Search PubMed⌕ Search

Biomedical subjects

S Deb

Publications and source records attributed to S Deb.

At least 37 records · Page 2Linked to original sources
PubMed1999

Modulation of the clastogenic activity of gamma-irradiation in buthionine sulphoximine-mediated glutathione depleted mammalian cells.

PURPOSE: Chromosome aberrations (CA) were used as an end-point to investigate the effect of buthionine sulphoximine (BSO), a potent glutathione-depleting agent, on the radiosensitivity of mammalian cells. The aim was to obtain information about the role of glutathione (GSH) in physicochemical and biochemical processes in irradiated cells. MATERIALS AND METHODS: CA were scored from first cycle metaphases in irradiated BSO-pretreated and untreated samples. BSO exposure was for 10h in mouse bone marrow cells in vivo and 5 h for human lymphocytes in vitro. In further experiments fresh blood was irradiated on ice and immediately after irradiation GSH/GSH-ester was added. RESULTS: In both the systems BSO-treated samples showed higher sensitivity to radiation than BSO untreated samples. The frequency of all types of CA increased except exchange aberrations. GSH/GSH-ester treatment given after irradiating the cells at 4 degrees C reduced the frequency of deletions and increased the frequency of exchange aberrations. CONCLUSIONS: Data indicate that BSO-mediated GSH depletion increased radiation-induced chromosome aberrations, apart from exchange aberrations. This could be due to reduction in the free-radical scavenging effect of GSH, a failure in rejoining of DNA double-strand breaks, or induction of apoptosis.

Animals↗
PubMed1999

Resuscitation with lactated Ringer's solution in rats with hemorrhagic shock induces immediate apoptosis.

BACKGROUND: We hypothesize that different resuscitative fluids may immediately affect the degree of apoptosis after hemorrhagic shock. METHODS: Rats (n = 35) were hemorrhaged 27 mL/kg over 5 minutes followed by 1 hour of shock, then resuscitation over 1 hour. The six treatment groups were sham hemorrhage, sham resuscitation, whole blood resuscitation, lactated Ringer's solution (LR) resuscitation with three times the volume bled, sham hemorrhage with LR infusion, and 7.5% hypertonic saline resuscitation (9.7 mL/kg). Liver and small intestine were harvested immediately after resuscitation. Apoptosis was evaluated by using in situ cell death detection method. RESULTS: Resuscitation with LR resulted in a significant increase in small intestinal and liver apoptosis. Animals that received LR infusion without hemorrhage had an increased level of apoptosis in the intestine. Apoptosis in the intestine was observed in both the mucosa and muscularis externa. There was no increase in apoptosis in either organ in the animals resuscitated with sham resuscitation, whole blood, and hypertonic saline compared with the sham hemorrhage group. CONCLUSION: Resuscitation with LR solution after hemorrhagic shock increased immediate cell death by apoptosis in both the small intestine and liver. There was no significant increase in apoptosis in the animals resuscitated with hypertonic saline, whole blood, or in unresuscitated animals. Thus, the type of resuscitation fluid used may affect the apoptotic cellular response to shock.

Animals↗
PubMed1999

Rate of psychiatric illness 1 year after traumatic brain injury.

OBJECTIVE: Neurobehavioral symptoms are not uncommon after a traumatic brain injury. However, psychiatric syndromes per se have rarely been studied in patients with such an injury. The purpose of this study was to evaluate the type and extent of psychiatric syndromes in patients with traumatic brain injury. METHOD: One hundred ninety-six hospitalized adults were studied 1 year after a traumatic brain injury with the use of a two-stage psychiatric diagnostic procedure. Psychiatric diagnoses were made according to ICD-10 criteria on the basis of data from the Schedules for Clinical Assessment in Neuropsychiatry interview. RESULTS: Of 164 patients interviewed, 30 (18.3%) had an ICD-10 diagnosis of a psychiatric illness. Among the 120 patients who were 18-64 years old, 21.7% had a psychiatric illness, compared with 16.4% in a study of the general population. A depressive illness was present in 13.9% of the traumatic brain injury patients, compared with 2.1% of the general population, and panic disorder was present in 9.0%, compared with 0.8% of the general population. CONCLUSIONS: In comparison with the general population, a higher proportion of adult patients had developed psychiatric illnesses 1 year after a traumatic brain injury; the rates of depressive episode and panic disorder were significantly higher in the study group. A history of psychiatric illness, an unfavorable global outcome according to the Glasgow Outcome Scale, a lower score on the Mini-Mental State examination, and fewer years of formal education seemed to be important risk factors in the development of a psychiatric illness. Compensation claims, however, were not associated with the rate of psychiatric illness.

Adolescent↗
PubMed1999

Neurobehavioural symptoms one year after a head injury.

BACKGROUND: Neurobehavioural symptoms are common immediately after a minor head injury but have not been studied one year after the injury. AIMS: To estimate the rate and pattern of neurobehavioural symptoms one year after a head injury of varying severity. METHOD: Adults who had been hospitalised after a head injury (n = 196, 164 of whom had a face-to-face interview) and showed indirect evidence of brain assault were assessed for the presence of neurobehavioural symptoms with the help of a behaviour rating scale. RESULTS: About 40% had three or more symptoms. Individual symptoms varied among 3% (social disinhibition), 15% (lack of initiative) and 35% (irritability) of the cohort. Premorbid factors such as lower social class and lower educational achievement, head-injury-related factors such a low Glasgow coma score, and outcome-related factors such as the presence of a disability according to the Edinburgh Rehabilitation Status Scale and psychiatric caseness according to the Clinical Interview Schedule--Revised, significantly influenced the rate and the pattern of behavioural symptoms. The pattern of symptoms varied between age groups and according to the severity of the head injury. CONCLUSIONS: A significant proportion of patients with varying degrees of severity of head injury showed behavioural symptoms after one year of head injury.

Adolescent↗
PubMed1999

The expression of interleukin-6 (IL-6), IL-6 receptor, and gp130-kilodalton glycoprotein in the rat decidua and a decidual cell line: regulation by 17beta-estradiol and prolactin.

The cytokine interleukin 6 (IL-6), a major mediator of immune and acute phase responses of the liver, has been implicated in the termination of pregnancy once expressed in the uterus. This study was undertaken to investigate the expression and regulation of genes encoding IL-6 and IL-6 receptor (IL-6R) in rat decidual tissue. Total RNA obtained from rat decidual tissue on different days of pseudopregnancy was analyzed by RT-PCR using specific primers for IL-6, IL-6R, and 130-kDa glycoprotein (gp130). Ribosomal L19 primers served as an internal control. IL-6R and gp130 were found to be expressed in the decidua throughout development, while no messenger RNA (mRNA) for IL-6 was detected. Interestingly, within several hours of culture, decidual explants acquired the ability to express IL-6. The apparent ability of decidual cells to express IL-6 and its lack of expression in vivo led us to examine whether the IL-6 gene is actively inhibited. Primary decidual cells were cultured in the presence of estradiol, progesterone, or PRL. Progesterone showed no effect, whereas estradiol and PRL reduced the level of IL-6 mRNA expression. To examine the mechanism by which these hormones inhibit IL-6 expression, we used a simian virus 40-transformed decidual cell line (GG-AD), which expresses only estrogen receptor-beta (ERbeta). Like primary decidual cells in culture, GG-AD cells express IL-6, IL-6R, and gp130 mRNA. When cultured in the presence of estradiol (0-100 ng/ml), mRNA for IL-6 and its receptor components were down-regulated in a dose-dependent manner. Estradiol also caused a dose-dependent decrease in IL-6 protein secretion into the culture medium. The inhibitory effect of estradiol on IL-6 mRNA expression was reversed by the antiestrogen ICI-164,384. Similar inhibition of IL-6 and gp130 mRNA expression was observed with PRL treatment. However, PRL had no effect on IL-6R mRNA levels. PRL inhibition of IL-6 expression was totally reversed by tyrphostin AG490, a JAK2 inhibitor. In summary, the results of this investigation indicate that IL-6 expression, which is detrimental to the maintenance of pregnancy, is inhibited in the rat decidual tissue. This inhibition is induced by PRL and estradiol, which down-regulate not only IL-6 expression, but also the expression of IL-6 receptor and signaling proteins. The results also suggest that PRL signaling to the IL-6 gene is mediated through the long form of PRL receptor and involves JAK2 activation, whereas that of estradiol can be transduced by estrogen receptor-beta.

Animals↗
PubMed1999

Disruption of functions of wild-type p53 by hetero-oligomerization.

We report that a p53 segment (p53 del 1-293) containing the oligomerization domain interferes with the functions of wild-type p53. Wild-type p53 inhibits transcription mediated by human cytomegalovirus (CMV) immediate-early promoter significantly; however, co-expression of p53 del 1-293 drastically reduces this repression. We show that wild-type p53 forms hetero-oligomers with p53 del 1-293 suggesting that the hetero-oligomers are defective in repressing the CMV promoter. A synthetic promoter with p53-binding sites is transactivated significantly by wild-type p53. However, co-expression of p53 del 1-293 drastically reduces this activation. At a high concentration, a deletion mutant of wild-type p53 (del 393-327) defective in oligomerization transactivates efficiently a promoter with synthetic p53-binding sites. This transactivation remains unaffected by co-expression of p53 del 1-293. p53 del 393-327 also fails to hetero-oligomerize with p53 del 1-293 indicating that hetero-oligomerization is necessary for disruption of wild-type p53-mediated transactivation. Immunostaining experiments show that hetero-oligomerization does not lead to changes in localization of nuclear p53 demonstrating that delocalization of p53 is not the reason for inactivation. We also show that co-expression of p53 del 1-293 significantly reduces the G1/S arrest by wild-type p53 suggesting that a proper oligomeric form is necessary for wild-type p53-mediated cell cycle arrest. Thus, our work shows that hetero-oligomerization disrupts wild-type p53's biological functions and suggests a mechanism by which p53 mutants may disrupt functions of wild-type p53.

Binding Sites↗
PubMed1999

Early up-regulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in rats with hemorrhagic shock and resuscitation.

This study evaluated the effect of resuscitation fluids on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Sprague-Dawley rats (n = 36) were subjected to a 27 mL/kg hemorrhage over 5 min followed by a 1 h shock and 1 h resuscitation. Animals groups included: 1) cannulation only (Sham); 2) hemorrhage only (NR); 3) resuscitation with 1:1 shed blood (Blood); 4) resuscitation with 3:1 lactated Ringer's (81 mL/kg, 3LR+); 5) no hemorrhage but infusion with 3:1 lactated Ringer's (3LR); and 6) resuscitation with .36:1 hypertonic saline (7.5%, 9.7 mL/kg, HTS). At the end of resuscitation, the spleen and lung were harvested for detection of adhesion molecule mRNA and protein by RT-PCR and immunostaining. ICAM-1 and VCAM-1 expression exhibited the following pattern: 3LR+ > HTS approximate to 3LR > Blood approximate to NR approximate to Sham. VCAM-1 mRNA in the lung of the 3LR+ group was 2 or more times more than the groups of Sham, NR, Blood, and 3LR (p < .05). ICAM-1 and VCAM-1 mRNA in the spleen was significantly increased in the 3LR+ group compared with the groups of Sham, NR, and Blood (p < .05). Animals in the 3LR+ group showed enhanced staining for ICAM-1 in the pulmonary microvessels and in the marginal and trabecular areas of the spleen. Pulmonary edema and inflammatory cell infiltration were observed only in the 3LR+ group. In summary, resuscitation with LR following hemorrhagic shock induced immediate up-regulation of ICAM-1 and VCAM-1, which was associated with tissue injury. Thus, the type of resuscitation fluid used affected resuscitation injury.

Animals↗
PubMed1998

'Gain of function' phenotype of tumor-derived mutant p53 requires the oligomerization/nonsequence-specific nucleic acid-binding domain.

Tumor-derived p53 mutants can transcriptionally activate a number of promoters of genes involved in cellular proliferation. For this transactivation, mutant p53 does not use the wild-type p53 DNA-binding site, suggesting a mechanism of transactivation that is independent of direct DNA binding. Here we describe our analysis of the domain requirements for mutant p53 to transactivate promoters of the human epidermal growth factor receptor (EGFR), human multiple drug resistance 1 (MDR-1) and human proliferating cell nuclear antigen (PCNA) genes. We also report the identification of a structural domain required for the 'gain of function' property of mutant p53-281G. 'Gain of function' is measured as the tumorigenicity (in nude mice) of 10(3) murine cells expressing mutant p53 constitutively. We have generated internal deletion mutants of p53-281G deleting conserved domains I, II, III, IV and V, individually. We have also generated one deletion mutant eliminating amino acids 100 through 300 that removes four of the five conserved domains (II - V); another mutant, p53-281G del 393-327, deletes the oligomerization and nonsequence-specific nucleic acid-binding domains of p53. For the EGFR and MDR-1 promoters, all these mutants have significantly lower transactivation ability than intact p53-281G. These deletion mutants, however, significantly activated the pCNA promoter, suggesting that the mechanism of transactivation of the PCNA promoter is different from that of the EGFR and MDR-1 promoters. When expressed constitutively in 10(3) cells, p53-281G del 393-327 was found to be defective in inducing tumor formation in nude mice although intact p53-281G was very efficient. Thus, our results suggest that structural domains near the C-terminus are needed for 'gain of function'.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Application of long chain amine activator in conventional acrylic bone cement.

A long chain acid derivative bearing an aromatic tertiary amine group, 4-N,N-dimethylaminobenzyl laurate (DML), which acts as an activator for the curing of acrylic cements at low temperature, has been synthesized and characterized to reduce the biological adverse effects usually associated with the classical activator N,N-dimethyl-4-toluidine (DMT). The effectiveness of the activator was tested on commercial formulations (e.g., Palacos R) and on experimental bone cements based on poly (methyl methacrylate) by using different benzoyl peroxide/amine molar ratios. The exotherms of polymerization were followed at three different temperatures: 25, 30, and 37 degrees C. The DML activator was found to be more sensitive to temperature than the corresponding DMT. DML provided exotherms of polymerization with decreasing peak temperatures and increasing setting times without impairing the mechanical properties. Residual monomer content was analyzed in a range of activator concentrations by keeping the benzoyl peroxide concentration constant. In all cases the residual monomer content was lower than 5%, indicating its good efficiency in the benzoyl peroxide initiated polymerization.

Bone Cements↗
PubMed1998

Regional and differential expression of gelatinases in rat brain after systemic kainic acid or bicuculline administration.

Indirect evidence from in vitro studies implicates a functional role for matrix metalloproteinases (MMPs) in the central nervous system (CNS), including induction of neuronal migration during development and enhancement of neurite extension. Few reports have documented the expression of these enzymes in the brain, especially after injury in vivo. The objective of this study was to determine whether MMPs are expressed in various regional areas of rat brain after administration of the neurotoxin, kainic acid. Limbic motor seizures and neuronal degeneration were induced in Sprague-Dawley rats by systemic administration of kainate (10 mg/kg). Rats were subsequently divided into convulsive and non-convulsive groups, after observing their behaviour in response to the drug. Animals were killed 6, 12, 24, 72 and 168 h (7 days) after injection of kainate. Gelatinases were extracted from various brain regions and assayed by gelatin-substrate zymography. Levels of glial fibrillary acidic protein (GFAP) in corresponding regions were measured by ELISA. In the absence of treatment, MMP-2 and MMP-9 activities were expressed differentially in various brain regions with the highest levels in the hippocampus and the lowest in the cerebellum. In areas from convulsive rats, MMP-9 activity was markedly elevated at 6 h, and reached a maximum at 12 h after injection of kainate (8.1-fold hippocampus, 7.7-fold diencephalon, 7.2-fold striatum, 5.7-fold frontal cortex, 5.5-fold cerebellum, 2.6-fold midbrain). MMP-2 activity was induced more than two-fold in the hippocampus, diencephalon and striatum, to a lesser extent in the frontal cortex and midbrain, and was unchanged in the cerebellum, 72 h after injection. Neither MMP activity was altered in any brain region derived from non-convulsive rats. Treatment with the GABAA antagonist, bicuculline, resulted in increased levels of MMP-9, 12 h after drug administration, but no change in levels of MMP-2 up to 3 days following treatment. GFAP levels were induced 3 days after kainic acid injection in brain regions where MMP-2 was elevated. Nissl staining displayed the classical, regional neurodegeneration in kainate-treated animals that exhibited seizures. No obvious degeneration was detected in kainate-treated, non-convulsive rats or bicuculline-treated animals. These data demonstrate that MMP-9 and MMP-2 are differentially expressed with respect to time after kainic acid injection, and suggest that they are regulated by convulsion and/or neurodegenerative-associated mechanisms, respectively. Although similar in catalytic activity, MMP-9 and MMP-2 may play different roles in response to kainic acid-induced seizure and neuronal degeneration.

Animals↗
PubMed1998

Influence of buthionine sulfoximine and reduced glutathione on arecoline-induced chromosomal damage and sister chromatid exchange in mouse bone marrow cells in vivo.

Arecoline (ARC), an alkaloid of the betel nut (Areca catechu), is a major ingredient of betel quid. The carcinogenic potentiality as well as its cell transformation ability has already been reported. Reduced glutathione (GSH), a major non-protein thiol substance plays an important role in protection of cells against the toxic effect of exogenous compounds. In order to understand the role of factors which affect ARC sensitivity, we have made an attempt to establish a relationship between ARC-induced DNA damage and the endogenous GSH status of the cells. ARC was administered to untreated and buthionine sulfoximine (BSO) (a GSH-depleting agent)-treated mice. Exogenous GSH was also added to ARC-administered mice. Cells were fixed at 20 h and both chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) were scored. Both CAs and SCEs were significantly induced by ARC and the frequency of both these parameters were increased further when ARC was given to BSO-treated mice. However, GSH reduced the frequency of CAs induced by ARC but failed to do so for SCEs. The data indicate that ARC-induced DNA damage is influenced by endogenous GSH level. The failure of GSH to reduce the frequency of SCEs indicates that the mechanism of induction of CAs and SCEs by ARC are different.

Animals↗
PubMed1998

Spectroscopic study of Y210C lambda-repressor: implications for cooperative interaction.

A non-cooperative mutant of lambda-repressor, Y210C, has been purified and characterized. The mutant protein does not show any evidence of cooperative interaction as judged by difference near-UV circular dichroism spectra of DNA. The mutant protein also shows much weaker self-assembly as revealed by fluorescence anisotropy measurement. The far-UV circular dichroism spectrum of the protein shows a modest but significant reduction in the 220 nm range, suggesting a structural change. The Lehrer plot of acrylamide quenching of Y210C repressor at a predominantly dimeric concentration (0.5 microM) is almost identical with that of the wild-type protein at the same concentration. Transmission of operator-induced conformational change is also preserved in the mutant protein. Like that of the wild-type protein, cysteines of the mutant protein are unreactive to sulfhydryl reagents under native conditions. Most importantly, C210 is unreactive to sulfhydryl reagents under native conditions. This fact, coupled with the structural change observed in the far-UV CD spectra, suggests that C210 is located at the interior of the protein and exerts its effect indirectly on cooperative contact probably through destabilization of a reverse turn, of which it is an important part.

Bacteriophage lambda↗
PubMed1998

Neuropsychiatric sequelae one year after a minor head injury.

OBJECTIVE: To assess neuropsychiatric sequelae 1 year after minor head injury in a cross sectional study using home interviews with patients and their relatives at 1 year after head injury. METHODS: The study cohort included 148 adults who were admitted to hospital after a minor head injury between 1 July 1994 and 30 June 1995 and showed clinical or radiological evidence of brain injury. Main outcome measures used in the study were the Glasgow outcome scale, Edinburgh rehabilitation status scale, Barthel index, clinical interview schedule-revised, mini mental state examination, and assessment of symptoms of postconcussional syndrome. RESULTS: At one year follow up, four (2.9%) patients had a severe disability, 35 (25.5%) had a moderate disability, and 95 (69.3%) had no disability according to the Glasgow outcome scale. A slightly higher proportion (33.3%, n=45) showed disability according to the Edinburgh rehabilitation status scale. Thirty one patients (23.1%) scored <24 in the mini mental state examination. These were mostly patients over the age of 65. Twenty three patients (17.2%) were diagnosed as psychiatric cases according to the clinical interview schedule-revised scale. Seventy four (55.2%) patients showed one of the symptoms of postconcussional syndrome. The most commonly shown neurobehavioural problems were irritability (30%), sleep disturbance (29%), and impatience (27%). CONCLUSION: One year after a minor head injury, a substantial proportion of patients showed neuropsychiatric sequelae.

Adolescent↗
PubMed1998

Self-injurious behaviour as part of genetic syndromes.

BACKGROUND: The purpose of this paper is to review the association between genetic syndromes and self-injurious behaviour. METHOD: The information available from the literature on the subject of self-injurious behaviours and genetic syndromes was collated and presented with a critical appraisal. RESULTS: Self-injurious behaviours are associated with some genetic syndromes. However, the causal relationship between the genetic syndromes and the self-injurious behaviour remains far from clear. CONCLUSIONS: Although self-injurious behaviour has been shown to be the part of a broader phenotype in many genetic disorders, the specificity and sensitivity of these behaviours in this context remain unclear.

Brain Damage, Chronic↗
PubMed1998

Neuroimaging in autism.

BACKGROUND: Childhood autism is a developmental disorder with distinctive clinical features and characteristic cognitive deficits. Neuroimaging techniques have been extensively used in the study of autism and related disorders. METHOD: Recent important literature reported on structural and functional neuroimaging in autism was reviewed and discussed in the context of other neurobiological research findings. RESULTS: Various abnormalities of brain structure and function have been proposed, but no focal defect has been reliably demonstrated. Important findings, so far, include increased brain volume, structural abnormality in frontal lobe and corpus callosum in a proportion of autistic individuals. Functional neuroimaging findings emphasised the imbalance in inter-regional and inter-hemispheric brain metabolism and blood flow as well as abnormality in the anterior cingulate gyrus. CONCLUSION: The research to date has been hindered by methodological difficulties. However, hypothesis-driven research, particularly involving activation studies and neurotransmitter/neuroreceptor activities, using functional neuroimaging will be very useful in unravelling the enigma associated with this intriguing and distressing condition.

Autistic Disorder↗