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Biomedical subjects

R Anand

Publications and source records attributed to R Anand.

At least 109 records · Page 6Linked to original sources
PubMed1995

Serum beta 2-microglobulin as a tumour marker in space occupying lesions of central nervous system.

We prospectively evaluated serum concentrations of beta 2-microglobulin in twenty healthy controls and fifty cases of CT scan proven and operated intracranial tumours. The later group comprised of twenty subjects of benign and thirty cases of malignant tumours respectively. Mean serum beta 2-microglobulin in healthy subjects was 1.80 +/- 0.5 mg/ litre, none had value of more than 3.0 mg/ltr. On the contrary 75% of benign and 63.3% of malignant tumour cases had statistically significant rise in the beta 2-microglobulin. Elevated serum level of beta 2-microglobulin may prove to be a reliable tumour marker.

Adult↗
PubMed1995

Cranial sonography in bacterial meningitis.

Cranial ultrasonography was performed on 61 infants with acute bacterial meningitis (ABM). Thirty nine, infants (64%) had acute meningitis with no clinical evidence of complications (Group-I) and 22 infants (36%) had clinical evidence of complications of ABM (Group-II). Cranial ultrasound was normal in 20 infants (32.8%). The spectrum of sonographic abnormalities included echogenic sulci (60.6%), sulcal separation (49.8%), abnormal parenchymal echoes (42.6%), ventriculomegaly (34.4%), ventriculitis (19.7%), abscess (3.3%), subdural empyema (1.63%) and hemorrhagic infarct (1.63%). Various abnormal findings were seen in all 22 patients of Group II (100%) and in only 19 out of 39 patients in Group I (31.9%). Cranial sonography was comparable to CT scan done in 10 cases of Group II. Our study suggests that ultrasound is a quick, reliable and effective diagnostic tool in diagnosis and management of infants with or without evidence of complications.

Acute Disease↗
PubMed1994

Recent translocation of variable and diversity segments of the human immunoglobulin heavy chain from chromosome 14 to chromosomes 15 and 16.

We studied the organization and origin of three orphon regions, VH-F, D5-a, and D5-b, of the human immunoglobulin heavy-chain gene using yeast artificial chromosomes. VH-F and two D5 regions were mapped to chromosome bands 16p11 and 15q11-q12, respectively, by using human/rodent somatic cell hybrids and fluorescence in situ hybridization. No D5 segments were found on chromosome 14, in contradiction to previous reports. The VH-F region consists of 7 VH segments and encompasses 160 kb of DNA. A cluster of VH segments homologous to the VH-F region orphons was found in the region 245-430 kb (V2-26 to V3-11) upstream of the JH cluster on chromosome 14. Comparison of VH sequences between the VH-F and the chromosome 14 loci indicates that the translocation of the VH-F region took place, at the earliest, 20 x 10(6) years ago. The D5-a and D5-b regions were obtained in two independent contigs. The former contains only D segments in 140 kb of DNA, while the latter carries 3 VH segments downstream of D segments in 110 kb of DNA. V54, one of these VH orphon segments, is about 95% homologous to V1-18, which is located within the putative ancestor of the VH-F region on chromosome 14. Furthermore, the region detected by two DNA probes flanking the V54 segment was found only in the proximity of V1-18 within the 0.8-Mb VH region on chromosome 14. These results suggest that the two orphon loci on chromosomes 15 and 16 may have been translocated simultaneously.

Animals↗
PubMed1994

Capacity of simian virus 40 T antigen to induce self-tolerance but not immunological privilege in the anterior chamber of the eye.

Transgenic mice bearing the simian virus 40 (SV40) large T oncogene developed progressively growing intraocular tumors and displayed characteristics of immunological tolerance to SV40 T antigen. Transgenic mice failed to mount CTL responses to SV40 T antigen-bearing tumor cell lines derived from the transgenic intraocular tumors. Spleen cells from transgenic hosts were able to prevent the in vivo and in vitro generation of CTL responses by lymphocytes from normal syngeneic FVB/N mice. Adoptive transfer of spleen cells from tolerant transgenic donors temporarily inhibited the immunological rejection of SV40 T antigen-positive tumor cells transplanted to normal syngeneic FVB/N recipients. Thus, introduction of SV40 transforming sequences into the mouse germline induced tolerance to SV40 T antigen. However, in normal FVB/N mice, SV40 T antigen-bearing tumor cells failed to experience immune privilege in the anterior chamber and did not elicit systemic down-regulation of delayed-type hypersensitivity responses that characteristically occur when antigens are introduced into the anterior chamber. The results indicate that within the anterior chamber of the eye, SV40 T antigen-bearing cells are perceived by the host's immune system much differently than are other categories of antigen. Thus, SV40 T antigen effectively induces self-immunological tolerance when its gene is introduced into the host's germline but fails to experience immunological privilege in the anterior chamber of the eye in normal hosts.

Animals↗
PubMed1994

Intravitreal drug administration with depot devices.

The administration of medications by depot devices is a rapidly developing technology in ocular therapeutics. Sustained delivery of ophthalmic medications is a novel approach to treating chronic ocular conditions where systemic therapy may be accompanied by unwanted side effects and where repeated intravitreal drug administration carries significant risks. Eye diseases particularly suitable to this form of treatment include proliferative vitreoretinopathy and chronic intraocular infections such as cytomegalovirus retinitis. Liposomes, which have been extensively investigated over the last two decades, have not found any acceptable clinical application. Nonerodible polymers such as the ethylvinyl acetate/polyvinyl alcohol cup are in advanced phase III trials. The current status of microsphere development in the treatment of posterior segment disease is examined in the review and studies investigating the potential uses of the osmotic minipump are mentioned.

Drug Administration Routes↗
PubMed1994

Certainty and uncertainty in science: the subjectivistic concept of probability in physiology and medicine.

Most physiological scientists have restricted understanding of probability as relative frequency in a large collection (for example, of atoms). Most appropriate for the relatively circumscribed problems of the physical sciences, this understanding of probability as a physical property has conveyed the widespread impression that the "proper" statistical "method" can eliminate uncertainty by determining the "correct" frequency or frequency distribution. However, many relatively recent developments in the theory of probability and decision making deny such exalted statistical ability. Proponents of Bayes's subjectivist theory, for example, assert that probability is "degree of belief," a more tentative idea than relative frequency or physical probability, even though degree of belief assessment may utilize frequency information. In the subjectivist view, probability and statistics are means of expressing a consistent opinion (a probability) to handle uncertainty but never means to eliminate it. In the physiological sciences the contrast between the two views is critical, because problems dealt with are generally more complex than those of physics, requiring judgments and decisions. We illustrate this in testing the efficacy of penicillin by showing how the physical probability method of "hypothesis testing" may contribute to the erroneous idea that science consists of "verified truths" or "conclusive evidence" and how this impression is avoided in subjectivist probability analysis.

Bayes Theorem↗
PubMed1994

Rejection of intraocular tumors from transgenic mice by tumor-infiltrating lymphocytes.

The present study examined the role of tumor infiltrating lymphocytes (TIL) in the rejection of intraocular tumors from SV40 transgenic mice. Tumor cells from an intraocular tumor arising in an SV40 transgenic FVB/N mouse were transplanted into the eyes of syngeneic FVB/N mice and the TIL isolated. TIL were assessed for direct cytolytic activity in vitro. TIL were also transferred passively to immunosuppressed FVB/N mice to determine if they could mediate intraocular tumor rejection. The role of CD4+ and CD8+ T cells in intraocular tumor rejection was evaluated by depleting the respective cell populations in FVB/N hosts prior to intraocular tumor challenge. The results showed that intraocular tumors undergoing rejection in immunocompetent syngeneic hosts became infiltrated with T cells, with the CD8+ subset predominating at the time of rejection. By contrast, athymic nude mice did not reject the intraocular tumors nor did the tumors become infiltrated with TIL. TIL displayed direct, tumor-specific cytolytic activity immediately after isolation from the tumor-containing eyes. FVB/N hosts depleted of CD4+ T cells were unable to reject their intraocular tumors. In vivo depletion of CD8+ T cells delayed, but did not prevent tumor rejection. Adoptively transferred TIL mediated swift rejection of intraocular tumors in immunoincompetent recipients. Recipients of TIL, but not recipients of normal spleen cells, acquired significant tumor-specific CTL activity that was demonstrable in vitro. The results strongly suggest, but do not prove, that TIL mediate rejection of intraocular tumors from transgenic mice by direct cytolysis. Although CD4+ T cells are necessary for tumor rejection and are capable of direct cytolysis, the predominant effector cells are CD8+ CTL.

Animals↗
PubMed1994

Homomers of alpha 8 and alpha 7 subunits of nicotinic receptors exhibit similar channel but contrasting binding site properties.

alpha 8 subunits of alpha-bungarotoxin-sensitive chick neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes from cRNA are shown to form homomeric, acetylcholine-gated, rapidly desensitizing, inwardly rectifying, Ca(2+)-permeable cation channels similar to those of alpha 7 homomers. alpha 8 forms oligomers of several sizes, of which < 14% are expressed on the oocyte surface, which is less efficient than for alpha 7 homomers. alpha 8 homomers are more sensitive to agonists but less sensitive to antagonists than are alpha 7 homomers, and some agonists for alpha 8 homomers are partial agonists or antagonists for alpha 7 homomers. The pharmacological properties of homomers of alpha 8 and alpha 7 subunits generally reflect those of native alpha 8 and alpha 7 receptors.

Animals↗
PubMed1994

Nicotine-induced increase in neuronal nicotinic receptors results from a decrease in the rate of receptor turnover.

Chronic nicotine exposure in tobacco smokers or experimental animals is known to cause an increase in brain binding sites for nicotine. It has been proposed that this is an adaptive response of neurons to accumulation of chronically desensitized receptors. Acetylcholine receptors of the same (alpha 4)2(beta 2)3 subunit composition as the predominant subtype of brain nicotinic receptors with high affinity for nicotine have been expressed in Xenopus oocytes and in a permanently transfected fibroblast cell line. Chronic exposure of these cells to nicotine or another agonist is shown to result in an increase in receptor amount, indicating that nicotine-induced up-regulation reflects properties of the alpha 4 beta 2 receptor protein, rather than being an adaptive response unique to the neurons in which these receptors are normally expressed. The nicotine concentration dependence, time course, and extent of receptor up-regulation are similar to those reported for receptors in brain. Up-regulation does not appear to require ion flow through the ion channel, because it is also caused by mecamylamine, which blocks the ion channel, and because after prolonged exposure to nicotine most receptors become permanently unable to open their channels in response to nicotine binding. The noncompetitive antagonist mecamylamine blocks open channels more effectively, and so it is more effective at blocking channels in the presence of nicotine. Mecamylamine and nicotine are also synergistic in causing receptor up-regulation. Ligands that cause up-regulation appear to induce a conformation of the receptor that is removed from the surface and degraded more slowly.

Animals↗
PubMed1994

Activity of certain fractions of Tribulus terrestris fruits against experimentally induced urolithiasis in rats.

An ethanolic extract of the fruits of T. terrestris showed significant dose dependent protection against uroliths induced by glass bead implantation in albino rats. On subsequent fractionation of the ethanol extract, maximum activity was localised in the 10% aqueous methanol fraction. It provided significant protection against deposition of calculogenic material around the glass bead. It also protected leucocytosis and elevation in serum urea levels. Further, fractionation lead to decreased activity. This could be either due to loss of active compounds during fractionation, or the antiurolithiatic activity of T. terrestris being a combined effect of several constituents present in the methanolic fraction.

Animals↗
PubMed1994

A YAC contig encompassing the Treacher Collins syndrome critical region at 5q31.3-32.

Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate. Previous studies have localized the TCOF1 locus between D5S519 (proximal) and SPARC (distal), a region of 22 centirays as estimated by radiation hybrid mapping. In the current investigation we have created a contig across the TCOF1 critical region, using YAC clones. Isolation of a novel short tandem repeat polymorphism corresponding to the end of one of the YACs has allowed us to reduce the size of the critical region to approximately 840 kb, which has been covered with three nonchimeric YACs. Restriction mapping has revealed that the region contains a high density of clustered rare-cutter restriction sites, suggesting that it may contain a number of different genes. The results of the present investigation have further allowed us to confirm that the RPS14 locus lies proximal to the critical region and can thereby be excluded from a role in the pathogenesis of TCOF1, while ANX6 lies within the TCOF1 critical region and remains a potential candidate for the mutated gene.

Annexin A6↗
PubMed1994

Characterization of intraocular tumors arising in transgenic mice.

PURPOSE: To characterize intraocular tumors that arise by in situ transformation in the choroid-retinal pigment epithelium (RPE) in transgenic mice bearing the SV40 oncogene under the control of the mouse tyrosinase promoter. METHODS: Tumors from TySV40 transgenic mice were characterized in vivo and in vitro by immunohistology, compound microscopy, and electron microscopy. Tumor cell lines were established and characterized for growth and metastatic potential in the eyes of nude mice. RESULTS: On light microscopy, ocular tumors were predominantly epithelioid, although occasional clusters of spindle cells were also present. Transmission electron microscopy revealed the presence of numerous basal infoldings and abundant multilaminated basement membranes on the ocular tumors. Tumors stained with antibodies to melanoma-associated antigens, gangliosides GD2 and GD3, and the SV40 T antigen. Radiolabeled transgenic tumor cells preferentially localized in the liver after intravenous injection in normal mice. Intracamerally transplanted transgenic tumors metastasized from the eyes to the livers of nude mice. CONCLUSIONS: In TySV40 transgenic mice, intraocular tumors develop that arise at the choroid-RPE interface, and they display morphologic and ultrastructural features consistent with RPE carcinomas. However, the transgenic tumors express melanoma-associated antigens and a propensity to metastasize to the liver, two features characteristic of uveal melanomas. The TySV40 transgenic murine tumors represent potentially useful tools for investigations into the biology and metastasis of intraocular neoplasms.

Animals↗
PubMed1994

Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes.

The alpha-bungarotoxin-binding acetylcholine receptors from the human neuroblastoma cell line SH-SY5Y were found to cross-react with some monoclonal antibodies to alpha 7 subunits of nicotinic acetylcholine receptors from chicken brain. The human alpha 7 subunit cDNA from SH-SY5Y was cloned, revealing 94% amino acid sequence identity to rat alpha 7 subunits and 92% identity to chicken alpha 7 subunits. Native human alpha 7 receptors showed affinities for some ligands similar to those previously observed with native chicken alpha 7 receptors, but for other ligands there were large species-specific differences in binding affinity. These results paralleled properties of alpha 7 homomers expressed in Xenopus oocytes. Human alpha 7 homomers exhibited rapidly desensitizing, inwardly rectifying, agonist-induced, cation currents that triggered Ca(2+)-sensitive Cl- channels in the oocytes. A change in efficacy from partial agonist for chicken alpha 7 homomers to full agonist for human alpha 7 homomers was exhibited by 1,1-dimethyl-4-phenylpiperazinium. This result reveals a large species-specific pharmacological difference, despite small differences in alpha 7 sequences. This is important for understanding the effects of these drugs in humans and for identifying amino acids that may contribute to the acetylcholine binding site, for analysis by in vitro mutagenesis. These results also characterize properties of native alpha 7 receptors and alpha 7 homomers that will provide criteria for functional properties expected of structural subunits, when these can be identified, cloned, and coexpressed with alpha 7 subunits.

Amino Acid Sequence↗
PubMed1993

Reporter epitopes: a novel approach to examine transmembrane topology of integral membrane proteins applied to the alpha 1 subunit of the nicotinic acetylcholine receptor.

The development of a novel immunological method called the "reporter epitope" technique to probe the transmembrane topology of integral membrane proteins is described. Using this method, synthetic oligonucleotides encoding epitopes (reporter epitopes) for well characterized monoclonal antibodies (reporter mAbs) were inserted at various locations within the human acetylcholine receptor (AChR) alpha 1 subunit cDNA. The engineered subunits were then expressed along with Torpedo beta 1, gamma, and delta subunits in Xenopus oocytes, and the transmembrane location of the site of insertion was determined by the binding of the 125I-labeled reporter mAbs to whole oocytes. Control reporter epitope insertions at alpha 347 exhibited the expected cytoplasmic location. Reporter epitopes inserted at alpha 429 are located on the extracellular surface. Reporter epitopes that are 16-48 amino acids long do not disrupt assembly or function of hybrid AChRs when inserted near the carboxy terminus (at alpha 429) or in the large cytoplasmic domain (at alpha 347). However, because two reporter epitopes inserted at alpha 157 obliterated subunit assembly and a third reporter epitope when tolerated at this position was inaccessible from the extracellular surface and only marginally accessible after detergent solubilization of the AChRs, a definitive transmembrane location for this region was not possible. Nonetheless, the use of this approach has been successfully demonstrated, and it may be generally applicable to the study of other integral membrane proteins.

Amino Acid Sequence↗
PubMed1993

Homomeric and native alpha 7 acetylcholine receptors exhibit remarkably similar but non-identical pharmacological properties, suggesting that the native receptor is a heteromeric protein complex.

Sucrose gradient analysis of chick acetylcholine receptor (AChR) alpha 7 subunits expressed in oocytes indicates that they form pharmacologically active homomers of the same size as native alpha 7 AChRs, a size compatible with a complex of five alpha 7 subunits. By immunoisolating the [35S]methionine-labeled alpha 7 subunits we also demonstrate that they do not appear to assemble with endogenous Xenopus AChR subunits. Pharmacological characterization of detergent-solubilized brain alpha 7 AChRs and alpha 7 homomers reveals that they have similar but nonidentical properties. The pharmacological difference is most accentuated for cytisine (approximately 50-fold). Thus, at least in E18 chicken brain, most or all of the native alpha 7 AChRs do not appear to be homomeric.

Animals↗
PubMed1993

N-terminal peptide fragments of lipocortin-1 inhibit A549 cell growth and block EGF-induced stimulation of proliferation.

Lipocortin-1 mediates growth inhibition of glucocorticoids in A549 cells by suppressing the release of PGE2 necessary for their proliferation. We now show that 2 peptide fragments derived from the N-terminal portion of lipocortin-1 corresponding to amino-acids 13-25 and 21-33 also inhibited A549 cell growth and suppressed release of PGE2, whereas peptides 1-12 and 13-25 (Phe21; in which the tyrosine at position 21 was replaced by a phenylalanine residue) were inactive. Similarly, peptide 21-33 (Phe21) and a scrambled sequence of 13-25 failed to inhibit cell growth. Moreover, the EGF-induced stimulation of cell proliferation and PGE2 release in these cells was blocked by peptides 13-25 and 21-33, and also by peptides 1-12, 13-25 (Phe21) and 21-33 (Phe21), but not by a scrambled sequence of peptide 13-25.

Adenocarcinoma↗