Biomedical subjects

T Johnson

Publications and source records attributed to T Johnson.

At least 37 records · Page 2Linked to original sources

PubMed2001

Prospective studies of cothymia (mixed anxiety-depression): how do they inform clinical practice?

We suggest that the diagnosis of mixed anxiety depression at syndromal level (i.e. both anxiety and depressive diagnoses present in the same person and given equal status) is valuable clinically and should be introduced into the formal classification of neurotic and mood disorders. Evidence is given from a systematic review that cothymia has a significantly worse outcome than either an anxiety or a depressive diagnosis alone (p < 0.0001). Long-term follow-up data in a 12-year outcome study of neurotic disorder reinforce this finding both with regard to social functioning and the clinical course of anxiety and depressive disorders; these were significantly worse (P < 0.001 and P < 0.02 respectively) in those with cothymia compared with single anxiety disorders. These outcome differences are much greater than those between anxiety and depressive disorders alone.

Anxiety Disorders↗

PubMed2001

Hormesis and debilitation effects in stress experiments using the nematode worm Caenorhabditis elegans: the model of balance between cell damage and HSP levels.

In this article, we discuss mechanisms responsible for the effects of heat treatment on increasing subsequent survival in the nematode worm Caenorhabditis elegans. We assume that the balance between damage associated with exposure to thermal stress and the level of heat shock proteins produced plays a key role in forming the age-pattern of mortality and survival in stress experiments. We propose a stochastic model of stress, which describes the accumulation of damage in the cells of the worm as the worm ages. The model replicates the age trajectories of experimental survival curves in three experiments in which worms were heat-treated for 0, 1, 2, 4, 6, or 8h. We also discuss analytical results and directions of further research. The proposed method of stochastic modelling of survival data provides a new approach that can be used to model, analyse and extrapolate experimental results.

Aging↗

PubMed2001

Sexual assault and alcohol abuse: a comparison of lesbians and heterosexual women.

PURPOSE: To compare and contrast lesbians' and heterosexual women's experiences of sexual assault and to investigate relationships between sexual assault and alcohol abuse. METHODS: In-depth interviews were conducted with 63 lesbians and a demographically matched comparison group of 57 heterosexual women. Lesbians' and heterosexual women's experiences of sexual assault, drinking levels, and alcohol-abuse indicators were compared using descriptive statistics. LISREL analysis was used to test the effects of sexual assault on a latent measure of alcohol abuse. RESULTS: Lesbians reported more childhood sexual experiences, were more likely to meet the study definition for childhood sexual abuse (CSA), and were more likely to perceive themselves as having been sexually abused as children. CSA was associated with lifetime alcohol abuse in both lesbian and heterosexual women. However, adult sexual assault (ASA) was associated with alcohol abuse only in heterosexual women. IMPLICATIONS: Sexual assault is a common experience among both lesbians and heterosexual women. Findings emphasize the importance of asking about sexual assault in health histories, and assessing clients for substance abuse and other sequelae of sexual assault.

Adult↗

PubMed2001

In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.

Africa, Western↗

PubMed2001

Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: We evaluated etanercept, a human soluble tumor necrosis factor receptor: Fc fusion protein, for the treatment of active Crohn's disease. METHODS: Forty-three patients with moderate to severe Crohn's disease were enrolled in an 8-week placebo-controlled trial. Patients were randomized to subcutaneous etanercept 25 mg or placebo twice weekly. The primary outcome measure was clinical response at week 4, defined as a decrease in the baseline Crohn's Disease Activity Index score > or =70 points or a Crohn's Disease Activity Index score <150 points. RESULTS: At week 4, 39% of etanercept-treated patients had clinical response as compared with 45% of placebo-treated patients (P = 0.763). The frequency of common adverse events including headache, new injection site reaction, asthenia, abdominal pain, Crohn's disease-related anemia, and skin disorders was similar in both groups. Likewise, the frequency of severe or serious adverse events was similar in both groups. CONCLUSIONS: Subcutaneous etanercept at a dose of 25 mg twice weekly is safe, but not effective, for the treatment of patients with moderate to severe Crohn's disease. The dose of etanercept administered in this study is that approved for rheumatoid arthritis. Higher doses or more frequent dosing may be required to attain a response in patients with active Crohn's disease.

Adult↗

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↗