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Biomedical subjects

S Johnson

Publications and source records attributed to S Johnson.

At least 271 records · Page 15Linked to original sources

A membrane-associated form of sucrose synthase and its potential role in synthesis of cellulose and callose in plants.

Sucrose synthase (SuSy; EC 2.4.1.13; sucrose + UDP reversible UDPglucose + fructose) has always been studied as a cytoplasmic enzyme in plant cells where it serves to degrade sucrose and provide carbon for respiration and synthesis of cell wall polysaccharides and starch. We report here that at least half of the total SuSy of developing cotton fibers (Gossypium hirsutum) is tightly associated with the plasma membrane. Therefore, this form of SuSy might serve to channel carbon directly from sucrose to cellulose and/or callose synthases in the plasma membrane. By using detached and permeabilized cotton fibers, we show that carbon from sucrose can be converted at high rates to both cellulose and callose. Synthesis of cellulose or callose is favored by addition of EGTA or calcium and cellobiose, respectively. These findings contrast with the traditional observation that when UDPglucose is used as substrate in vitro, callose is the major product synthesized. Immunolocalization studies show that SuSy can be localized at the fiber surface in patterns consistent with the deposition of cellulose or callose. Thus, these results support a model in which SuSy exists in a complex with the beta-glucan synthases and serves to channel carbon from sucrose to glucan.

Amino Acid Sequence↗

Simultaneous determination of dihydrocodeine and dihydromorphine in serum by gas chromatography-tandem mass spectrometry.

A sensitive and specific method was developed for the determination of dihydrocodeine and its metabolite dihydromorphine in human serum using codeine and morphine as internal standards. Measurement is performed with GC-tandem MS after one simple extraction step and derivatization to the pentafluoropropionic esters. Sensitivity of the method is excellent and allows for the reproducible quantification of dihydrocodeine and dihydromorphine with limits of quantification of 2 ng/ml and 40 pg/ml serum, respectively. The method is therefore well suited for investigation of the pharmacokinetics and the metabolism of dihydrocodeine.

Codeine↗

Development of body image, eating disturbance, and general psychological functioning in female adolescents: covariance structure modeling and longitudinal investigations.

OBJECTIVE: Covariance structure modeling (CSM) and longitudinal analyses were used to identify a possible causal sequence for factors that might lead to the development of body image and eating disturbance in adolescent females. METHOD: In Study 1, subjects were measured for level of obesity, perceived weight status, maturational timing, history of being teased about weight/size, body image, eating disturbance, and global psychological functioning. Study 2 was a systematic replication of Study 1 using different indices of body image and a more comprehensive assessment of eating disturbance. In Study 3, subjects from Study 1 were reassessed at a 3-year follow-up. RESULTS: The findings from Study 1 indicated that level of obesity and perceived weight, but not maturational timing, had a directional influence on the other variables. In addition, teasing history was significantly related to the development of body image and eating disturbance. CSM and path analyses with Studies 2 and 3 data generally replicated and extended the results from Study 1. DISCUSSION: These findings offer important insights into possible causal sequences for the development of body image and eating disturbance.

Adaptation, Psychological↗

BSH distributions in the canine head and a human patient using 11B MRI.

A 3D projection reconstruction (3DPR) method was used to obtain in vivo 11B images in a large canine brain tumor model and in a human infused with borocaptate sodium (BSH). Studies were performed in dogs with and without gliosarcomas implanted and grown to a size of 2-3 cm. The 3DPR method demonstrates a signal-to-noise ratio (SNR) that allows qualitative kinetic studies of the boron compound in normal and tumor tissue of the head. The measurements indicate initial uptake of the BSH compound in tumor to be less than that in muscle with no uptake in normal brain tissue. Moreover, uptake of BSH in tissue was found to lag the boron concentration in blood with delays that depend on tissue type. In addition, the first human boron images were obtained on a patient who underwent surgical resection and volumetric debulking of a large (7 cm) glioblastoma multiforme. BSH was readily taken up in residual tumor tissue, while diffusion into the resection volume was slower.

Animals↗

Rationale, design, and conduct of the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions.

There is growing and consistent evidence that estrogen use in postmenopausal women is associated with a substantial reduction in the occurrence of cardiovascular disease. However, remarkably little is known about the biological mechanisms by which estrogen therapy may influence risk. Even less information is available on the cardiovascular effects of combined estrogen-progestin use. PEPI was not designed to test whether estrogen and estrogen-progestin therapy is efficacious in the prevention of cardiovascular disease, as a much larger trial with clinical disease outcomes is needed to answer that question. However, PEPI will provide critical evidence regarding the potential effectiveness of the various estrogen and estrogen/progestin regimens ni altering risk factors for cardiovascular disease in women. Detailed information on factors such as adherence, side effects, and general patient acceptability will also be ascertained. The main results from PEPI will provide the scientific community with information on the basic actions of estrogen and estrogen/progestin therapy on four biological systems believed to be causally associated with cardiovascular disease occurrence. Further, since the trial is designed to continue for 3 years, PEPI will be able to provide information on longer term as well as short-term effects on these systems. Finally, the results from PEPI should enable women and their physicians to select an optimal hormonal regimen, i.e., one that is acceptable, safe, and provides the most beneficial and least deleterious changes in cardiovascular and other risk factors.

Bone Density↗

To use or to refuse cocaine--the deciding factors.

Two types of narratives were obtained from 35 cocaine-addicted patients: narratives about using cocaine and narratives about not using cocaine. The most prevalent factors in using cocaine were (a) having enough money, (b) wish to end physical/emotional pain, and (c) wish/decision to use. The factors in narratives about not using cocaine were (a) patient arranged conditions to be nonstimulating for using cocaine, (b) recognition of bad consequences, and (c) wish/decision not to use. It is clear in both the cocaine-using episodes and not-using episodes that the patient's wish/decision is important. The conditions for using cocaine tended to be more external, whereas those for not using tended to be more internal. Similar conditions were found by a questionnaire method. A major treatment implication of these findings is that the focus of therapy can be directed to planning strategies to minimize influence of the external factors and to rehearse strategies to prepare for situations involving cues that influence use of cocaine.

Adult↗

Insight and psychosis: a social perspective.

The last 5 years have seen a resurgence of interest in insight, with better definitions and operationalizations of the concept. However, recent work has paid little attention to the ways in which patients' understanding of their illnesses may be shaped by perceptions of mental illness and treatment prevailing in their cultures and social groups. We review work by social scientists on cultural and social variations in lay perceptions of mental illness and on the stigma attached to mental illness, and argue that these varying views are likely to be one of the influences on insight, requiring further exploration in research on this subject.

Attitude↗

Natural history of trisomy 21 fetuses with increased nuchal translucency thickness.

Increased fetal nuchal translucency thickness at 10-14 weeks of gestation can identify 80% of trisomy 21 pregnancies. However, a potential disadvantage of screening in the first trimester of pregnancy is that earlier screening preferentially identifies those chromosomally abnormal pregnancies that are destined to miscarry. In this study, we report on the outcome of six fetuses with increased nuchal translucency thickness and trisomy 21 whose parents chose to continue with the pregnancy. During the second trimester, the nuchal translucency resolved in five of the cases and in one it evolved into nuchal edema. Therefore, resolution of translucency with advancing gestation is not indicative of a normal karyotype. All pregnancies resulted in live births, suggesting that increased nuchal translucency does not necessarily identify those trisomic fetuses that are destined to die in utero.

Adult↗

Clostridium difficile-associated diarrhea and colitis.

OBJECTIVES: To review and summarize the status of diagnosis, epidemiology, infection control, and treatment of Clostridium difficile-associated disease (CDAD). DIAGNOSIS: A case definition of CDAD should include the presence of symptoms (usually diarrhea) and at least one of the following positive tests: endoscopy revealing pseudomembranes, stool cytotoxicity test for toxin B, stool enzyme immunoassay for toxin A or B, or stool culture for C difficile (preferably with confirmation of organism toxicity if a direct stool toxin test is negative or not done). Testing of asymptomatic patients, including those who are asymptomatic after treatment, is not recommended other than for epidemiologic purposes. Lower gastrointestinal endoscopy is the only diagnostic test for pseudomembranous colitis, but it is expensive, invasive, and insensitive (51% to 55%) for the diagnosis of CDAD. Stool culture is the most sensitive laboratory test currently in clinical use, but it is not as specific as the cell cytotoxicity assay. EPIDEMIOLOGY: C difficile is the most frequently identified cause of nosocomial diarrhea. The majority of C difficile infections are acquired nosocomially, and most patients remain asymptomatic following acquisition. Antimicrobial exposure is the greatest risk factor for patients, especially clindamycin, cephalosporins, and penicillins, although virtually every antimicrobial has been implicated. Cases of CDAD unassociated with prior antimicrobial or antineoplastic use are very rare. Hands of personnel, as well as a variety of environmental sites within institutions, have been found to be contaminated with C difficile, which can persist as spores for many months. Contaminated commodes, bathing tubs, and electronic thermometers have been implicated as sources of C difficile. Symptomatic and asymptomatic infected patients are the major reservoirs and sources for environmental contamination. Both genotypic and phenotypic typing systems for C difficile are available and have enhanced epidemiologic investigation greatly. INFECTION CONTROL: Successful infection control measures designed to prevent horizontal transmission include the use of gloves in handling body substances and replacement of electronic thermometers with disposable devices. Isolation, cohorting, handwashing, environmental disinfection, and treatment of asymptomatic carriers are recommended practices for which convincing data of efficacy are not available. The most successful control measure directed at reduction in symptomatic disease has been antimicrobial restriction. TREATMENT: Treatment of symptomatic (but not asymptomatic) patients with metronidazole or vancomycin for 10 days is effective; metronidazole may be preferred to reduce risk of vancomycin resistance among other organisms in hospitals. Recurrence of symptoms occurs in 7% to 20% of patients and is due to both relapse and reinfection. Over 90% of first recurrences can be treated successfully in the same manner as initial cases. Combination treatment with vancomycin plus rifampin or the addition orally of the yeast Saccharomyces boulardii to vancomycin or metronidazole treatment has been shown to prevent subsequent diarrhea in patients with recurrent disease.

Bacterial Proteins↗

Elevated serum antibody response to toxin A following splenic abscess due to Clostridium difficile.

Splenic abscess and segmental small-bowel infarction were documented in a patient from whose splenic culture Clostridium difficile was isolated. A week and a half after splenectomy and partial bowel resection, diarrhea developed and stool cultures yielded an isolate of C. difficile that was identical to the abscess isolate when subjected to restriction endonuclease analysis. The level of IgG antibody to toxin A was markedly higher in serum from this patient than in sera from patients with C. difficile diarrhea alone. This case illustrates a rare but serious extraintestinal manifestation of infection with C. difficile and suggests a correlation between serum levels of IgG antibody to toxin A and systemic exposure to C. difficile, a typically noninvasive enteric pathogen.

Abscess↗

Further characterisation of a monoclonal antibody reactive with Escherichia coli O157:H7.

Monoclonal antibody (MAb) 4E8C12 has been previously reported to recognise low mol. wt proteins from enterohaemorrhagic Escherichia coli (EHEC) serotypes O157:H7 and O26:H11. Crude lipopolysaccharide (LPS) preparations from proteinase K-digested bacterial suspensions reacted in Western blots with MAb 4E8C12, as did highly purified LPS from O157:H7 strains. The material recognised by this antibody was, therefore, LPS. The LPS epitope was identified by a whole-cell ELISA in several EHEC, verotoxin producing E. coli (VTEC) and verotoxin-negative strains in addition to E. coli serotypes O157:H7 and O26:H11. Acriflavine and bile salts enhanced the production or availability of the epitope at the cell surface and in culture supernates. These data indicate that the presence of the epitope did not correlate with the virulence of these organisms.

Animals↗

Short stature in homozygous beta-thalassaemia is due to disproportionate truncal shortening.

BACKGROUND AND OBJECTIVE: Growth failure in homozygous beta-thalassaemia has been recognized for many years, and has persisted despite major treatment advances. In this cross-sectional study, sitting and standing height were measured to determine whether growth failure was disproportionate. DESIGN: Patient data were analysed in three age groups, 2-10 years, 11-18 years and 19 and over. Sitting height and subischial leg length were also determined in a cohort of parents (n = 19) and normal Greek adolescents (n = 32). PATIENTS AND MEASUREMENTS: Of the known 156 patients with homozygous beta-thalassaemia in the State of Victoria, 154 (98.7%) attend our institution. Sitting and standing heights were measured, using Harpenden stadiometers, in 57 of 60 (95%) patients aged 2-18 years and in a random selection of 51 of 89 patients aged 19 and over (57%). Measurements are expressed as mean +/- SDS. Other data analysed included serum concentrations of ferritin, zinc, copper, FSH, LH, oestradiol and testosterone, according to standard laboratory assays, together with pubertal status and bone age in patients aged less than 19 years. RESULTS: Standing height standard deviation scores in the 2-10 age group were -0.687 +/- 0.861 (n = 9), in the 11-18 age group were -1.838 +/- 1.413 (n = 48) and in the age group 19 and over were -1.175 +/- 1.126. In individuals aged 2-10 years, sitting height standard deviation scores (SDS) were -1.56 +/- 1.02, in individuals 11-18 years were -3.76 +/- 1.51 (n = 48), and in individuals 19 years and over were -2.77 +/- 1.20 (n = 51), compared with subischial leg length SDS which were, in individuals aged 2-10 years 0.214 +/- 0.91; in 11-18 years, -0.063 +/- 1.347, and in individuals 19 and over, 0.37 +/- 1.18. These data show that the reduction in standing height was the result of truncal shortening. Mean sitting height SDS was significantly lower in children with homozygous beta-thalassaemia, compared with their parents (P < 0.001), and in a subgroup of Greek adolescents with homozygous beta-thalassaemia compared with age and sex matched normal Greek adolescents (P < 0.001). No correlation was found between truncal shortening and other clinical and biochemical variables measured. CONCLUSIONS: Short stature in our patients with homozygous beta-thalassaemia is due to disproportionate truncal shortening. The aetiology of truncal shortening in this patient group is likely to be multifactorial, although hypogonadism and chelation therapy may be contributory factors.

Adolescent↗

Selective neutralization of a bacterial enterotoxin by serum immunoglobulin A in response to mucosal disease.

One-third of convalescent-phase serum samples (6 of 18) from patients with Clostridium difficle-associated diarrhea demonstrated neutralization of the clostridial enterotoxin, toxin A. Although appreciable amounts of toxin A-specific immunoglobulin G (IgG) and IgA were present in these sera, the ability to neutralize the cytotoxic activity of toxin A on OTF9-63 cells in vitro was confined to the IgA fraction and the IgA1 subclass in serum samples from all six patients. In contrast to the patients with C. difficile diarrhea, this activity was present in both the IgA and IgG fractions in sera from two C. difficile-infected patients without diarrhea, one of whom presented with a splenic abscess. Sera and purified IgA which neutralized the cytotoxicity of toxin A on OTF9-63 cell cultures in vitro also neutralized the enterotoxicity of toxin A in rabbit ileal loops in vivo. This activity was not Fc dependent, since IgA retained neutralizing activity after pepsin digestion and F(ab')2 purification. The transition from nonneutralizing toxin A-specific IgA in the acute-phase sera to neutralizing specific IgA in the convalescent-phase sera was accompanied by a shift from a polymeric to a predominantly monomeric form of specific IgA. However, the neutralizing activity in convalescent-phase sera was present as both monomeric and polymeric IgA. Convalescent-phase sera from other patients with C. difficile diarrhea that failed to neutralize toxin A also failed to produce a predominantly monomeric-form specific IgA response. We conclude that serum IgA, not IgG, characteristically neutralizes toxin A in patients with C. difficile diarrhea who develop neutralizing systemic responses. This neutralization of an enteric bacterial toxin is a unique and selective role for serum IgA which provides a novel functional link between the systemic and mucosal immune systems.

Acute Disease↗

Comparison of arbitrarily primed PCR with restriction endonuclease and immunoblot analyses for typing Clostridium difficile isolates.

Arbitrarily primed PCR (AP-PCR) was used to genotype 26 clinical isolates of Clostridium difficile previously analyzed by immunoblotting (IB) and 20 isolates typed by restriction endonuclease analysis (REA) with HindIII. Two levels of differentiation were achieved with the AP-PCR approach by use of two different arbitrary primers. With the 19-mer arbitrary primer T-7 (first level of differentiation), a good correlation was found between IB and AP-PCR typing. Twenty isolates grouped into six IB types were separated into seven major AP-PCR types. These seven AP-PCR groups were further discriminated into 12 subtypes after genotyping with the arbitrary primer PG-05 (second level of differentiation). The remaining six isolates, all of different IB types, showed a unique and distinct DNA banding pattern with both of the arbitrary primers, T-7 and PG-05. Twenty isolates representing 20 REA types from 15 REA groups were resolved into 13 AP-PCR DNA profiles with the arbitrary primer T-7. A good correlation was found at this level of differentiation between the major REA groups, Y and M, and AP-PCR typing. While AP-PCR with this primer failed to differentiate isolates in REA groups J, G, R, and B, AP-PCR with PG-05 resolved these four isolates into four distinct AP-PCR types. In addition, one of three M strains and one of four Y strains displayed a slightly different DNA banding pattern by AP-PCR (with PG-05) from that of the other strains in the group. We conclude that AP-PCR is a rapid and sensitive method which not only complements other typing schemes but also may be a substitute and prove to be especially suited for immediate epidemiological tracking of nosocomial infections due to C. difficile.

Bacterial Typing Techniques↗