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Biomedical subjects

S Johnson

Publications and source records attributed to S Johnson.

At least 181 records · Page 10Linked to original sources

Optical sensor arrays for odor recognition.

Optical sensor arrays containing fluorescent solvatochromatic dyes immobilized in a plurality of polymers generate information-rich responses upon exposure to organic vapors. The response profiles are used to train a variety of computational networks such that subsequent exposure of the array to the vapors enables them to be classified and/or quantified. A number of strategies can be taken to enhance sensitivity and to increase sensor diversity.

Animals↗

Antibacterial agents that inhibit two-component signal transduction systems.

A class of antibacterials has been discovered that inhibits the growth of Gram-positive pathogenic bacteria. RWJ-49815, a representative of a family of hydrophobic tyramines, in addition to being a potent bactericidal Gram-positive antibacterial, inhibits the autophosphorylation of kinase A of the KinA::Spo0F two-component signal transduction system in vitro. Analogs of RWJ-49815 vary greatly in their ability to inhibit growth of bacteria and this ability correlates directly with their activity as kinase A inhibitors. Compared with the potent quinolone, ciprofloxacin, RWJ-49815 exhibits reduced resistance emergence in a laboratory passage experiment. Inhibition of the histidine protein kinase::response regulator two-component signal transduction pathways may present an opportunity to depress chromosomal resistance emergence by targeting multiple proteins with a single inhibitor in a single bacterium. Such inhibitors may represent a class of antibacterials that potentially may represent a breakthrough in antibacterial therapy.

Anti-Bacterial Agents↗

Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea.

BACKGROUND: Little is known about whether patients who develop Clostridium-difficile-associated diarrhoea (CDAD) are culture-positive or culture-negative before illness. The most important risk factor is antibiotic exposure. We aimed to find out whether patients identified as primary symptom-free C difficile carriers are at higher risk of developing CDAD than patients who are culture-negative. METHOD: We reviewed four longitudinal studies in which 810 patients admitted to hospital were followed up by prospective rectal-swab culture. At least two consecutive weekly cultures were obtained. We calculated the difference in risk of CDAD between colonised and non-colonised patients in each study and combined the results of the four studies in a random-effects model. FINDINGS: Of 618 non-colonised patients (mean follow-up 1.7 weeks [SD 1.3]), 22 (3.6%) developed CDAD, whereas only two (1.0%) of 192 primary symptom-free carriers (1.5 [1.5]) developed CDAD (pooled risk difference -2.3% [95% CI 0.3-4.3], p=0.021). Of patients who received antibiotics, the risk difference was increased: 22 (4.5%) of 491 non-colonised patients compared with two (1.1%) of 176 colonised patients developed CDAD (-3.2% [0.4-6.0], p=0.024). Of the primary symptom-free C difficile carriers, 95 were colonised with toxigenic strains, 76 with non-toxigenic strains, 12 with both toxigenic and non-toxigenic strains (non-concurrently), and nine with strains of undetermined toxigenicity. Nine of the 12 toxogenic strains of C difficile isolates that cause CDAD were also recovered from stools of symptom-free patients. INTERPRETATION: Primary symptomless C difficile colonisation is associated with a decreased risk of CDAD. Although the mechanism is unknown, risk reduction is found in colonisation with non-toxigenic and toxigenic strains.

Adult↗

Vinorelbine in the treatment of lymphoma.

Seventeen patients with previously treated Hodgkin's disease or non-Hodgkin's lymphoma (NHL) were treated with single-agent vinorelbine (Navelbine Pierre-Fabre Medicament) in an open study to assess the activity of this new-generation vinca alkaloid. Responses were obtained in four out of eight patients with Hodgkin's disease and four out of nine patients with NHL, including four patients who had been previously treated with high-dose therapies. Toxicity was very mild. The study demonstrates worthwhile activity and justifies the inclusion of vinorelbine in combination therapies for lymphoma.

Adult↗

Development of immune hyperinnervation in NGF-transgenic mice.

Sympathetic innervation of lymphoid tissues is localized to specific tissue compartments, but little is known of the "factors" that are important in establishing this pattern during development. Numerous studies have shown interactions of nerve growth factor (NGF) with the immune system, which may include modulation of immune innervation. We previously have shown that NGF transgenic mice, which overexpress NGF in skin and not immune tissues, have a dramatic hyperinnervation of splenic marginal zone and peripheral lymph node medulla and capsule. The purpose of the current studies was to determine if the presence of elevated NGF would alter immune system development and the process of sympathetic ingrowth. The results show that the splenic innervation in NGF transgenics gradually diverged from controls during the first two postnatal weeks, with the greatest change occurring between postnatal days 13 and 16 when the splenic organization was reaching the adult pattern. In contrast, the peripheral lymph nodes were hyperinnervated at an earlier age. mesenteric lymph nodes never diverged from the normal pattern. NGF levels in transgenic spleen were much higher than controls at postnatal days 1 and 2, when little innervation was present, and declined as the tissue matured, possibly because of NGF uptake by the ingrowing sympathetic fibers. This suggests that immune tissues are capable of concentrating NGF, which in turn may modulate the level of innervation by the sympathetic nervous system.

Animals↗

Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial.

OBJECTIVE: To assess pair-wise differences between placebo, estrogen, and each of three estrogen-progestin regimens on selected symptoms. METHODS: This was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 postmenopausal women aged 45-64 years at baseline. Participants were assigned randomly to one of five groups: 1) placebo, 2) daily conjugated equine estrogens, 3) conjugated equine estrogens plus cyclical medroxyprogesterone acetate, 4) conjugated equine estrogens plus daily medroxyprogesterone acetate, and 5) conjugated equine estrogens plus cyclical micronized progesterone. Symptoms were self-reported using a checklist at 1 and 3 years. Factor analysis reduced 52 symptoms to a set of six symptom groups. RESULTS: In intention-to-treat analyses at 1 year, each active treatment demonstrated a marked, statistically significant, protective effect against vasomotor symptoms compared with placebo (odds ratios [ORs] 0.17-0.28); there was no additional benefit of estrogen-progestin over estrogen alone. Only progestin-containing regimens were significantly associated with higher levels of breast discomfort (OR 1.92-2.27). Compared with placebo, women randomized to conjugated equine estrogens reported no increase in perceived weight. Those randomized to medroxyprogesterone acetate reported less perceived weight gain (OR 0.61-0.69) than placebo. Anxiety, cognitive, and affective symptoms did not differ by treatment assignment. Analyses restricted to adherent women were not materially different than those using intention-to-treat, except that women adherent to medroxyprogesterone acetate and micronized progesterone regimens reported fewer musculoskeletal symptoms (OR 0.62-0.68). CONCLUSION: These results confirm the usefulness of post-menopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.

Double-Blind Method↗

Data elements for emergency department systems, release 1.0 (DEEDS): a summary report. DEEDS Writing Committee.

Variations in the way that data are entered in ED record systems impede the use of ED records for direct patient care and deter their reuse for many other legitimate purposes. To foster more uniform ED data, the Centers for Disease Control and Prevention's (CDC) National Center for Injury Prevention and Control is coordinating a public-private partnership that has developed recommended specifications for many observations, actions, instructions, conclusions, and identifiers that are entered in ED records. The partnership's initial product. Data Elements for Emergency Department Systems, Release 1.0 (DEEDS), is intended for use by individuals and organizations responsible for ED record systems. If the recommended specifications are widely adopted, then problems--such as data incompatibility and high costs of collecting, linking, and using data--can be substantially reduced. The collaborative effort that led to DEEDS, Release 1.0 sets a precedent for future review and revision of the initial recommendations.

Emergency Service, Hospital↗

The in vivo effects of bisGMA on murine uterine weight, nucleic acids and collagen.

The aim of this investigation was to evaluate the ability of commercial bisGMA to stimulate growth in an estrogen-sensitive target tissue. Adult, female, Swiss-Webster mice were ovariectomized and received either oil, estradiol (100 microg/kg), or one of two bisGMA doses (25 microg/kg or 100 microg/kg). Starting on the day of surgery, the hormone, drug or oil was injected subcutaneously 3 times a week. After 3 wk of treatment, the animals were sacrificed, the uteri removed, weighed and stored at -80 degrees C for biochemical analysis. The uteri from ovariectomized mice receiving high dose (100 microg/kg) bisGMA or estradiol showed a significant increase in normalized wet weight that was 29% and 786%, respectively, greater than the ovariectomized control uterine normalized weights. In the low bisGMA dose (25 microg/kg) group, normalized uterine wet weights were not statistically significant from ovariectomized controls. Biochemical analyses of uterine tissues revealed that estradiol resulted in maintaining DNA content, RNA content, RNA/DNA ratios and collagen content significantly above the ovariectomized control. Neither the low nor high doses of bisGMA stimulated RNA content, DNA content or RNA/DNA ratios above ovariectomized controls. However, the high dose (100 microg/kg) of bisGMA caused a significant increase above ovariectomized controls in uterine collagen content.

Animals↗

BAC representation of two low-copy regions of the genome of Arabidopsis thaliana.

Two regions of Arabidopsis chromosome 4, totalling 4.7 Mb, were assayed for representation in the TAMU and IGF BAC libraries. A directed approach to BAC identification was developed. Gel-purified DNA samples of YACs selected from the YAC-based physical map of chromosome 4 were used to probe high-density colony arrays of the BAC libraries. Strategies were developed that allowed the efficient construction of restriction maps and BAC contigs. Four hundred and sixty-four BACs were mapped, assembled into two complete contigs and used to analyse genomic representation. These BACs provided a mean of 9.4-fold redundant coverage, with a range of 2- to 22-fold. The representation provided by the two libraries showed almost coincident peaks and troughs, with a periodicity of approximately 200 kb. These results demonstrate that, provided both TAMU and IGF libraries are used in their entirety, BACs should provide an excellent resource for both physical mapping and sequencing of the Arabidopsis genome.

Arabidopsis↗

Resistance mutations in protease and reverse transcriptase genes of human immunodeficiency virus type 1 isolates from patients with combination antiretroviral therapy failure.

High-density oligonucleotide arrays were used to determine the sequence of the protease (PR) and reverse transcriptase (RT) genes of human immunodeficiency virus type 1 isolates from 35 patients in whom combination therapy that included a protease inhibitor had failed. Isolates had a median of three PR mutations (range, none to six). Three isolates had no known resistance mutations in PR. Twelve isolates (34%) had two or fewer resistance mutations in PR. The most commonly observed PR mutations were L10I, V82A/T/F, and L90M. No mutations were observed at codons 30 or 48. Mutations at RT codons 215 and 184 were observed in the majority of isolates. These data suggest that therapy can fail in some patients with relatively few PR resistance mutations. Clinical failure in the absence of resistance mutations implies inadequate drug exposure due to pharmacologic factors or suboptimal patient adherence to drug therapy.

Anti-HIV Agents↗

Menopause and tear function: the influence of prolactin and sex hormones on human tear production.

PURPOSE: The onset of dry eye is very common during menopause and may result from the loss of hormonal support. The purpose of this study was to assess the effect that changes in sex hormone and prolactin levels have on tear function in premenopausal and menopausal woman. METHODS: Women between the ages of 30 and 60 were solicited to participate in a study concerning menopause and tear function. One-hundred and ten women were given tear function tests (osmolarity, tear volume, tear flow, Schirmer's test) and serum levels were measured for total testosterone, estradiol, prolactin, and follicle stimulating hormone. RESULTS: For all women on hormone replacement therapy, we found a strong negative correlation between serum prolactin level and tear function. For women in menopause, total testosterone correlated positively with tear function, whereas for premenopausal women there was a negative correlation between total testosterone and tear function. Serum estradiol levels correlated positively with tear function for women 30-39 years of age, whereas for menopausal women the correlation was negative. CONCLUSIONS: This is the first demonstration in humans that tear production is correlated with serum prolactin and sex hormone levels prior to and during the menopause.

Adult↗

An in vitro study of the use of chelating agents in cleaning nickel-contaminated human skin: an alternative approach to preventing nickel allergic contact dermatitis.

The purpose of this study was to investigate the efficacy of organic ligands in cleaning human skin contaminated with nickel. 4 ligands were investigated, 5-chloro-7-iodoquinolin-8-ol (either as HL(1) or NaL(1)), ethylenediaminetetraacetic acid (either as H4L(2) or Na2H2L(2)), sodium diethyldithiocarbamate (NaL(3)) and L-histidine (HL(4)). The cytotoxicity of these ligands was assessed using HaCaT cells (a transformed human keratinocyte cell line). The cytotoxicity order of the ligands was NaL(1) >Na2H2L(2)>NaL(3)>HL(4). An in vitro methodology for examining nickel removal from viable human skin was developed. This methodology was then used to compare the efficiency of the ligands in removing nickel from skin, both alone and in combination with soap solutions. HL(1) and NaL(3) were no more effective than control solutions in removing nickel over the pH range 2-11. In contrast, both H4L(2) and HL(4) removed between 74 and 87% (mean=82+/-3%) of nickel from human skin over the same pH range. Nickel removal from skin by sodium lauryl ethoxy sulfate (SLES, the active ingredient in most liquid skin cleansers) was independent of concentration and no more effective than phosphate-buffered saline (PBS). The amount of nickel removed by PBS solutions of Na2H2L(2) and HL(4) was significantly greater than the amount removed by SLES and was concentration dependent. An evaluation of nickel removal from skin by commercial solid soap, liquid soap and PBS, both alone and with added Na2H2L(2) or HL(4), was conducted. Commercial liquid soap with added HL(4) was more effective than the untreated soap. PBS with either added Na2H2L(2) or HL(4) was more effective than PBS alone.

Buffers↗

Substance misuse and risk of aggression and offending among the severely mentally ill.

BACKGROUND: The aim of this study was to investigate whether 'dual diagnosis' (substance misuse and severe mental illness) is associated with aggression and offending. METHOD: Twenty-seven people meeting the criteria for both psychotic illness and a substance use disorder and 65 people with psychosis only were interviewed. Case notes were also examined and keyworkers asked to rate substance misuse and aggression. RESULTS: The severity of aggression and offending among this community treatment sample was low. Individuals with a dual diagnosis were significantly more likely than those with psychosis only to report any history of committing an offence (P = 0.001), or recent hostile behaviour (P = 0.001). Keyworkers were more likely to report recent aggression among the dually diagnosed (P = 0.01). Significant differences persisted when we used logistic regression to control for potentially confounding demographic and clinical variables. CONCLUSIONS: Dual diagnosis may be an important factor in aggression and offending among severely mentally ill individuals in inner-city areas. Accurate risk assessment requires examination of substance use.

Adult↗

Rationale and design. PRiSM Psychosis Study I.

BACKGROUND: This paper sets out the rationale for the PRiSM Psychosis Study, and the research design used. Nine accompanying papers present the main results. The questions addressed by the PRiSM Psychosis Study are: can the gains of experimental studies which have demonstrated benefits arising from treatment by community mental health teams be translated to routine settings? If so, are the benefits diluted in ordinary clinical practice? What are the costs? METHOD: A prospective nonrandomised controlled trial of two types of community mental health service, in two phases: case identification followed by patient interviews. For the case identification the research team conducted the complete ascertainment of all prevalent cases of psychosis in the two study catchment areas in the index year (1991-1992). From all 514 patients with psychotic disorders thus identified, 302 were randomly allocated for interview, along with a key informant clinician and a carer. Interviews were under taken at two time points, two years apart. RESULTS: This paper presents the socio-demographic, clinical and ethnic characteristics of the patients. CONCLUSIONS: The people with psychosis interviewed for the PRiSM Psychosis Study are representative of the whole epidemiologically based patient population identified.

Adult↗