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Biomedical subjects

K Roy

Publications and source records attributed to K Roy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Climate-driven range expansion and morphological evolution in a marine gastropod.

Little is known about the phenotypic consequences of global climate change, despite the excellent Pleistocene fossil record of many taxa. We used morphological measurements from extant and Pleistocene populations of a marine gastropod (Acanthinucella spirata) in conjunction with mitochondrial DNA sequence variation from living populations to determine how populations responded phenotypically to Pleistocene climatic changes. Northern populations show little sequence variation as compared to southern populations, a pattern consistent with a recent northward range expansion. These recently recolonized northern populations also contain shell morphologies that are absent in extant southern populations and throughout the Pleistocene fossil record. Thus, contrary to traditional expectations that morphological evolution should occur largely within Pleistocene refugia, our data show that geographical range shifts in response to climatic change can lead to significant morphological evolution.

Animals↗
PubMed2001

Effects of sampling standardization on estimates of Phanerozoic marine diversification.

Global diversity curves reflect more than just the number of taxa that have existed through time: they also mirror variation in the nature of the fossil record and the way the record is reported. These sampling effects are best quantified by assembling and analyzing large numbers of locality-specific biotic inventories. Here, we introduce a new database of this kind for the Phanerozoic fossil record of marine invertebrates. We apply four substantially distinct analytical methods that estimate taxonomic diversity by quantifying and correcting for variation through time in the number and nature of inventories. Variation introduced by the use of two dramatically different counting protocols also is explored. We present sampling-standardized diversity estimates for two long intervals that sum to 300 Myr (Middle Ordovician-Carboniferous; Late Jurassic-Paleogene). Our new curves differ considerably from traditional, synoptic curves. For example, some of them imply unexpectedly low late Cretaceous and early Tertiary diversity levels. However, such factors as the current emphasis in the database on North America and Europe still obscure our view of the global history of marine biodiversity. These limitations will be addressed as the database and methods are refined.

Animals↗
PubMed2001

Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency.

Chitosan-DNA nanoparticles were prepared using a complex coacervation process. The important parameters for the nanoparticle synthesis were investigated, including the concentrations of DNA, chitosan and sodium sulfate, temperature of the solutions, pH of the buffer, and molecular weights of chitosan and DNA. At an amino group to phosphate group ratio (N/P ratio) between 3 and 8 and a chitosan concentration of 100 microg/ml, the size of particles was optimized to approximately 100--250 nm with a narrow distribution, with a composition of 35.6 and 64.4% by weight for DNA and chitosan, respectively. The surface charge of these particles was slightly positive with a zeta potential of +12 to +18 mV at pH lower than 6.0, and became nearly neutral at pH 7.2. The chitosan-DNA nanoparticles could partially protect the encapsulated plasmid DNA from nuclease degradation as shown by electrophoretic mobility analysis. The transfection efficiency of chitosan-DNA nanoparticles was cell-type dependent. Typically, it was three to four orders of magnitude, in relative light units, higher than background level in HEK293 cells, and two to ten times lower than that achieved by LipofectAMINE-DNA complexes. The presence of 10% fetal bovine serum did not interfere with their transfection ability. Chloroquine could be co-encapsulated in the nanoparticles at 5.2%, but with negligible enhancement effect despite the fact that chitosan only showed limited buffering capacity compared with PEI. The present study also developed three different schemes to conjugate transferrin or KNOB protein to the nanoparticle surface. The transferrin conjugation only yielded a maximum of four-fold increase in their transfection efficiency in HEK293 cells and HeLa cells, whereas KNOB conjugated nanoparticles could improve gene expression level in HeLa cells by 130-fold. Conjugation of PEG on the nanoparticles allowed lyophilization without aggregation, and without loss of bioactivity for at least 1 month in storage. The clearance of the PEGylated nanoparticles in mice following intravenous administration was slower than unmodified nanoparticles at 15 min, and with higher depositions in kidney and liver. However, no difference was observed at the 1-h time point.

Animals↗
PubMed2001

Depression in Singapore: failure to demonstrate an age effect on clinical features.

OBJECTIVES: Studies comparing older and younger depressed patients have variably identified differing and similar clinical feature patterns, an inconsistency requiring clarification and explanation. If influential, age may have a true phenotypic effect or be a secondary influence reflecting depressive sub-type differences. If age is primarily influential, then, after controlling for depressive sub-type differences its effect should impact on clinical features - even in non-western regions. METHODS: We therefore undertook a study in Singapore, comparing 42 elderly and 28 younger patients of a Singapore psychiatric hospital, and with the diagnostic sub-type profile similar across the age-based groups. RESULTS: Despite the elderly group being some 35 years older, both at first episode and when surveyed, and having a distinctly higher rate of physical disorders, few clinical differences were identified. While the elderly group reported a less severe depressed mood and more 'somatic' symptoms, analyses indicated that such differences were accounted for by education and language factors, and were compatible with the view that Chinese subjects historically report depression more 'somatically'. CONCLUSION: We conclude that, in a non-western, largely Chinese sample of depressed patients, few differences in the phenotypic expression of depression were identified, perhaps reflecting similar distributions of depressive sub-types across the groups, an issue which may have muddied interpretation of western studies.

Adolescent↗
PubMed2001

Do the Chinese somatize depression? A cross-cultural study.

BACKGROUND: A large literature argues for the Chinese--whether in mainland China or elsewhere--being highly likely to express depression somatically, leading to predictable detection and diagnostic difficulties. If true, detection might be assisted if a set of somatic proxies of depression were identified, and this was the principal initial objective in mounting this study. METHODS: We studied two sets of depressed outpatients, one of Malaysian Chinese and the other of Australian Caucasians, matched by age and sex. We identified the prime symptom nominated by them when they first sought assistance, and required them to complete an inventory of both somatic and cognitive symptoms, and rank the three items they judged as most capturing their distress. RESULTS: The Chinese were distinctly more likely to nominate a somatic symptom as their presenting complaint (60% vs 13%), while the Australian subjects were more likely to nominate depressed mood, cognitive and anxiety items. Responses to the inventory established that the Chinese did score somewhat higher on a somatic set of items, but differed far more distinctly in being less likely to affirm cognitive items of depression, resulting in significantly lower total inventory scores. Variation across the contrast samples in acknowledging the presence of symptoms did not relate simply to the prevalences of those symptoms. CONCLUSIONS: Our failure to identify a culture-specific somatic factor as a proxy of depression, together with establishing a high rate of somatic and related items (e. g. insomnia) in both samples, may largely reflect the phenomenon of 'corporization', whereby depressed patients irrespective of culture are more likely to experience and report in response to a 'somatosensory amplification' influence.

Adult↗
PubMed2001

The differential impact of age on the phenomenology of melancholia.

BACKGROUND: We pursue an observation that age may influence the clinical features of melancholia and, in particular, psychomotor disturbance. METHODS: Two large clinical databases were amalgamated allowing the clinical features of 124 depressed subjects meeting DSM-III-R and clinical criteria for melancholia to be contrasted with 218 subjects diagnosed as having a non-melancholic depression by both criteria sets. Psychomotor disturbance was assessed by the CORE measure and by seven classical endogeneity symptoms of melancholia which, when summed, created a ENDOG score. RESULTS: There was no impact of age on ENDOG scores in either the melancholics or non-melancholics. In the melancholics, increasing age was associated with increasing CORE scores and with agitation scale scores in particular. In a set of discriminant function analyses seeking to identify the comparative utility of a set of predictors of melancholic (versus non-melancholic) groups, age was significant, and while CORE and ENDOG scores were individual predictors, their combined entry established that the CORE score alone made the ENDOG score redundant, and that the addition of age then made little impact. CONCLUSIONS: Melancholia appears to have a later age of onset than non-melancholic depression, while its phenotypic expression appears to change with age, with psychomotor disturbance being more distinct in older subjects. Such an effect may have a number of clinical implications, including possible differential effects of varying antidepressant treatments.

Adult↗
PubMed2001

Purification, characterization and partial amino acid sequencing of a 70 kD inhibitor protein of Na+,K+-ATPase from goat testis cytosol.

A protein isolated from goat testis cytosol is found to inhibit Na+,K+-ATPase from rat brain microsomes. The inhibitor has been purified by ammonium sulphate precipitation followed by hydroxyapatite column chromatography. The purified fraction appears as a single polypeptide band on 10% SDS-PAGE of approximate molecular mass of 70 kDa. The concentration at which 50% inhibition (I50) occurs is in the nanomolar range. The inhibitor seems to bind Na+,K+-ATPase reversibly at ATP binding site in a competitive manner with ATP, but away from ouabain binding site. It does not affect p-nitrophenyl-phosphatase activity. The inhibitor is found to inhibit the phosphorylation step of the Na+,K+-ATPase. The enhancement of tryptophan fluorescence and changes in CD pattern suggest conformational changes of Na+,K+-ATPase on binding to the inhibitor. Amino acid sequence of the trypsinised fragments show some homology with aldehyde reductase.

Amino Acids↗
PubMed2001

Depression and smoking: examining correlates in a subset of depressed patients.

OBJECTIVE: The objective of this study was to examine for associations between depression and cigarette smoking. METHOD: A sample of 92 depressed smokers was compared with a control sample of depressed non-smokers, matched for age, gender and diagnostic variables. Comparisons were made across a range of demographic, depression, family history, developmental factors, anxiety and personality style variables, as well as use of alcohol and illicit drugs. RESULTS: We failed to find any difference between smokers and non-smokers in history or severity of depression. Cigarette smokers were distinguished principally by greater exposure to aversive experiences in childhood, disordered personality function, greater use of illicit drugs, anxiolytics and alcohol. Logistic regression identified dysfunctional personality 'domains', physical violence in childhood, long-term anxiolytic use and illicit drug use as the most significant predictor set. CONCLUSIONS: Results favour a model of cigarette smoking and depression as linked by shared early deprivational variables, rather than cigarette smoking causing depression or the converse.

Adult↗
PubMed2001

Adolescent depression: a review.

OBJECTIVE: To review the characteristic clinical, illness course and risk factors to adolescent depression. METHOD: A literature review is provided with interpretive comments. RESULTS: The clinical feature profile is likely to reflect the rarity of melancholic depression, while the non-melancholic "irritable hostile" pattern appears distinctly increased. A "reactive depressive disorder" is rare in those who get to psychiatric assessment, while comorbidity (e.g. anxiety and personality disorders, illicit drug use) is the rule. Aetiological determinants and the prognosis generally more relate to comorbid factors than to depression per se. Predisposing and precipitating psychological and social determinants are considered, while the efficacies of varying antidepressant strategies remain unclear apart from those with an "anxious" or "irritable" depression where selective serotonin re-uptake inhibitor medication has shown utility and where cognitive-behavioural therapy may be relevant. CONCLUSIONS: For the majority who develop adolescent depression, its expression and outcome appear more a reflection of the propagating determinants, most commonly anxiety and personality style. The clinician should determine a treatment plan that not only addresses the depression but which identifies and addresses the contributing features.

Adolescent↗
PubMed2001

Antibiotic prescribing knowledge of National Health Service general dental practitioners in England and Scotland.

The inappropriate use of antibiotics has contributed to the worldwide problem of antimicrobial resistance. Information on the knowledge, understanding and training of dental practitioners in the use of antibiotics in clinical practice is scarce. This study assessed the level of knowledge of general dental practitioners and the need for educational initiatives. An anonymous postal questionnaire was sent to National Health Service dental practitioners working in 10 Health Authorities in England (1544) and four Health Boards in Scotland (672). Each correct answer to the questionnaire was given a score of one mark; there were 84 questions. The scores for each section of the questionnaire were compared. Responses were received from 1338 (60.4%) of practitioners, of whom 22.1% had attended postgraduate courses in the previous 2 years on antibiotic prescribing. Practitioners who had attended courses had a significantly greater knowledge of antibiotic use (P < 0.05) than those who had not. There was no significant difference in knowledge between all age groups under 60 years of age. There were significant differences in knowledge between dentists practising in English Health Authorities and Scottish Health Boards (P < 0.01). Knowledge was good for clinical signs that are indicators for prescribing antibiotics and for a number of non-clinical factors, e.g. patient expectation. Knowledge of therapeutic prescribing for commonly presenting clinical conditions and prophylactic prescribing for medically compromised patients, however, was generally poor. This study has shown that an urgent review of dental undergraduate and postgraduate education in antibiotic prescribing is required. Provision of prescribing guidelines may improve knowledge and encourage the appropriate use of antibiotics in clinical dental practice.

Anti-Bacterial Agents↗
PubMed2001

Double blind, randomised controlled clinical trial of hypo-osmolar oral rehydration salt solution in dehydrating acute diarrhoea in severely malnourished (marasmic) children.

AIMS: To compare the clinical efficacy of hypo-osmolar oral rehydration salt (ORS) solution (224 mmol/l) and standard ORS solution (311 mmol/l) in severely malnourished (marasmic) children having less than 60% Harvard standard weight for age with dehydrating acute watery diarrhoea. METHODS: In a double blind, randomised, controlled trial, 64 children aged 6-48 months were randomly assigned standard (n = 32) or hypo-osmolar ORS (n = 32). RESULTS: Stool output (52.3 v 96.6 g/kg/day), duration of diarrhoea (41.5 v 66.4 hours), intake of ORS (111.5 v 168.9 ml/kg/day), and fluid intake (214.6 v 278.3 ml/kg/day) were significantly less in the hypo-osmolar group than in the standard ORS group. Percentage of weight gain on recovery in the hypo-osmolar group was also significantly less (4.3 v 5.4% of admission weight) than in the standard ORS group. A total of 29 (91%) children in the standard ORS group and 32 (100%) children in the hypo-osmolar group recovered within five days of initiation of therapy. Mean serum sodium and potassium concentrations on recovery were within the normal range in both groups. CONCLUSION: Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating acute watery diarrhoea in severely malnourished (marasmic) children. Furthermore, children did not become hyponatraemic after receiving hypo-osmolar ORS.

Child, Preschool↗
PubMed2001

Culture condition-dependent senescence-like growth arrest and immortalization in rodent embryo cells.

Culture Condition-Dependent Senescence-Like Growth Arrest and Immortalization in Rodent Embryo Cells. We investigated the telomerase activity, telomere length, and replicative life span of cells from human embryos and rodent embryos (mouse, rat and Syrian hamster). We used two culture conditions for rodent embryo cells whereby the cells were plated at a density of 2 x 10(5) into a 25-cm(2) flask and subcultured every 3 days or every 10 days. We found that nearly 100% of the cultures of rodent embryo cells become immortal when they are subcultured using the 10-day culture protocol. These rodent embryo cells retain telomerase activity and long telomeres (19-50 kb) in the long-term cultures, whereas human embryo cells rapidly deplete telomerase activity associated with significant shortening of telomeres, and then they senesce. In contrast to the results from 10-day cultures, we found that some mouse cell cultures and most Syrian hamster cell cultures arrest cell growth after 13 and 29 population doublings, respectively, while retaining substantial levels of telomerase activity and experiencing no significant loss of telomeres when the cells were subcultured using the 3-day culture protocol. This growth arrest is phenotypically indistinguishable from cellular senescence. The present results suggest that in rodent cells the onset of senescence-like arrest can be activated without repression of telomerase, and that this activation pathway can be bypassed easily under certain culture conditions, such as the 10-day culture protocol.

Animals↗
PubMed2001

Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study.

BACKGROUND: Although efficacy studies suggest equal potency among antidepressant treatments, their effectiveness in clinical practice appears more variable, particularly in that the newer antidepressants may be less effective in either more severe depression or the melancholic subtype of depression. We pursue some factors that may impact the effectiveness of antidepressant treatments in a clinical sample. METHOD: A sample of 182 patients with DSM-IV major depressive disorder was assessed at baseline and 12 months later to establish treatments provided, identify patients who had recovered from the index episode, and quantify likely treatment determinants. Four systems for distinguishing patients with melancholic and non-melancholic depression were examined to assess for differential effects of the antidepressant strategies across those subtypes. RESULTS: Multimodal therapy (commonly, psychotherapy combined with an antidepressant drug) and patients' frequent attribution of recovery to spontaneous improvement made for difficulty in disentangling recovery determinants. After excluding a spontaneous improvement component, electroconvulsive therapy (ECT) and the irreversible monoamine oxidase inhibitors (MAOIs) appeared to be the most effective therapies across the sample, while the reversible inhibitor of monoamine oxidase-A (RIMA) appeared to be the least effective. The distinct gradient of suggested effectiveness of various strategies appeared to be contributed to principally by the varied effectiveness of alternate treatments across the melancholic subtype, whereby ECT, tricyclic antidepressants, and MAOIs were the most effective, and the selective serotonin reuptake inhibitors (SSRIs), RIMAs, and antipsychotic drugs were much less effective. For the nonmelancholic disorders, the effectiveness of SSRIs appeared to be comparable with that of older antidepressants. CONCLUSION: Although most patients received a physical treatment, they commonly judged psychotherapy and spontaneous improvement to be influential in their recovery. Reasons for such attributions are worthy of clarifying studies. Despite patients' concerns about the side effects and stigma of ECT as well as the side effects associated with the older antidepressants, these therapies were rated as more helpful by patients-and were more strongly associated with recovery-than the newer antidepressant drugs. Such overall results are compatible with an earlier study undertaken by us involving an independent sample and retrospective data. The overall gradient is clarified by studying depressive subtypes, allowing an important conclusion. Although the newer and older antidepressant drugs may be of similar effectiveness in nonmelancholic depression, the newer agents appear comparatively inferior for the treatment of melancholia, findings that have clinical implications and perhaps inform us about the pathogenesis of melancholia.

Adult↗
PubMed2001

QSAR of antineoplastics IV: Hansch analysis of N-(7-indolyl)benzenesulfonamides against KB human nasopharynx carcinoma, colon 38 murine adenocarcinoma and P388 murine leukemia cell lines.

Hansch analysis of recently reported antitumor activities of novel N-(7-indolyl)benzenesulfonamide derivatives against KB human nasopharynx carcinoma, colon 38 murine adenocarcinoma and P388 murine leukemia cell lines reveals that the pattern of receptor interactions in human KB cells differs from that in murine (colon 38 and P388 leukemia) cells. The latter two activities are autocorrelated and show similar receptor specificity. It seems that two binding sites, one interacting with the indole fragment and another with phenyl fragment of the indolylbenzenesulfonamide compounds, are present on the murine cell receptors (colon 38 and P388 leukemia) while only the latter binding site is active on the human KB cell receptors. For the activity against KB cells, a para-methyl or paramethoxy substituent on the phenyl ring of benzenesulfonamide moiety greatly enhances the activity. For the other two activities, a 3-chloro or 3-cyano substituent on indole nucleus enhances activities, while presence of bulkier meta or para substituent on the phenyl ring decreases activities. Presence of an ortho substituent on the phenyl ring appears to be detrimental for all the three activities. Equations generated by both QSAR and QAAR studies are quite robust as evidenced from cross-validation by 'leave-one-out' technique.

Adenocarcinoma↗
PubMed2001

QSAR of antineoplastics V: Exploration of receptor interaction sites of antitumor N-(7-indolyl)benzenesulfonamides targeting GI phase using electrotopological state atom index.

Quantitative structure activity relationship (QSAR) study of antiproliferative activities of N-(7-indolyl)benzenesulfonamides with electrotopological state atom (ETSA) index corroborates the conclusions of the previously reported Hansch analysis that the structural requirements for interactions with receptors of human KB nasopharynx cell line are different from that for murine colon 38 and P388 leukemia cell lines. The study suggests that both phenyl ring and indole moiety are the important receptor interaction sites present on the ligands for the murine cell lines, while the latter site does not appear to play significant role in case of human KB cell carcinoma.

Animals↗
PubMed2001

QSAR of matrix metalloproteinase inhibitor N-[(substituted phenyl)sulfonyl]-N-4-nitrobenzylglycine hydroxamates using LFER model.

QSAR analyses of matrix metalloproteinase (MMP) inhibitor N-[(substituted phenyl)sulfonyl]-N-4-nitrobenzylglycine hydroxamates, recently reported by Scozzafava and Supuran, have been attempted using linear free energy related (LFER) model of Hansch to explore the contribution patterns of the phenyl ring substitutions (P1' anchoring site of the ligands) to the activities against MMP-1, -2, -8 and -9 (pC1, pC2, pC, and pC9) and C. histolyticum collagenase (pC(ChC)) and also to find out relations among the activities. Multiple regression analyses applied on the data set reveal that electron withdrawing meta substituents and lipophilic ortho and meta substituents are conducive to pC1 while presence of substituents (larger than hydrogen) at vicinal positions on the phenyl ring and bulkier ortho substituents are detrimental to the activity. Again, the electronic and steric parameters of meta substituents (sigmam and MRm) and lipophilicity parameter of ortho substituents (pio) contribute significantly to pC2, pC8 and pC9: sigmam shows parabolic relationships (optimum sigmam values being 0.518, 0.584 and 0.522 respectively) and steric bulk of meta substituents has negative impact while presence of hydrophilic groups at the ortho positions increases the activities. Further, presence of electron withdrawing meta substituents and hydrophilic para substituents is conducive to the C. histolyticum collagenase (pC(ChC)) activity. The study suggests that the structural and physicochemical requirements of the P1' anchoring site for the activities against MMP-2, -8 and -9 are highly intercorrelated and these are comparatively less correlated with those for the activities against MMP-1 and C. histolyticum collagenase.

Glycine↗