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Biomedical subjects

S John

Publications and source records attributed to S John.

At least 19 recordsLinked to original sources
PubMed2006

3D-2D-3D photonic crystal heterostructures fabricated by direct laser writing.

Using direct laser writing, we fabricate photoresist templates for 3D-2D-3D photonic crystal heterostructures for what we believe to be the first time. The optical properties of these structures are directly compared with the theoretical ideal, revealing good agreement and hence good sample quality. This provides an experimental starting point for the microfabrication and testing of broadband, 3D air-waveguide microcircuitry in photonic bandgap materials.

Journal Article↗
PubMed2006

Linkage to nodal osteoarthritis: quantitative and qualitative analyses of data from a whole-genome screen identify trait-dependent susceptibility loci.

OBJECTIVE: To identify susceptibility loci for nodal osteoarthritis. METHODS: A genome screen at an average marker spacing of 9.29 cM was carried out on 558 people from 202 families, of whom 491 had nodal osteoarthritis. All genotyped people were graded for the incidence and severity of distal interphalangeal (DIP) nodes, and radiographs from 354 people were graded for joint-space narrowing (JSN) and osteophytes (OSTs). Age-regressed indices for DIP nodes, JSN and OSTs were calculated using these phenotypic data. Affected sibling pair (ASP) and quantitative trait analyses were carried out using MERLIN. RESULTS: The data analysis identified suggestive linkage to loci on chromosomes 3 (for JSN and OST), 4 (for JSN), 8 (for DIP), 11 (for radiographic osteoarthritis) and 16 (for JSN). Both the ASP and quantitative analyses identified the loci on chromosomes 4 and 11. The loci on chromosomes 3 and 16 overlap with those previously identified for large-joint osteoarthritis. Of the loci identified by the quantitative analyses with the logarithm of the odds of linkage >1.5, two were linked to more than one trait, whereas nine were linked to single traits: one for DIP, six for JSN and two for OST. CONCLUSION: The ASP and quantitative analyses of the cohort with nodal osteoarthritis suggest that multiple susceptibility loci for osteoarthritis influence the traits, which combine to form the osteoarthritis phenotype, and that these loci may not act exclusively on the joints of the hand.

Cohort Studies↗
PubMed2006

Endoluminal formalin application for haemorrhagic radiation proctitis.

BACKGROUND: Radiation proctitis is a common complication following radiation therapy for pelvic malignancies. This is associated with significant morbidity which adversely affects the quality of life. Local application of formalin has been used effectively in the treatment of radiation proctitis. METHODOLOGY: Thirty patients with haemorrhagic radiation proctitis who underwent endoluminal application of 4% formalin between January 1998 to October 2002 were followed up prospectively to assess the efficacy of the treatment. RESULTS: The follow up ranged from 5 to 36 months (mean 18.1 months). Nineteen (63.3%) patients had complete response to formalin application while 7 (23.3%) patients had partial response. There were 4 (13.3%) failures. No procedure related complication was observed. CONCLUSION: Local application of formalin is a simple, safe, inexpensive and fairly effective outpatient treatment modality for chronic radiation proctitis.

Adult↗
PubMed2006

Validation and usefulness of the Tamil version of the GHQ-12 in the community.

The 12-item General Health Questionnaire (GHQ-12), increasingly used to screen for common mental disorders (CMD) in primary care, has been validated in different languages and cultures. However, the validity and usefulness of the Tamil version has not been established for use in the community. This article reports a study to validate the Tamil version of the GHQ-12 in a rural setting in southern India. The research found that 16.5% of people interviewed satisfied international criteria for CMD. However, the predictive value of the tool as a tool for screening was found to differ from that found in studies undertaken in a hospital setting. While screening instruments need to be validated in specific types of populations before being employed, such tests may be less useful in community surveys where the prevalence of common mental disorders is low. Strategies which artificially increase the prevalence of common mental disorders in the sample screened will improve the performance of the instrument.

Adult↗
PubMed2006

Voltammetric studies of sparfloxacin and application to its determination in pharmaceuticals.

A detailed study of the electrochemistry of sparfloxacin at a glassy carbon electrode was carried out in the pH range 2.0-10.0 in aqueous solution using cyclic and differential pulse voltammetry. Influence of different supporting electrolytes, pH, scan rate and concentrations were studied on the voltammetric response. The studies revealed the irreversible oxidation of sparfloxacin at basic pH in a diffusion controlled manner. In addition, a differential pulse voltammetric method was proposed for the determination of the drug in different pharmaceutical formulations.

Antitubercular Agents↗
PubMed2005

Transgenic mice overexpressing nNOS in the adult nervous system.

Nitric oxide (NO) has a profound role in the generation, differentiation, survival, and physiology of neurons. We have created a novel transgenic model to study the action of NO in the adult brain, in which the neuronal isoform of NO synthase (nNOS) is expressed under control of the promoter of the calcium-calmodulin multifunctional kinase IIalpha (CaMKIIalpha) gene. We show that the transgenic nNOS RNA and protein are expressed in the cortex, the hippocampus and the striatum of the transgenic mice. We also show that expression of several genes involved in the protection of neurons from oxidative stress and cell death is not affected in neurons of the transgenic mice. Furthermore, generation of new cells is depressed in the neurogenic brain areas in transgenics. In addition, we analyze gene expression in the hippocampus of the transgenic animals using microarray RNA profiling and Q-PCR. Our experiments describe specific changes in cell division and gene activity in the CaMKII-nNOS transgenic model and demonstrate its utility for studying the action of NO in the adult brain.

Animals↗
PubMed2005

A multicenter phase II study of gemcitabine, paclitaxel, and cisplatin in chemonaïve advanced ovarian cancer.

OBJECTIVES: The objectives of this multicenter phase II study were to evaluate the effects of gemcitabine-paclitaxel-cisplatin combination chemotherapy on response rate, survival, and toxicity in patients with advanced epithelial ovarian cancer (AEOC). METHODS: Chemonaive AEOC patients with bidimensionally measurable disease or an elevated serum cancer antigen 125 level received cisplatin (70 mg/m(2)) on day 1 and paclitaxel (80 mg/m(2)) and gemcitabine (1000 mg/m(2)) on days 1 and 8, every 3 weeks. RESULTS: Between October 2000 and September 2001, 46 patients were enrolled. Sixteen patients underwent debulking surgery prior to chemotherapy. In 45 evaluable patients, overall response rate was 64.4% (7 CR and 22 PR). Median time-to-progression was 13.4 months (95% CI, 9.6-17.4 months); median progression-free survival was 12.3 months (95% CI, 8.8-15.6 months); median overall survival was 26.0 months (95% CI, 18 months-not reached); and 1-year survival was 74% (95% CI, 60-88%). The relative dose intensities of gemcitabine, paclitaxel, and cisplatin were 81.4%, 80.2%, and 89.8%, respectively. Grade 3/4 neutropenia was the predominant hematologic toxicity observed (73.9% of patients) followed by grade 3/4 leukopenia (56.5%), anemia (45.7%), thrombocytopenia (23.9%), and febrile neutropenia/neutropenic sepsis (26.1%). The predominant grade 3 nonhematologic toxicities were alopecia (43.5%) and diarrhea (19.6%). Grade 4 nonhematologic toxicities were nausea/vomiting, constipation, and uremia (2.2% each). Two treatment-related deaths occurred (neutropenic sepsis and uremia). CONCLUSION: Gemcitabine-paclitaxel-cisplatin combination chemotherapy is active with manageable toxicity in chemonaive patients with advanced ovarian cancer and should be explored in larger phase III trials.

Adult↗
PubMed2005

Cigarette advertising in Mumbai, India: targeting different socioeconomic groups, women, and youth.

BACKGROUND: Despite a recent surge in tobacco advertising and the recent advertising ban (pending enforcement at the time of this study), there are few studies describing current cigarette marketing in India. This study sought to assess cigarette companies' marketing strategies in Mumbai, India. METHODS: A two week field study was conducted in Mumbai in September 2003, observing, documenting, and collecting cigarette advertising on billboards, storefronts and at point of sale along two major thoroughfares, and performing a content analysis of news, film industry, and women's magazines and three newspapers. RESULTS: Cigarette advertising was ubiquitous in the environment, present in news and in film magazines, but not in women's magazines or the newspapers. The four major advertising campaigns all associated smoking with aspiration; the premium brands targeting the higher socioeconomic status market utilised tangible images of westernization and affluence whereas the "bingo" (low priced) segment advertisements invited smokers to belong to a league of their own and "rise to the taste" using intangible images. Women were not depicted smoking, but were present in cigarette advertisements--for example, a woman almost always accompanied a man in "the man with the smooth edge" Four Square campaign. Advertisements and product placements at low heights and next to candies at point of sale were easily accessible by children. In view of the imminent enforcement of the ban on tobacco advertisements, cigarette companies are increasing advertising for the existing brand images, launching brand extensions, and brand stretching. CONCLUSION: Cigarette companies have developed sophisticated campaigns targeting men, women, and children in different socioeconomic groups. Many of these strategies circumvent the Indian tobacco advertising ban. Understanding these marketing strategies is critical to minimise the exploitation of loopholes in tobacco control legislation.

Adolescent↗
PubMed2004

Association of protein kinase C alpha (PRKCA) gene with multiple sclerosis in a UK population.

Twin, family and adoption studies suggest that susceptibility to multiple sclerosis is substantially mediated by genetic factors. Linkage to human chromosome 17q, homologous to a locus linked to experimental animal models of multiple sclerosis, has been widely replicated and the region likely to harbour a multiple sclerosis susceptibility gene has recently been refined to a 2.5 Mb region of 17q22-24. The candidate multiple sclerosis susceptibility gene, protein kinase C alpha (PRKCA), maps within this interval and association with 35 single-nucleotide polymorphism (SNP) markers, spanning the gene with a median spacing of 7.8 kb, was tested using a case-control approach. Single-marker genotype and estimated haplotype frequencies were compared in UK unrelated cases with multiple sclerosis (n = 184) and healthy controls (n = 340) in order to investigate association with susceptibility to disease. A haplotype of two SNPs mapping to the proximal region of the gene showed evidence for association with susceptibility (Bonferroni-corrected P value = 1.1 x 10(-5)). These findings suggest that further investigation of the PRKCA gene is warranted, particularly in cohorts with evidence of linkage to 17q22. Most of the SNPs investigated in this study were intronic and screening to identify disease-associated functional mutations is now required. Our results suggest that the promoter and proximal gene region should be not only included but prioritized in any screening strategy.

Adult↗
PubMed2004

The effect of statins on angiotensin II-induced hemodynamic changes in young, mildly hypercholesterolemic men.

BACKGROUND: Angiotensin II type 1 (AT(1)) receptors are well known to mediate angiotensin II (Ang II)-induced pro-atherosclerotic effects. It has been found that hypercholesterolemia influences the expression of AT(1) receptors on vascular smooth muscle cells and that increased density of AT(1) receptors exaggerates the hemodynamic response to Ang II. We analyzed to what extent statins and AT(1) receptor antagonists diminish the vasoconstrictive response to Ang II infusion in hypercholesterolemic patients. METHODS: A total of 24 male patients with LDL cholesterol levels >130 mg/dL were enrolled in a randomized, cross-over study. After baseline evaluation, 12 patients received first cerivastatin (0.3 mg/day) and the other 12 patients initially received candesartan (8 mg/day) for 3 weeks, with subsequent cross-over of the medication for the second 3-week drug period. The vascular response was analyzed by the increase in mean arterial pressure (MAP) and total peripheral resistance (TPR) during infusion of increasing doses of Ang II at baseline and the end of each treatment period. Hemodynamic changes were also compared with those in 24 normocholesterolemic subjects without any therapy. RESULTS: At baseline, Ang II provoked a similar increase of MAP and TPR in patients and control subjects. Treatment with cerivastatin did not affect the response to Ang II compared with baseline. By contrast, treatment with candesartan attenuated significantly the response to Ang II compared with baseline and cerivastatin. CONCLUSIONS: Our hemodynamic data indicate the hypothesis that statins do not reduce the responsiveness to Ang II in resistance arteries of young, mildly hypercholesterolemic patients.

Adolescent↗
PubMed2004

Men deny and women cry, but who dies? Do the wages of "denial" include early ischemic coronary heart disease?

OBJECTIVES: In this study patients with documented ischemic coronary heart disease (ICHD; prior MI or CAD per catheterization) were tested for the association of various measures of emotional distress with Age at Initial Diagnosis. METHODS: The measures were chosen because of a published track record at predicting mortality in this population. Females were oversampled to achieve equivalent numbers of each sex (n=50), and thus equivalent statistical power. In a subset of patients (38 males and 32 females), Spouse/Friend Ketterer Stress Symptom Frequency Checklists (KSSFCs) were received. RESULTS: Females reported more depression and anxiety than males. However, spouses or friends reported more anger for males. Denial (spouse/friend minus self-ratings) was greater in males for all three scales of the KSSFC (Anger, P=.005; Depression, P=.024; Anxiety, P=.001). Although females showed the same trend, self and spouse or friend ratings of distress were significantly associated with Age at Initial Diagnosis only in males. When split at the sample mean on the Spouse/Friend KSSFC AIAI (Anger) scale, Age at Initial Diagnosis occurred 14.2 years earlier in males. CONCLUSIONS: Use of a significant other in assessing psychosocial/emotional distress in males may confer greater accuracy, and therefore predictive power for clinical endpoints.

Coronary Disease↗
PubMed2004

The efficacies of affected-limb care with penicillin diethylcarbamazine, the combination of both drugs or antibiotic ointment, in the prevention of acute adenolymphangitis during bancroftian filariasis.

Repeated attacks of adenolymphangitis (ADL) contribute significantly to the progression of chronic lymphoedema in lymphatic filariasis. They are a cause of stigma and, since they may prevent work and require treatment for which payment must be made, of economic loss. The aim of the present study was to improve the treatment of ADL attacks, which is currently mostly empirical. In a double-blind, placebo-controlled, clinical study, 150 subjects who had each suffered at least two ADL attacks in the preceding year were enrolled and randomly allocated to a programme of self-care of the affected limb (after an intensive training programme) and one of five treatments for 12 months. The subjects were supplied with tablets and ointment so that they could take oral penicillin (800 mg/day), oral diethylcarbamazine (DEC; 1 mg/kg.day) or both of these drugs (at the same doses), or apply framycetin ointment to the affected limb, or just take placebo tablets and apply placebo (zinc-oxide) ointment. Placebo tablets and placebo ointment were used so that neither the subjects nor those assessing the responses to treatment were aware of the treatment arm to which each subject had been assigned. The subjects were requested to continue with the affected-limb care after they had stopped taking the tablets and applying the cream, and were followed-up for 24 months from the first treatment.Overall, the mean incidence of ADL attacks decreased from 2.7 episodes/person-year in the pre-treatment year to just 0.38 episode/person-year during the treatment year (P< 0.01). The greatest reduction in incidence was seen in the 58 subjects who received penicillin (with or without DEC). Even in the placebo group, however, the incidence of ADL in the treatment year was significantly lower than that seen in the pre-treatment year, indicating that affected-limb care on its own helps to prevent some attacks. In all groups except the placebo, the incidence of ADL attacks in the year post-treatment exceeded that seen in the treatment year, indicating that chemoprophylaxis needs to be continued for more than a year if such attacks are to be prevented. In most (84%) of the attacks recorded, titres of anti-streptococcal antibodies were seen to be elevated (compared with those recorded during convalescence),indicating that streptococci have a role in the aetiology of ADL. It is recommended that a combination of penicillin prophylaxis and affected-limb care be incorporated into filariasis-control programmes, to decrease morbidity.

Acute Disease↗
PubMed2003

Gap junctional hemichannels in the heart.

Upon contacting each other, cells form gap junctions, in which each cell contributes half of the channel linking their cytoplasms, enabling them to share their metabolome up to a molecular weight of 1000. Each hemichannel (or connexon) is randomly inserted into the plasma membrane and then migrates to the site of cell-to-cell contact before pairing with the neighbouring cell's hemichannel to form a communicating conduit. This review summarizes the evidence for hemichannels in heart ventricular myocytes. Morphological findings are summarized describing how hemichannels are inserted into the plasma membrane. Once in the plasma membrane, hemichannels can be functionally detected electrophysiologically or by dye uptake assays. Each technique reveals specific aspects of hemichannel function. Using dye uptake studies, it is possible to investigate the biological regulation of hemichannels in vivo. Evidence is summarized which indicates that hemichannels are normally kept closed in the presence of normal extracellular Ca because they are phosphorylated at residues in the C-terminus regulated by the MAPK signalling pathway. When hemichannels are dephosphorylated, the channels open and allow dye uptake into the cells, as well as potentially deleterious ion exchange. Biological stresses, such as hyperosmolarity and metabolic inhibition, open hemichannels by this mechanism through activating phosphatases. The resulting ion fluxes may have important roles in heart physiology and pathophysiology.

Calcium↗
PubMed2003

[Early results of ultrasound based calculation of broadband ultrasound attenuation and speed of sound in children and adolescents suffering from asthma].

PURPOSE: To determine broadband ultrasound attenuation (BUA) and speed of sound (SOS) on the os caicis in asthmatic children. To correlate these findings with sex, age, weight and height, topical steroid intake, and asthma severity grade (ASG). PATIENTS AND METHODS: 178 children (ASG 1 - 3)/(98 m, 80 f; mean age 11.9 +/- 3.1 y) were consecutively chosen from 4/00 to 9/01. Children with any other chronic disease were excluded. BUA and SOS were measured using SAHARA (Hologic lnc. Waltham, USA). Regional normative BUA and SOS data of 3 299 children (obtained with the same system), were used to calculate age-, weight- and height-matched standard-deviation-scores (SDS) for both sexes. Asthma severity grade and steroidal intake were determined. The highest topical steroid dosage was 500 micro g Fluticasone or 800 micro g Budesonide per day. RESULTS: 10/178 children were small and 7/178 tall per age (5.6 %/3.9 %), 11/178 children were light (6.2 %) and 9 heavy per age (5.0 %). 19 and 45 children had reduced BUA and SOS values, respectively. The following rates of reduced values were observed: girls: BUA 15.0 % (12/80), SOS 25.0 % (20/80); boys: BUA 7.1 %, SOS 25.5 % (7/98 and 25/98). Sexual differences were not significant. Reduced SOS-values were associated with higher severity and occurred significantly more frequent at children under steroidal intake (0.09 vs. 0.25 [BUA] and - 0.37 vs. - 0.07 [SOS]). CONCLUSION: Following our results an increase incidence of reduced speed of sound occurs in asthmatic children which is attributed to asthma severity and seems to be negatively influenced even by topically applied low dose steroids. This could be attributed to a steroid induced collagen synthesis deficiency followed by a reduced bone elasticity. Further studies, especially using a longitudinal study design are required to verify these findings.

Adolescent↗
PubMed2001

Histone H3 specific acetyltransferases are essential for cell cycle progression.

Longstanding observations suggest that acetylation and/or amino-terminal tail structure of histones H3 and H4 are critical for eukaryotic cells. For Saccharomyces cerevisiae, loss of a single H4-specific histone acetyltransferase (HAT), Esa1p, results in cell cycle defects and death. In contrast, although several yeast HAT complexes preferentially acetylate histone H3, the catalytic subunits of these complexes are not essential for viability. To resolve the apparent paradox between the significance of H3 versus H4 acetylation, we tested the hypothesis that H3 modification is essential, but is accomplished through combined activities of two enzymes. We observed that Sas3p and Gcn5p HAT complexes have overlapping patterns of acetylation. Simultaneous disruption of SAS3, the homolog of the MOZ leukemia gene, and GCN5, the hGCN5/PCAF homolog, is synthetically lethal due to loss of acetyltransferase activity. This key combination of activities is specific for these two HATs because neither is synthetically lethal with mutations of other MYST family or H3-specific acetyltransferases. Further, the combined loss of GCN5 and SAS3 functions results in an extensive, global loss of H3 acetylation and arrest in the G(2)/M phase of the cell cycle. The strikingly similar effect of loss of combined essential H3 HAT activities and the loss of a single essential H4 HAT underscores the fundamental biological significance of each of these chromatin-modifying activities.

Acetylation↗
PubMed2001

Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia.

BACKGROUND: Hypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. METHODS AND RESULTS: Fifteen patients with moderate hypercholesterolemia and 15 healthy control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 was analyzed on monocytes before and under therapy with the statin cerivastatin by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. Our main findings were as follows. Patients with moderate hypercholesterolemia showed a significant increase of CD154 and P-selectin on platelets and CD40 on monocytes compared with healthy subjects. Soluble CD154 showed a nonsignificant trend for higher plasma levels in patients. A positive correlation was found for total or LDL cholesterol and CD154, but not for CD40 on monocytes. The latter was upregulated in vitro by C-reactive protein, which was found to be significantly elevated in patients with moderate hypercholesterolemia. CD154 on platelets proved to be biologically active because it enhanced the release of MCP-1, which was markedly elevated in an in vitro platelet-endothelial cell coculture model and in the serum of patients. Short-term therapy with a HMG-CoA reductase inhibitor significantly downregulated CD40 on monocytes and serum levels of MCP-1. CONCLUSION: Patients with moderate hypercholesterolemia show upregulation of the CD40 system, which may contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Adult↗