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Biomedical subjects

P Kannan

Publications and source records attributed to P Kannan.

At least 19 recordsLinked to original sources
PubMed2006

T-h-2 immunity and CD3+CD45RBlow-activated T cells in mice immunized with recombinant bacillus Calmette-Guérin expressing HIV-1 principal neutralizing determinant epitope.

The genetic engineering of Mycobacterium bovis-bacillus Calmette-Guérin to express foreign epitopes is an attractive strategy in the field of epitope vaccines. We constructed an 'epitope-trap vector' with Mycobacterium tuberculosis chaperonin-10 as a carrier antigen and used it to express the HIV-1 principal neutralizing determinant epitope. We also identified a new chaperonin-10 promoter that was hyperexpressive compared with the heat shock protein-65 promoter. Splenocytes from recombinant bacillus Calmette-Guérin-immunized mice showed enhanced lymphocyte proliferation and interleukin-4 (but not interferon-gamma) secretion. The recombinant bacillus Calmette-Guérin-immunized group also exhibited mild delayed-type hypersensitivity reaction and a high frequency of CD3+CD45RBlow-activated T cells, together with high titer of antiprincipal neutralizing determinant immunoglobulin G antibodies. Thus, this epitope delivery system induced strong epitope-specific T-h-2 polarization.

Animals↗
PubMed2006

Prevalence of dermatophytes and other fungal agents isolated from clinical samples.

The common cause of skin infections are dermatophytes and opportunistic fungi. Aim of this study was to isolate and identify the fungal agents from clinical samples from patients with different mycoses. Clinical samples from 165 patients were subjected to potassium hydroxide (KOH) examination and culture isolation; causative agents were identified macroscopically and microscopically. All the 165 specimens were KOH positive and 110/165 (66.7%) samples were culture positive. Of these, highest isolation rate was obtained in opportunistic mycoses such as candidiasis (29/29, 100%). Dermatophytes were isolated in 53/80 (66.3%) specimens and Trichophyton rubrum was the commonest isolate in skin samples (17/24) among the patients suffering from dermatophytosis. Phaeoannellomyces wernecki was isolated in a patient suffering from tinea nigra. The study signifies the importance of mycological examination in the diagnosis of various mycoses for their effective management.

Arthrodermataceae↗
PubMed2000

Characterization of the activation domains of AP-2 family transcription factors.

Despite sequence variation, all AP-2 isotypes are capable of activating transcription, which indicates a functional conservation. We used this property to gain a unique insight into the structure and function of the activation motifs of AP-2 family transcription factors. We have precisely localized the activation motif of human AP-2 alpha to amino acids 52-108. Our experiments indicate that similar sequence of amino acids in all AP-2 isotypes except Drosophila AP-2 alpha harbor their activation motifs. Within this sequence, fewer than 36 residues are critical for transcription activation. Our comparison studies and site-directed mutagenic analyses show that these critical amino acids are strategically placed within this sequence. These residues are interspersed with nonessential and influential residues that vary in composition and length, indicating a structural flexibility. The Drosophila AP-2 alpha has its partly conserved activation motif in an extended region about twice the length of other AP-2 isotypes. Our results reveal essential elements of the amino acid composition of activators in general and shed new light on the mechanism of transcription activation.

Amino Acid Sequence↗
PubMed1999

Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes. Implications for the arrhythmogenesis of human siderotic heart disease.

BACKGROUND: Patients with chronic iron overload may develop a cardiomyopathy manifested by ventricular arrhythmias and heart failure. We hypothesized that iron-loaded cardiomyocytes may have abnormal excitability. METHODS AND RESULTS: We examined a new model of human iron overload, the Mongolian gerbil given repeated injections of iron dextran. In ventricular myocytes, we measured iron concentration and distribution, action potential, sodium and potassium currents, and sodium channel protein. We showed for the first time that (1) the iron content of gerbil ventricular cardiomyocytes was increased to amounts similar to those of patients with iron-induced cardiomyopathy; (2) the overshoot and duration of the cardiac action potential decreased; (3) sodium current was reduced, steady-state inactivation was enhanced, and single-channel currents were unchanged; and (4) transient outward potassium current was increased, but inwardly rectifying potassium current was unchanged. Neonatal rat cardiomyocytes incubated with iron for 1 to 3 days showed similar changes, and levels of cardiac sodium channel proteins were unchanged. CONCLUSIONS: Abnormal excitability and heterogeneous cardiac iron deposition may cause the arrhythmogenesis of human siderotic heart disease.

Action Potentials↗
PubMed1999

PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation.

Overexpression of transcription factor AP-2 has been implicated in the tumorigenicity of the human teratocarcinoma cell lines PA-1 that contain an activated ras oncogene. Here we show evidence that overexpression of AP-2 sequesters transcriptional coactivators which results in self-inhibition. We identified AP-2-interacting proteins and determined whether these proteins were coactivators for AP-2-mediated transcription. One such interacting protein is polyADP-ribose polymerase (PARP). PARP suppresses AP-2 self-inhibition and enhances AP-2 activity in PA-1 cells indicating that it is a coactivator for AP-2-transcription. PARP significantly restores AP-2 transcriptional activity in ras oncogene-transformed cells suggesting that it might suppress transformation in these cells. Another AP-2-interacting protein, RAP74, a subunit of transcription factor TFIIF, does not affect AP-2-mediated transcriptional activation alone or in the presence of RAP30, the other subunit of TFIIF. RAP74 also fails to relieve AP-2-mediated transcriptional self-interference and cross-interference. These studies suggest that the interaction between AP-2 and RAP74 may have functions other than activation of AP-2-mediated transcription.

Binding Sites↗
PubMed1999

Coactivator PC4 mediates AP-2 transcriptional activity and suppresses ras-induced transformation dependent on AP-2 transcriptional interference.

ras oncogene-transformed PA-1 human teratocarcinoma cells have abundant AP-2 mRNA but, paradoxically, little AP-2 transcriptional activity. We have previously shown that overexpression of AP-2 in nontumorigenic variants of PA-1 cells results in inhibition of AP-2 activity and induction of tumorigenicity similar to that caused by ras transformation of PA-1 cells. Evidence indicated the existence of a novel mechanism of inhibition of AP-2 activity involving sequestering of transcriptional coactivators. In this study, we found that PC4 is a positive coactivator of AP-2 and can restore AP-2 activity in ras-transformed PA-1 cells. Relative to vector-transfected ras cell lines, ras cell lines stably transfected with and expressing the PC4 cDNA have a diminished growth rate and exhibit a loss of anchorage-independent growth, and they are unable to induce the formation of tumors in nude mice. These data suggest that a transcriptional coactivator, like a tumor suppressor, can have a growth-suppressive effect on cells. Our experiments are the first to show that ras oncogenes and oncogenic transcription factors can induce transformation through effects on the transcription machinery rather than through specific programs of gene expression.

Animals↗
PubMed1996

Functional interaction between a RARE and an AP-2 binding site in the regulation of the human HOX A4 gene promoter.

HOX A genes are induced in a temporal fashion after retinoic acid (RA) treatment in non-N-ras-transformed PA-1 human teratcarcinoma cells. However, In N-ras-transformed PA-1 cells, RA-Induced expression of HOX A genes is delayed. The mRNA for the transcriptional activator AP-2 is overexpressed in these ras-transformed cells, but AP-2 transcriptional activity is inhibited relative to non ras-transformed PA-1 cells. Constitutive expression of AP-2 mimics the effect of ras by transforming cells and inhibiting differentiation in culture. We analyzed 4 kb of the human HOX A4 gene promoter and identified seven putative AP-2-binding sites in the DNA sequence. Transcription assays with variably sized HOX A4 promoter reporter constructs revealed that a 365 bp region of the promoter, -2950 to -3315 relative to the mRNA start, controls RA responsiveness and ras-mediated inhibition of HOX A4 activity. This region contains an AP-2 binding site and a RARE. Elimination of the AP-2 site by site-directed mutagenesis demonstrated that the AP-2 site is involved in RA-mediated transcriptional activation of the human HOX A4 promoter in combination with the RA receptor response element (RARE). In N-ras-transformed cells, low HOX A4 promoter activity results from ras inhibition of AP-2 transactivation.

Base Sequence↗
PubMed1995

Oesophageal motility disorders: rapid functional diagnosis using computerised radionuclide oesophageal transit study.

Ten patients presenting with central chest pain and/or dysphagia were diagnosed to have oesophageal motility disorders (OMD) with an incoordinate motor function using computerised radionuclide oesophageal transit study (RT). The criteria for diagnosis of OMD with incoordination using RT were: an 'incoordinate' or 'to and fro' pattern characterised by multiple peaks of activity, prolonged total transit time or radionuclide bolus through entire length of oesophagus and a significant portion of bolus entering the stomach. These features are characteristic but not pathognomonic of diffuse oesophageal spasm (DES) as they are also seen in non-specific motility disorders (NSMD) and occasionally in order oesophageal motility disorders. Mechanical obstruction in the oesophagus and coronary artery disease were excluded appropriately in these patients. When manometry is not available, RT is a sensitive, safe, simple, rapid and non-invasive alternative modality in confirming certain oesophageal motility disorders.

Adult↗
PubMed1994

N-ras oncogene causes AP-2 transcriptional self-interference, which leads to transformation.

Genetic alterations in elements of normal signal transduction mechanisms are known to be oncogenic events often resulting in aberrant activation of programs of gene transcription. We have investigated the effect of N-ras oncogene-induced tumorigenic transformation on the transcription factor AP-2. N-ras oncogene-induced transformation of human teratocarcinoma cells PA-1 results in sixfold elevated AP-2 mRNA levels. However, the level of AP-2-mediated trans-activation is dramatically inhibited in these cells. We show here that the high-level expression of AP-2 ultimately results in transcriptional "self-interference". The activation domain of AP-2, when fused to the DNA-binding domain of GAL4, is sufficient for self-interference. Non-N-ras PA-1 cells constitutively expressing AP-2 or GAL4-AP-2 fusion protein from an SV40 promoter exhibit reduced AP-2-mediated transcriptional activation, inhibition of differentiation, and promotion of anchorage-independent growth, properties that are similar to N-ras-transformed PA-1 cells. Thus, AP-2 is placed in the N-ras signal transduction pathway, and many of the biological effects of N-ras can be accomplished by overexpression of AP-2. This is the first evidence that inhibition of the activity of a transcription factor by self-interference contributes to a physiological process.

Base Sequence↗
PubMed1994

Recurrent acute pulmonary oedema associated with obstructive sleep apnoea.

A patient had recurrent acute nocturnal pulmonary oedema following an anterior myocardial infarction despite a normal maximal stress electrocardiogram. He had a history of chronic heavy snoring and other symptoms to suggest a diagnosis of obstructive sleep apnoea (OSA) which was supported by an overnight sleep study. The recurrent acute pulmonary oedema was most likely due to a combination of poor left ventricular function and obstructive sleep apnoea.

Acute Disease↗
PubMed1993

An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2.

AP-2 is a retinoic acid-inducible and developmentally regulated activator of transcription. We have cloned an alternative AP-2 transcript (AP-2B) from the human teratocarcinoma cell line PA-1, which encodes a protein differing in the C terminus from the previously isolated AP-2 protein (AP-2A). This protein contains the activation domain of AP-2 and part of the DNA binding domain but lacks the dimerization domain which is necessary for DNA binding. Analysis of overlapping genomic clones spanning the entire AP-2 gene proves that AP-2A and AP-2B transcripts are alternatively spliced from the same gene. Both transient and stable transfection experiments show that AP-2B inhibits AP-2 transactivator function, as measured by an AP-2-responsive chloramphenicol acetyltransferase reporter plasmid. Furthermore, constitutive AP-2B expression in PA-1 cells causes a retinoic acid-resistant phenotype, anchorage-independent growth in soft agar, and tumorigenicity in nude mice, in a fashion similar to transformation of these cells by oncogenes. To determine the mechanism by which AP-2B exerts its inhibitory function, we purified bacterially expressed AP-2A and AP-2B proteins. While bacterial AP-2B does not bind an AP-2 consensus site, it strongly inhibits binding of the endogenous AP-2 present in PA-1 cell nuclear extracts. However, DNA sequence-specific binding of bacterially expressed AP-2A cannot be inhibited by bacterially expressed AP-2B. Therefore, inhibition of AP-2 activity by the protein AP-2B may require an additional factor or modification supplied by nuclear extracts.

Alternative Splicing↗
PubMed1993

Total occlusion of left main coronary artery in Orientals: profile of 4 cases.

The authors report 4 Oriental cases of total occlusion of the left main coronary artery (LMCA) with differing presentations. The first patient had a twelve-year history of stable angina pectoris. The second patient had angina for a year, which became unstable two months prior to diagnosis. The third patient had myocardial infarction seven years ago and presented with a one-month history of rest angina. The fourth patient had stable effort angina for six years but presented with accelerated angina three months prior to diagnosis. The incidence of total occlusion of the LMCA is rare and survival depends on the existence of collateral circulation. In LMCA disease, there is usually disease in other parts of the coronary arterial tree, and hence, the need for urgent coronary bypass surgery.

Angina Pectoris↗
PubMed1992

Hepatotoxicity of amiodarone.

Amiodarone, a commonly used antiarrhythmic agent, has numerous adverse effects. The purpose of this case report is to highlight its hepatotoxicity, an unusual complication of long term amiodarone therapy. Our patient is a 76-year-old man with underlying ischaemic heart disease and recurrent ventricular tachycardia. Eleven months after commencing amiodarone, he developed asymptomatic raised aminotransferases which resolved following drug withdrawal. Amiodarone was then reintroduced and four years later, the patient developed hepatomegaly, worsening liver biochemistry and histopathological changes consistent with early cirrhosis. His symptoms improved following discontinuation of amiodarone. However, hepatomegaly and a low serum albumin still persist four years later.

Aged↗
PubMed1992

Acute myocardial infarction after blunt chest injury.

A 20-year-old male sustained an inferior myocardial infarction following blunt chest trauma, after a motor vehicle accident. Though coronary arteriograms 9 months later were normal, LV angiography revealed severe hypokinesia of the inferobasal and diaphragmatic segments. The literature is reviewed with respect to mechanisms of injury, autopsy and angiographic findings and clinical outcome in this condition.

Adult↗
PubMed1991

Identification of a retinoic acid-inducible endogenous retroviral transcript in the human teratocarcinoma-derived cell line PA-1.

Retinoic acid (RA), a developmental morphogen, causes activation of a transcript of an endogenous retrovirus-related element in the human teratocarcinoma-derived cell line PA-1. This provirus is defective, and the provirus-related sequences exist as multicopy elements (more than 20 copies) in human DNA. This is the first human endogenous retroviral mRNA that is known to be transcriptionally activated by RA. The nucleotide sequence of the 3,357 bp of this viral cDNA was determined and shows a strong homology to the type C-related human endogenous retroviral proviruses ERV3 and 4-1. This cDNA contains 'R-U5-delta pol-env-U3-R sequences of the provirus. Adjacent to the putative 5' long terminal repeat of this provirus there is an 18-bp sequence complementary to the 3' end of isoleucine tRNA. We named this RA-responsive virus RRHERV-I.

Base Sequence↗