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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effect of porosity and surface hydrophilicity on migration of epithelial tissue over synthetic polymer.

The relative effects of porosity and surface chemistry on the migration of epithelial tissue over the surface of a polymer were determined in vitro. These studies compared nonporous polymers with those having 0.1-microm diameter track-etched pores and were conducted on polycarbonate and polyester. Epithelial tissue migration over the polymer surface was stimulated by the presence of these pores. The surface chemistries of the polymers were modified by deposition of various polymer films using radio frequency gas deposition, giving a range of surfaces that varied in air:water sessile contact angle (SCA) of between 26 and 100 degrees. Tissue migration on the nonporous surfaces was affected by the surface chemistry, being generally linear as a function of the SCA and higher on hydrophilic than on hydrophobic surfaces but reduced if the hydrophilic surface had a mobile chemistry. The effects of the 0.1-microm diameter pores and the surface hydrophilicity were additive with the maximal level of epithelial tissue migration occurring on a porous, hydrophilic polymer surface.

Animals↗
PubMed2000

Kabat database and its applications: 30 years after the first variability plot.

The Kabat Database was initially started in 1970 to determine the combining site of antibodies based on the available amino acid sequences at that time. Bence Jones proteins, mostly from human, were aligned, using the now-known Kabat numbering system, and a quantitative measure, variability, was calculated for every position. Three peaks, at positions 24-34, 50-56 and 89-97, were identified and proposed to form the complementarity determining regions (CDR) of light chains. Subsequently, antibody heavy chain amino acid sequences were also aligned using a different numbering system, since the locations of their CDRs (31-35B, 50-65 and 95-102) are different from those of the light chains. CDRL1 starts right after the first invariant Cys 23 of light chains, while CDRH1 is eight amino acid residues away from the first invariant Cys 22 of heavy chains. During the past 30 years, the Kabat database has grown to include nucleotide sequences, sequences of T cell receptors for antigens (TCR), major histocompatibility complex (MHC) class I and II molecules and other proteins of immunological interest. It has been used extensively by immunologists to derive useful structural and functional information from the primary sequences of these proteins. An overall view of the Kabat Database and its various applications are summarized here. The Kabat Database is freely available at http://immuno.bme.nwu.edu

Animals↗
PubMed2000

Dynamic susceptibility contrast MR imaging: correlation of signal intensity changes with cerebral blood volume measurements.

Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging provide valuable information regarding intracranial micro-hemodynamics and have been helpful in characterizing primary brain tumors and guiding stereotactic biopsy. Another parameter, the maximum signal drop (MSD) during the first pass of intravascular contrast bolus due to T2* effect, can also be measured directly without extensive post-processing and data manipulation. The purpose of our study is to determine whether MSD maps provide information similar to CBV maps in patients presenting with intracranial mass lesions. Twenty-nine patients with various intracranial mass lesions were studied with DSC MR imaging prior to stereotactic biopsy or volumetric resection. Maps of both CBV and MSD are calculated on a pixel-by-pixel basis and displayed as color overlays over the raw images. Relative CBV (rCBV) and MSD (rMSD) values were measured in regions of interest (ROIs) within areas of abnormality and compared. In addition, computer-generated noise was added to the data to estimate the sensitivity of each measurement to noise. The rMSD values were strongly correlated with rCBV values (r = 0.87, P = 0.0001). CBV values were much more sensitive to added noise than MSD values (P < 0.01). MSD maps derived from DSC MR imaging provide information similar to CBV maps in patients with intracranial mass lesions. MSD maps are a simple and reliable indicator of vascularity that can easily be incorporated into routine MR imaging.

Brain Neoplasms↗
PubMed2000

Normalization rate and cellular localization of phosphatidylethanol in whole blood from chronic alcoholics.

Phosphatidylethanol (PEth) is an abnormal phospholipid which is formed in the presence of ethanol, via the action of phospholipase D (PLD). PEth in blood is a potential marker of alcohol abuse. The present study was made to determine the compartmentalization and the elimination rate of PEth in human whole blood. PEth was assayed by an improved HPLC technique, with evaporative light-scattering detection. Blood from six alcoholic males was separated into different blood cell fractions. The PEth concentration in whole blood was 2.5+/-0.9 and 1.9+/-1.1 micromol/l in erythrocytes. Only one subject had detectable PEth in the mononuclear cells. Fifteen patients (13 men, two women) with chronic alcoholism, were followed as inpatients, after admission to an alcohol detoxification clinic. PEth, carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) were measured on days 1, 3, 5 and 7 after admission. Linear regression analysis of logarithmic PEth values in individuals, with measurable PEth at day 1, gave a good fit (P<0.001) with the one-compartment elimination model. The half-life was calculated as 4.0+/-0.7 days. A weak significance (P<0.05) was observed in the correlation of PEth at day 1 and half-life values of the same subjects.

Alcoholism↗
PubMed2000

Preserved priming in auditory perceptual identification in Alzheimer's disease.

To examine the status of auditory perceptual priming in Alzheimer's disease (AD), this study examined the performance of AD patients in auditory perceptual identification of words. In Experiment 1, the processing operations required to perform the tasks at study and test were matched, whereas in Experiment 2, processing operations at study and test were mismatched. AD patients showed normal priming in both experiments, despite impaired recognition memory. These findings extend to the auditory domain the finding of intact perceptual implicit memory in AD. Preserved auditory priming in AD may reflect the operation of a pre-semantic, phonological representation system, localized to posterior neocortical areas that are functionally spared in AD.

Aged↗
PubMed2000

Cholinesterases modulate cell adhesion in human neuroblastoma cells in vitro.

Cholinesterases are expressed non-synaptically during embryonic development, neoplasia and neurodegeneration. We have investigated the effects of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and, conversely, anti-AChE and -BChE antibodies and inhibitors on cell adhesion and neurite outgrowth in human neuroblastoma cells. Analysis of cholinesterase levels and isoforms in undifferentiated and differentiated cells indicated a significant rise in AChE levels on differentiation. This increase was related to both cell-associated and secreted enzyme, and was predominantly the G4 isoform. BChE levels and isoforms, on the other hand, showed no significant variation. Coating the tissue culture plate with AChE stimulated neurite outgrowth, while BChE had an anti-adhesive effect. Cell adhesion was affected by the BChE inhibitor, ethopropazine, and the AChE peripheral site inhibitor, BW284c51, but not by eserine which binds to the active site. This indicates that the adhesion function is non-cholinergic, a finding supported by the lack of effect of AE-2, a monoclonal antibody that inhibits AChE, on cell adhesion. Four out of a panel of nine anti-AChE antibodies inhibited adhesion to varying degrees. Of these antibodies, two are catalytic, with epitopes associated with the peripheral anionic site of AChE, and the remaining two have epitopes overlapping this site. Neither of the two anti-BChE antibodies used had any effect on adhesion. These results indicate the importance of AChE in neuroblastoma cell adhesion and neurite outgrowth, and suggest that the peripheral anionic site may be involved in these processes.

Acetylcholinesterase↗
PubMed2000

Should nurses practise complementary therapies?

This paper is based on the review of the literature that was undertaken as part of a Research Dissertation, submitted as part of an MSc in Nursing at Coventry University. The subsequent study was a comparison of Nurse and Non-nurse Aromatherapists, exploring their beliefs about the therapy and their reasons for practice. The author questions whether nurses should practise complementary therapies and if so why? If the nursing curriculum is to be developed to incorporate complementary therapies then we must be able to justify their inclusion in terms of patient outcomes, rather than in terms of meeting the needs of the nurse. The paper raises many questions, not all of which can be answered at this stage, but which can be considered and reflected on in depth.

Aromatherapy↗
PubMed2000

Elevated tissue immunoglobulins in Hirschsprung's disease--indication of early immunologic response.

Hirschsprung's disease is of multifactorial origin including genetic as well as other region-specific neuroenvironmental factors as well as focal contact with the extracellular matrix. Immunological activity is elevated in patients with enterocolitis associated with Hirschsprung's disease suggesting an immunological role in HD. Increased expression of major histocompatibility complexes (MHC) class II antigens and ICAM-1 in the aganglionic segments of bowel further strengthen this association and suggest early immunologic involvement. In this study, immunoglobulin activity was biochemically assessed in surgically resected specimens of 23 patients with Hirschsprung's disease in whom there was no clinical or histological evidence of enterocolitis. IgG and IgM were significantly increased in segments of bowel histologically identified as aganglionic or transitional zone, suggesting an area of maximal immunological activity in the transitional zone. The lack of an increase in IgA immunoglobulin activity in the same bowel segments suggests that IgA response may be related to associated enterocolitis in HD. Elevated tissue IgG and IgM levels were observed in 5 neonates presenting within the first week of life and older patients did not have significantly higher immunoglobulin levels, suggesting that the immunological response was not part of an ongoing infection or progressive condition. Increased IgM in the neonatal period suggests an early immune response in Hirschsprung's disease and strengthens the hypothesis that the immune system may be involved in its pathogenesis. Possible causes include the effects of an antenatal infection or local microenvironmental influences on the differentiation or maturation of migrating neuroblasts of the enteric nervous system.

Age Factors↗
PubMed2000

The Drosophila embargoed gene is required for larval progression and encodes the functional homolog of schizosaccharomyces Crm1.

The CRM1 (Exportin 1) protein is a receptor for leucine-rich nuclear export signal sequences. We have molecularly characterized the Drosophila melanogaster embargoed (emb) gene and find that it encodes a product with 49 and 71% sequence identity to the fission yeast Schizosaccharomyces pombe and human CRM1 proteins, respectively. We show that expression of the emb cDNA is sufficient to suppress the growth phenotype of both conditional-lethal and null S. pombe crm1(-) mutant strains, suggesting that emb encodes the functional homologue of the S. pombe Crm1 protein. Through mutagenesis screens we have recovered a series of recessive lethal emb mutations. There is a substantial maternal contribution of emb mRNA and animals hemizygous for our emb alleles can develop to second instar larvae but persist at this stage and consistently fail to undergo the molt to the third instar stage. We see a nuclear accumulation of endogenous actin in the intestinal epithelial cells of the emb mutant larvae, consistent with a role for the emb gene product in nuclear export of actin protein.

Actins↗
PubMed2000

Efficacy of venlafaxine and predictors of response in a prospective open-label study of patients with treatment-resistant major depression.

The aim of this study was to replicate the findings of a 1994 study, in which a 30% response rate to venlafaxine was found in patients with treatment-refractory depression, as well as to examine for any predictors of such an outcome. The study was an 8-week, open-label, prospective investigation of venlafaxine in doses up to 300 mg in 312 patients fulfilling criteria for either "absolute" or "relative" treatment resistance. By week 8, 52.6% of the patients had responded, which was defined as a 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale; 49% of those defined with "absolute resistance" demonstrated such an outcome. Forty-five percent of the patients with absolute resistance who had failed to respond to at least one tricyclic antidepressant responded to venlafaxine. Response rates were higher in those with an absence (57.5%) compared with the presence (31.0%) of any comorbid psychiatric disorder (p < 0.001), "marked" (60.3%) compared with "mild or moderate" (51.6%) or "severe" (43.4%) baseline ratings on the patient-rated Clinical Global Impressions Scale (p < 0.05), and "relative" (61%) compared with "absolute" resistance (49%) (p = 0.06). Furthermore, improvement in scores of 20% or 30% at weeks 1 or 2 was associated with higher rates of final response (p < 0.0005). After logistic regression, both comorbid psychiatric illness (p < 0.001) and early improvement (p < 0.0001) remained significant and independent predictors of final response.

Adult↗
PubMed2000

Potential for community-based screening, treatment, and antibiotic prophylaxis for syphilis prevention.

BACKGROUND: The recent syphilis epidemic in Louisiana occurred predominantly among disadvantaged African Americans who may distrust public health agencies and prevention efforts. OBJECTIVES: To determine community perceptions regarding trust and use of public health clinics, to assess whether race of provider is important to persons at risk for syphilis, and to assess the willingness of persons to participate in syphilis screening, treatment, and antibiotic prophylaxis. STUDY DESIGN: Qualitative interviews were conducted with 18 community leaders and 38 community members who were at risk for syphilis. Quantitative surveys were completed by persons with primary or secondary syphilis (n = 92), their sexual contacts (n = 56), and with neighborhood controls (n = 143). Three possible programs for syphilis screening and antibiotic prophylaxis were proposed (1) bar setting; (2) home setting, and (3) mobile health-van setting in high-risk communities. RESULTS: In qualitative interviews, community leaders and community members reported a high degree of trust in the public sexually transmitted disease clinic. A majority of respondents felt that race was not a factor in choosing healthcare providers. Respondents favored the provision of services in a mobile health van over in a bar or in their homes. In quantitative interviews, more than 80% of community members surveyed reported that they would go to a mobile health van for syphilis testing. Nearly two thirds of respondents reported that they would be willing to take oral prophylaxis for syphilis, and more than half of respondents reported that they would accept an injection. CONCLUSIONS: Community members trust the public sexually transmitted disease (STD) clinic, are generally not concerned with the race of healthcare providers, and are supportive of community-based STD screening, treatment, and antibiotic prophylaxis provided from a mobile clinic.

Adolescent↗
PubMed2000

Strategies for syphilis prevention: findings from surveys in a high-incidence area.

BACKGROUND: The persistence of syphilis in the United States suggests that a better understanding is needed of the potential for various public health approaches to prevent the spread of the disease. STUDY DESIGN: The authors conducted surveys of 92 persons with early syphilis, 56 uninfected sexual contacts, and 143 neighborhood controls in the Baton Rouge, Louisiana area. The surveys collected information regarding sexual behavior, access to and use of healthcare services, encounters at sites at which serologic screening for syphilis could be done, and exposure to interventions designed to prevent HIV infection. RESULTS: All groups reported high-risk sexual behavior. Cases and contacts were more likely than controls to report two or more sex partners in the previous year, but the three groups were similar in the percentage reporting five or more sex partners. Cases had poor access to health care and by some measures this access was less than that of controls. The potential screening site visited most frequently by cases was the public hospital emergency room (40%). Cases were less likely to have been exposed to programs designed to prevent HIV infection than uninfected contacts and controls combined (odds ratios, 0.51-0.66). CONCLUSIONS: Persons with syphilis were not unlike others in their neighborhoods, suggesting that syphilis is a sentinel event that indicates an entire neighborhood is at risk. Improvements in access to health care for sexually transmitted disease-related symptoms, screening in sites such as public hospital emergency rooms, and emphasizing sexual risk-reduction interventions may limit the spread of syphilis in these neighborhoods. To prevent syphilis in the long term, public health programs should also try to better understand and change other community-level socioeconomic factors that influence sexual behavior.

Adult↗
PubMed2000

Three coupled oscillators as a universal probe of synchronization stability in coupled oscillator arrays

We show that the stability surface that governs the synchronization of a large class of arrays of identical oscillators can be probed with a simple array of just three identical oscillators. Experimentally this implies that it may be possible to probe the synchronization conditions of many arrays all at the same time. In the process of developing a theory of the three-oscillator probe, we also show that several regimes of asymptotic coupling can be derived for the array classes, including the case of large imaginary coupling, which apparently has not been explored.

Journal Article↗
PubMed2000

Change in dimerization mode by removal of a single unsatisfied polar residue located at the interface.

The importance of unsatisfied hydrogen bonding potential on protein-protein interaction was studied. Two alternate modes of dimerization (conventional and flipped form) of an immunoglobulin light chain variable domain (V(L)) were previously identified. In the flipped form, interface residue Gln89 would have an unsatisfied hydrogen bonding potential. Removal of this Gln should render the flipped dimer as the more favorable quaternary form. High resolution crystallographic studies of the Q89A and Q89L mutants show, as we predicted, that these proteins indeed form flipped dimers with very similar interfaces. A small cavity is present in the Q89A mutant that is reflected in the approximately 100 times lower association constant than found for the Q89L mutant. The association constant of Q89A and Q89L proteins (4 x 10(6) M(-1) and >10(8) M(-1)) are 10- and 1,000-fold higher than that of the wild-type protein that forms conventional dimers clearly showing the energetic reasons for the flipped dimer formation.

Crystallography, X-Ray↗
PubMed2000

Substrate specificity of atrazine chlorohydrolase and atrazine-catabolizing bacteria.

Bacterial atrazine catabolism is initiated by the enzyme atrazine chlorohydrolase (AtzA) in Pseudomonas sp. strain ADP. Other triazine herbicides are metabolized by bacteria, but the enzymological basis of this is unclear. Here we begin to address this by investigating the catalytic activity of AtzA by using substrate analogs. Purified AtzA from Pseudomonas sp. strain ADP catalyzed the hydrolysis of an atrazine analog that was substituted at the chlorine substituent by fluorine. AtzA did not catalyze the hydrolysis of atrazine analogs containing the pseudohalide azido, methoxy, and cyano groups or thiomethyl and amino groups. Atrazine analogs with a chlorine substituent at carbon 2 and N-alkyl groups, ranging in size from methyl to t-butyl, all underwent dechlorination by AtzA. AtzA catalyzed hydrolytic dechlorination when one nitrogen substituent was alkylated and the other was a free amino group. However, when both amino groups were unalkylated, no reaction occurred. Cell extracts were prepared from five strains capable of atrazine dechlorination and known to contain atzA or closely homologous gene sequences: Pseudomonas sp. strain ADP, Rhizobium strain PATR, Alcaligenes strain SG1, Agrobacterium radiobacter J14a, and Ralstonia picketti D. All showed identical substrate specificity to purified AtzA from Pseudomonas sp. strain ADP. Cell extracts from Clavibacter michiganensis ATZ1, which also contains a gene homologous to atzA, were able to transform atrazine analogs containing pseudohalide and thiomethyl groups, in addition to the substrates used by AtzA from Pseudomonas sp. strain ADP. This suggests that either (i) another enzyme(s) is present which confers the broader substrate range or (ii) the AtzA itself has a broader substrate range.

Adenosine Diphosphate↗
PubMed2000

Comprehensive PCR-based assay for detection and species identification of human herpesviruses.

The description and evaluation of a PCR-based assay for the detection and species identification of the eight known human herpesviruses are presented. Two primer pairs targeting well-conserved regions of the genome allowed the amplification of the DNAs of all known human herpesviruses at a high level of sensitivity (10 to 100 genome copies for most viruses). Identification of the virus species was achieved through restriction enzyme digestion with BamHI and BstUI, which yielded fragment sizes that were characteristic for each herpesvirus. Furthermore, it was demonstrated that this restriction enzyme panel allowed the discrimination between human herpesvirus 6 variant A and variant B. This assay format was validated over the course of 1 year in a clinical virology laboratory setting, where it was shown that it readily detected human herpesviruses, including occasional multiple infections, in a variety of clinical samples. The PCR assay was compared to isolation and electron microscopy for the detection of herpes simplex (HSV) and varicella-zoster virus (VZV) in clinical samples. All specimens positive by conventional methods were also positive by PCR. However, in a number of clinical specimens in which HSV or VZV could not be detected by conventional methods, PCR was able to demonstrate the presence of the virus.

Blood↗