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T Johnson

Publications and source records attributed to T Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Genetic variability in responses to caloric restriction in animals and in regulation of metabolism and obesity in humans.

Panel 5 focused on genetic factors that might mediate or moderate the effects of caloric restriction (CR) on longevity. Panel members stated that currently there is limited information directly addressing these issues. Therefore, they focused attention on what studies could be done. In addition, the panel believed that certain conceptual issues merited clarification and focused attention on this issue. Human studies and studies of nonhuman model organisms were discussed. The panel found at least three reasons why it would be valuable to find genes that influence the (putative) longevity-promoting effect of CR in humans. Such knowledge would offer: (a) the ability to predict individual responses to CR; (b) increased understanding of physiological mechanisms; and (c) the potential to develop mechanism-based interventions to promote longevity or healthy aging. In addition, the panel emphasized several macro-level recommendations regarding research strategies to avoid, research strategies to emphasize, and resources needing development.

Animals↗
PubMed2001

An audit into homeless families in temporary accommodation.

This article describes a clinical audit project undertaken in a number of hostels providing temporary housing for homeless families and individuals in Hinckley, Leicestershire. The audit, carried out over a 6-week period, aimed to collect information about the health and social needs of the residents in the hostels to determine whether an on-site dedicated health visiting service would be of any benefit to them. Family members housed in three council-run hostels were interviewed and a detailed questionnaire was completed. This was used to gather information about the facilities in the hostels, the nutritional and mental status and health and social needs of the residents, the uptake of childhood immunizations and child health surveillance. It also provided information about the resident families' contact with their family health visitor. Families were living in cramped conditions with shared facilities and no safe play areas for their children. The audit clearly demonstrated that the residents living in the hostels had a range of health problems similar to those described in the literature about the homeless. As a result of the audit, a number of recommendations were made which are discussed in this article.

Adolescent↗
PubMed2000

Substituted benzamide inhibitors of human rhinovirus 3C protease: structure-based design, synthesis, and biological evaluation.

A series of nonpeptide benzamide-containing inhibitors of human rhinovirus (HRV) 3C protease was identified using structure-based design. The design, synthesis, and biological evaluation of these inhibitors are reported. A Michael acceptor was combined with a benzamide core mimicking the P1 recognition element of the natural 3CP substrate. alpha,beta-Unsaturated cinnamate esters irreversibly inhibited the 3CP and displayed antiviral activity (EC(50) 0.60 microM, HRV-16 infected H1-HeLa cells). On the basis of cocrystal structure information, a library of substituted benzamide derivatives was prepared using parallel synthesis on solid support. A 1.9 A cocrystal structure of a benzamide inhibitor in complex with the 3CP revealed a binding mode similar to that initially modeled wherein covalent attachment of the nucleophilic cysteine residue is observed. Unsaturated ketones displayed potent reversible inhibition but were inactive in the cellular antiviral assay and were found to react with nucleophilic thiols such as DTT.

3C Viral Proteases↗
PubMed2000

A novel precursor recognition element facilitates posttranslational binding to the signal recognition particle in chloroplasts.

Signal recognition particles (SRPs) in the cytosols of prokaryotes and eukaryotes are used to target proteins to cytoplasmic membranes and the endoplasmic reticulum, respectively. The mechanism of targeting relies on cotranslational SRP binding to hydrophobic signal sequences. An organellar SRP identified in chloroplasts (cpSRP) is unusual in that it functions posttranslationally to localize a subset of nuclear-encoded thylakoid proteins. In assays that reconstitute thylakoid integration of the light harvesting chlorophyll-binding protein (LHCP), stromal cpSRP binds LHCP posttranslationally to form a cpSRP/LHCP transit complex, which is believed to represent the LHCP form targeted to thylakoids. In this investigation, we have identified an 18-aa sequence motif in LHCP (L18) that, along with a hydrophobic domain, is required for transit complex formation. Fusion of L18 to the amino terminus of an endoplasmic reticulum-targeted protein, preprolactin, led to transit complex formation whereas wild-type preprolactin exhibited no ability to form a transit complex. In addition, a synthetic L18 peptide, which competed with LHCP for transit complex formation, caused a parallel inhibition of LHCP integration. Translocation of proteins by the thylakoid Sec and Delta pH transport systems was unaffected by the highest concentration of L18 peptide examined. Our data indicate that a motif contained in L18 functions in precursor recruitment to the posttranslational SRP pathway, one of at least four different thylakoid sorting pathways used by chloroplasts.

Amino Acid Sequence↗
PubMed2000

Quantitative genetics: Resolving wing shape genes.

Recent high-resolution quantitative mapping experiments aimed at elucidating the genetics of natural variation for wing shape in fruit-flies suggest that very many genes can subtly influence the trait.

Animals↗
PubMed2000

Evaluation of efficacy and complications: primary pediatric orbital implants after enucleation.

BACKGROUND: Orbital implants are used routinely in pediatric patients at the time of enucleation. Complications, such as exposure, ptosis, and infection, may occur after implantation. Controversy continues regarding the rate of complications with newer implants in the pediatric population. OBJECTIVE: To examine the effects of orbital implants on children whose eyes have been enucleated. METHODS: Records of orbital implantation after enucleation performed by 5 surgeons on 120 pediatric patients (123 eyes) over a 10.5-year period were reviewed retrospectively. Demographic data, ocular diagnosis, prior ophthalmic surgery, implant characteristics, and postoperative complications were described using a standardized format for all patients, with a minimum of 6 months of follow-up (mean, 3 years). RESULTS: Complications were observed in 7 eyes (5.7%). Implant exposure (1 [0.8%]), implant extrusion (0 [0%), and implant migration (3 [2.4%) were rare. One hundred eighteen eyes (96%) had good cosmesis and 120 (98%) had good motility. CONCLUSIONS: Orbital implantation after enucleation is successful in the pediatric population. Complications are minimal. Hydroxyapatite implants were not associated with unacceptable complications in this pediatric population.

Adolescent↗
PubMed2000

Liquid-based cervical-cell collection with brushes and wooden spatulas: a comparison of 100 conventional smears from high-risk women to liquid-fixed cytocentrifuge slides, demonstrating a cost-effective, alternative monolayer slide preparation method.

Our purpose was to demonstrate that 17.5-mm liquid-based cytocentrifuge circle-slides made using a Hettich (Andreas Hettich Co., Tuttlingen, Germany) cytocentrifuge are at least as efficacious as conventional smears for detecting cervical abnormalities. One hundred conventional smears were collected with cytobrushes and wooden spatulas from high-risk women. Both devices were then placed into CytoRich Red (AutoCyte, Inc., Burlington, NC). Cells were concentrated from CytoRich Red by centrifugation and suspended in CytoRich Yellow. Two 17.5-mm circle-slides were produced, compared to each other in order to test reproducibility of diagnoses between slides, and compared to conventional slides. Sixty-five normals, three ASCUS, three LSIL, and two HSIL matched. Overall, cytocentrifugation yielded 27 additional findings among 25 cases. Also, it downgraded one conventional ASCUS to normal (immature metaplasia and chronic inflammation) and one conventional HSIL to normal (transitional cell metaplasia). Cytocentrifugation of 14 conventional normals afforded four ASCUS and 10 LSIL. Cytocentrifugation of 11 conventional ASCUS afforded nine LSIL and two HSIL (one with AIS). One HSIL + AIS was found with a conventional HSIL. Cytobrushes and wooden spatulas can be used to collect material for liquid-based cervico-vaginal cytology if they are placed into CytoRich Red. Hettich cytocentrifuge slides were more reliable than conventional smears in presenting well-dispersed, sharply imaged cells, affording greater diagnostic sensitivity and certainty. Compared to previous split-sample studies, three different outcomes were noted: 1) the endocervical component was consistently well-represented; 2) AIS was seen more often in liquid-based slides; and 3) the liquid-based slide did not underdiagnose its conventional companion. The liquid-based preparations downgraded one ASCUS to normal and one conventional HSIL to transitional-cell metaplasia. Histology correlation of these two cases agreed with the liquid-based cytology diagnoses, which validates their specificity. These improvements are ascribed to differences in fixation and processing. The low cost, ease of operation, and reusable chambers of the Hettich cytocentrifuge make it a cost-effective liquid-based cytology instrument, especially for small to intermediate-size laboratories. The claims that this paper makes must be proven by additional studies, and test implementation needs to be scrutinized by appropriate regulatory agencies whose standards may vary from country to country. Diagn. Cytopathol. 2000;22:86-91.

Centrifugation↗
PubMed2000

The evolution of mutation rates: separating causes from consequences.

Natural selection can adjust the rate of mutation in a population by acting on allelic variation affecting processes of DNA replication and repair. Because mutation is the ultimate source of the genetic variation required for adaptation, it can be appealing to suppose that the genomic mutation rate is adjusted to a level that best promotes adaptation. Most mutations with phenotypic effects are harmful, however, and thus there is relentless selection within populations for lower genomic mutation rates. Selection on beneficial mutations can counter this effect by favoring alleles that raise the mutation rate, but the effect of beneficial mutations on the genomic mutation rate is extremely sensitive to recombination and is unlikely to be important in sexual populations. In contrast, high genomic mutation rates can evolve in asexual populations under the influence of beneficial mutations, but this phenomenon is probably of limited adaptive significance and represents, at best, a temporary reprieve from the continual selection pressure to reduce mutation. The physiological cost of reducing mutation below the low level observed in most populations may be the most important factor in setting the genomic mutation rate in sexual and asexual systems, regardless of the benefits of mutation in producing new adaptive variation. Maintenance of mutation rates higher than the minimum set by this "cost of fidelity" is likely only under special circumstances.

Animals↗
PubMed2000

Expression of cytoskeletal proteins during the course of experimental diabetic nephropathy.

AIMS/HYPOTHESIS: Diabetic nephropathy is characterised by structural changes known to be associated in non-diabetic nephropathies with the expression of the cytoskeletal proteins a-smooth muscle actin and vimentin. We aimed to investigate the expression of cytoskeletal proteins in experimental diabetic nephropathy. METHODS: Rats were made diabetic by an injection of streptozotocin (45 mg/kg). Groups of rats (n = 6) and their respective controls (n = 4) were killed at different time intervals. (days 7, 15, 30, 60, 90 and 120). We also studied two groups of diabetic rats treated with a long-acting insulin; the first (n = 8) was treated from the induction of diabetes and the second (n = 8) received insulin from day 15 onward. At each time-point, kidney function, proteinuria and histology were evaluated. Cytoskeletal proteins and collagens III and IV deposition was determined by immunohistochemistry. Changes in the transcription of the cytoskeletal proteins was determined by northern blot analysis. RESULTS: Although normal glomeruli did not express alpha-smooth muscle actin until late in the time course, it was detected in diabetic mesangium from day 7 onward. In the interstitium, it appeared in a perivascular and peritubular distribution. Vimentin was detectable within normal glomerular epithelial cells and increased rapidly (days 7 and 15) in diabetic rats. Vimentin also appeared early within the lining of the peritubular capillaries and damaged diabetic tubules. These changes were associated with a delayed increased transcription of alpha-smooth muscle actin and vimentin. Treatment with insulin (early or late) attenuated and reversed respectively the expression of cytoskeletal proteins and collagens within diabetic kidneys. Close correlations were noted between the number of alpha-smooth muscle actin positive cells within diabetic glomeruli and mesangial expansion (r = 0.46, p < 0.02) as well as interstitial alpha-smooth muscle actin positive cells and interstitial fibrosis (r = 0.51, p < 0.002). CONCLUSION/INTERPRETATION: Changes in the expression of cytoskeletal proteins within the kidneys of diabetic rats suggest a role for alpha-smooth muscle actin and vimentin in the pathogenesis of diabetic kidney disease.

Actins↗
PubMed2000

TA90-IC, a new marker for advanced colon cancer.

BACKGROUND: Although carcinoembryonic antigen (CEA) is the most frequently used marker for colon cancer, it is elevated in only 70% of patients with advanced disease and in even fewer patients with earlier stages of disease. We previously identified a 90-kDa glycoprotein, TA90, which is present in serum in the form of circulating immune complexes. TA90 is found in a variety of solid neoplasms but rarely in healthy controls (3.2%). We hypothesized that this new tumor-associated antigen may be a useful marker for colon cancer. METHODS: Serum samples from 59 patients with known colon adenocarcinoma were analyzed for the presence of CEA and TA90. Fifty-one (86%) patients had distant metastases; the remaining patients had clinically localized primary colon cancer. A murine monoclonal antibody-based enzyme-linked immunosorbent assay was used to measure concentrations of TA90-specific circulating immune complexes (TA90-IC). A positive value was defined as an optical density of more than 0.410 at 405 nm. Forty-seven (80%) of the 59 patients had serum samples for TA90 and CEA drawn at the same time. RESULTS: TA90-IC concentrations were elevated more frequently than CEA concentrations (82.9% vs. 70.2%; P = .134). The combination of both markers identified more patients with colon carcinoma than did either marker alone (93.6%; P < .001). CONCLUSIONS: Concomitant use of TA90-IC and CEA identified 93.6% of patients with advanced colon cancer. The role of TA90-IC in screening and monitoring progression of earlier disease deserves further investigation.

Adult↗
PubMed2000

Cytotoxic clerodane diterpene esters from Laetia corymbulosa.

Three cytotoxic clerodane diterpene esters, corymbulosins A-C, were isolated from an organic extract of the fruit of Laetia corymbulosa (Flacourtiaceae) from Peru. The structures were determined by spectroscopic methods as clerodane diterpenes unsaturated at C-3, C-13(16) and C-14. Corymbulosin A was esterified at C-2 with a decadienoate moiety, while corymbulosins B and C were C-2 epimers esterified at C-6 with a decanoate moiety.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Differences in somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia.

BACKGROUND: Irritable bowel syndrome (IBS) and fibromyalgia (FM) are considered chronic syndromes of altered visceral and somatic perception, respectively. Because there is a significant overlap of IBS and FM, shared pathophysiological mechanisms have been suggested. Although visceral perception has been well studied in IBS, somatic perception has not. AIMS: To compare hypervigilance and altered sensory perception in response to somatic stimuli in patients with IBS, IBS+FM, and healthy controls. METHODS: Eleven IBS females (mean age 40), 11 IBS+FM females (mean age 46), and ten healthy female controls (mean age 39) rated pain perception in response to pressure stimuli administered to active somatic tender points, non-tender control points and the T-12 dermatome, delivered in a predictable ascending series, and delivered in an unpredictable randomized fashion (fixed stimulus). RESULTS: Although IBS patients had similar pain thresholds during the ascending series compared with controls, they were found to have somatic hypoalgesia with higher pain thresholds and lower pain frequency and severity during fixed stimulus series compared with IBS+FM patients and controls (P<0.05). Patients with IBS+FM were more bothered by the somatic stimuli and had somatic hyperalgesia with lower pain thresholds and higher pain frequency and severity. CONCLUSIONS: Both hypervigilance and somatic hypoalgesia contribute to the altered somatic perception in IBS patients. Co-morbidity with FM results in somatic hyperalgesia in IBS patients.

Adult↗
PubMed2000

Novel cytotoxic diterpenes from Casearia arborea.

Cytotoxicity-guided fractionation of the dichloromethane-methanol extract of the roots of Casearia arborea yielded five novel clerodane diterpenes, casearborins A-E (1-5), as well as cucurbitacin B. The presence of cucurbitacins glycosides was also detected. The absolute configuration of casearborin E was determined by X-ray crystallography.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Listeners as co-narrators.

A collaborative theory of narrative story-telling was tested in two experiments that examined what listeners do and their effect on the narrator. In 63 unacquainted dyads (81 women and 45 men), a narrator told his or her own close-call story. The listeners made 2 different kinds of listener responses: Generic responses included nodding and vocalizations such as "mhm." Specific responses, such as wincing or exclaiming, were tightly connected to (and served to illustrate) what the narrator was saying at the moment. In experimental conditions that distracted listeners from the narrative content, listeners made fewer responses, especially specific ones, and the narrators also told their stories significantly less well, particularly at what should have been the dramatic ending. Thus, listeners were co-narrators both through their own specific responses, which helped illustrate the story, and in their apparent effect on the narrator's performance. The results demonstrate the importance of moment-by-moment collaboration in face-to-face dialogue.

Adult↗
PubMed2000

Continuous pH and Pco2 monitoring during respiratory failure in children with the Paratrend 7 inserted into the peripheral venous system.

CONTEXT: The Paratrend monitor provides continuous arterial blood gas monitoring after insertion through a >/=20-gauge arterial cannula. OBJECTIVE: To determine the correlation of arterial blood gas values and the Paratrend monitor placed through a peripheral intravenous catheter. DESIGN: Prospective, open-label evaluation. SETTING: University-based pediatric intensive care unit. PATIENTS: Infants and children with respiratory failure and arterial access. RESULTS: The cohort included 23 infants and children. A total of 100 sample sets (Paratrend/ABG Pco(2) and pH values) were collected. The absolute difference between the arterial and Paratrend Pco(2) was 2. 9 +/- 1.8 mm Hg (range 0 to 9 mm Hg). Linear regression analysis of Paratrend Pco(2) versus arterial Pco(2) resulted in r = 0.97 and r(2) = 0.9479 (P <.001). Bland-Altman analysis of Pco(2) values demonstrated a bias +/- precision of -2.1 +/- 2.7 mm Hg. The absolute difference between arterial and Paratrend pH was 0.04 +/- 0. 02 units (range 0 to 0.15 units). Linear regression analysis of Paratrend pH versus arterial pH resulted in r = 0.83 and r(2) = 0. 7016 (P <.0001). Bland-Altman analysis of pH values revealed a bias +/- precision of 0.03 +/- 0.03 units. CONCLUSIONS: Inserted through a peripheral intravenous cannula, the Paratrend monitor can be used to provide an accurate estimation of arterial blood gas values in children with respiratory failure.

Adolescent↗
PubMed2000

Intravenous azathioprine in severe ulcerative colitis: a pilot study.

OBJECTIVE: Azathioprine use in acute ulcerative colitis has been limited by its perceived long onset of action. The aim of this study was to determine the safety and clinical effect of an i.v. loading dose of azathioprine in the setting of severe steroid refractory ulcerative colitis. METHODS: Nine hospitalized patients with severe steroid refractory ulcerative colitis were enrolled. Patients 1-3 received 20 mg/kg i.v. azathioprine over 36 h. Patients 4-6 received 40 mg/kg i.v. azathioprine over 36 h. Patients 7-9 received 40 mg/kg i.v. azathioprine as three 8-h infusions over 3 days. Clinical remission was defined as steroid withdrawal and an Ulcerative Colitis Disease Activity Index score of 0. The Inflammatory Bowel Disease Questionnaire was obtained at each visit. White blood cell concentrations and erythrocyte concentrations of 6-thioguanine were obtained. RESULTS: Five of nine patients (56%) had a response and avoided colectomy. Three of nine patients (33%) met the definition for clinical remission. Response was seen within 4 wk. The mean 6-thioguanine concentration for those five patients at 12 wk after infusion was 148.2 pmol/8 x 10(8). Two patients had transient leukopenia and one had transient hepatotoxicity. CONCLUSIONS: Intravenous azathioprine appears to be safe and of clinical benefit in inducing response and avoiding colectomy in severe steroid refractory ulcerative colitis. Data from an i.v. azathioprine trial in Crohn's disease suggests oral dosing alone may obtain the same results. The role of oral dosing alone in severe ulcerative colitis and the role of azathioprine metabolite levels in monitoring efficacy should be investigated further.

Adult↗
PubMed2000

Gay and lesbian couples in therapy: perspectives for the contemporary family therapist.

This paper outlines the major concerns of gay and lesbian couples who seek therapy. Presenting problems are classified as either internal to the relationship or as external (contextual) ones that reflect the influence of oppressive cultural and gender biases. Throughout the article, distinctive therapy methods are described that address the unique concerns of lesbian and gay couples, with special sensitivity to heterosexist and homophobic bias.

Adult↗