Biomedical subjects

K Roy

Publications and source records attributed to K Roy.

At least 55 records · Page 3Linked to original sources

PubMed2001

Distribution of Cancer Patients According to Time Taken From Starting Day of Symptoms to Reporting at a Regional Cancer Institute in Eastern India.

A retrospective study of the patients registered during 1997 aiming the time taken by the patients from their starting day of symptoms of cancer to reporting i.e. duration of symptoms at Chittaranjan National Cancer Institute (CNCI) a regional cancer institute in Eastern India. During 1997 a total of 3628 cancer patients registered at CNCI. Out of these, 716(19.74%) could not remember the duration of symptoms of their diseases at the time of first reporting. For this reason only the remaining 2912 cases were considered in the present study. Only 83(2.85%) reported within one month of the initial onset of symptoms. The vast majority of patients, a toal of 2829 (97.15%), appeared at hospital after several months, contributing to a moderate to advanced stage of their disease at first contact. This would clearly be expected to lead to poor success in treatment. Late reporting by the patients is most probably due to lack of awareness about the symptoms of cancer. The patients were from rural, semi-urban and urban populations. Measures of association showed significant links between the place of residence (p<0.55), age (p<0.001), sex (p<0.001), general health condition of the patients at first contact (p<0.052), the economic status (p<0.51) and the treatment compliance (p<0.26) with the duration of symptoms. Tumours of some primary sites like the cervix, breast (female), oral cavity, thyroid and penis, for which treatment responses are good to very good in early stages were also considered. For these primary sites, statistical measures showed late reporting by the patients which resulted in poor treatment compliance as well as a poor treatment response.

Journal Article↗

PubMed2000

Invariant size-frequency distributions along a latitudinal gradient in marine bivalves.

In the most extensive analysis of body size in marine invertebrates to date, we show that the size-frequency distributions of northeastern Pacific bivalves at the provincial level are surprisingly invariant in modal and median size as well as size range, despite a 4-fold change in species richness from the tropics to the Arctic. The modal sizes and shapes of these size-frequency distributions are consistent with the predictions of an energetic model previously applied to terrestrial mammals and birds. However, analyses of the Miocene-Recent history of body sizes within 82 molluscan genera show little support for the expectation that the modal size is an evolutionary attractor over geological time.

Animals↗

PubMed2000

A new class of potential chloroquine-resistance reversal agents for Plasmodia: syntheses and biological evaluation of 1-(3'-diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines.

1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.

Animals↗

PubMed2000

Dissecting latitudinal diversity gradients: functional groups and clades of marine bivalves.

The latitudinal diversity gradient, with maximum taxonomic richness in the tropics, is widely accepted as being pervasive on land, but the existence of this pattern in the sea has been surprisingly controversial. This is partly due to Thorson's influential claim that the normal latitudinal diversity gradient occurs in marine epifauna (taxa living on the surface of the substratum) but not in infauna (burrowing or boring into the substratum), a contrast he attributed to the greater spatial and temporal environmental homogeneity of infaunal habitats. In an analysis of 930 species of north-eastern Pacific marine shelf bivalves, we found that bivalves as a whole, and both infauna and epifauna separately, show a strong latitudinal diversity gradient (measured as number of species per degree latitude) that is closely related to mean sea surface temperature (SST), even in analyses of residuals and first differences. This agrees with results for marine gastropods, but contradicts Thorson's environmental homogeneity hypothesis. The relationship between SST and diversity is consistent with a species-energy hypothesis, but the linkages from SST to diversity remain unclear. Most bivalve clades within broad functional groups conform to the general latitudinal trend, except for the deposit-feeding protobranchs. This group's non-directional pattern may be related to its mode of development, because a similar effect is seen in several other groups locked into this low-fecundity, non-feeding larval mode.

Animals↗

PubMed2000

Two promoters regulate transcription of the mouse folylpolyglutamate synthetase gene three tightly clustered Sp1 sites within the first intron markedly enhance activity of promoter B.

The process of polyglutamylation mediated by folylpolyglutamate synthetase (FPGS) in mammalian cells has nutritional and pharmacological importance. In murine cells, FPGS expression is controlled by two promoters that, as we show here, vary substantially in their efficiency, at least in the context of a reporter gene assay. Characteristics of the most efficient promoter (promoter B) were examined in the present studies. Insertion in pGL3 of a 1635 bp segment of upstream sequence including the most upstream exon (B1c), intron B1c and only 26 bp of the more downstream exon Bla resulted in a 15-20-fold increase in transcription in NIH3T3 and Hep1-6 cells compared with the promoterless vector. Deletion analysis of DNA sequence upstream of exon B1c showed that transcription was regulated by putative cis active elements only within two distally located upstream segments which when deleted cumulatively increased transcription three- to four-fold. However, deletion of the 56 bp intron B1c immediately downstream of the most upstream exon (Blc) resulted in 1/10 the rate of transcription. Primer extension analysis with NIH3T3 cells revealed start sites for transcription appreciably upstream of and within exon B1c as well as downstream in exon B1a. This result is consistent with the frequent occurrence in murine cells of an FPGS variant (variant III) incorporating exon B1c [Roy et al., J. Biol. Chem. 271 (1996) 23820; 272 (1997) 5587]. Site-directed mutagenesis and DNAse I footprinting revealed that three canonical GC boxes, either overlapping or tightly clustered within intron B1c, bound Sp1 and markedly enhanced transcription, accounting for the maximal promoter B activity. Moreover, in a cellular background devoid of Sp1 activity, we demonstrate that Spl can induce high levels of promoter B activity in pGL3 transfectants, but only when intron B1c is included within the reporter gene construct used. These results suggest that the unusually tight cluster of active Sp1 sites within intron B1c are essential and sufficient for maximal activity of this promoter. These tightly clustered sites appear to act as an enhancer element in promoting transcription and efficiently stabilize transcription initiation complexes at both distal and proximal start sites.

3T3 Cells↗

PubMed2000

Developmental regulation of amyloid precursor protein at the neuromuscular junction in mouse skeletal muscle.

Amyloid precursor protein (APP), associated with Alzheimer's disease plaques, is known to be present in synapses of the brain and in the adult neuromuscular junction (NMJ). In the present study we examined protein and gene expression of APP during the development of mouse skeletal muscle. Using immunocytochemical approaches, we found that APP is first detected in myotube cytoplasm at embryonic day 16 and becomes progressively concentrated at the NMJ beginning at birth until adulthood. The colocalization between APP and acetylcholine receptors at the NMJ is only partial at birth, but becomes complete upon reaching adulthood. We observed that all APP isoforms, including the Kunitz-containing (protease inhibitor or KPI) forms, are up-regulated from birth to postnatal day 5 and then decreased to reach the low levels observed in the adult. This suggests the involvement of APP during the events which lead to a mature mono-innervated synapse. A 92-kDa band, characteristic of a cleaved APP695 isoform and not due to a new muscle-specific alternative spliced form, was observed from postnatal day 15 following completion of polyneuronal synapse elimination. Taken together, these data suggest that skeletal muscle APP may well play a role in the differentiation of skeletal muscle and in the formation and maturation of NMJs.

Alternative Splicing↗

PubMed2000

Evaluation and validation of a measure profiling needs and problems of psychiatric patients in the community: a Malaysian study.

BACKGROUND: The Profile of Community Psychiatry Clients (PCPC) was developed in a Sydney-based sample of those with a mental illness as a 35-item measure of likely need for service recognition, review and possible assistance. METHODS: This study has three principal objectives. Firstly, to test the utility of the PCPC measure in a very different region and culture. Secondly, to review the factor structure in an independent sample. Thirdly, to pursue the extent to which the PCPC might serve as a measure of likely need, by obtaining three differing reference viewpoints of need (i.e. clients, their carers, and case managers) and examining responses against PCPC scores. The PCPC was given to a sample of 333 Malaysian clients living in the community, together with two other measures of morbidity and disability. In addition, case managers, family members and clients were requested to directly rate the level of need for service assistance. RESULTS: A principal components analysis favoured a six-factor solution, with PCPC factor scores and total scores intercorrelated with subscale and total scores on the Life Skills Profile (LSP) and Health of the Nation Outcome Scales (HoNOS). The correlation coefficients supported the concurrent validity of the derived PCPC scales. Family members rated the clients' needs as greater than did case managers who, in turn, rated severity of needs greater than the clients themselves. Most importantly, PCPC scores correlated more highly than did LSP and HoNOS scores with need estimates derived by all three rating groups, providing strong support for the PCPC meeting its objective as a measure of putative need. In addition, a refined 23-item version of the PCPC was derived, which retained the capacity of the PCPC to correlate strongly with needs estimates. CONCLUSIONS: This Malaysian study supports the use of the PCPC in a culture where service provision and family support for those with a mental illness vary considerably from Western regions, while its validation as a measure of need for service is supported.

Adult↗

PubMed2000

The nature of bipolar depression: implications for the definition of melancholia.

AIM: To examine if melancholic depression is over-represented in those with 'bipolar depression' and, if confirmed, to use that phenomenon to assist the clinical definition of melancholia. METHODS: We contrast 83 bipolar and 904 unipolar depressed patients on three melancholic sub-typing systems (DSM, Clinical and CORE system) and compare representation of their clinical depressive features. RESULTS: By all three melancholic sub-typing systems, the bipolar patients were more likely to receive diagnoses of 'melancholia' and of psychotic depression. To the extent that this differential prevalence of depressive sub-types was reflected in varying patterns of clinical features, we so indirectly identified a set of items defining 'melancholia'. By such a strategy, melancholia was most clearly distinguished by behaviourally-rated psychomotor disturbance. While a number of 'endogeneity symptoms' were significantly over-represented, logistic regression analyses refined the set to psychomotor disturbance (both as a symptom and as a sign) and pathological guilt. We also established a distinctly higher prevalence of bipolar depression in those where a refined diagnosis of melancholia was made. CONCLUSIONS: Bipolar depression appears to be more likely to be 'melancholic' in type, thus providing an indirect strategy for the clinical definition of melancholia.

Adult↗

PubMed2000

Subtyping depression by clinical features: the Australasian database.

OBJECTIVE: To distinguish psychotic, melancholic and a residual non-melancholic class on the basis of clinical features alone. Previous studies at our Mood Disorders Unit (MDU) favour a hierarchical model, with the classes able to be distinguished by two specific clinical features, but any such intramural study risks rater bias and requires external replication. METHOD: This replication study involved 27 Australasian psychiatrist raters, thus extending the sample and raters beyond the MDU facility. They collected clinical feature data using a standardized assessment with precoded rating options. A psychotic depression (PD) class was derived by respecting DSM-IV decision rules while a cluster analysis distinguished melancholic (MEL) and non-melancholic classes. RESULTS: The MELs were distinguished virtually entirely by the presence of significant psychomotor disturbance (PMD), as rated by the observationally based CORE measure, with over-representation on only three of an extensive set of 'endogeneity symptoms'. CONCLUSION: In comparison to PMD, endogeneity symptoms appear to be poor indicators of 'melancholic' type, confounding typology with severity. Results again support the hierarchical model.

Adult↗

PubMed2000

How long does it take for antidepressant therapies to act?

OBJECTIVE: To review the proposition that antidepressants have a delayed onset of action by employing measurement and analytic strategies that overcome problems confounding interpretation of many efficacy studies. METHOD: A subset of patients was recruited to the longitudinal component of the Australasian database study, was assessed at baseline, and then completed measures of depression and anxiety when treatment commenced, and every 3 days over the next 4 weeks. The trajectories of defined 4-week outcome responders and non-responders were compared. RESULTS: Both groups showed a similar decrease in depression (and anxiety) over the first 3 days. A clear trend break then occurred, with little further improvement in the non-responders, as against distinct and progressive improvement in the responders. Ongoing early improvement (across days 3-6) was a strong predictor of responder status. CONCLUSIONS: The small sample size limits firm interpretation, although distinct interpretive advantages to the study design are evident. Findings are compatible with a number of recent studies arguing against any extensive delayed onset of action for the antidepressant drugs, but argue for caution in interpreting immediate improvement as predicting likely responder status, and more for examining early and sustained improvement as such a marker.

Adult↗

PubMed2000

Costing depression and its management: an Australian study.

OBJECTIVE: To examine the cost impact of referral to a Mood Disorders Unit (MDU), by comparing pre-service and post-service costs, and MDU and control samples. METHOD: We studied tertiary referral MDU patients and a control group of consultants' depressed patients, with the principal comparison intervals being: (i) 12 months prior to and (ii) 6 months following baseline assessment, with costs annualised to allow the impact of assessment and treatment recommendation to be determined. In addition, we assessed any 'personal cost' of depression. RESULTS: Following baseline assessment, MDU referrals showed a reduction in costs, while controls' costs increased, largely driven by contrasting directions in hospitalisation and social welfare costs. We identify variables associated with high and increased costs, including features of the earlier stages of the disorder, whether social welfare was received, diagnostic subtype and personality dysfunction, with multivariate analyses refining the variable sets. Self-report data indicated that patients judged the 'personal cost' of depression to exceed more formal cost parameters, so that to experience depression is itself depressogenic. CONCLUSIONS: This first Australian attempt to cost depression and its management in the clinical setting more provides a methodology for wider application in service evaluation studies rather than delivers an unequivocal answer to whether a specialist Mood Disorders Unit is cost efficient or not.

Adult↗

PubMed2000

Hypoxia relieves X-ray-induced delayed effects in normal human embryo cells.

We studied the effect of hypoxia on X-ray-induced delayed effects in normal human embryo cells to elucidate the role of oxidative stress in the susceptibility of cells to induction of genetic instability by radiation. We examined X-ray-induced delayed cell death, giant cell formation, and chromosome aberrations under normally oxygenated (20%) and hypoxic (2%) conditions at 28-38 population doublings postirradiation. The results revealed that hypoxia reduced the X-ray-induced delayed effects, suggesting that radiation enhances cellular oxidative stress, which plays a significant role in determining the susceptibility of irradiated cells to genetic instability. The present study emphasizes the biological significance of epigenetic effects, such as oxygen tension, as well as direct DNA damage in the induction of genetic instability by radiation.

Cell Count↗

PubMed2000

Hansch analysis of antimalarial cyclic peroxy ketals with physicochemical and electrotopological parameters.

Hansch analysis of some antimalarial cyclic peroxy ketals (IV) having structural variations at the para substituted phenyl ring and an alicyclic ring of different size reveals that electronic and steric parameters of the phenyl ring substituents are important for explaining the variation in the activity while hydrophobicity parameter is of little significance. Electron withdrawing substituents with higher MR (molar refractivity) or V(W) (van der Waals volume) are preferred for the activity. Use of structural descriptors suggests that presence of a seven membered alicyclic ring attached to the peroxy bridge containing ring is conducive to the activity. Application of electrotopological state atom index (ETSAI) suggests a pharmacophore containing the peroxy bridge. This is corroborated by earlier observation on importance of oxygen atoms of the peroxy linkage of artemisinin for antimalarial activity. Although incorporation of ETSAI into Hansch model does not improve the relations, the electronic parameter sigma is found to be significantly correlated with it.

Algorithms↗

PubMed2000

Evaluation of glutathione and ascorbic acid as suppressors of drug-induced lipid peroxidation.

In different sets of experiment lipid peroxidation induction capacity of two drugs, viz., ceftizoxime sodium, a third generation cephalosporin antibiotic, and acyclovir, an antiviral agent, was studied using goat whole blood as the lipid source. Ceftizoxime sodium caused significant extent of lipid peroxidation. Lipid peroxidation being a toxicity mediating process, such observation may be related to the toxic potential of the drug. Insignificant induction of lipid peroxidation was found in case of acyclovir and this is in good agreement with the safety record of the drug. Glutathione and ascorbic acid could significantly reduce ceftizoxime sodium induced lipid peroxidation, suggesting that free radical scavenging action of antioxidants may be exploited by possible antioxidant co-therapy to reduce iatrogenicity of the drug in persons with impaired endogenous antioxidant defence. Glutathione and ascorbic acid appear to be promising candidates for further investigation in this regard.

Acyclovir↗

PubMed1999

Unsaturated fatty acid-activated protein kinase (PKx) from goat testis cytosol.

The cytosolic fraction of goat cauda epididymis possesses a protein kinase (PKx) activity which is stimulated by a number of unsaturated fatty acids of which arachidonic acid is the best activator in absence of cAMP or Ca(2+). Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and diacylglycerol have no effect either alone or in combination. The membrane fraction does not show any appreciable kinase activity even after detergent treatment. PKx migrates as a single band of apparent molecular mass of 116 kDa on 10% SDS-PAGE after sequential chromatographic separation on DEAE-cellulose, phenyl-Sepharose, high-Q anion exchange and protamine-agarose affinity column. PKx phosphorylates histone H1, histone IIIs and protamine sulfate, but not casein. However, the best phosphorylation was obtained with a substrate based on PKC pseudosubstrate sequence (RFARKGSLRQKNV). The kinase phosphorylates two endogenous cytosolic proteins of 60 and 68 kDa. Ser residues are primarily phosphorylated although a low level of phosphorylation is observed on Thr residues also. Ca(2+) and Mn(2+) inhibit PKx activity in the micromolar range. Staurosporine is found to inhibit the PKx activity to a significant level at sub-nanomolar concentration. Lyso-phosphatidylcholine and certain detergents at very low concentrations (<0.05%) stimulate enzyme activity to some extent. The immuno-crossreactivity study with antibody against different PKC isotypes suggests that the protein kinase under study is not related to any known PKC family. Even the antibody against PKN (a related protein kinase reported in rat testis found to be activated by arachidonic acid) does not cross-react with this protein kinase. Hence we believe that the protein kinase (PKx) reported here is different even from the PKN of rat testis. The phosphorylation of endogenous proteins by the protein kinase may be involved in cell regulation including fertility regulation and signal transduction.

Animals↗

PubMed1999

Transcription of the mouse RFC-1 gene encoding a folate transporter. Multiplicity and properties of promoters with minimum requirements for their basal activity.

The mouse RFC-1 gene incorporates alternates of exon 1 (exon 1 and 1a) which encode different 5' ends. This finding, and the elucidation of a promoter-like sequence immediately upstream of these alternates of exon 1, suggest that two separate promoters drive transcription of this gene. The regions upstream of either exon 1 or exon 1a inserted in pGL3 will separately promote transcription in NIH3T3 cells of the luciferase reporter gene, with the region upstream of exon 1 having the strongest promoter activity. Tissue-specific expression in the form of RFC-1 mRNA splice variants reflects the separate action of each promoter. In the most upstream portion of the region proximal to exon 1a, elements were revealed that enhance transcription along with a more downstream element that suppresses transcription in NIH3T3 cells. Three Sp1 sites closely proximal to exon 1a within a region spanning 123 nucleotides were shown to be transcriptionally active by site-directed mutagenesis, with the middle SP1 site found to be the most important of the three in maintaining basal promoter activity. A poly (GT) 21 di-nucleotide repetitive element upstream of these Sp1 sites was found in a region which, when deleted, increased transcription. In the region upstream of exon 1, two elements were elucidated which enhanced transcription. Site-directed mutagenesis showed that two adjacent SP1 sites proximal to exon 1 were equally important in sustaining basal promoter activity. The role of each Sp1 site in maintaining basal activity of each promoter was confirmed by DNase I footprinting analysis. In addition, a binding site of unknown significance was identified by this analysis within the upstream promoter sequence between the two Sp1 sites proximal to exon 1a. These data show that both promoters regulating expression of the RFC-1 gene utilize closely spaced Sp1 sites in tandem to sustain basal transcription, at least in NIH3T3 cells, in a manner characteristic of TATA-less promoters.

3T3 Cells↗

PubMed1999

[Vascular injuries complicating osteosynthesis in proximal femur fractures].

While there are quite a number of reports on vascular injuries complicating hip arthropasty by acetabular component screw fixation, retractor tip pressure or extruding bone cement, the incidence of deep femoral vessel injuries in operative fixation of proximal femoral fractures is comparatively seldom described. We report on two patients with per- and subtrochanteric femoral fractures who sustained injuries of deep femoral artery branches during the implantation of a dynamic hip screw (DHS) and a dynamic condylar screw (DCS), which resulted in a massive thigh hematoma and a fist-size pseudoaneurysm respectively and necessitated surgical intervention in either case. We blame these vascular injuries on the pressure of Hohmann retractors exposing the femoral bone or on the drilling of boreholes for plate attachment. After discussing various operative procedures, we conclude that intramedullar implants are safer than plates with regard to potential vascular complications.

Aged↗

PubMed1999

Sub-grouping non-melancholic depression from manifest clinical features.

AIM: To determine whether clinical symptoms manifested during an episode of major depression are sufficient to allow meaningful sub-groups of non-melancholic depression to be identified. METHODS: A sample of 178 non-melancholic patients with a major depressive episode was studied. The initial set of clinical variables was refined to 38 (21 depression, 17 anxiety) items and a cluster analysis undertaken. RESULTS: A four-cluster solution identified 'anxiety', 'irritability', 'depressed mood' and 'residual' clusters, with these labels clarified by reference to a large data bank of non-symptomatic variables. These analyses suggested that members of the first two clusters could be viewed as having spectrum conditions (whereby Axis I symptom states are able to be linked with precursor or prodromal states and personality). CONCLUSIONS: We confirm the long-standing suggestion that the non-melancholic depressive class contains sub-groups of those with manifest states of anxious depression and of an irritable or 'hostile' depression, and that such manifest symptoms are likely to be rooted in and fed by temperament and personality characteristics. The delineation of such sub-groups should assist studies designed to identify underlying neurobiological underpinnings and clinical management of the non-melancholic depressive disorders.

Adult↗