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Biomedical subjects

N A Rao

Publications and source records attributed to N A Rao.

At least 19 recordsLinked to original sources
PubMed1992

A novel intermediate in the interaction of thiosemicarbazide with sheep liver serine hydroxymethyltransferase.

An unusual intermediate bound to the enzyme was detected in the interaction of thiosemicarbazide with sheep liver serine hydroxymethyltransferase. This intermediate had absorbance maxima at 464 and 440 nm. Such spectra are characteristic of resonance stabilized intermediates detected in the interaction of substrates and quasi-substrates with pyridoxal phosphate enzymes. An intermediate of this kind has not been detected in the interaction of thiosemicarbazide with other pyridoxal phosphate enzymes. This intermediate was generated slowly (t 1/2 = 4 min) following the addition of thiosemicarbazide (200 microM) to sheep liver serine hydroxymethyltransferase (5 microM). It was bound to the enzyme as evidenced by circular dichroic bands at 464 and 440 nm and the inability to be removed upon Centricon filtration. The kinetics of interaction revealed that thiosemicarbazide was a slow binding reversible inhibitor in this phase with a k(on) of 11 M-1 s-1 and a k(off) of 5 x 10(-4) s-1. The intermediate was converted very slowly (k = 4 x 10(-5) s-1) to the final products, namely the apoenzyme and the thiosemicarbazone of pyridoxal phosphate. A minimal kinetic mechanism involving the initial conversion to the intermediate absorbing at longer wavelengths and the conversion of this intermediate to the final product, as well as, the formation of pyridoxal phosphate-thiosemicarbazone directly by an alternate pathway is proposed.

Animals↗
PubMed1992

Arginine residues involved in binding of tetrahydrofolate to sheep liver serine hydroxymethyltransferase.

The arginine residue(s) necessary for tetrahydrofolate binding to sheep liver serine hydroxymethyltransferase were located by phenylglyoxal modification. The incorporation of [7-14C]phenylglyoxal indicated that 2 arginine residues were modified per subunit of the enzyme and the modification of these residues was prevented by tetrahydrofolate. In order to locate the sites of phenylglyoxal modification, the enzyme was reacted in the presence and absence of tetrahydrofolate using unlabeled and radioactive phenylglyoxal, respectively. The labeled phenylglyoxal-treated enzyme was digested with trypsin, and the radiolabeled peptides were purified by high-performance liquid chromatography on reversed-phase columns. Sequencing the tryptic peptides indicated that Arg-269 and Arg-462 were the sites of phenylglyoxal modification. Neither a spectrally discernible 495-nm intermediate (characteristic of the native enzyme when substrates are added) nor its enhancement by the addition of tetrahydrofolate, was observed with the phenylglyoxal-modified enzyme. There was no enhancement of the rate of the exchange of the alpha-proton of glycine upon addition of tetrahydrofolate to the modified enzyme as was observed with the native enzyme. These results demonstrate the requirement of specific arginine residues for the interaction of tetrahydrofolate with sheep liver serine hydroxymethyltransferase.

Amino Acid Sequence↗
PubMed1992

Postnatal development of the ciliary body and pars plana. A morphometric study in childhood.

The ciliary body of the human eye serves many vital functions and provides important access to the posterior segment of the globe in vitreoretinal surgery. Although embryogenesis and prenatal development of the ciliary body have been well documented, continuing development of the ciliary body during early childhood has not been studied extensively. We determined the lengths of the ciliary body and pars plana in 76 normal eyes of subjects who ranged in age from 1 week to 6 years. The ciliary body was found to be of substantial length soon after birth; it measured a mean of 3.06 mm nasally and 3.31 mm temporally. Three quarters of the final length of the ciliary body at adulthood was achieved by age 24 months. The growth of the ciliary body is discussed in relation to the growth of the eye.

Age Factors↗
PubMed1992

Anti-inflammatory effects of vitamin E on experimental lens-induced uveitis.

The anti-phlogistic effect of dietary vitamin E supplementation on the acute inflammation observed in experimental lens-induced uveitis in Brown Norway rats was studied. The effects of vitamin E were examined using histopathologic parameters as well as by measuring the levels of arachidonic acid metabolites. Histologic examination of the eyes revealed that the vitamin E-deficient animals had the most severe destruction of the retina, while those animals receiving the vitamin E-supplemented diet exhibited the best preservation of the retinal architecture. Levels of arachidonic acid metabolites, as determined by radioimmunoassay, were significantly higher in vitamin E deficient rats as compared with rats on a normal diet.

Animals↗
PubMed1992

Detection of retinal lipid hydroperoxides in experimental uveitis.

In our on-going studies of experimental uveitis, we previously obtained a preliminary indication of phagocyte-mediated retinal lipid peroxidation by measuring conjugated dienes (CD), thiobarbituric acid reactive substances (TBARS) and fluorescent chromolipids. Using gas chromatography/mass spectrometry (GC/MS), the current study detected hydroperoxide-derived 10-, 11-, 13-, 14-, and 17-hydroxydocosahexaenoic acid (HDHE) in retinal membranes. Docosahexaenoic acid (22:6) is the major polyunsaturated fatty acid (PUFA) in photoreceptor membranes. Hydroperoxides from other retinal PUFA were found also. Arachidonic acid (20:4) yielded 8-, 9-, 11-, 12-hydroxyeicosatetraenoic acid (HETE) as major products. Since 12-HETE could also arise from lipoxygenase catalyzed oxygenation of free 20:4, the source of 12-HETE could be both peroxidative and lipoxygenase pathways. Concomitantly, peroxidative loss of 22:6 and accumulation of 20:4 were also noted. At the peak of inflammation, loss of 22:6 was close to 50% of the original amount in the control retinas. In the same time period, 20:4 increased more than two-fold. The present data suggest that the oxygen radicals derived from phagocytes initiate the retinal lipid peroxidation, and the resultant formation of hydroperoxides, oxidative loss of 22:6 and accumulation of 20:4 appear to serve as amplification factors in subsequent biochemical events, such as chemotaxis of PMNs and activation of cyclooxygenase.

Animals↗
PubMed1992

Pars plana vitrectomy for intraocular inflammation-related cystoid macular edema unresponsive to corticosteroids. A preliminary study.

PURPOSE: To determine the role of pars plana vitrectomy in patients with intraocular inflammation-related cystoid macular edema that is unresponsive to corticosteroids. METHODS: Eleven eyes of nine patients underwent a standard three-port pars plana vitrectomy. The primary indication was intraocular inflammation-related cystoid macular edema that was unresponsive to oral, sub-Tenon's, and topical corticosteroids. Preoperative follow-up ranged from 20 months to 144 months (average, 70 months). Postoperative follow-up ranged from 3 months to 108 months (average, 21 months). RESULTS: Seven eyes (64%) improved 4 or more lines of Snellen visual acuity within 4 weeks. Two eyes (18%) remained unchanged and 2 eyes (18%) worsened. Cystoid macular edema improved by clinical examination and fluorescein angiography in 9 eyes (82%) and by clinical examination alone in 2 eyes (18%). No intraoperative complications were noted. Postoperative complications consisted of cataract formation in 1 eye (9%), glaucoma in 2 eyes (18%), and epiretinal membrane formation in 1 eye (9%). CONCLUSION: Pars plana vitrectomy may have a role in the treatment of intraocular inflammation-related cystoid macular edema that fails to respond to corticosteroids. The subgroup of patients who benefit most remains to be identified.

Administration, Topical↗
PubMed1992

Treatment of ocular adnexal Kaposi's sarcoma in acquired immune deficiency syndrome.

PURPOSE: To determine the most effective, safe, and cost-efficient treatment for ocular adnexal Kaposi's sarcoma in the acquired immune deficiency syndrome. METHODS: Eighty-two patients with ocular adnexal Kaposi's sarcoma related to the acquired immune deficiency syndrome were examined, and 25 were selected to participate in a 3-year study that treated the ocular lesions based on stage of development and location. RESULTS: Of 14 patients with bulbar conjunctival Kaposi's sarcoma treated with surgical excision, 2 stage III lesions recurred during a follow-up that ranged from 8 to 31 months; no stage I or stage II lesion recurred. Of 7 patients with eyelid Kaposi's sarcoma treated with cryotherapy, 2 stage III lesions recurred during a follow-up that ranged from 9 to 24 months; no stage I or stage II lesion recurred. Four patients with stage III Kaposi's sarcoma of the bulbar conjunctiva were treated with fluorescein angiography-based surgical excision. None of these lesions recurred during a follow-up that ranged from 4 to 8 months. CONCLUSION: A treatment regimen for ocular adnexal Kaposi's sarcoma related to the acquired immune deficiency syndrome based on tumor stage and location, using cryotherapy and surgical excision with or without fluorescein angiography, is effective, safe, and cost-efficient.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Antigen-specific suppressor cells in experimental autoimmune uveitis.

Anti-I-A antibodies, administered in vivo at the time of S-antigen injection, suppress development of experimental autoimmune uveitis (EAU) in Lewis rats. While the effects of anti-I-A are profound, the exact mechanism for this suppression is unknown. We attempted adoptive transfer of this form of suppression by injecting lymphocytes from anti-I-A-treated animals into syngeneic recipients which were later injected with S-antigen. Histologically, globes of 75% of the anti-I-A-treated animals showed no inflammation while 25% of these animals developed mild uveitis. In the group of animals which were injected with S-antigen and also received spleen cells from anti-I-A-treated rats, only 1 showed mild uveitis while the remaining 7 had no inflammation. The animals undergoing adoptive transfer of spleen cells and which were primed with an irrelevant antigen, readily developed uveitis. Suppression of S-antigen-induced EAU was abrogated by pretreatment of donor animals with cyclophosphamide. In vitro studies revealed that spleen cells of S-antigen-primed, anti-I-A-treated donors specifically suppressed lymphocyte responses to S-antigen. These in vivo and in vitro results suggest that generation of antigen-specific suppressor cells play a role in the anti-I-A immunotherapy of EAU.

Animals↗
PubMed1992

Lipid peroxidation in experimental uveitis: sequential studies.

Previously we have detected the occurrence of retinal lipid peroxidation initiated by phagocyte-derived oxygen radicals in experimental autoimmune uveitis (EAU). In the current studies, the confirmation of inflammation-mediated lipid peroxidation was proceeded further to include measurement of multiple parameters, including conjugated dienes, ketodienes, thiobarbituric acid reactive substances and fluorescent chromolipids. The assay for myeloperoxidase, a measure for the number of polymorphonuclear leukocytes in the inflammatory sites was also carried out. The levels of all these parameters were followed through the course of EAU development. The sequential evaluation of histologic changes using both light and electron microscopy was also carried out and the results were correlated with lipid peroxidation indices. These data suggest that the retinal lipid peroxidation plays a causative role in the subsequent retinal degeneration.

Animals↗
PubMed1992

Ultrastructural localization of hydrogen peroxide in experimental autoimmune uveitis.

One of the most prominent features of S-antigen induced uveitis is the massive infiltration of polymorphonuclear leukocytes (PMNs) and mononuclear cells in the ocular tissues and fluids. These inflammatory cells generate reactive oxygen metabolites as microbicidal agents and release these oxidants into the surrounding tissues. Using the cerium perhydroxide method, we have localized subcellular hydrogen peroxide in various inflamed ocular tissues. Most notably, the positive electron-dense granules were seen in the plasma membranes of PMNs that were infiltrating in the retina and uvea. These deposits were noted also in PMNs located within the extravascular spaces. For the intravascular PMNs, the positive reaction products were seen in much lower concentrations. A direct demonstration of substantial concentrations of hydrogen peroxide in experimental autoimmune uveitis, therefore, suggests the possibility that this reactive metabolite is an inflammatory mediator in this condition.

Animals↗
PubMed1992

Opportunistic intraocular infections in AIDS.

In conclusion, this clinicopathologic study has shown that CMV ocular infection is present in about 16% of terminal AIDS patients. The treatment of CMV retinitis reduces the number of CMV-infected nonocular organs and may also lessen the severity and control the spread of concurrent nonocular infection, both of which may prolong survival in AIDS patients. Other opportunistic infections, involving primarily the choroid, were also seen in a number of patients, some of whom had concurrent intraocular infections with CMV and P carinii, M avium-intracellulare, C neoformans. In addition, all of these choroidal infections were components of disseminated infection, underscoring the increasingly important role of the ophthalmologist in the diagnosis and treatment of disseminated opportunistic infections in AIDS.

AIDS-Related Opportunistic Infections↗