Search PubMed⌕ Search

Biomedical subjects

P Rajan

Publications and source records attributed to P Rajan.

34 records · Page 2Linked to original sources

STAT proteins are activated by ciliary neurotrophic factor in cells of central nervous system origin.

Neuropoietic cytokines, including ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), have survival effects on cells of the peripheral and central nervous systems (PNS and CNS). CNTF and LIF also produce differentiation in some cells of the PNS. We have shown previously that CNTF activates the signal transducers and activators of transcription (STAT) family of transcription factors, and that this signaling pathway may be one of several employed by CNTF to regulate the expression of the vasoactive intestinal peptide (VIP) gene in cells of the PNS (Symes et al.: Proc Natl Acad Sci USA 90:572-576, 1993; Symes et al.: Mol Endocrinol 8:1750-1763, 1994). To investigate the mechanisms of action of CNTF in the CNS, we have analyzed the activation of STAT proteins in a septal-derived cell line, SN48, and in primary CNS cultures. CNTF treatment of SN48 cells produces a sustained activation of Stat3. CNTF treatment of SN48 cells also activated transcription mediated by the VIP cytokine responsive element (CyRE) which contains a STAT binding site. Mutation of the STAT site in the CyRE attenuated transcriptional activation by CNTF, indicating the importance of STAT proteins to CNTF-dependent transcriptional activation of SN48 cells. In cultures of embryonic rat septum and other brain areas, in addition to Stat3, CNTF also activates Stat1. As in cells of the PNS and non-neuronal cells, the Janus kinase (Jak)-STAT pathway is activated in CNS cells by cytokines. The SN48 cell line may be valuable in further characterization of regulation of the Jak-STAT pathway by neuropoietic cytokines.

Animals↗

LIF-mediated activation of STAT proteins after neuronal injury in vivo.

Leukemia inhibitory factor (LIF) is a member of a family of neuropoietic cytokines which influence neuronal survival, differentiation and response to injury. In cell lines LIF activates the Jak/Tyk tyrosine kinases and the STAT family of transcription factors. We have investigated whether the Jak-STAT intracellular signaling pathway is activated by LIF after neuronal injury in vivo. Axotomy of postganglionic sympathetic nerves resulted in sustained activation of members of the STAT transcription factor family. This activation is dependent on LIF as axotomy failed to activate STAT proteins in LIF-deficient mice. These data indicate that LIF-dependent activation of STAT proteins is one of the signal transduction pathways activated after neuronal injury.

Animals↗

C/EBP-related sites in addition to a STAT site are necessary for ciliary neurotrophic factor-leukemia inhibitory factor-dependent transcriptional activation by the vasoactive intestinal peptide cytokine response element.

The neuropoietic cytokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) regulate VIP gene expression through a cytokine response element (CyRE) which interacts with members of the STAT transcription factor family. The CyRE STAT site is, however, insufficient to mediate full transcriptional activation by CNTF/LIF, suggesting that other sequences and nuclear proteins are also important. As C/EBP proteins participate in the transcriptional effects of the related cytokine, interleukin-6, we investigated the role of possible C/EBP-binding sites in the response of the VIP CyRE to CNTF/LIF. Using DNase I footprinting, transactivation studies, DNA mobility shift assays, and mutational analysis, three sites within the VIP CyRE were identified as C/EBP-related binding sites and shown to be important to CNTF/LIF-mediated transcriptional activation. The CyRE C/EBP-related sites interact with nuclear proteins from the human neuroblastoma cell line, NBFL, including a novel, protein synthesis-dependent, nuclear protein complex, induced by CNTF treatment. These nuclear proteins are not, however, recognized by antisera to known C/EBP proteins. Therefore, other nuclear proteins regulated by independent pathways act in concert with the JAK-STAT pathway to mediate CNTF/LIF regulation of VIP gene expression through the CyRE.

Base Sequence↗

A novel translational regulation function for the simian virus 40 large-T antigen gene.

Cells use the interferon-induced, double-stranded-RNA-dependent protein kinase PKR as a defense against virus infections. Upon activation, PKR phosphorylates and thereby inactivates the protein synthesis initiation factor eIF-2, resulting in the cessation of protein synthesis. Viruses have evolved various strategies to counteract this cellular defense. In this paper, we show that simian virus 40 (SV40) large-T antigen can antagonize the translational inhibitory effect resulting from the activation of PKR in virus-infected cells. Unlike the situation with other virus-host cell interactions, SV40 large-T antigen does not block the activation of PKR, suggesting that SV40 counteracts the cellular antiviral response mediated by PKR at a step downstream of PKR activation. Mutational analysis of large-T antigen indicates that a domain located between amino acids 400 and 600 of large-T antigen is responsible for this function. These results define a novel translational regulatory function for the SV40 large-T antigen.

Adenosine Triphosphatases↗

Standards for ultrasonographic measurements of the hip joint in Indian adults.

Synovitis in the hip joint, in contrast to that in other limb joints, is extremely difficult to evaluate clinically. In the hip joint synovitis manifests as an increase in the distance between the iliofemoral ligament and the femoral neck. The present ultrasonographic study was undertaken in 110 healthy Indian adults to establish standards for the depth of the normal hip joint space in the normal Indian adult population. The shortest distance was 4 mm, the longest was 9 mm. The mean distance was 6.4 (S.D. 1.1) mm. The mean difference between the right and left hips was 0.42 (S.D. 0.49) mm. An age-specific reference curve with 95% confidence limits was constructed. No correlation was found between hip joint space and the subjects' height, weight, age or sex. It is concluded that a distance between the iliofemoral ligament and the femoral neck of more than 9 mm or a difference in measurement between the hips of 1 mm or more suggests an intracapsular effusion or active synovitis. These figures are at variance with the measurements obtained in studies on Western white populations.

Adolescent↗

STAT proteins participate in the regulation of the vasoactive intestinal peptide gene by the ciliary neurotrophic factor family of cytokines.

Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are members of a family of neuropoietic cytokines that have a broad range of actions on many different neuronal populations. In cultured sympathetic neurons, CNTF and LIF induce transcription of the VIP and other neuropeptide genes as part of a program of differentiation. To gain insight into the nuclear events involved in cytokine-mediated activation of the neuropeptide genes involved in neuronal differentiation, we have investigated the mechanisms of transcriptional activation of the vasoactive intestinal peptide (VIP) gene by the CNTF family of cytokines. In the neuroblastoma cell line NBFL, CNTF, LIF, and a related cytokine, oncostatin-M, activate VIP gene transcription through a 180-base pair cytokine response element (CyRE). Deletion analysis of the VIP CyRE showed that multiple regions within the 180 base-pairs are important for cytokine-mediated transcriptional activation of the VIP gene. To one of these regions within the CyRE, cytokine treatment induces binding of a protein complex composed of members of the signal transducers and activators of transcription (STAT) transcription factor family. Mutation of this STAT-binding site attenuates cytokine-mediated transcriptional activation. LIF treatment of primary sympathetic neurons also induced binding of a STAT-containing protein complex to the VIP CyRE. Thus, activation of STAT transcription factors contributes to the induction of the VIp gene by the CNTF family of cytokines and may be involved in cytokine-mediated differentiation of sympathetic neurons.

Base Sequence↗

Blood basopenia as an indicator of ovulation.

Direct basophil counts were done on capillary blood samples in thirteen normal young women, during the different phases of their menstrual cycles. Mean basophil counts during the follicular and progestational phases were 36.6/cumm and 39.3/cumm respectively. A significant midcycle fall in counts of 36% and a premenstrual fall of 22% were observed. These changes are probably due to migration of the cells from the peripheral blood into the rupturing follicle of the ovary and into the ischemic premenstrual endometrium.

Adolescent↗

Simian virus 40 small-t does not transactivate RNA polymerase II promoters in virus infections.

Transcriptional stimulatory properties of virus-encoded transactivators appear to be critical for viral gene expression and may be linked to cellular transformation in certain cases. Recently, the simian virus 40 (SV40) 17-kDa small-t antigen was shown to stimulate transcription of polymerase II and III genes in transient transfection assays. In experiments performed in our laboratory, two of the polymerase II promoters of the adenovirus genome, namely, the EII-early and EIII promoters, were transactivation, we examined the transient transfection assays. To further elucidate the mechanism of this transactivation, we examined the ability of small-t to transactivate the adenovirus type 5 EII-early and EIII promoters in CV-1 cells under conditions in which the small-t gene or the reporter genes were introduced into the cells through transfection and other routes. In one approach, we used established CV-1 cell lines which constitutively express the small-t gene, and study of the EII-early promoter was afforded by infection of an EIA-negative adenovirus type 5 variant. For the second approach, a recombinant adenovirus was constructed in which small-t was expressed from a replication origin-negative SV40 early promoter in the EIA region of an adenovirus vector (Ad-SV-t). The effect of small-t on adenovirus EII-early and EIII promoter expression was studied in coinfection or single-infection experiments. In both cases, transcription of the adenovirus early promoters was not stimulated by small-t. These and other results indicate that transactivation of polymerase II promoters by small-t occurs only when the target gene is in a transiently transfected state. Thus, small-t-mediated transactivation of polymerase II promoters is dependent on the type of assay system used and may be mechanistically different from that of the widely studied EIA.

Adenoviruses, Human↗

British community norms for the Brief Symptom Inventory.

British community norms (N = 376) for the Brief Symptom Inventory (Derogatis & Spencer, 1982) are presented. Means are significantly higher than previously published US norms for all symptom dimensions, and show variability according to age, sex and work status. The proportion of 'cases' in the sample is similar to other British estimates. It is recommended that culturally relevant norms should be established and used in future work with this instrument.

Adolescent↗

The impact of hand dominance and ulnar and median nerve impairment on strength and basic daily activities.

The authors sought to determine the impact of hand dominance and its relation to function among ulnar alone and combined ulnar and median nerve lesions in leprosy patients. The study sample consisted of 62 persons affected with leprosy (mean age 36.1 years) who were either suffering from ulnar nerve lesions alone (34 patients) or combined ulnar and median lesions (28 patients). The data from the earlier work of this institution with normal hands in the adjacent rural uninvolved population were taken as controls. Grip, pulp-to-pulp, lateral, and three-jaw-chuck pinch strengths were measured using a hydraulic hand dynamometer and a pinch gauge. Basic daily activities were assessed using the battery developed at Karigiri. Means, standard errors, correlations, and t-tests were used in the analyses. The overall difference between grip and pinch strength measurements in both dominant and nondominant hands was 40% less than those in normal hands if the ulnar nerve alone was involved. If impairment of this nerve was combined with that of the median nerve, the overall difference in strength measurements increased to 51%. The hand strength of the dominant side was statistically significant between single and two nerves for pulp-to-pulp pinch (p = 0.019). No other strength tests produced statistically significantly results related to hand dominance (grip strength, lateral, chuck pinch) with either one or two nerve involvement. To observe differences in basic daily activities, scores were compared to Karigiri norms. The bilateral basic daily activities score was impaired by 45% compared with norms with only ulnar nerve involvement and by 59% with ulnar and median nerve involvement. The different pinch strengths related to basic daily activities was not significantly affected in nondominant hands, whether it was ulnar alone or combined ulnar and median nerve lesions. In this population diagnosed with leprosy, ulnar nerve impairment at the level of the elbow reduced the grip and pinch strengths and performance in basic daily activities by 40% and 45%, respectively. If combined with median nerve lesion at wrist level, the strengths and daily activity losses increased to 50% and 60%, respectively. There is no effect on grip strength either in ulnar or ulnar and median nerve injuries, irrespective of whether dominant or nondominant hands were involved. Different pinch strengths related to basic daily activities were significantly affected only in the dominant hand with involvement of these nerves.

Activities of Daily Living↗

Opponens plasty rehabilitation protocol--a case report.

In this case report of opponens plasty, we will attempt to accomplish two objectives: 1) to characterize some innovative modifications to the standard rehabilitation protocol for an opponens plasty and 2) to explain the role and advantages of a new muscle re-education splint in this modified protocol.

Adult↗

Gingival fibromatosis and growth hormone deficiency syndrome--report of a rare case and review of literature.

Oikarinen et al in 1989 reported a syndrome associated with generalized gingival fibromatosis and growth hormone deficiency. This is a case report of a 15-year-old female patient who presented to the Government Dental College, Chennai with generalized gingival fibromatosis and growth hormone deficiency. Interestingly, the histopathology of the excised gingival overgrowth showed dense collagenous connective tissue in which were strewn calcified structures that resembled cementum. This syndrome is being reported for the second time after its first case report in 1989 by Oikarinen et al. We are herewith reporting this case for its rarity with a brief review of literature of syndromes associated with generalized gingival fibromatosis.

Adolescent↗