all progeny of rabbits exposed to 3 or 4 mg/kg of cocaine during pregnancy, there was a significant change in the structure of apical dendrites, a significant increase in the number of dendrites of GABAergic neurons which were parvalbumin immunoreactive, and a significant reduction in D1/G protein coupling. In assays of apical dendrites, the effects on offspring of rabbits given 2 mg/kg cocaine were as pronounced as in offspring of rabbits given 3 or 4 mg/kg, but the effects on parvalbumin immunoreactivity and D1/G protein coupling were reduced at this low dose. Thus, previous findings of ACC developmental abnormalities in offspring of rabbits given a dose of 4 mg/kg were replicated, the effects were shown to be dose-related and to be independent of maternal seizures. A mechanism by which dysfunction of the D1 receptor system could mediate cocaine-associated changes in all three parameters of ACC structure and function is discussed.

Animals↗
PubMed1997

Effects of lesions invading the postcentral gyrus on somatosensory thresholds on the face.

Patients with unilateral removals from either the parietal, frontal or temporal lobe and normal control subjects were examined on three tests of tactile sensibility. The patients with surgical excisions from the parietal lobe were subdivided into two groups: those whose lesions invaded the face area in the primary sensory cortex and those whose lesions spared this area. A significant percentage of patients with lesions that invaded the face area had mild to severe sensory deficits on the side of the face contralateral to the lesion. A much smaller number of patients had deficits on the ipsilateral side. Lesions to the face area in the primary sensory cortex were, however, associated with a lower incidence of severe and persistent sensory deficits when compared to previous results on the effects of lesions to the hand area on the sensory capacity of the hand. These results suggest that there is some preservation of sensory function after damage to the face area in the primary sensory cortex, presumably due to the bilateral representation of the face.

Adolescent↗
PubMed1997

Mechanism of late prosthetic vascular graft infection.

This study was a retrospective analysis of 41 patients with late prosthetic graft infections (> 30 days after operation) from six hospitals in the south-west of England. The 41 patients had a median age of 66 years and generally accepted risk factors for infection were documented in 19 patients preoperatively. Thirteen patients had postoperative wound complications and three had early reoperation at the site of subsequent infection. The median time between index operation and symptoms of infection was 10 (range 1-224) months. Abscess (46%) was the most common presentation followed by false aneurysm (20%) and graft thrombosis (20%). All patients had reoperations (median two per patient, range one to seven). Seven (17%) patients died and 10 (24%) required a major amputation. Bacteria were isolated from retrieved grafts in 23/41 patients (high virulence 14, low virulence nine) and the most frequent organism was coagulase-negative Staphylococcus epidermidis (nine patients). In the majority of cases the aetiology of the late infections in this series was consistent with bacterial implantation at the index operation, but in four cases bacteraemia or intraperitoneal spread was more likely. Dental-type antibiotic prophylaxis would not have prevented any of the infections in this study. Aggressive treatment of recognized sources of infection in patients with vascular grafts is imperative.

Aged↗
PubMed1997

Clinical comparison of three polyhexanide-preserved multi-purpose contact lens solutions.

This study investigated the clinical differences between three commercially available polyhexanide (PHMB) preserved disinfection systems containing varying percentages of PHMB, when used with FDA group II and group IV disposable contact lenses. After 1 month of wear the product with the highest concentration of PHMB ('All-in-One') was graded as being less comfortable on insertion (P<0.003), had lower overall satisfaction (P<0.05) when compared with the other two products. Corneal staining was also significantly higher with this product after both 14 days (P<0.001 with group II and P<0.02 with group IV) and 28 days (P<0.00001 with group II and P<0.03 ith group IV).

Journal Article↗
PubMed1997

Preclinical pharmacokinetic, antitumor and toxicity studies with CI-994 (correction of CL-994) (N-acetyldinaline).

CI-994, a substituted benzamide derivative, is a compound that showed solid tumor selectivity for a variety of solid tumor models compared to L1210 leukemia. Due to its lack of aqueous solubility, it requires oral administration. Female B6D2F1 mice were treated with CI-994 once daily by oral administration of 50 mg/kg for 14 days. Following treatment mice were evaluated for pharmacodynamic effects as well as the pharmacokinetic behavior of CI-994 and the de-acetylated derivative dinaline. Mice samples (plasma, urine, feces) were analyzed using solid phase extraction, reverse phase HPLC and ultraviolet detection. The plasma distribution and elimination half-lives for CI-994 were 51 minutes and 9.4 hours, respectively, on D-1; 31 minutes and 3.4 hours, respectively on D-14. The apparent plasma distribution and elimination half-lives for dinaline were 27 minutes and 2.4 hours, respectively, on D-1; 40 minutes and 7.3 hours, respectively on D-14. The CI-994 AUC on D-1 and D-14 were 2879 and 2407 micrograms/ml x minutes, respectively; while the dinaline AUC on D-1 and D-14 were 87 and 92 micrograms/ml x minutes, respectively. Urinary excretion for CI-994 and dinaline was higher on D-14, while the fecal excretion was the same on both days. The Colon #38 tumor growth in treated mice was reduced to 22% of that observed in the controls by D-19. The levels of all blood cells were reduced in the treated mice when compared to controls and the total WBC was the most affected (median 38%). Recovery to pretreatment levels occurred quickly following treatment cessation. Phase I evaluation of chronic oral administration of CI-994 is currently ongoing.

Adenocarcinoma↗
PubMed1997

Breast cancer care: women's experience.

Medical treatments for breast cancer are undergoing rapid change. Studies of the management of breast cancer have investigated the psychosocial consequences of the diagnosis as expressed by the patients themselves, but infrequently relate these women's views directly to improvements in health care systems. The following study explores the experience of 18 women recently diagnosed as having breast cancer. The findings illustrate to both clinicians and managers the importance of considering a number of dimensions relevant to the psychosocial care of patients and suggest areas where health care systems may be modified to address the psychosocial needs of women. The results demonstrate the positive impact patient views can have on the development of health care services.

Adolescent↗
PubMed1997

Viscosity discrimination: a comparison of an adaptive two-alternative forced-choice and an adjustment procedure.

Differential thresholds for viscosity were measured in ten subjects with the use of an adaptive two-alternative forced-choice procedure. An electromagnetic linear motor was connected to each wrist and the viscosity of the motors was under computer servo control. For each block of 50 trials the viscosity of one motor was fixed at a reference value which ranged from 4 to 512 N s m-1, and the viscosity of the other motor varied according to the subject's responses. On each trial subjects were required to indicate which motor had the greater viscosity and were given feedback of the correct response. By this procedure the Weber fraction for viscosity was calculated to be 19%, which is lower than the Weber fraction of 34% estimated by using the method of adjustment. The criterion used for determining the threshold differs in the two procedures (71% and 84% correct, respectively), and the results from the two studies were found to be consistent. They suggest that the Weber fraction for viscosity remains remarkably stable despite differences in the methods of measurement.

Adult↗
PubMed1997

Five antithrombin variants, four associated with thrombosis.

We have identified five mutations in antithrombin by direct sequencing of exons amplified using polymerase chain reaction. Four of these mutations are associated with thrombosis, three cause type I antithrombin deficiency and one has features of a type II deficiency. The fifth variant appears to have no functional consequences. The type I mutations are in exon 2, exon 3b and exon 4. The first of these is a nonsense mutation causing substitution of a Tyr-->stop at position -16 within the secretion signal sequence. The second is a missense mutation resulting in the substitution Cys-->Ser at position 247. This disrupts the disulphide bond with Cys 430 leaving a free cysteine residue and the C-terminus unconstrained. The third type I mutation is an in-frame deletion resulting in the loss of Ile 186. This is a highly conserved residue in the serpin superfamily and will predictably result in the disruption of the F-helix. The fourth mutation, in exon 3a, results in the substitution of Ser 162 by Asn. This residue is sited in the E-helix and the replacement of the buried side chain of serine by the larger asparagine side chain will predictably cause structural perturbation. The last example, Val 415-->Asp, was an incidental finding as a follow up investigation of a nephrotic patient. Although one other member of the family also had the mutation there was no linked history of thrombotic disease.

Adult↗
PubMed1997

The relation between leadership style and empowerment on job satisfaction of nurses.

OBJECTIVE: The authors explore the relation between leadership style and empowerment and its effect on job satisfaction among the nursing staff of a regional medical center. BACKGROUND: Several empirical studies on transformational leadership-found that transformational leadership behaviors were positively related to work team success and leadership effectiveness. Transformational leadership processes have also been suggested to enhance followers' work-oriented values and shape the self-efficacies of followers. Employee empowerment may be influenced by the perception that the organization cares about its employees' well-being and that their work is valued. Empowering nurses may increase job satisfaction and improve patient care. Leadership style and empowerment influence job satisfaction among workers. METHODS: All nursing department staff were invited to complete a self-report questionnaire with no identifying information. Leadership style was measured using Bass's Multifactor Leadership Questionnaire, empowerment was measured with items from Spreitzer's Psychological Empowerment instrument, and job satisfaction was measured by Warr, Cook, and Wall's job satisfaction questionnaire. RESULTS: Both transformational and transactional leadership were positively related to job satisfaction, as was empowerment. Differences in the contributions of empowerment and leadership style in predicting job satisfaction for licensed and unlicensed workers was evident. CONCLUSION: Designing interventions that allow for the relative influence of leadership style as well as empowerment on varying classifications of nursing personnel may be a more effective strategy and have a greater effect on staff attitudes and behaviors.

Decision Making, Organizational↗