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Biomedical subjects

A Sehgal

Publications and source records attributed to A Sehgal.

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

The prevalence of uveitis in juvenile rheumatoid arthritis.

BACKGROUND: Because asymptomatic uveitis has been an important cause of visual loss in children with juvenile rheumatoid arthritis, periodic ophthalmologic screenings of such patients have been recommended. Recently, some authors have found a decreased prevalence of uveitis in children with juvenile rheumatoid arthritis. METHODS: We studied a total of 76 patients (63 girls and 13 boys, aged 1 to 16 years), referred to 3 pediatric ophthalmology practices between March 1976 and October 1999. Follow-up examinations were performed at intervals of 3 to 6 months according to current guidelines, during the following 6 months to 23 years (mean, 55 months). RESULTS: Uveitis developed in 10 children (13%). Of these 10 children, 2 were symptomatic (blurred vision, discomfort) and 7 were diagnosed with uveitis at the initial visit. Only 1 patient had asymptomatic uveitis after initial negative findings on screening examination. Final visual acuity for all the compliant children in the uveitis group was better than 20/30. DISCUSSION: The prevalence of uveitis in our study is similar to rates found by other recent authors. This decrease may reflect a tendency for systemic medications to prevent the development of ocular inflammation. We believe that screening guidelines should be reevaluated, especially for asymptomatic children with negative findings on initial examinations.

Adolescent↗
PubMed2001

Photic signaling by cryptochrome in the Drosophila circadian system.

Oscillations of the period (per) and timeless (tim) gene products are an integral part of the feedback loop that underlies circadian behavioral rhythms in Drosophila melanogaster. Resetting this loop in response to light requires the putative circadian photoreceptor cryptochrome (CRY). We dissected the early events in photic resetting by determining the mechanisms underlying the CRY response to light and by investigating the relationship between CRY and the light-induced ubiquitination of the TIM protein. In response to light, CRY is degraded by the proteasome through a mechanism that requires electron transport. Various CRY mutant proteins are not degraded, and this suggests that an intramolecular conversion is required for this light response. Light-induced TIM ubiquitination precedes CRY degradation and is increased when electron transport is blocked. Thus, inhibition of electron transport may "lock" CRY in an active state by preventing signaling required either to degrade CRY or to convert it to an inactive form. High levels of CRY block TIM ubiquitination, suggesting a mechanism by which light-driven changes in CRY could control TIM ubiquitination.

Animals↗
PubMed2001

Molecular components of the circadian system in Drosophila.

Much of our current understanding of how circadian rhythms are generated is based on work done with Drosophila melanogaster. Molecular mechanisms used to assemble an endogenous clock in this organism are now known to underlie circadian rhythms in many other species, including mammals. The genetic amenability of Drosophila has led to the identification of some genes that encode components of the clock (so-called clock genes) and others that either link the clock to the environment or act downstream of it. The clock provides time-of-day cues by regulating levels of specific gene products such that they oscillate with a circadian rhythm. The mechanisms that synchronize these oscillations to light are understood to some extent. However, there are still large gaps in our knowledge, in particular with respect to the mechanisms used by the clock to control overt rhythms. It has, however, become clear that in addition to the brain clock, autonomous or semi-autonomous clocks occur in peripheral tissues where they confer circadian regulation on specific functions.

Animals↗
PubMed2001

Molecular regulation of circadian rhythms in Drosophila and mammals.

Through the use of genetically amenable model systems, we have begun to form a relatively clear idea as to the molecular mechanisms that constitute a functioning circadian clock. It is now known that mechanisms that underlie overt rhythms are conserved across species. At the basic core of the clock lies a transcriptional/translational feedback loop. The primary components of this loop are called clock genes and are similar for the fruit fly, Drosophila melanogaster, and mammalian systems. However, many questions regarding their regulation remain unanswered. In addition to their localization in brain areas associated with pacemaking function, clock genes are also found in peripheral tissues where their presence may confer circadian regulation upon local, tissue-specific functions. The light-dark cycle is the primary environmental stimulus for the synchronization of the circadian clock. In Drosophila, light is known to induce the degradation of a clock component resulting in the synchronization of the core clock mechanism. Photic signals are transmitted to the clock, at least in part, by the blue light photoreceptor cryptochrome. Although expression of several mammalian clock gene products is also altered in response to light, the photoreceptor(s) involved have not yet been defined.

Animals↗
PubMed2001

Early detection of cervical cancer through acetic acid application--an aided visual inspection.

OBJECTIVE: To assess the sensitivity and specificity of visual inspection of cervix for detection of precancerous and early cancerous lesions of cervix. METHODS: In a Maternal and Child Health Care setting of New Delhi women underwent a detailed pelvic examination, visual inspection of cervix after 5% acetic acid application, cytology (pap smear), detailed colposcopic examination and colposcopic directed biopsy when indicated. RESULTS: Findings of aided visual inspection using 5% acetic acid and of cytology were evaluated among symptomatic 402 women against colposcopic findings and/or histologic reports. Seventy-three mild dysplasias, 50 moderate dysplasias, 45 severe dysplasias/Carcinoma in-situ and 40 early invasive cancerous cases were diagnosed histologically. The sensitivity of cytology (75.3%) was higher compared to that of acetic acid application (52.0%) for mild dysplasias. On the other hand, the sensitivity for detecting moderate dysplasias was 78% for cytology and 81.6% for acetic acid; for severe dysplasias/carcinoma in-situ it was 73.3% for cytology and 86.7% for acetic acid. For invasive cancers sensitivity for acetic acid application and cytology (95% for both modalities) was comparable. The specificity of cytology (99%) was higher compared to that of acetic acid application (94.3%). The false positive rate for cytology was 1.0% as against 5.7% for acetic acid application. The results of acetic acid application also showed a remarkable improvement in the sensitivity of unaided visual inspection for early cancerous lesion which was about 60% for early cancerous lesion and only 12% for mild dysplastic and 20% for moderate and severe dysplastic lesions in our earlier experience. It also reduced the false positive rates from 12% by unaided visual inspection to 5.7% by acetic acid application. Furthermore, cost of detection of one true lesion through acetic acid application (Rs.1689.00) was much lower as compared to the cost involved in cytology detected true lesions (Rs.2227.00). Visual inspection without acetic acid incurred Rs.6608.60 for detection of true lesion. CONCLUSION: Screening for cervical precancerous and cancerous lesions using visual inspection aided by acetic acid may be a suitable low-cost and a feasible alternative modality for control of cervical cancer in a resource poor setting.

Acetic Acid↗
PubMed2001

Neuroglial cyst: a rare occurence in abdomen and pelvis.

We hereby report a case of a child who presented with abdominal distension and urinary retention. Radiological investigations and exploratory laparotomy revealed a cystic mass in the sacral region pushing the urinary bladder anteriorly and upwards. Histopathological examination revealed neuroglial elements. Neuroglial cysts are uncommon outside the central nervous system and this is the first report of its occurrence in abdomen and pelvis.

Abdomen↗
PubMed2000

Basic concepts of immunology and neuroimmunology.

The immune system is a complex network of specialized cells and organs that defends the human body against attack from foreign pathogens. The major lymphocytes involved in protecting the body against potential infections are B and T cells, which also play an important role in combating tumor growth. The cells of the immune system patrol the tissues and organs through both blood and lymphatic vessels, but some organs--including cornea, testes, and brain--are usually not patrolled by these cells. The brain has been thought to be an immune-privileged site because of the tight blood-brain barrier (BBB) that protects it. Few cells migrate to the brain under normal circumstances, because the BBB permits only certain molecules to cross into brain tissue. Recently, however, studies have shown that activated T cells exposed to antigen can cross the intact BBB and migrate into brain. This finding opens the path to developing effective means of immunotherapy for lesions of the central nervous system. The authors discuss basic facets of the immune system, review the current knowledge about human neuroimmunology, and survey current strategies for developing immunotherapy-based treatments for human brain tumors.

Allergy and Immunology↗
PubMed2000

The chicken c-Jun 5' untranslated region directs translation by internal initiation.

The 5' untranslated region (UTR) of the chicken c-jun message is exceptionally GC rich and has the potential to form a complex and extremely stable secondary structure. Because stable RNA secondary structures can serve as obstacles to scanning ribosomes, their presence suggests inefficient translation or initiation through alternate mechanisms. We have examined the role of the c-jun 5' UTR with respect to its ability to influence translation both in vitro and in vivo. We find, using rabbit reticulocyte lysates, that the presence of the c-jun 5' UTR severely inhibits translation of both homologous and heterologous genes in vitro. Furthermore, translational inhibition correlates with the degree of secondary structure exhibited by the 5' UTR. Thus, in the rabbit reticulocyte lysate system, the c-jun 5' UTR likely impedes ribosome scanning resulting in inefficient translation. In contrast to our results in vitro, the c-jun 5' UTR does not inhibit translation in a variety of different cell lines suggesting that it may direct an alternate mechanism of translational initiation in vivo. To distinguish among the alternate mechanisms, we generated a series of bicistronic expression plasmids. Our results demonstrate that the downstream cistron, in the bicistronic gene, is expressed to a much higher level when directly preceded by the c-jun 5' UTR. In addition, inhibition of ribosome scanning on the bicistronic message, through insertion of a synthetic stable hairpin, inhibits translation of the first cistron but does not inhibit translation of the cistron downstream of the c-jun 5' UTR. These results are consistent with a model by which the c-jun message is translated through cap independent internal initiation. Oncogene (2000) 19, 2836 - 2845

3T3 Cells↗
PubMed2000

Altered entrainment and feedback loop function effected by a mutant period protein.

The period (per) and timeless (tim) genes encode interacting components of the circadian clock. Levels and phosphorylation states of both proteins cycle with a circadian rhythm, and the proteins drive cyclic expression of their RNAs through a feedback mechanism that is, at least in part, negative. We report here that a hypophosphorylated mutant PER protein, produced by creating a small internal deletion, displays increased stability and low-amplitude oscillations, consistent with previous reports that phosphorylation is required for protein turnover. In addition, this protein appears to be defective in feedback repression because it is associated with relatively high levels of RNA and high levels of TIM. Transgenic flies carrying the mutant PER protein display a temperature-dependent shortening of circadian period and are impaired in their response to light, particularly to pulses of light in the late night that normally advance the phase of the rhythm. Interestingly, per RNA is induced by light in these flies, most likely because of the removal of the light-sensitive TIM protein, thus implicating a more direct role for TIM in transcriptional inhibition. These data have relevance for mechanisms of feedback repression, and they also address existing models for the differential behavioral response to light at different times of the night.

Adaptation, Physiological↗
PubMed2000

The need for a simple animal model to understand sleep.

Simple animal models have allowed biologists to apply the tools of modern molecular genetics to such complex behaviors as circadian rhythms and long-term memory consolidation. The mechanisms and molecules discovered in these simple animals are evolutionarily conserved in other species, including mammals. Sleep research lacks a simple animal model because criteria based on the electroencephalogram have been met only in birds and mammals. We argue that straightforward behavioral criteria could allow the identification of a sleep-like rest state that might be useful for molecular investigations to understand the regulation and function of sleep. Candidate model systems are discussed, leading to the conclusion that several species have complementary strengths. Specifically, techniques developed for larval zebrafish can be used to visualize neural firing patterns in the living animal, and the fruit fly Drosophila melanogaster has been used successfully for molecular and genetic dissection of complex behaviors. We conclude with a hypothesis that one putative function of sleep, the optimization of neural plasticity, would also have adaptive value in simple organisms and might therefore be evolutionarily conserved.

Animals↗
PubMed2000

Rest in Drosophila is a sleep-like state.

To facilitate the genetic study of sleep, we documented that rest behavior in Drosophila melanogaster is a sleep-like state. The animals choose a preferred location, become immobile for periods of up to 157 min at a particular time in the circadian day, and are relatively unresponsive to sensory stimuli. Rest is affected by both homeostatic and circadian influences: when rest is prevented, the flies increasingly tend to rest despite stimulation and then exhibit a rest rebound. Drugs acting on a mammalian adenosine receptor alter rest as they do sleep, suggesting conserved neural mechanisms. Finally, normal homeostatic regulation depends on the timeless but not the period central clock gene. Understanding the molecular features of Drosophila rest should shed new light on the mechanisms and function of sleep.

Animals↗
PubMed2000

Characterization of a differential immunoscreen epitope of Plasmodium falciparum using combinatorial agents.

A differential serological screening of a lambdagt11 cDNA expression library has identified several clones, which react exclusively to sera samples from persons clinically immune to malaria but not to acute malaria patient sera. One such clone, IPf9, has a 315-bp cDNA insert, which was found to be conserved in different strains of the human and rodent malarial parasite Plasmodium falciparum and Plasmodium berghei, respectively. The induced expression product of IPf9 was used to generate polyclonal sera in rabbits. The IPf9 expression product was also screened with phage surface display combinatorial libraries to isolate reagents that specifically bound to the IPf9 product. The polyclonal antisera and the combinatorial reagents recognized a 50-kDa protein from P. falciparum, and a 53-kDa product from P. berghei. Immunofluorescence studies using asexual and sexual stages of P. falciparum showed the protein to be present within the parasite in each of the asexual and sexual stages. The combinatorial reagents showed a partial inhibition in the growth of P. falciparum in vitro. Mice infected with the P. berghei showed the presence of T-cells that exhibited lymphoproliferation when stimulated with the IPf9 protein. It is suggested that IPf9 protein is a conserved protein epitope, and may be relevant for a protective immune response to malaria.

Animals↗
PubMed2000

Free oxygen radicals and immune profile in newborns with lung diseases.

Respiratory difficulties constitute the commonest cause of morbidity in new born infants and pulmonary pathology is the most frequent autopsy finding. Various components, such as free oxygen radicals, immunoglobulins, and compliment systems, play an important role in immunopathology and immune defence. The aim of the present study was to assess free oxygen radical markers in neonatal lung diseases, studying their relationship with immune profile and ascertaining their relevance as predictors of clinical outcome. Full term newborns with respiratory distress and X-ray proven lung disease formed the study group. Blood samples were assessed for lipid peroxide (LPO), superoxide dismutase (SOD), glutathione peroxidase (GPx), immunoglobulins IgM and G, CD4 and CD8 subpopulations of T-lymphocytes. Levels of free radical markers were significantly higher in the study group. The humoral immune response was seen in terms of raised IgM levels in the study group which were still within the normal range. The cellular immune response was demonstrated by a raised percentage of CD4 T-lymphocytes which in turn accentuated the CD4:CD8 ratio. Higher levels of reactive oxygen species (ROS) were associated with a prolonged duration of respiratory distress and oxygen dependence. Since the free radicals have emerged as the major final common pathway of tissue injury, free radical ablation offers substantial potential for treatment; but whether antioxidants, scavengers and other modalities would have a significant impact on clinical outcome, remains to be investigated.

Biomarkers↗