Biomedical subjects

D Karan

Publications and source records attributed to D Karan.

17 recordsLinked to original sources

PubMed2006

Aqueous extract of Rhodiola imbricata rhizome stimulates proinflammatory mediators via phosphorylated IkappaB and transcription factor nuclear factor-kappaB.

Modulation of immune response to alleviate diseases has long since been of interest. Plant extracts have been widely investigated for their possible immunomodulatory properties. We have evaluated the immunomodulatory activity of aqueous extract of Rhodiola rhizome in human peripheral blood mononuclear cells (PBMCs) and mouse macrophage cell line RAW 264.7. The Rhodiola extract was found to stimulate production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in human PBMCs as well as RAW 264.7 cell line. It also increased production of nitric oxide synergistically in combination with lipopolysaccharide (LPS) in RAW 264.7. Rhodiola at 250 microg/ml increased the p-IkappaB expression in human PBMCs. Aqueous extract of Rhodiola (250 microg/ml) also activated the nuclear translocation of NF-kappaB in human PBMCs, which is comparable to the positive stimulant LPS. Thus, our present study suggests that Rhodiola most likely activates proinflammatory mediators via phosphorylated inhibitory kB and transcription factor NF-kB. Our study demonstrates immunostimulatory potential of aqueous extract of Rhodiola rhizome, that can be used for upregulation of immune response in patients with inadequate functioning of the immune system.

Active Transport, Cell Nucleus↗

PubMed2001

Mucins in protozoan parasites.

Studies on host-pathogen interactions have led to the discovery of various cell surface associated and secretory molecules. Mucins and mucin-like molecules have recently been described in several protozoan parasites, at different stages of the life cycle. These share many structural and compositional features with mammalian mucins, but vary in several other aspects. It is now becoming evident that mucins in parasite are involved in cell-cell interaction and cell surface protection, thus helping the parasite to establish infection. A large number of mucin like genes from the parasite genome have been reported, and their expression differ during the developmental stages of the parasite. In this review, we describe the structure and functions of mucin and mucin-like molecules in parasitic protozoa.

Animals↗

PubMed2001

Molecular evolution of the AMP-forming Acetyl-CoA synthetase.

Acetyl-CoA-Synthetase (ACS) is involved in the production of acetate, a major metabolite in numerous organisms. There are two forms of this enzyme: ADP-forming ACS and ATP-forming ACS. We focus mainly on the AMP-forming ACS gene, which is relatively well conserved in eubacteria, archeaebacteria, and eukaryotes. BLAST searches in databases showed 30 protein sequences significantly related to the ACS. Most of these sequences were identified as ACS but three of them, belonging to the mammalian species, were annotated as another gene named: the SA gene, which is involved in the essential hypertension. The ACS and SA genes probably derived from a duplication of an ancestral gene but have acquired different functions. Six conserved regions of the ACS protein were defined across the three domains of life. While the precise function of the conserved regions remains unknown, they are probably involved in the enzymatic activity. Among eukaryotes, we found a high variability with respect to the number and the position of introns. However, some positions are conserved between fungi and a nematode. A maximum likelihood tree based upon the conserved regions showed that all sequences except the one from B. subtilis, belong to two basic groups: one the SA-like group including sequences from Archaeoglobus fulgidus and Streptomyces coelicolor, and second, the ACS group. The later can be further divided in two parts: a prokaryotic one including eubacteria and an archaebacterium, and a eukaryotic group within which two proteobacterial sequences branch including ACS from the alpha-proteobacterium Rhodobacter capsulatus. Within the eukaryotic group, bootstrap support is very low, but overall the data are consistent with the view that eukaryotes acquired their ACS gene from the ancestors of mitochondria. The localization of this enzyme in eukaryotic mitochondria is the additional evidence in favor of this interpretation.

Acetate-CoA Ligase↗

PubMed2001

Chill-coma tolerance, a major climatic adaptation among Drosophila species.

Most drosophilid species can be classified either as temperate or tropical. Adults of species were submitted to a cold treatment (0 degrees C) and then brought back to ambient temperature. They generally exhibited a chill coma and the time needed to recover was measured. We found in a set of 26 temperate species that recovery was rapid (average 1.8 min, range 0.15-4.9). In contrast, a long recovery time (average 56 min, range 24-120) was observed for 48 tropical species. A few species, like Drosophila melanogaster, are cosmopolitan and can proliferate under temperate and tropical climates. In 9 of 10 such species, slight genetic differences were found: a shorter recovery in temperate than in tropical populations. Comparing physiological data to phylogeny suggests that chill-coma tolerance has been a recurrent adaptation that is selected for in cold climates but tends to disappear under a permanently warm environment. This major climatic adaptation, evidenced in drosophilids, seems to occur in other insect groups also.

Acclimatization↗

PubMed2001

Decreased androgen-responsive growth of human prostate cancer is associated with increased genetic alterations.

Genetic mechanisms involved in prostate tumor progression from the androgen-responsive to androgen-unresponsive stage are not well understood because of the tremendous heterogeneity in the tumor as well as the lack of suitable models. Using 165 repeat microsatellite DNA markers distributed equally over all of the chromosomes, we determined an association between genetic alterations and androgen-unresponsive growth in three stages of LNCaP cell model (C33: early, androgen-responsive; C51: mid, decreased androgen-responsive; and C81: late, androgen-unresponsive and increased tumorigenicity). Furthermore, the genetic alterations were confirmed in laser microdissected normal and cancerous tissues from 15 clinical samples of human prostatic adenocarcinomas using selected markers. A stem-line karyotype analysis exhibited an identical chromosomal pattern in both C33 and C81 stage cells except for the structural rearrangements of chromosome 3 and a gain of one copy of the Y chromosome in the androgen-unresponsive C81 stage cells. Nine microsatellite DNA markers on seven different chromosomes (1, 4, 5, 11, 17, 18, and 19) showed microsatellite instability (MSI) in both C51 and C81 stage cells. Additionally, 23 markers on 15 different chromosomes revealed MSI in C81 cells. Chromosomal regions demonstrating allelic loss (AL) include 1q, 3p, 5p, 8q, 9q, and 13q in C51 and C81 cells. In clinical human specimens, MSI was observed on chromosomes 1 (20%), 5 (23%), 17 (40%), and 19 (36%), whereas ALs were found 40% on chromosomal region 1q, 20% on 3p, 26% on 5p and 8q, and 33% on 13q. In conclusion, the LNCaP cell model showed the increasing number of genetic changes including MSI and AL. These increased genetic alterations may be associated with the development of the androgen-unresponsive phenotype.

Androgens↗

PubMed2000

Cold tolerance in Drosophila: adaptive variations revealed by the analysis of starvation survival reaction norms.

Three species of Drosophila were investigated for their capacity to survive without food (starvation tolerance) at seven different temperatures ranging from 0 to 25 degrees C. In all cases biphasic response curves (reaction norms) were observed, corresponding either to special deleterious effects of cold or to a progressive exhaustion of reserves proportional to metabolic rate. The temperature at which survival was longest was called the threshold temperature. The position of the threshold exhibited adaptive changes, either due to acclimation in the same species, or to genetic variations evidenced between species. In D. melanogaster, adults grown at lower temperature (12 degrees C) were more tolerant to cold than adults grown at higher temperatures (21, 25 or 30 degrees C). This acclimation process shifted, in an adaptive way, the position of the threshold temperature from 6.2 to 7.5 degrees C. A comparison of three different species grown at a single developmental temperature (21 degrees C) revealed similar but greater adaptive differences in their threshold temperature: 4.8 degrees C in the temperate D. subobscura, 7 degrees C in the cosmopolitan D. melanogaster and 14.6 degrees C in the tropical D. ananassae.

Journal Article↗

PubMed2000

Geographical clines for quantitative traits in natural populations of a tropical drosophilid: Zaprionus indianus.

We analyzed natural populations of Zaprionus indianus in 10 Indian localities along a south-north transect (latitude: 10-31 degrees 3 N). Size traits (body weight, wing length and thorax length) as well as a reproductive trait (ovariole number) followed a pattern of clinal variation, that is, trait value increased with latitude. Wing/thorax ratio, which is inversely related to wing loading, also had a positive, but non-significant correlation with latitude. By contrast, bristle numbers (sternopleural and abdominal) exhibited a non-significant but negative correlation with latitude. Sex dimorphism, estimated as the female/male ratio, was very low in Z. indianus, contrasting with results already published in other species. Genetic variations among populations were also analyzed according to other geographic parameters (altitude and longitude) and to climatic conditions from each locality. A significant effect of altitude was found for size traits. For abdominal bristles, a multiple regression technique evidenced a significant effect of both latitude and altitude, but in opposite directions. Genetic variations were also correlated to climate, and mainly with average year temperature. Taking seasonal variations into account failed however to improve the predictability of morphometrical variations. The geographic differentiation of Z. indianus for quantitative traits suggests adaptive response to local conditions, especially to temperature, but also reveals a complex situation according to traits investigated and to environmental parameters, which does not match results on other drosophilid species.

Altitude↗

PubMed2000

The genetics of phenotypic plasticity. IX. Genetic architecture, temperature, and sex differences in Drosophila melanogaster.

We examined the genetic architecture of plasticity of thorax and wing length in response to temperature in Drosophila melanogaster. Reaction norms as a function of growth temperature were analyzed in 20 isofemale lines in a natural population collected from Grande Ferrade near Bordeaux (southern France) in two different years. We found evidence for a complex genetic architecture underlying the reaction norms and differences between males and females. Reaction norms were negative quadratics. Genetic correlations were moderately high between traits within environments. Among characteristic values, the magnitudes of genetic correlations varied among traits and sexes. We hypothesized that genetic correlations among environments would decrease as temperatures became more different. This expectation was upheld for only one trait, female thorax length. For males for both traits, the correlations were large for both very similar and very different temperatures. These correlations may constrain the evolution of the shape of the reaction norms. Whether the extent of independence implies specific regulatory genes or only a specific allelic regulation of trait genes can not be decided from our results.

Animals↗

PubMed1999

Microspatial genetic differentiation for tolerance and utilization of various alcohols and acetic acid in Drosophila species from India.

In five Indian localities, it was possible to collect D. melanogaster in two different types of habitats, namely ordinary domestic and alcohol rich ones. Tolerance and utilization capacity of several alcohols and of acetic acid were analyzed in a total of 10 local populations. Results on two other species (D. repleta and D. immigrans) were also available from one place. In each locality, the population from alcohol rich habitat proved to be more tolerant to all the investigated products and also to be more capable of using them as a resource. Alcohols toxicity increased with increasing carbon chain length and secondary alcohols were more toxic than primary ones. Utilization capacity of all products was relatively independent of their toxicity. Especially acetic acid, the toxicity of which was low and similar to that of ethanol, was always a fairly poor resource. From a genetic point of view, tolerance and utilization capacity appeared as two relatively independent traits. Natural selection, which is responsible for the genetic differentiation of local populations, is likely to act simultaneously on both traits.

Acetic Acid↗

PubMed1999

Growth temperature and reaction norms of morphometrical traits in a tropical drosophilid: Zaprionus indianus.

Ten isofemale lines of Zaprionus indianus were analysed to study the reaction norms of five morphometrical traits (wing and thorax length, body weight, sternopleural bristle and ovariole number) in relation to growth temperature. All these traits exhibited nonlinear concave reaction norms and were characterized by the coordinates of their maximum: MV (maximum value), and TMV (temperature of maximum value). Wing/thorax ratio, which is related to flight capacity, was also calculated and exhibited a monotonically decreasing reaction norm. Intraclass correlations were on average quite low, with no significant differences between traits, temperature or sex; a highly significant trait-temperature interaction was, however, observed. Sex dimorphism was very low in Zaprionus, contrasting with data previously obtained in other species. MVs among lines were positively correlated for the three size-related traits, whereas sternopleural bristle and ovariole number were genetically independent. TMVs were different between the traits, but higher than in D. melanogaster and other cold-adapted species, in agreement with the hypothesis that the norm shape evolves according to species thermal adaptation. MVs and TMVs were never correlated, indicating that mean values and plasticity are genetically independent. Some positive correlations were observed among TMVs of different traits, suggesting that the same genetic system might regulate plasticity of different traits.

Animals↗

PubMed1999

Immunomodulatory effect of laser on whole body exposure.

All biomedical laser applications are based on the interaction of laser light with biological system. During the past decade considerable evidence has accumulated demonstrating that non-thermal exposure to laser can elicit cellular changes in the immune system. In the present study, we have analyzed the effect of laser on immune response in rats. A group of rats were exposed to 0.225 mu j/cm2 for 90 min for 3 days in specially designed fiberglass chambers. The whole body exposure of rats of He-Ne laser modulated both the humoral and cellular responses to tetanus toxoid stimulation. Plain red light used as a control for red laser light showed an appreciable degree of response as compared to the control groups, but not to the extent of the response to laser. Non-responders turned responders after exposure to laser. There was no response in unimmunized groups when exposed to laser and red light alone. The early and heightened immune response and proliferation of lymphocytes after exposure to laser is suggestive of a complex interaction at the cellular immune response level.

Animals↗

PubMed1999

Induction of stress proteins in response to hypoxia.

Hypoxia is a severe stress factor to which man and most other mammalian species are capable of adapting. However, the cellular mechanism which enable cells to adapt are still unknown. Effect of hypoxia was studied on the synthesis of hypoxia induced proteins in rat kidney and in vero cell line (monkey kidney). These were exposed to hypoxia at 240 mmHg pressure for 1 hr. The induction of stress protein was determined by probing with monoclonal antibodies against 65 kDa heat shock protein (hsp65). The induction of a 65 kDa protein was 3.6 fold higher to the total cellular protein, both in cell lines and kidney of rats. In vivo response was predominantly observed in renal cortical region particularly in glomeruli. The induction of stress proteins during hypoxia suggests their importance in the maintenance of cellular integrity under hypoxia.

Animals↗

PubMed1998

Latitudinal clines for morphometrical traits in Drosophila kikkawai: a study of natural populations from the Indian subcontinent.

Natural populations of Drosophila kikkawai were collected in India and Sri Lanka, along a latitudinal transect ranging from 6.8 degrees to 31.8 degrees N latitude. Six morphometrical traits were analysed: wing and thorax length, body weight, ovariole number, and abdominal and sternopleural bristle numbers. Significant clines were observed for the three-size related traits and for ovariole number, corresponding to a regular increase in the mean value with latitude, but not for bristle numbers. Due to the utilization of two types of laboratory food, data were distributed into two separate data sets. A low-nutrient food produced smaller flies on average because of more intense crowding. The two rearing conditions produced significant clines but with significantly different slopes. The wing/thorax ratio, which is inversely related to wing loading, also increased with latitude. The analysis of Indian climatic conditions suggested that winter temperature, decreasing from south to north, could be more efficient than summer temperature, which varies in an opposite way, as a selective factor for inducing the clinal variations. The sibling species D. leontia, which is known only from the humid tropics, was found to be much smaller than D. kikkawai and did not fit the clinal regressions. Such morphological differences should help to identify the two species when found in sympatry.

Animals↗

PubMed1998

Geographical divergence for quantitative traits in colonising populations of Drosophila kikkawai from India.

There are significant geographical variations for four quantitative traits among eight natural populations of Drosophila kikkawai along the Indian latitudinal transect (8.29 to 33 degrees N). Body weight, wing length, thorax length, and ovariole number exhibit significant clinal variation with increase in latitutde. Genetic correlations between all the four traits are significantly higher. Slope values for body weight and wing length are higher (2.32 per degree latitude) while lower for thorax length (0.70) and ovariole number (0.56). South Indian populations are characterised by lower mean values but higher variances as well as CV values as compared with northern populations. Multiple regression analyses (on the basis of temperature related climatic variables) evidence significantly higher association between all the four traits and coefficient of variation of mean annual temperature (seasonal thermal amplitude; TCV). Thus, genetic differentiations for quantitative traits in D. kikkawai are due to selective pressure from variable seasonal environmental conditions occurring on the southern tropical versus northern subtropical regions of the Indian subcontinent.

Adaptation, Physiological↗

PubMed1984

Thermodynamics of all-or-none water channel closure in red cells.

The relation of osmotic to diffusional water permeability of human red blood cells was compared after treating the cells with different concentrations of PCMBS (p-chloromercuribenzene sulfonate). After subtracting the PCMBS-insensitive permeability (presumably the water permeability of the lipid bilayer) from each, the ratio of osmotic to diffusional permeability remains invariant (approximately equal to 11) as more and more water channels are inhibited by increasing concentrations of PCMBS. This result implies that the channels close in an all-or-none way and suggests a two-state model. Analysis of the dependence of osmotic water permeability on PCMBS concentration in terms of the model reveals a 1:1 stoichiometry and a dissociation constant for the PCMBS/membrane receptor complex of about 0.019 mM at 37 degrees C. Temperature dependence studies show that the reaction is entropically driven (delta H degrees approximately equal to 25 kcal/mol, delta S degrees approximately equal to 100 cal/mol-deg) and suggest the involvement of hydrophobic interactions.

Cell Membrane Permeability↗

PubMed1980

Validating optimal response modes of learning disabled children.

To determine optimal and least effective response modes of learning disabled children, the procedure described by Owen, Braggio, and Ellen (1976) and the Illinois Test of Psycholinguistic Abilities were used. On the basis of pretest and posttest comparisons on selected subtests, the performance of these children could be described as individual or multiple combinations of covert-, vocal-, or visual/manual-response modes. This learning style analysis was validated by presenting a paired-associate task to the children using an administration similar to (matched condition) or different from (unmatched condition) the child's optimal response mode. More items were recalled under the matched condition than under the unmatched condition. Also, the children with multiple response modes recalled more items than the learning disabled children with single optimal response modes. These results suggest that disabled children may do poorly on academic tasks because they may not have enough optimal response modes, or are unable to select the most appropriate mode of responding as required by a task. The use of optimal response modes as an aid in the diagnosis and remediation of educational handicaps is discussed.

Child↗

PubMedDate not supplied

Expression of tumor-associated glycoprotein-72 (TAG-72) antigen in human prostatic adenocarcinomas.

Tumor-specific antigens are usually defined by monoclonal antibodies (MAbs) and can play critical roles in the diagnosis and therapy of carcinomas. Despite advances in the understanding of the molecular genetics of human prostate carcinomas, therapeutic approaches require that tumor-specific markers, preferably on the cell surface, should be defined. In this study, we examined the expression of an oncofetal antigen tumor-associated glycoprotein-72 (TAG-72) in prostatic adenocarcinomas with a Gleason grade of six or higher. Using a second generation MAb CC49 against TAG-72, immunoreactivity was detected in 88% (29/33) of the prostatic cancer tissues. Occasionally, the benign epithelium showed a very faint immunostaining but in most of the specimens, no reactivity was detected. Positive staining was present in the cytoplasm and the cell membrane of the malignant cells similar to reports on other cancer tissues. A weaker staining pattern of this antigen was seen in poorly differentiated areas. A significant negative correlation (r = -0.36, p < 0.05) was observed between TAG-72 antigen expression and Gleason grade. The TAG-72 antigen expression in prostatic adenocarcinomas may be used as a target for radioimmunotherapy by the multivalent single chain antibody CC49 constructs recently generated by our group.

Adenocarcinoma↗