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J Smith

Publications and source records attributed to J Smith.

At least 109 records · Page 6Linked to original sources
PubMed2001

Analysis of multiple samples using multiplex sample NMR: selective excitation and chemical shift imaging approaches.

Two improved approaches for the rapid analysis of multiple samples using multiplex sample NMR are described. In the first approach, frequency-selective 90 degrees radio frequency pulses and large pulsed field gradients are applied to excite and detect multiple samples in rapid succession. This method is advantageous for samples with relatively long longitudinal (T1) relaxation times. In the second approach, chemical shift imaging is applied to acquire both the spectral and spatial information of multiple samples simultaneously. Chemical shift imaging is more time-consuming than selective excitation; however, it is advantageous for detecting samples with short T1's and for signal averaging. Both approaches demonstrate the potential of multiplex sample NMR for carrying out high-throughput NMR detection.

Journal Article↗
PubMed2001

Synthesis of functional aromatic multisulfonyl chlorides and their masked precursors.

The synthesis of functional aromatic bis(sulfonyl chlorides) containing an acetophenone and two sulfonyl chloride groups, i.e., 3,5-bis[4-(chlorosulfonyl)phenyl]-1-acetophenone (16), 3,5-bis(chlorosulfonyl)-1-acetophenone (17), and 3,5-bis(4-(chlorosulfonyl)phenyloxy)-1-acetophenone (18) via a sequence of reactions, involving in the last step the quantitative oxidative chlorination of S-(aryl)- N,N'-diethylthiocarbamate, alkyl- or benzyl thiophenyl groups as masked nonreactive precursors to sulfonyl chlorides is described. A related sequence of reactions was used for the synthesis of the aromatic trisulfonyl chloride 1,1,1-tris(4-chlorosulfonylphenyl)ethane (24). 4-(Chlorosulfonyl)phenoxyacetic acid, 2,2-bis[[[4-(chlorosulfonyl)phenoxyacetyl]oxy]methyl]-1,3-propanediyl ester (27), 5,11,17,23-tetrakis(chlorosulfonyl)-25,26,27,28-tetrakis(ethoxycarbonylmethoxy)calix[4]arene (38), 5,11,17,23,29,35-hexakis(chlorosulfonyl)-37,38,39,40,41,42-hexakis(ethoxycarbonylmethoxy)calix[6]arene (39), 5,11,17,23,29,35,41,47-octakis(chlorosulfonyl)-49,50,51,52,53,54,55,56-octakis(ethoxycarbonylmethoxy)calix[8]arene (40), 5,11,17,23-tetrakis(tert-butyl)-25,26,27,28-tetrakis(chlorosulfonyl phenoxyacetoxy)calix[4]arene (44), 5,11,17,23,29,35-hexakis(tert-butyl)-37,38,39,40,41,42-hexakis(chlorosulfonylphenoxyacetoxy)calix[6]arene (45), and 5,11,17,23,29,35,41,47-octakis(tert-butyl)-49,40,51,52,53,54,55,56-octakis(chlorosulfonylphenoxyacetoxy)calix[8]arene (46) were synthesized by two different multistep reaction procedures, the last step of both methods consisting of the chlorosulfonation of compounds containing suitable activated aromatic positions. 2,4,6-Tris(chlorosulfonyl)aniline (47) was obtained by the chlorosulfonation of aniline. The conformation of two series of multisulfonyl chlorides i.e., 38, 39, 40 and 44, 45, 46, was investigated by (1)H NMR spectroscopy. The masked nonreactive precursor states of the functional aromatic multisulfonyl chlorides and the aromatic multisulfonyl chlorides reported here represent the main starting building blocks required in a new synthetic strategy elaborated for the preparation of dendritic and other complex organic molecules.

Journal Article↗
PubMed2001

Vaccination with Her-2/neu DNA or protein subunits protects against growth of a Her-2/neu-expressing murine tumor.

The present study utilizes an in vivo murine tumor expressing human Her-2/neu to evaluate potential Her-2/neu vaccines consisting of either full length or various subunits of Her-2/neu delivered in either protein or plasmid DNA form. Our results demonstrate that protective immunity against Her-2/neu-expressing tumor challenge can be achieved by vaccination with plasmid DNA encoding either full length or subunits of Her-2/neu. Partial protective immunity was also observed following vaccination with the intracellular domain (ICD), but not extracellular domain (ECD), protein subunit of Her-2/neu. The mechanism of protection elicited by plasmid DNA vaccination appeared to be exclusively CD4 dependent, whereas the protection observed with ICD protein vaccination required both CD4 and CD8 T cells.

Animals↗
PubMed2001

Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial.

PURPOSE: Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer. PATIENTS AND METHODS: One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks. RESULTS: Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P =.04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P =.01) and a more modest difference between the supervised and control groups (6.3 points; P =.09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P =.01) and reduced body weight (-4.8 kg; P <.05) compared with usual care only in participants not receiving chemotherapy. CONCLUSION: Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Catalytic turnover of substrate benzylamines by the quinone-dependent plasma amine oxidase leads to H2O2-dependent inactivation: evidence for generation of a cofactor-derived benzoxazole.

Incubation of bovine plasma amine oxidase (BPAO) with benzylamine and various p-substituted analogues results in a time-dependent inactivation that is attributable to buildup of the H(2)O(2)-turnover product on the basis of protection afforded by coincubation with catalase. The mechanism of inactivation is distinct from that effected by H(2)O(2) itself, which requires higher concentrations. Solution studies using models for the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor reveal a loss of catalytic activity arising from oxidation of the dihydrobenzoxazole tautomer of the product Schiff base, that competes with hydrolytic release of benzaldehyde product. The resulting stable benzoxazole exhibits a characteristic absorption depending on the nature of the benzylamine p-substituent. For benzylamine itself, the model benzoxazole absorbs at 313 nm, in an area of strong absorption by the enzyme, whereas for 4-nitrobenzylamine, the absorption of the model benzoxazole is sufficiently red-shifted (at 365 nm) to be discerned above the background enzyme absorption. Inactivation of BPAO by 4-nitrobenzylamine is accompanied by loss of the resting TPQ anion absorption at 480 nm concomitant with generation of a new absorption near 360 nm. Resonance Raman spectra of the inactivated enzyme show a close correspondence with those for the model 4-nitrobenzylamine-derived benzoxazole. Substrate-dependent inactivation is also observed for the other two mammalian enzymes examined, equine plasma amine oxidase and human kidney amine oxidase. Catalase provides complete protection in these instances as well. Benzoxazole formation may constitute a common mechanism of inactivation of quinone-dependent amine oxidases by normal substrates in vitro if the product H(2)O(2) is permitted to accumulate. More importantly, the results suggest that the benzoxazole inactivation pathway may be important physiologically and may have influenced the distribution of amine oxidases and catalase in cells.

Amine Oxidase (Copper-Containing)↗
PubMed2001

Partial lumbosacral transitional vertebra resection for contralateral facetogenic pain.

STUDY DESIGN: Case report of surgically treated mechanical low back pain from the facet joint contralateral to a unilateral anomalous lumbosacral articulation (Bertolotti's syndrome). OBJECTIVES: To describe the clinical presentation, diagnostic evaluation, and management of facet-related low back pain in a 17-year-old cheerleader and its successful surgical treatment with resection of a contralateral anomalous articulation. SUMMARY OF BACKGROUND DATA: Lumbosacral transitional vertebrae are common in the general population. Bertolotti's syndrome is mechanical low back pain associated with these transitional segments. Little is known about the pathophysiology and mechanics of these vertebral segments and their propensity to be pain generators. Treatment of this syndrome is controversial, and surgical intervention has been infrequently reported. METHOD: A retrospective chart analysis and radiographic review were performed. RESULTS: Repeated fluoroscopically guided injections implicated a symptomatic L6-S1 facet joint contralateral to an anomalous lumbosacral articulation. Eventually, a successful surgical outcome was achieved with resection of the anomalous articulation. CONCLUSION: Clinicians should consider the possibility that mechanical low back pain may occur from a facet contralateral to a unilateral anomalous lumbosacral articulation, even in a young patient. Although reports of surgical treatment of Bertolotti's syndrome are infrequent, resection of the anomalous articulation provided excellent results in this patient, presumably because of reduced stresses on the symptomatic facet.

Adolescent↗
PubMed2001

The social evolution of bacterial pathogenesis.

Many of the genes responsible for the virulence of bacterial pathogens are carried by mobile genetic elements that can be transferred horizontally between different bacterial lineages. Horizontal transfer of virulence-factor genes has played a profound role in the evolution of bacterial pathogens, but it is poorly understood why these genes are so often mobile. Here, I present a hypothetical selective mechanism maintaining virulence-factor genes on horizontally transmissible genetic elements. For virulence factors that are secreted extracellularly, selection within hosts may favour mutant 'cheater' strains of the pathogen that do not produce the virulence factor themselves but still benefit from factors produced by other members of the pathogen population within a host. Using simple mathematical models, I show that if this occurs then selection for infectious transmission between hosts favours pathogen strains that can reintroduce functional copies of virulence-factor genes into cheaters via horizontal transfer, forcing them to produce the virulence factor. Horizontal gene transfer is thus a novel mechanism for the evolution of cooperation. I discuss predictions of this hypothesis that can be tested empirically and its implications for the evolution of pathogen virulence.

Bacteria↗
PubMed2001

Information provision for stroke patients and their caregivers.

BACKGROUND: The provision of information has been recommended as a key component of service provision after stroke. However, research suggests that patients' understanding of stroke and associated issues remains poor. We determined to undertake a systematic review of information provision strategies for patients and their carers after stroke. OBJECTIVES: To examine the effectiveness of an information and/or education strategy to improve the outcome of stroke patients and/or their identified caregivers. SEARCH STRATEGY: Relevant trials were identified in the Cochrane Stroke Group Specialised Trials Register (last searched: June 2000). Additional intervention-based search strategies were developed for: The Cochrane Controlled Trials Register (CENTRAL/CCTR) Medline; Embase; CINAHL; ISI citation index; Science and Social Science Citation Indexes; ISI Web of Science Service; Aslib Index to UK theses; Dissertation Abstracts International, ASSIA and Psychlit/PsycINFO. We also searched the Journal of Advanced Nursing, bibliographies of retrieved papers, relevant articles and books. SELECTION CRITERIA: Two or three investigators independently assessed trials and abstracts identified for eligibility, methodological quality and other participant characteristics. DATA COLLECTION AND ANALYSIS: Data were extracted independently using piloted data extraction forms. The primary outcomes were knowledge about stroke and stroke services, and impact on health, specifically mood. MAIN RESULTS: We identified 152 abstracts, of which 36 studies were potentially relevant to this review. The current analysis includes nine completed trials, a further eight studies are ongoing. Of the nine trials, three evaluated a programme of lectures and the remaining trials evaluated the provision of information. There is some evidence that information combined with educational sessions improved knowledge and was more effective than providing information only. Information provision only had no effect on mood, perceived health status or quality of life for patients or carers. Two trials used an objective measure of satisfaction and no significant differences were found between groups. One trial reported that information and education sessions for carers improved 'family functioning'. REVIEWER'S CONCLUSIONS: The results of the review are limited by the variable quality of the trials and the wide range of outcome measures used. The general effectiveness of information provision has not been conclusively demonstrated. Future work should address the expressed needs of patients and carers and seek to identify appropriate teaching strategies which can be successfully implemented within clinical practice.

Caregivers↗
PubMed2001

Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone population.

Anergic/suppressive CD4(+)CD25(+) T cells exist in animal models but their presence has not yet been demonstrated in humans. We have identified and characterized a human CD4(+)CD25(+) T cell subset, which constitutes 7-10 % of CD4(+) T cells in peripheral blood and tonsil. These cells are a CD45RO(+)CD45RB(low) highly differentiated primed T cell population that is anergic to stimulation. Depletion of this small subset from CD4(+) T cells significantly enhances proliferation by threefold in the remaining CD4(+)CD25(-) T cells, while the addition of isolated CD4(+)CD25(+) T cells to CD4(+)CD25(-) T cells significantly inhibits proliferative activity. Blocking experiments suggest that suppression is not mediated via IL-4, IL-10 or TGF-beta and is cell-contact dependent. Isolated CD4(+)CD25(+) T cells are susceptible to apoptosis that is associated with low Bcl-2 expression, but this death can be prevented by IL-2 or fibroblast-secreted IFN-beta. However, the anergic/suppressive state of these cells is maintained after cytokine rescue. These human regulatory cells are therefore a naturally occurring, highly suppressive, apoptosis-prone population which are at a late stage of differentiation. Further studies into their role in normal and pathological situations in humans are clearly essential.

Apoptosis↗
PubMed2001

Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth-promoting class of macroglia.

The molecular mechanisms that drive glia-glial interactions and glia-neuronal interactions during the development of the nervous system are poorly understood. A number of membrane-bound cell adhesion molecules have been shown to play a role, although the precise nature of their involvement is unknown. One class of molecules with cell adhesive properties used in the nervous system is the serine-esterase-like family of transmembrane proteins. A member of this class, a glia-specific protein called gliotactin, has been shown to be necessary for the development of the glial sheath in the peripheral nervous system of Drosophila melanogaster. Gliotactin is essential for the development of septate junctions in the glial sheath of individual and neighboring glia. Mutations that remove this protein result in paralysis and eventually death due to a breakdown in the glial-based blood-nerve barrier. To study the role of gliotactin during vertebrate nervous system development, we have isolated a potential vertebrate gliotactin homologue from mice and rat and found that it corresponds to neuroligin 3. Using a combination of RT-PCR and immunohistochemistry, we have found that neuroligin 3 is expressed during the development of the nervous system in many classes of glia. In particular neuroligin 3 is expressed in the olfactory ensheathing glia, retinal astrocytes, Schwann cells, and spinal cord astrocytes in the developing embryo. This expression is developmentally controlled such that in postnatal and adult stages, neuroligin 3 continues to be expressed at high levels in the olfactory ensheathing glia, a highly plastic class of glia that retain many of their developmental characteristics throughout life.

Animals↗
PubMed2001

Adeno-associated virus seropositivity and HPV-induced cervical cancer in Spain and Colombia.

Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinic-based controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5+/6+ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1-0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1-1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3-6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix.

Adult↗
PubMed2001

Preserved implicit learning on both the serial reaction time task and artificial grammar in patients with Parkinson's disease.

Thirteen nondemented patients with Parkinson's disease (PD) were compared with age-matched controls on two standard tests of implicit learning. A verbal version of the Serial Reaction Time (SRT) task was used to assess sequence learning and an artificial grammar (AG) task assessed perceptual learning. It was predicted that PD patients would show implicit learning on the AG task but not the SRT task, as motor sequence learning is thought to be reliant on the basal ganglia, which is damaged in PD. Patients with PD demonstrated implicit learning on both tasks. In light of these unexpected results the research on SRT learning in PD is reconsidered, and some possible explanations for the sometimes conflicting results of PD patient samples on the SRT task are considered. Four factors which merit further study in this regard are the degree to which the SRT task relies on overt motor responses, the effects of frontal lobe dysfunction upon implicit sequence learning, the effects of cerebellar degeneration, and the degree to which the illness itself has advanced.

Adult↗
PubMed2001

Coagulation factor activity during neonatal extra-corporeal membrane oxygenation.

OBJECTIVE: To ascertain the activity of major coagulation factors during the first 24 h of extra-corporeal membrane oxygenation (ECMO) used to support hypoxaemic neonates. DESIGN AND SETTING: A prospective observational study in a regional centre for ECMO and paediatric cardiac surgery, placing 15-20 neonates on ECMO per year. PATIENTS: Ten neonates receiving ECMO for severe hypoxaemia. MEASUREMENT AND RESULTS: The activity of major clotting factors, of the inhibitor anti-thrombin III and of markers of blood activation were measured during the first 24 h of neonatal extra-corporeal membrane oxygenation (ECMO) and prior to initiation of ECMO. There was laboratory evidence of factor deficiency and of activation of coagulation at all stages. The initiation of ECMO leads to an initial worsening of coagulopathy, but factor deficiency and abnormal activation of coagulation is also seen prior to ECMO in these very sick neonates. CONCLUSION: If factor deficiency is to be avoided a pro-active approach is required to rapidly correct factor activity. This would include the use of fresh frozen plasma. The effect of such an approach on outcome is at yet uncertain.

Biomarkers↗
PubMed2001

Malignancy in chronic ulcers and scars of the leg (Marjolin's ulcer): a study of 21 patients.

OBJECTIVE: To study the imaging features of patients with chronic ulcers of the leg that were associated with malignancy. DESIGN AND PATIENTS: All patients who on biopsy were proven to have malignancy--the majority of which were squamous cell carcinoma-were included in a prospective study. Ulcers limited to the foot were excluded but ulcers of the leg which extended into the foot were included. Amputation was performed in all but two patients, due to pain, bleeding or tissue necrosis. RESULTS: The etiology was multifactorial. The mean duration of the ulcers was 36 years including venous ulcers, extensive scarring of the leg secondary to infection, injury or burns. One ulcer was secondary to a snake bite. The remainder, usually in the upper part of the leg, had repeated episodes of blunt trauma or knife wounds, which were also complicated by infections which failed to heal or, if they healed, regularly recurred. Although arterial insufficiency was not primary in any patient, most were of advanced age and it may have been an element in some patients. Despite infection, osteomyelitis was present in only one patient. The essential features were bone destruction, soft tissue mass and periosteal reaction. The bone destruction was visible on the radiographs in all but one case. The soft tissue masses varied in size but in general were very large. The periosteal reaction varied in type but most commonly was lamellated. The classic undulating solid periosteal reaction of venous stasis was only occasionally present. The periosteal reaction was nonspecific in the majority of cases and did not aid in the diagnosis or etiology. MRI and CT studies were performed in six patients. These were helpful in defining the extent of bone destruction and periosteal reaction but were not essential in management. CONCLUSION: Chronic ulcer present for decades that then undergoes malignant change is a disease of developing countries where patients only consult physicians when they have developed complications such as pain, bleeding or tissue necrosis. Chronic ulcers may require to be biopsied at regular intervals as malignant change in these ulcers is directly related to their duration.

Aged↗