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Biomedical subjects

P N Nair

Publications and source records attributed to P N Nair.

At least 19 recordsLinked to original sources
PubMed2001

Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the pancreatic cancer cell line MIA PaCa-2.

In the present study we investigated the mechanisms responsible for and the biological consequences of the constitutive activation of the insulin-like growth factor-1 receptor (IGF-1R) in the MIA PaCa-2 cells. An aberrant increase in the expression and activation of the IGF-1R was observed during the transition of growth states from exponential to quiescent. The increase in IGF-1R expression is preceded by an increase in IGF-1R mRNA transcript and is associated with an increase in the IGF-1R promoter activity. Inhibition of de novo transcription by actinomycin D increased the stability of IGF-1R mRNA in exponentially growing cells, thereby increasing the expression of IGF-1R to a level similar to that seen in quiescent cells. Increased IGF-1R signaling mediated the growth factor independence of quiescent MIA PaCa-2 cells through the constitutive activation of mitogen-activated protein kinase (MAPK). Exogenous IGF-1 increased cell proliferation and activated MAPK and AKT signaling pathways. The resistance of cells to apoptosis by IGF-1R signaling was mediated through MAPK and phosphatidylinositol 3-kinase (PI3K) pathways and a yet unidentified pathway(s). Thus, aberrant regulation of IGF-1R signaling is required for resistance to apoptosis and growth factor independence of MIA PaCa-2 cells. This likely protects cells from unfavorable conditions and allows cells to rapidly re-enter the cell cycle when conditions are favorable.

Apoptosis↗
PubMed2001

Glutathione protects chemokine-scavenging and antioxidative defense functions in human RBCs.

Oxidant stress, in vivo or in vitro, is known to induce oxidative changes in human red blood cells (RBCs). Our objective was to examine the effect of augmenting RBC glutathione (GSH) synthesis on 1) degenerative protein loss and 2) RBC chemokine- and free radical-scavenging functions in the oxidatively stressed human RBCs by using banked RBCs as a model. Packed RBCs were stored up to 84 days at 1-6 degrees C in Adsol or in the experimental additive solution (Adsol fortified with glutamine, glycine, and N-acetyl-L-cysteine). Supplementing the conventional additive with GSH precursor amino acids improved RBC GSH synthesis and maintenance. The rise in RBC gamma-glutamylcysteine ligase activity was directly proportional to the GSH content and inversely proportional to extracellular homocysteine concentration, methemoglobin formation, and losses of the RBC proteins band 3, band 4.1, band 4.2, glyceraldehyde-3-phosphate dehydrogenase, and Duffy antigen (P < 0.01). Reduced loss of Duffy antigen correlated well with a decrease in chemokine RANTES (regulated upon activation, normal T-cell expressed, and secreted) concentration. We conclude that the concomitant loss of GSH and proteins in oxidatively stressed RBCs can compromise RBC scavenging function. Upregulating GSH synthesis can protect RBC scavenging (free radical and chemokine) function. These results have implications not only in a transfusion setting but also in conditions like diabetes and sickle cell anemia, in which RBCs are subjected to chronic/acute oxidant stresses.

Acetylcholinesterase↗
PubMed2000

Apical inflammatory root resorption: a correlative radiographic and histological assessment.

AIM: To assess the reliability of routine single radiographs in the diagnosis of inflammatory apical root resorption by correlating the radiographic and histological findings. METHODOLOGY: The material comprised serial and step serial sections of plastic-embedded root-apices with attached apical periodontitis lesions that were prepared for a previous study and the diagnostic radiographs. The histological sections of 114 specimens were analysed by light microscopy and categorized into three groups: (i) those without any resorption (0); (ii) those with moderate resorption (+); and (iii) those with severe resorption (+ +). The radiographs were examined by a separate examiner and graded with a similar categorization of no resorption (0); moderate (+); and severe (+ +) apical resorption. RESULTS: Radiographically, 19% of the teeth were diagnosed as having apical inflammatory root resorption, whereas histologically, 81% of the teeth revealed apical inflammatory root resorption. A correlative radiographic and histological assessment (n = 104) revealed a coincidence of diagnosis in 7% of the specimens and noncoincidence of diagnosis in 76% of the specimens. CONCLUSIONS: The results indicate that routine single radiographs are not sufficiently accurate or sensitive to consistently diagnose apical root resorptive defects developing as a consequence of apical periodontitis.

Dental Cementum↗
PubMed1999

Persistent periapical radiolucencies of root-filled human teeth, failed endodontic treatments, and periapical scars.

OBJECTIVE: This report describes 6 cases that demonstrate persistent periapical radiolucent lesions after conventional root canal treatment. STUDY DESIGN: Six teeth that had conventional root canal treatment or re-treatment with nonresolving periapical radiolucencies underwent periapical surgery. Biopsies were obtained and analyzed descriptively by correlative light and transmission electron microscopy for general features and microbial findings. RESULTS: Three findings were identified: periapical lesions with persisting infection in the apical root canal system (2 cases); a cyst (1 case); and periapical healing by scar tissue formation (2 cases). CONCLUSIONS: These results confirm previous observations that associated factors in the failure of endodontic treatment include persistent intraradicular infection and periapical cysts. In addition, unresolved periapical radiolucencies may occasionally be due to healing by scar tissue, which may be mistaken as a sign of failed endodontic treatment.

Adult↗
PubMed1999

Cholesterol as an aetiological agent in endodontic failures--a review.

Presence of cholesterol clefts in apical periodontitis lesions is a common histopathological observation. However, a potential aetiological association of cholesterol crystals to non-resolving apical periodontitis lesions after endodontic treatment has been suggested only recently. This article is an attempt to explain the biological basis for the inability of body cells to eliminate the local accumulation of cholesterol crystals, and to consolidate available clinical and experimental data in support of the view that massive accumulation of cholesterol crystals in inflamed periapical tissues can interfere with the periapical healing after conventional root canal treatment. As the irritating cholesterol crystals and certain other aetiological agents of failed endodontic treatment exist outside the root canal system, it is concluded that re-treatment alone, of such cases, is unlikely to resolve the factors that sustain the lesion. Apical surgery is indicated for successful management of such cases.

Animals↗
PubMed1998

Cholesterol crystals as an etiological factor in non-resolving chronic inflammation: an experimental study in guinea pigs.

The presence of cholesterol crystals has been suggested to be a factor interfering with periapical healing after conventional endodontic treatment. This investigation addresses the role of cholesterol crystals in impairing healing by studying the tissue response to the crystals, which were implanted in animals. Pure cholesterol crystals, prepared to a mushy form, were placed in Teflon cages that were implanted subcutaneously in guinea pigs. The cage-contents were retrieved after 2, 4 and 32 wk of implantation and processed for light and electron microscopy. The cages revealed delicate connective tissue that grew in through perforations on the cage-wall. The crystals were densely surrounded by numerous macrophages and multinucleated giant cells, forming a well-circumscribed area of tissue reaction. The cells, however, were unable to eliminate the crystals during an observation period of 8 months. The congregation of macrophages and giant cells, known to be major sources of apical inflammatory and bone resorptive mediators, suggest that accumulation of cholesterol crystals can be a factor in the failure of certain apical periodontitis lesions to resolve after conventional root-filling therapy.

Animals↗
PubMed1998

New perspectives on radicular cysts: do they heal?

During the past few decades several authors have perpetuated the notion that nearly half of all periapical lesions are radicular cysts. A few studies, based on meticulous serial sectioning of periapical lesions retrieved in toto, have shown that the actual incidence of radicular cyst is only about 15% of all periapical lesions. Equally significant was the discovery in 1980 and recent confirmation that radicular cysts exist in two structurally distinct classes namely, those containing cavities completely enclosed in epithelial lining (periapical true cysts) and those containing epithelium-lined cavities that are open to the root canals (periapical pocket cysts). From a clinical point of view a periapical pocket cyst may heal after conventional root canal therapy whereas an apical true cyst is less likely to be resolved without surgical intervention.

Humans↗
PubMed1995

Number and size spectra of non-myelinated axons of human premolars.

The aim of this study was to determine the number and size of apical non-myelinated (C) axons of healthy human premolars. The material was derived from a large collection of specimens prepared for a previous quantitative investigation on the myelinated (A) axons of human premolars. A total of 16 teeth (six maxillary first and five each of mandibular first and second premolars), removed from adolescents for orthodontic reasons, were used. Root discs of about 0.6 mm thickness were prepared at about 2 mm cervical to the root apex and processed for light and electron microscopy. The number of non-myelinated axons was determined by taking a total census of such fibres that could be identified and reconstructed by standardized composite electron micrographs from each root disc. The measurement of axons was done on a statistically representative sample of axons (n = 1810) using an electronic image processing unit. The 16 teeth had an average of 2000 +/- 1023 non-myelinated axons at the juxta-apical level (range 534-3912). The average diameter of the non-myelinated axons was found to be 0.5 +/- 0.4 microns (range 0.05-2.4 microns).

Axons↗
PubMed1995

Neural elements in dental pulp and dentin.

This article addresses the structural and quantitative aspects of human tooth innervation and briefly considers the functions and clinical relevance of tooth axons. The classification of peripheral axons, the pulpal and dentinal innervation, and the theories of dentin sensitivity are discussed. Quantitative studies on tooth innervation are also reviewed. Human premolars receive about 2300 axons at the root-apex of which about 13% are myelinated and 87% are nonmyelinated fibers. Most apical myelinated axons are fast-conducting A delta-fibers with their receptive fields located at the pulpal periphery and inner dentin. These fibers are probably activated by a hydrodynamic mechanism and conduct impulses that are perceived as a short well-localized sharp pain. Most C-fibers are slow-conducting fine sensory afferents with their receptive fields located in the pulp and transmit impulses that are experienced as dull poorly localized and lingering pain. In addition to the nociceptive alarm signaling, the intradental sensory axons may play a regulatory role in the maintenance and repair of the pulpodentinal complex.

Animals↗
PubMed1995

Tissue reaction to gutta-percha particles of various sizes when implanted subcutaneously in guinea pigs.

Tissue reaction to gutta-percha was studied using subcutaneously implanted Teflon cages in guinea pigs. Gutta-percha was tested in three forms: (i) as large particles prepared by dividing gutta-percha cones into pieces, (ii) as fine particles prepared by ball-milling of gutta-percha, and (iii) as particles produced by dissolving gutta-percha in rosin-chloroform. Gutta-percha evoked two distinct types of tissue response. The large pieces were well encapsulated and the surrounding tissue was free of inflammation. The fine particles evoked an intense, localized tissue response, characterized by the presence of macrophages and multinucleated giant cells. The rosin-chloroform treated gutta-percha induced a similar tissue reaction to that observed with the fine particles of gutta-percha. In addition, cell remnants were present in association with the material, which indicates an initial toxicity to rosin-chloroform treated gutta-percha. These results show that the size and surface character of gutta-percha can determine the type of tissue reaction to the material. The accumulation of macrophages around gutta-percha may be an important factor in the impairment of healing of periapical lesions when teeth are root filled with excess material.

Animals↗
PubMed1994

Isolation, cloning, and characterization of new chitinase stored in active form in chitin-lined venom reservoir.

A 52-kDa protein was purified from the venom gland of an endoparasitic wasp Chelonus sp. near curvimaculatus. The acidic protein (pl 4.8-5.0) was purified, and the NH2-terminal amino acid sequence was determined by direct protein sequencing. A vector-anchored primer and a degenerate primer derived from an 8-amino acid region of the NH2 terminus were used in anchored polymerase chain reaction to generate a probe for screening a cDNA library prepared from mRNA from the venom gland of this wasp. A positive clone of 1596 nucleotides was isolated, sequenced, and found to contain an open reading frame encoding a protein of 483 amino acids. The amino acid sequence encoded in the cDNA clone at the amino terminus was identical to the sequence determined from the purified 52-kDa protein. Comparison of the inferred protein sequence against all of the sequences in the GenBank data base revealed a high degree of similarity to a 62-kDa insect chitinase that is expressed at each molt for the purpose of digesting the chitinous insect cuticle. Two regions that are conserved in a group of chitinases from insects, bacteria and fungi, were also conserved in the wasp 52-kDa protein. The region between amino acid residues 382 and 464 in the 52-kDa wasp chitinase markedly differed in primary sequence from the corresponding region in the 62-kDa insect chitinase, although this region in both the proteins is predicted to have a similar secondary structure predominantly of coils and turns. This region may impart unique structural properties to the 52-kDa chitinase that enables it to exist in an active form in a chitin-lined reservoir without exerting an autotoxic effect to digest the cuticular storage reservoir. Chitinolytic activity occurring in the total venom gland extract was kinetically indistinguishable from that observed for the purified 52-kDa protein, including the substrate concentrations at which maximal velocity and substrate inhibition were reached. The kinetic properties of the 52-kDa wasp chitinase were quite distinct from Serratia marcescens chitinase for both catalytic rate and substrate inhibition.

Amino Acid Sequence↗
PubMed1993

Radicular cyst affecting a root-filled human tooth: a long-term post-treatment follow-up.

Apical periodontitis is caused primarily by microorganisms residing in the root canals of affected teeth. Nevertheless, there is convincing evidence implicating other independent factors that adversely affect the outcome of conventional root canal therapy. In this paper, morphological evidence is presented in support of the potential role of two endogenous factors that may interfere with post-endodontic healing of the periapex. The specimens consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted for a follow-up period of 44 months. The biopsy was processed for correlated light and electron microscopy. The lesion was characterized by the presence of a large central lumen lined by a stratified squamous epithelium. The most striking feature of the lesion was the presence of vast numbers of cholesterol crystals which congregated in the connective tissue surrounding the cyst cavity. Extensive light and electron microscopic investigation of the apical part of the root canal and the lesion failed to reveal the presence of microorganisms. These findings strongly suggest that intrinsic factors like the accumulation of certain tissue break-down products such as cholesterol crystals, and the cystic condition of the lesion itself, can adversely affect the healing process of the periapex following root canal therapy. Consequently, such apical lesions can remain refractory to conventional endodontic therapy for long periods of time.

Adult↗
PubMed1993

Innervation of root dentine in human premolars.

Based on autoradiographic studies it is generally held that the mammalian root dentine is only sparsely innervated. Previous electron microscopic studies on human teeth did not reveal nerve fibres beyond radicular predentine. It is the purpose of this communication to provide ultrastructural evidence for the presence of nerve fibres in apical root dentine of human premolars. Two healthy mandibular second premolars, removed due to orthodontic reasons, which formed part of a previous study, were utilized for this investigation. Root discs of about 0.6 mm thickness were removed at about 2 mm cervical to the root apex and processed for light and electron microscopy. Transmission electron microscopic examination revealed numerous nerve fibres along the pulp-predentine border and in patches of predentine. Distinct nerve fibres were observed in the inner mineralized portion of the radicular dentine. The axons existed in close association to the odontoblastic processes, but no synaptic contacts or junctional complexes could be observed.

Axons↗
PubMed1992

Number and size-spectra of myelinated nerve fibers of human premolars.

The primary objective of this study was to determine the number and size of myelinated nerve fibers at the subcervical, midroot and juxta-apical levels of human premolars. Sixty-seven healthy premolars extracted from adolescents were utilized. Root-discs were prepared from the three sites and processed for light and electron microscopy. The myelinated nerve fibers were counted from semithin sections using a sampling microscope. The measurements were taken from composite electron micrographs using an electronic image processing unit. A total of 1883 myelinated axons from seven mandibular second premolars was gauged. The 67 teeth had an average of 312 +/- 149 myelinated nerve fibers at the juxta-apical level (range 18 to 728). The contra- and ipsilateral differences in means among the four groups of premolars were not significant (P > 0.05). The number of nerves increased significantly (P < 0.05) toward midroot and subcervical (P < 0.001) levels in all groups. The average neural diameter was 3.5 + 1.0 microns at the juxta-apical level, and the between-teeth difference in mean was found to be significant (P < 0.01). There was no decline (P > 0.05) in the diameter of myelinated nerve fibers toward midroot and subcervical levels.

Adolescent↗
PubMed1992

Pathogenicity of Actinomyces israelii and Arachnia propionica: experimental infection in guinea pigs and phagocytosis and intracellular killing by human polymorphonuclear leukocytes in vitro.

Strains of Actinomyces israelii and Arachnia propionica, isolated from clinical cases of failed endodontic therapy, were examined for: (i) their ability to survive and establish themselves in the soft connective tissue that grew into subcutaneously implanted tissue cages in guinea pigs; (ii) cell-surface hydrophobicity; and (iii) phagocytosis and killing by human polymorphonuclear leukocytes (PMNs) under aerobic and anaerobic conditions. Bacteria were inoculated into the tissue cages in guinea pigs and the cage contents were retrieved after 1, 7, 14 and 21 d for culturing and light and electron microscopy. Both bacterial species showed substantial decline in the number of bacteria by day 7 after the inoculation. Thereafter, the A. israelii strain recovered and, by day 21, had started to increase in number. Light and electron microscopy revealed the formation of typical actinomycotic colonies. A. propionica, on the other hand, continued to decline in number during the entire period of experimental infection and did not form colonies. Both strains were hydrophobic, readily phagocytosed and were efficiently killed by human PMNs under aerobic and anaerobic conditions in vitro. These results suggest that the pathogenicity of A. israelii is due to its ability to establish characteristic cohesive colonies consisting of branching filamentous organisms that are enmeshed in an extracellular matrix. It seems that the organisms existing in such colonies can collectively evade destruction and elimination by host phagocytic cells, whereas in vitro suspensions of the bacteria are easily phagocytosed and efficiently killed by PMNs. With respect to A. propionica, further investigations are necessary to understand its pathogenicity.

Actinomyces↗
PubMed1990

Intraradicular bacteria and fungi in root-filled, asymptomatic human teeth with therapy-resistant periapical lesions: a long-term light and electron microscopic follow-up study.

Light and electron microscopy were used to analyze nine therapy-resistant and asymptomatic human periapical lesions, which were removed as block biopsies during surgical treatment of the affected teeth. The cases that required surgery represented about 10% of all of the cases which received endodontic treatment and root fillings during the period 1977 to 1984. These cases revealed periapical lesions when they were examined 4 to 10 yr after treatment. The biopsies were processed for correlated light and electron microscopy. Six of the nine biopsies revealed the presence of microorganisms in the apical root canal. Four contained one or more species of bacteria and two revealed yeasts. Of the four cases in which bacteria were found, only in one biopsy could they be found by light microscope. In the other three specimens, the bacterial presence could be confirmed only after repeated electron microscopic examination of the apical root canal by serial step-cutting technique. Among the three cases in which no microorganisms could be encountered, one showed histopathological features of a foreign body giant cell granuloma. These findings suggest that in the majority of root-filled human teeth with therapy-resistant periapical lesions, microorganisms may persist and may play a significant role in endodontic treatment failures. In certain instances such lesions may also be sustained by foreign body giant cell type of tissue responses at the periapex of root-filled teeth.

Adult↗
PubMed1990

Therapy-resistant foreign body giant cell granuloma at the periapex of a root-filled human tooth.

Although the primary etiological factor of periapical lesions is microbial, there are other independent factors that can adversely affect the outcome of endodontic treatment. In this communication, we present morphological evidence in support of the role of a foreign body reaction of periapical tissue to root-filling materials. The specimen consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted after a decade of postendodontic follow-up. The biopsy was processed for correlated light and electron microscopy and was analyzed by various microtechniques. The unique feature of the lesion was the presence of vast numbers of large multinucleated cells and their cytoplasmic inclusion bodies. Morphologically, these multinucleated cells resembled foreign body giant cells. They contained characteristic birefringent cytoplasmic inclusions which on electron-probe X-ray microanalysis consistently revealed the presence of magnesium and silicon. The magnesium and silicon are presumably the remnants of a root-filling excess which protruded into the periapex and had been resorbed during the follow-up period. These observations strongly suggest that in the absence of microbial factors, root-filling materials which contain irritating substances can evoke a foreign body reaction at the periapex, leading to the development of asymptomatic periapical lesions that may remain refractory to endodontic therapy for long periods of time.

Biopsy↗