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Biomedical subjects

R Sen

Publications and source records attributed to R Sen.

At least 91 records · Page 5Linked to original sources
PubMed1991

Lung puncture aspiration in the diagnosis of acute pneumonias.

The present study was carried out in 100 children of acute pneumonia to establish the diagnosis of etiologic agents. Clinico-radiological assessment and routine investigations including sputum, throat swab and blood culture did not help in identifying the offending micro-organisms. The bacteriological examination of lung puncture aspirate was the most satisfactory tool for the etiological diagnosis. Direct smear examination/culture were positive in 50% aspirates. On cytology, definite epithelioid granulomas indicated tuberculous infection. However, in direct smear/culture negative patients, predominant mononuclear cell infiltration in the aspirated material may indicate non-pyogenic infection. Staphylococcus aureus (22%) was the commonest organism causing pneumonia in the present study.

Acute Disease↗
PubMed1990

Multiple nuclear factors interact with sequences within the J beta 2-C beta 2 intron of the murine T cell receptor beta-chain gene.

Identification of tissue-specific DNaseI hypersensitive sites in the TCR J beta 2-C beta 2 intron has suggested the presence of sequences involved in the regulation of gene expression. Therefore, we have searched for protein-DNA interactions within a 930-bp fragment derived from the J beta 2-C beta 2 intron by in vitro DNaseI protection experiments and electrophoretic mobility-shift assays. This analysis has revealed, in addition to a previously characterized NF-kappa B binding site, the presence of seven potential protein-DNA interaction sites within this fragment. Interestingly, they are clustered in the regions where in vivo T cell-specific nuclease hypersensitive sites have been previously identified. Binding sites for four potential transcription factors have been mapped precisely by methylation-interference experiments. Sequence comparisons show that one of them is homologous to the Y box present in the promoter regions of MHC class II genes. Identification of several protein-DNA interactions clustered within the J beta 2-C beta 2 intron and the presence of binding sites for two well-characterized transcription factors suggest a transcriptional regulatory function for this region.

Animals↗
PubMed1990

Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivity to TNF-alpha-mediated cell death.

The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharide on the sensitivity to tumor necrosis factor (TNF)-alpha-mediated cell death was studied in an in vitro system. Since secretion of TNF-alpha is a part of the early host response to viral and bacterial infection, we examined whether mimicking the infection with viral and bacterial products could affect the response of cells to TNF-alpha. Incubation of WEHI 164 fibrosarcoma cells with dsRNA or lipopolysaccharide (LPS) significantly increased their sensitivity to TNF-alpha-mediated lysis and to TNF-secreting inflammatory T cell-mediated lysis. Thus, these products could induce increased sensitivity to TNF-alpha in cells in an inflammatory focus, possibly contributing to selective elimination of infected but not healthy cells by this non-specific cytokine. Additionally, our data show that both dsRNA and LPS, as well as TNF-alpha itself, rapidly induce nuclear factor-kappa B (NF-kappa B), a DNA-binding protein implicated in regulation of gene expression. We suggest that NF-kappa B could regulate genes crucial for the induction of cell death by TNF-alpha.

Animals↗
PubMed1990

Functional analysis of the murine T-cell receptor beta enhancer and characteristics of its DNA-binding proteins.

The minimal T-cell receptor (TCR) beta-chain (TCR beta) enhancer has been identified by transfection into lymphoid cells. The minimal enhancer was active in T cells and in some B-lineage cells. When a larger fragment containing the minimal enhancer was used, its activity was apparent only in T cells. Studies with phytohemagglutinin and 4 beta-phorbol-12,13-dibutyrate revealed that the enhancer activity was increased by these agents. By a combination of DNase I footprinting, gel mobility shift assay, and methylation interference analysis, seven different motifs were identified within the minimal enhancer. Furthermore, competition experiments showed that some of these elements bound identical or similar factors that are known to bind to the TCR V beta promoter decamer or to the immunoglobulin enhancer kappa E2 or muEBP-E motif. These shared motifs may be important in the differential gene activity among the different lymphoid subsets.

Animals↗
PubMed1990

Complex regulation of the immunoglobulin mu heavy-chain gene enhancer: microB, a new determinant of enhancer function.

The B-lymphocyte-specific activity of the immunoglobulin mu heavy-chain gene enhancer has been attributed to the octamer motif (ATTTGCAT) present within the enhancer that binds a B-cell-specific factor designated NF-A2/OTF-2. However, significant residual enhancer activity even after deletion of this element has suggested the presence of a second critical functional determinant. We have used deletion and mutational analyses to define an element, microB (TTTGGGGAA), that is essential for B-cell-specific enhancer activity in S194 myeloma cells in the absence of the octamer. Transfection analysis in a panel of lymphoid cell lines suggests that the presence of either microB or octamer leads to considerable enhancer activity in cell lines representing later stages of B-cell differentiation, whereas both elements are needed for function in cell lines representing earlier stages. Furthermore, in contrast to the results in pre-B-cell lines, both microB and octamer elements function independently in certain T-cell lines in which the mu enhancer is active.

Animals↗
PubMed1990

Patterns of erythropoiesis and anaemia in malaria.

Of 138 patients with malaria, 90 were found to be having Plasmodium falciparum in their peripheral blood smears. Megaloblastosis alone or in combination with the other patterns of erythropoiesis was observed in 82.1 percent cases of chronic P. falciparum malaria as compared to 36.3 and 26.5 per cent cases of acute P. falciparum and P. vivax malaria respectively. Iron deficiency was observed in 15.5 percent cases of chronic P. falciparum, 18.2 per cent cases of acute P. falciparum and 13.3 per cent patients of P. vivax infection. Of patients with chronic falciparum malaria, 33.3 percent revealed features of both megaloblastosis and defective iron utilization and transient hypoplasia of marrow was observed in 8.9 per cent of these cases.

Adolescent↗
PubMed1989

A second sequence element located 3' to the NF-kappa B-binding site regulates IL-2 receptor-alpha gene induction.

Transcriptional induction of the gene encoding the alpha-subunit of IL-2R has been shown to be mediated by a sequence element (GGGGAATCTCCC) that is homologous to the NF-kappa B-binding site of the kappa Ig gene enhancer. In this report we demonstrate that the induced transcription of this gene by mitogen and by the tax gene product of the type-I human T cell leukemia virus is dependent upon an additional sequence motif (GGGCGTAGC) located approximately 10 bp downstream of the previously identified site. This newly identified motif binds a factor that is present in extracts derived from different cell types and does not appear to be required for basal promoter activity. We conclude that proteins binding at both sites act coordinately, leading to maximal induction of the receptor gene.

Base Sequence↗
PubMed1989

Adenovirus E1A products activate the Ig k-chain enhancer in fibroblasts. A possible involvement of the NF-kB binding site.

Proteins encoded by the early region 1A (E1A) regulate transcription of viral and cellular genes. The mechanism of this trans-regulation remains unclear but it is of considerable interest as an example of transcription regulation through cellular intermediates. We have therefore studied the effect of E1A products on the activity of the k-L chain gene enhancer. In our previous studies we have found that the k-chain enhancer is activated by E1A products in fibroblasts. Using in vivo competition experiments we found that the E1A regulatory effect involves trans-acting factors that can be titrated out by the k-chain enhancer sequences. Our transfection experiments suggest that the k3 enhancer fragment, encompassing the NF-kB binding site, is one of the sites through which the adenovirus E1A products exert their transactivation effect. The level of the nuclear factors that bind to the NF-kB binding site increases in fibroblasts that constitutively express E1A products. Understanding the mechanisms through which E1A regulates transcription should help to illuminate cellular mechanisms of gene control in normal and transformed cells.

Adenovirus Early Proteins↗
PubMed1989

Identification of a functional NF-kappa B binding site in the murine T cell receptor beta 2 locus.

We have identified a sequence in the TCR beta 2 locus that is homologous to the kappa B site in the Ig kappa light chain enhancer. This element, TCR beta-B, is located in the vicinity of previously identified T cell-specific DNase1 hypersensitive sites. Transfection analysis shows that a 60-bp fragment encompassing this site is preferentially active in T cells stimulated with phorbol esters or the HTLV-1 tax gene product compared with a B cell line that constitutively expresses NF-kappa B. Our results provide the first evidence for transcriptional regulatory sequences residing within the J beta 2-C beta 2 intron and suggest the possible involvement of these sequences in modulation of TCR beta gene expression upon cellular activation.

Animals↗
PubMed1989

A brain-specific transcription activator.

We have identified a DNA binding protein, named BETA, that interacts with the same (B) transcriptional regulatory sequence as the known transcription factor NF-kappa B. BETA is found only in gray matter throughout the brain, and not in a variety of other rat tissues. Two binding sites for BETA are present adjacent to the promoter of the rat proenkephalin gene. Transfection of primary brain cultures that express BETA, with a reporter gene driven by the SV40 promoter linked to BETA DNA binding sites, results in transcriptional activation. We infer that BETA is a brain-specific transcription activator.

Animals↗
PubMed1989

Alteration of a single nucleotide allows efficient binding of H2TF1/KBF1 to the immunoglobulin kappa enhancer B motif.

NF-kappa B (a protein present constitutively only in B cells) and H2TF1/KBF1 (a more ubiquitously distributed protein[s]) are two transcription factors that recognize very similar DNA sequences. However, the binding site associated with the kappa immunoglobulin gene enhancer (kappa B) is recognized predominantly by NF-kappa B. Using synthetically altered recognition sequences, we showed that the B-cell-specific NF-kappa B-binding site in the kappa enhancer can be converted to one that binds both NF-kappa B and the ubiquitous protein(s) H2TF1/KBF1 by substitution of a single nucleotide. Furthermore, transient transfection experiments suggested that NF-kappa B and H2TF1/KBF1 are functionally different even though their DNA recognition specificities are very similar.

Animals↗
PubMed1989

Bacillaemia and bone marrow involvement in leprosy.

Fifty patients (24 new and 26 receiving specific treatment) of leprosy were investigated to study the concentration and morphological index (MI) of the lepra bacilli in skin, peripheral blood and bone marrow. The organisms were detected in 28 cases on skin slit smear examination, in 38 cases on bone marrow examination and in 38 cases on examination of smears made from buffy coat of peripheral blood. Out of 22 cases negative for the bacilli on skin slit smears, 15 had the organisms either in buffy coat or bone marrow or both. Acid fast bacilli in peripheral blood and bone marrow with skin smear negativity were mainly observed in patients with paucibacillary type of the disease and in those who were receiving treatment. Examination of buffy coat and bone marrow for presence of lepra bacilli is suggested to establish the diagnosis in doubtful cases.

Bone Marrow↗
PubMed1988

The NF-kappa B-binding site mediates phorbol ester-inducible transcription in nonlymphoid cells.

The mouse immunoglobulin kappa light-chain enhancer can interact with at least three independent nuclear proteins. One of these proteins, NF-kappa B, is constitutively present only in nuclear extracts derived from B cells and plasma cells. A DNA-binding protein with the same sequence specificity (and therefore presumed to be NF-kappa B itself) can be induced in pre-B cells, T cells, and nonlymphoid cells by phorbol 12-acetate-13-myristate (PMA); however, it is not clear whether the induced factor can activate transcription in nonlymphoid cells as NF-kappa B does in B cells. In this paper we show that multimerization of a fragment of the mouse kappa enhancer that carried only the binding site for NF-kappa B behaved like a B-cell-specific regulatory element. Furthermore, this unit served to activate transcription in nonlymphoid cells after treatment with PMA (but not with cyclic AMP derivatives), and the kinetics of transcription activation correlated well with the kinetics of factor induction. Thus, the induced DNA-binding activity appeared to be functionally indistinguishable from that of NF-kappa B.

B-Lymphocytes↗
PubMed1988

Leukemoid reaction in erythema nodosum leprosum in a leprosy patient.

A case of lepromatous leprosy with erythema nodosum leprosum (ENL) presenting as a myeloid leukemoid reaction is reported. Very high leucocyte count with immaturity of the cells in myeloid series was present in peripheral blood. High leucocyte alkaline phosphatase score, absence of hepatosplenomegaly and transient nature of leukemoid reaction differentiated it from chronic myeloid leukemia and acute myeloblastic leukemia. The possible mechanisms of leukemoid reaction in ENL are discussed.

Adult↗
PubMed1987

In vitro transcription of immunoglobulin genes in a B-cell extract: effects of enhancer and promoter sequences.

Transfection experiments have led to the identification of three DNA sequences that are responsible for the tissue-specific expression of immunoglobulin genes. As a first step toward characterizing these regulatory phenomena at the biochemical level, we report the development of an in vitro transcription system from cells of the B lymphoid lineage. In these extracts, transcription of the MOPC41 kappa promoter is correctly initiated and dependent on the presence of an upstream sequence element located between -44 and -79 base pairs from the cap site. Second, although standard in vitro transcriptions are not affected by the presence or absence of enhancer sequences, we observed that the addition of polyethylene glycol led to a B-cell extract-specific suppression of transcription from a template that carries an immunoglobulin enhancer.

B-Lymphocytes↗