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Biomedical subjects

R Krishnamurthy

Publications and source records attributed to R Krishnamurthy.

At least 19 recordsLinked to original sources
PubMed2001

Pentopyranosyl oligonucleotide systems. Part 11: Systems with shortened backbones: (D)-beta-ribopyranosyl-(4'-->3')- and (L)-alpha-lyxopyranosyl-(4'-->3')-oligonucleotides.

The (L)-alpha-lyxopyranosyl-(4'-->3')-oligonucleotide system-a member of a pentopyranosyl oligonucleotide family containing a shortened backbone-is capable of cooperative base-pairing and of cross-pairing with DNA and RNA. In contrast, corresponding (D)-beta-ribopyransoyl-(4'-->3')-oligonucleotides do not show base-pairing under similar conditions. We conclude that oligonucleotide systems can violate the 'six-bonds-per-backbone-unit' rule by having five bonds instead, if their vicinally bound phosphodiester bridges can assume an antiperiplanar conformation. An additional structural feature that seems relevant to the cross-pairing capability of the (L)-alpha-lyxopyranosyl-(4'-->3')-oligonucleotide system is its (small) backbone/basepair axes inclination. An inclination which is similar to that in B-DNA seems to be a prerequisite for an oligonucleotide system's capability to cross-pair with DNA.

Base Pairing↗
PubMed2001

An evaluation of the effects of Rorschach EB style on the diagnostic utility of the Depression Index.

Several empirical studies have found the Rorschach Depression Index (DEPI) to have questionable diagnostic utility. Studies using adolescent samples suggest that the DEPI has limited sensitivity and fails to differentiate effectively between adolescents with and without depression diagnoses. The present study was conducted to evaluate Viglione, Brager, and Haller's suggestion that the DEPI may have better discriminative ability for individuals with extratensive problem-solving styles, measured by the Rorschach EB (Erlebnistypus) variable, compared to those with introversive and ambitent styles. Comparisons were conducted between adolescents with depression-related diagnoses and adolescents with other diagnoses for each of the three EB groups. The results failed to support the hypothesized greater discriminative power of DEPI for depressed extratensives, and suggest caution in using the DEPI to evaluate adolescent depression.

Adolescent↗
PubMed2001

Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development.

We report loss- and gain-of-function analyses that identify essential roles in development for Drosophila transcription factor AP-2. A mutagenesis screen yielded 16 lethal point mutant alleles of dAP-2. Null mutants die as adults or late pupae with a reduced proboscis, severely shortened legs (approximately 30% of normal length) lacking tarsal joints, and disruptions in the protocerebral central complex, a brain region critical for locomotion. Seven hypomorphic alleles constitute a phenotypic series yielding hemizygous adults with legs ranging from 40-95% of normal length. Hypomorphic alleles show additive effects with respect to leg length and viability; and several heteroallelic lines were established. Heteroallelic adults have moderately penetrant defects that include necrotic leg joints and ectopic growths (sometimes supernumerary antennae) invading medial eye territory. Several dAP-2 alleles with DNA binding domain missense mutations are null in hemizygotes but have dominant negative effects when paired with hypomorphic alleles. In wild-type leg primordia, dAP-2 is restricted to presumptive joints. Ectopic dAP-2 in leg discs can inhibit but not enhance leg elongation indicating that functions of dAP-2 in leg outgrowth are region restricted. In wing discs, ectopic dAP-2 cell autonomously transforms presumptive wing vein epithelium to ectopic sensory bristles, consistent with an instructive role in sensory organ development. These findings reveal multiple functions for dAP-2 during morphogenesis of feeding and locomotor appendages and their neural circuitry, and provide a new paradigm for understanding AP-2 family transcription factors.

Alleles↗
PubMed2001

Isolation of group A beta-hemolytic streptococci in the tonsillopharynx of school children in Madras City and correlation with their clinical features.

Today, rheumatic fever is the most common cause of heart disease in children and young adults, and it accounts for about half of all cardiovascular diseases causing death in the first four decades of life, in India. In the present study, conducted during 1991-1992 at Chennai, India, a total of 666 school girls aged 5-15 years were examined clinically for one or more of the following signs and symptoms: repeated sore throat, joint pain/swelling, epistaxis, chest pain, breathlessness, palpitation, abdominal pains, etc. Out of the 666 children screened, 124 were recruited for the present study, based on their meeting one or more of the above mentioned clinical criteria. They were screened for the presence of group A beta-hemolytic streptococci, and for antistreptolysin O and C-reactive protein. Thus, the aim of the present study was to reduce the load of streptococcal infection and the consequent risk of developing rheumatic fever and rheumatic heart disease. In the present study group, 89.5% of the children indicated a history of repeated sore throat. However, only 4.0% of the children in the study group were positive for group A beta-hemolytic streptococci. The antistreptolysin O and C-reactive protein levels were higher in 11- to 15-year-old patients than in 5- to 10-year-old patients in the study group.

Adenoids↗
PubMed2000

Chemical etiology of nucleic acid structure: the alpha-threofuranosyl-(3'-->2') oligonucleotide system.

TNAs [(L)-alpha-threofuranosyl oligonucleotides] containing vicinally connected (3'-->2') phosphodiester bridges undergo informational base pairing in antiparallel strand orientation and are capable of cross-pairing with RNA and DNA. Being derived from a sugar containing only four carbons, TNA is structurally the simplest of all potentially natural oligonucleotide-type nucleic acid alternatives studied thus far. This, along with the base-pairing properties of TNA, warrants close scrutiny of the system in the context of the problem of RNA's origin.

Base Pairing↗
PubMed2000

Inactivation of lysozyme by sonication under conditions relevant to microencapsulation.

Controlled release dosage forms of proteins and other biomolecules can be prepared by microencapsulating them in polymeric microspheres. Proteins are subjected to potentially damaging effects of sonication and exposure to organic solvents during the microencapsulation process. The relatively stable enzyme lysozyme was dissolved in aqueous buffer and sonicated in the presence of methylene chloride to mimic the initial step of the microencapsulation process. The stability of lysozyme was evaluated by determining the enzyme activity before and after sonication, size-exclusion chromatography, native polyacrylamide gel electrophoresis, and by measuring the amount of precipitates formed. Following sonication, the total protein introduced was distributed between a soluble and an insoluble fraction. Sonication of lysozyme solutions in the presence of methylene chloride led to an increase in precipitates. The precipitates were enzymatically inactive, did not dissolve easily, and were held by non-covalent interactions. No fragments or aggregates of lysozyme were detectable in the soluble fraction. Sonicating aqueous lysozyme solutions with and without methylene chloride decreased the specific activity of the enzyme in the soluble fraction. Excipients such as dimethyl sulfoxide (DMSO), mannitol, sucrose, and tween 80 were included in the sonication mixtures containing lysozyme. With the exception of tween 80, the addition of the excipients to aqueous solutions of lysozyme led to a greater decrease in the specific activity of lysozyme when sonicated in the presence of methylene chloride. DMSO caused the greatest loss of enzyme activity following sonication. Sonication of lysozyme with water, methylene chloride, and DMSO yielded methyl radicals, which were trapped with alpha-phenyl N-tert-butylnitrone and detected by ESR spectroscopy.

Anti-Bacterial Agents↗
PubMed2000

Ectopic expression of luteinizing hormone-releasing hormone and peripherin in the respiratory epithelium of mice lacking transcription factor AP-2alpha.

The vertebrate transcription factor activator protein-2 (AP-2alpha) is involved in craniofacial morphogenesis. In the nasal placode AP-2alpha expression delineates presumptive respiratory epithelia from olfactory epithelia, with AP-2alpha expression restricted to the anterior region of the respiratory epithelium (absent from the olfactory epithelium) at later stages. To address the role AP-2alpha plays in differentiation of cell groups in the nasal placode, the spatiotemporal expression pattern of four markers normally associated with olfactory epithelial structures was analyzed in mice lacking AP-2alpha. These markers were the intermediate filament protein peripherin, the neuropeptide luteinizing hormone-releasing hormone (LHRH), the neural cell adhesion molecule (NCAM) and the olfactory transcription factor Olf-1. Development of cells expressing these markers was similar in both genotypes until embryonic day 12.5 (E12.5), indicating that the main olfactory epithelium and olfactory pit formation was normal. At E13.5 in mutant mice, ectopic LHRH neurons and peripherin axons were detected in respiratory epithelial areas, areas devoid of Olf-1 and NCAM staining. Over the next few days, an increase in total nasal LHRH neurons occurred. The increase in nasal LHRH neurons could be accounted for by LHRH neurons arising and migrating out of respiratory epithelial regions on peripherin-positive fibers. These results indicate that AP-2alpha is not essential for the separation of the olfactory and respiratory epithelium from the nasal placode and is consistent with AP-2alpha preventing recapitulation of developmental programs within the respiratory epithelium that lead to expression of LHRH and peripherin phenotypes.

Animals↗
PubMed2000

Mitochondrial calcium signaling driven by the IP3 receptor.

Many agonists bring about their effects on cellular functions through a rise in cytosolic [Ca2+] ([Ca2+]c) mediated by the second messenger inositol 1,4,5-trisphosphate (IP3). Imaging studies of single cells have demonstrated that [Ca2+]c signals display cell specific spatiotemporal organization that is established by coordinated activation of IP3 receptor Ca2+ channels. Evidence emerges that cytosolic calcium signals elicited by activation of the IP3 receptors are efficiently transmitted to the mitochondria. An important function of mitochondrial calcium signals is to activate the Ca2+-sensitive mitochondrial dehydrogenases, and thereby to meet demands for increased energy in stimulated cells. Activation of the permeability transition pore (PTP) by mitochondrial calcium signals may also be involved in the control of cell death. Furthermore, mitochondrial Ca2+ transport appears to modulate the spatiotemporal organization of [Ca2+]c responses evoked by IP3 and so mitochondria may be important in cytosolic calcium signaling as well. This paper summarizes recent research to elucidate the mechanisms and significance of IP3-dependent mitochondrial calcium signaling.

Animals↗
PubMed2000

Transcription factor activator protein-2 is required for continued luteinizing hormone-releasing hormone expression in the forebrain of developing mice.

LHRH is the neuropeptide responsible for reproductive function. Prenatally, LHRH expression begins when neurons are in the olfactory pit and continues as these cells migrate into the brain. Thus, LHRH neurons maintain neuropeptide expression through very distinct environments. The regulatory interactions that control onset and continued expression of the LHRH phenotype are unknown. To begin to address this question primary LHRH neurons were removed from nasal explants at different ages. A complementary DNA (cDNA) subtraction screen was performed comparing a 3.5-days in vitro LHRH neuron [approximately embryonic day 15 (E15) in vivo] to two 10.5-days in vitro LHRH neurons (approximately postnatal day 1 in vivo). The transcription factor activator protein-2 (AP-2alpha) was differentially expressed and was present in the developmentally younger LHRH neuron. In vivo analysis revealed that LHRH neurons expressed AP-2 as they migrated across the cribriform plate and into the forebrain beginning on E13.5, but that coexpression of LHRH and AP-2 was no longer detected in postnatal day 1 animals. This suggested a regulatory role for AP-2 in LHRH neurons. Analysis of animals lacking AP-2alpha revealed a dramatic decrease in forebrain LHRH neurons between E13.5 and E14.5, correlating with normal onset of AP-2 expression in LHRH neurons as they entered the central nervous system. Nasal cells robustly expressing LHRH were still present on E 14.5. The continued presence of forebrain LHRH cells is proposed based on a second marker, galanin, and lack of increased apoptotic/necrotic cells in this region. A decrease in LHRH messenger RNA in forebrain neurons indicates regulation of LHRH occurred at the transcriptional or posttranscriptional level in mutant animals. These results indicate a developmentally restricted involvement of the transcription factor AP-2 in LHRH expression once the LHRH neurons have migrated into the forebrain, but before establishment of an adult-like distribution.

Animals↗
PubMed1999

Keratin 10 gene expression during differentiation of mouse epidermis requires transcription factors C/EBP and AP-2.

The epidermis forms a vital barrier composed of stratified keratinocytes and their differentiated products. One of these products, keratin K10, is critical to epidermal integrity, because mutations in k10 lead to abnormal blistering. For the normal expression of k10, differentiation-associated transcription factors C/EBPalpha, C/EBPbeta, and AP-2 are well positioned to play an important role. Here, regulation of the k10 gene is examined in keratinocytes in the skin of normal mice and in transgenic mice carrying targeted deletions of c/ebpbeta and ap-2alpha. In cultured cells, C/EBPalpha and C/EBPbeta are each capable of activating the k10 promoter via three binding sites, identified by site-directed mutagenesis. In a given epidermal cell in vivo, however, the selection of C/EBPalpha versus C/EBPbeta for k10 regulation is determined via a third transcription factor, AP-2. This novel regulatory scheme involves: (1) unique gradients of expression for each transcription factor, i.e., C/EBPbeta and AP-2 most abundant in the lower epidermis, C/EBPalpha in the upper; (2) C/EBP-binding sites in the ap-2alpha gene promoter, through which C/EBPbeta stimulates ap-2alpha; and (3) AP-2 binding sites in the c/ebpalpha promoter, through which AP-2 represses c/ebpalpha. Promoter-analysis and gene-expression data presented herein support a regulatory model in which C/EBPbeta activates and maintains AP-2 expression in basal keratinocytes, whereas AP-2 represses C/EBPalpha in those cells. In response to differentiation signals, loss of AP-2 expression leads to derepression of the c/ebpalpha promoter and activation of k10 as cells migrate upward.

Animals↗
PubMed1999

Promiscuous Watson-Crick cross-pairing within the family of pentopyranosyl (4'-->2') oligonucleotides.

[formula: see text] The D-beta-ribo, D-beta-xylo, L-alpha-lyxo, and L-alpha-arabino members of the pentopyranosyl (4'-->2') oligonucleotide family show efficient intersystem cross-pairing among each other. This family of configurationally isomeric and conformationally well-defined pairing systems offers an opportunity to study structural factors that determine cross-communication between informational oligonucleotide systems of different backbone structure.

Base Pairing↗
PubMed1999

L-alpha-lyxopyranosyl (4'-->3') oligonucleotides: a base-pairing system containing a shortened backbone.

[formula: see text] The L-alpha-lyxopyranosyl (4'-->3') oligonucleotide system shows cooperative base-pairing in spite of containing only five instead of the usual six covalent bonds per repetitive backbone unit. In contrast, corresponding D-beta-ribofuranosyl (4'-->3') oligonucleotides do not show adenine-thymine pairing under comparable conditions. The difference in pairing behavior relates to the conformation of the two systems' vicinal 3',4'-phosphodiester substituents, which is diaxial in the lyxopyranosyl system and 3'-axial-4'-equatorial in the ribopyranosyl system.

Base Pairing↗
PubMed1999

Apoptosis driven by IP(3)-linked mitochondrial calcium signals.

Increases of mitochondrial matrix [Ca(2+)] ([Ca(2+)](m)) evoked by calcium mobilizing agonists play a fundamental role in the physiological control of cellular energy metabolism. Here, we report that apoptotic stimuli induce a switch in mitochondrial calcium signalling at the beginning of the apoptotic process by facilitating Ca(2+)-induced opening of the mitochondrial permeability transition pore (PTP). Thus [Ca(2+)](m) signals evoked by addition of large Ca(2+) pulses or, unexpectedly, by IP(3)-mediated cytosolic [Ca(2+)] spikes trigger mitochondrial permeability transition and, in turn, cytochrome c release. IP(3)-induced opening of PTP is dependent on a privileged Ca(2+) signal transmission from IP(3) receptors to mitochondria. After the decay of Ca(2+) spikes, resealing of PTP occurs allowing mitochondrial metabolism to recover, whereas activation of caspases is triggered by cytochrome c released to the cytosol. This organization provides an efficient mechanism to establish caspase activation while mitochondrial metabolism is maintained to meet ATP requirements of apoptotic cell death.

Adenosine Triphosphate↗
PubMed1999

Chemical etiology of nucleic acid structure: comparing pentopyranosyl-(2'-->4') oligonucleotides with RNA.

All four members of the family of pentopyranosyl-(2'-->4') oligonucleotide systems that contain beta-ribo-, beta-xylo-, alpha-lyxo-, or alpha-arabinopyranosyl units as repeating sugar building blocks are found to be much stronger Watson-Crick base-pairing systems than RNA. The alpha-arabinopyranosyl system is the strongest of all and in fact belongs to the strongest oligonucleotide base-pairing systems known. Whatever the chemical determinants by which nature selected RNA as a genetic system, maximization of base-pairing strengths within the domain of pentose-derived oligonucleotide systems was not the critical selection criterion.

Arabinose↗
PubMed1999

Mineral induced formation of pentose-2,4-bisphosphates.

Formation of rac.-pentose-2,4-bisphosphates is demonstrated, starting from glycolaldehyde phosphate and glyceraldehyde-2-phosphate, and induced by mixed valence double layer metal hydroxide minerals. The reactions proceed from dilute aqueous reactant solutions (1.5 mM) at near neutral pH. Conditions have been established, where ribose-2,4-bisphosphate is the major product (approximately 48%) among the pentose-2,4-bisphosphates, which are formed with up to 25% yield.

Aluminum Hydroxide↗
PubMed1999

Formation of glycolaldehyde phosphate from glycolaldehyde in aqueous solution.

Amidotriphosphate (0.1 M) in aqueous solution at near neutral pH in the presence of magnesium ions (0.25 M) converts glycolaldehyde (0.025 M) within days at room temperature into glycolaldehyde phosphate in (analytically) nearly quantitative yields (76% in isolated product). This robust phosphorylation process was observed to proceed at concentrations as low as 30 microM glycolaldehyde and 60 microM phosphorylation reagent under otherwise identical conditions. In sharp contrast, attempts to achieve a phosphorylation of glycolaldehyde with cyclotriphosphate ('trimetaphosphate') as phosphorylating reagent were unsuccessful. Mechanistically, the phosphorylation of glycolaldehyde with amidotriphosphate is an example of intramolecular delivery of the phosphate group.

Acetaldehyde↗
PubMed1999

Mammographic findings after breast conservation therapy.

Breast conservation therapy for breast cancer involves lumpectomy or segmental mastectomy followed by radiation therapy. Masses, fluid collections, architectural distortion, scarring, edema, skin thickening, and calcifications are posttreatment findings that may mimic or mask local tumor recurrence. Despite the overlap between posttreatment changes and tumor recurrence, the two entities can usually be distinguished by the characteristic mammographic appearances of posttreatment sequelae and by comparing interval findings on successive studies. Postoperative masses and fluid collections slowly diminish in size and usually resolve by 1 year after surgery. Radiation-induced edema gradually resolves; increasing edema may be due to recurrent cancer. Postsurgical scarring usually appears as a poorly marginated soft-tissue mass with interspersed radiolucent areas. Recurrent cancer is usually seen as a mass with no central radiolucent areas. Pleomorphic and granular microcalcifications are important markers for recurrent cancer and can usually be distinguished from the thick, calcified plaques and elongated dystrophic calcifications associated with scarring.

Breast↗