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Biomedical subjects

N Agarwal

Publications and source records attributed to N Agarwal.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effective control of cisplatin induced emesis by combination drug regimen.

Thirty two cycles of chemotherapy were administered to sixteen patient containing 50-75 mg/msq. of cisplatin. For antiemetic prophylaxis, each patient received metoclopramide alone in the first cycle and a combination of metoclopramide + dexamethasone + lyrazepam in the next cycle. Effective control of emesis was achieved in 81% cycles on the combination antiemetic regime as compared to 19% on MCP alone. There was no statistical difference in the relief of nausea by the two regimens.

Adult↗
PubMed1994

Osmoregulatory alterations in myo-inositol uptake by bovine lens epithelial cells. Part 2: Cloning of a 626 bp cDNA portion of a Na+/myo-inositol cotransporter, an osmotic shock protein.

PURPOSE: Bovine lens epithelial cells (BLECs) accumulate osmotically active organic solutes (i.e., osmolytes) including myo-inositol when exposed to hypertonic stress (osmotic shock). In hypertonic medium, the increase in myo-inositol accumulation is attributed to an elevation in activity of Na+/myo-inositol cotransporter(s). The authors report the nature of the hypertonicity-induced enhancement of myo-inositol uptake in cultured BLECs by amplifying a 626 bp cDNA from lens cell RNA. METHODS: A portion of cDNA encoding a Na+/myo-inositol cotransporter was isolated from cultured BLECs using PCR primers designed from an established myo-inositol transporter from Madin-Darby canine kidney (MDCK) cells. Using the reverse transcription-polymerase chain reaction, a 626 bp PCR product was amplified. Its nucleic acid sequence was determined by the dideoxynucleotide method using Sequenase kit. Na+/Myo-inositol cotransporter mRNA expression in the cultured cells was demonstrated under physiological and hypertonic conditions by northern analysis of poly(A)+ RNA using the lens cell 626 bp cDNA as probe. RESULTS: The BLEC cDNA sequence was 92% identical with the Na+/myo-inositol cotransporter of MDCK cells. Myo-inositol transporter mRNA was demonstrated in cultured BLECs and was significantly induced by hypertonic stress. CONCLUSIONS: These data suggest that cultured bovine lens epithelial cell adaptation to hypertonicity involves intracellular accumulation of small organic osmolytes (i.e., myo-inositol) through elevation of myo-inositol uptake activity resulting from the upregulation of transporter mRNA.

Amino Acid Sequence↗
PubMed1993

Blood transfusion increases the risk of infection after trauma.

To determine whether blood transfusion influences infection after trauma, we analyzed data on 5366 consecutive patients hospitalized for more than 2 days at eight hospitals over a 2-year period. The incidence of infection was significantly related to the mechanism of injury: penetrating injuries, 8.9%; blunt injuries, 12.9%; and low falls, 21.4%. Stepwise logistic regression analyses of infection using the variables age, sex, respiration rate in the emergency department, Glasgow Coma Scale in the emergency department, Injury Severity Score, shock (systolic blood pressure < 90 mm Hg on admission to the emergency department), and log of total amount of blood transfused during hospitalization showed that amount of blood received and Injury Severity Score were the only two variables that were significant predictors of infection across groups. Even when patients were stratified by Injury Severity Score, the infection rate increased significantly with increases in numbers of units of blood. Blood transfusion in the injured patients is an important independent statistical predictor of infection. Its contribution cannot be attributed to age, sex, or the underlying mechanism of severity of injury.

Abbreviated Injury Scale↗
PubMed1993

Molecular characterization of the murine neural retina leucine zipper gene, Nrl.

The NRL gene (D14S46E) is expressed in cells of human retina and encodes a putative DNA-binding protein of the leucine zipper family. Here we describe the analysis of the murine homolog of the NRL gene, Nrl. Various cDNAs resulting from alternate polyadenylation are characterized. The deduced polypeptide sequence is highly conserved between mouse and human, with an identical basic motif and leucine zipper domain. The nucleotide sequences in the 5' and 3'-untranslated regions also show significant homology. The 3'-untranslated region contains a polymorphic AGG-trinucleotide repeat. The murine Nrl gene consists of three exons; of these, the first is untranslated. The 5'-upstream promoter region has no canonical TATA box, but contains consensus binding site sequences for several DNA-binding proteins. Analysis of RNA from adult mouse tissues confirms the retina-specific expression of Nrl. This study provides the basis for dissecting the cis-regulatory elements involved in the retina-specific expression and for the development of an experimental model to investigate the function or any diseases associated with this gene in humans.

Amino Acid Sequence↗
PubMed1993

Diurnal expression of c-fos in the mouse retina.

The diurnal levels of c-fos mRNA were studied in the mouse retinas by means of RNA blot analysis. Mice were kept on a 12/12 h dark/light cycle and gene expression was studied at various time points during the day and night periods. The highest levels of c-fos mRNA were measured during the first half of the night period. The high levels persisted for about 4-5 h. The c-fos mRNA levels declined during the second half of the night period and remained low during the day period. Continuous illumination of mice during the first hours of the night period prevented the increase in c-fos mRNA. If mice were kept in the dark during the day period, they failed to show an increase in c-fos mRNA levels in the subsequent night period. Hence, following activation of c-fos during the night period, a refractory period exists at which illumination is required before c-fos can be induced again by dark. Although light appears to suppress the activation of c-fos in the night period, a short lived burst in c-fos expression of 30-60 min in duration was observed when dark-adapted animals were illuminated, either at the transition between the dark and light period or during the dark period. Thus, it appears that c-fos is activated in at least two different cell types in the retina which respond differently to light and dark stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Acute pancreatitis: a multisystem disease.

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.

Acute Disease↗
PubMed1992

A conserved retina-specific gene encodes a basic motif/leucine zipper domain.

Using subtraction cloning, we have isolated a human cDNA, AS321, which is expressed in retina and retinoblastoma cell lines but not in any other tissue or cell line tested. AS321 mRNA is detected in all cells of neural retina, with a high level of expression in photoreceptors. The polypeptide sequence deduced from the cDNA reveals consensus phosphorylation sites for protein kinase A and proline-directed protein kinase. Its C-terminal region contains a basic motif and a leucine zipper domain similar to the DNA binding proteins of the jun and fos oncoprotein family, and it shows a strong similarity to the product of an avian retroviral oncogene, v-maf. The gene for AS321 is conserved during evolution and is expressed in vertebrate retina. We propose to name the gene NRL (neural retina leucine zipper.

Amino Acid Sequence↗
PubMed1992

Maintenance of opsin and S-antigen gene expression in RCS dystrophic rats following RPE transplantation.

The effects of retinal pigment epithelium (RPE) transplantation in rescuing photoreceptor cells (PRC) were studied in RCS rats bearing the rdy mutation. RPE preparations from Long-Evans rats were transplanted into the subretinal space of post-natal (P) 17-19-day-old RCS rats. Age-matched RCS animals in the control group received injections of the transplantation vehicle buffer alone. The animals were killed at various post-natal ages after RPE transplantation. Immunocytochemical studies using antibodies to opsin and S-antigen indicated intact photoreceptor cells in the transplanted retinas. In contrast age-matched sham-injected animals did not show any rescue of photoreceptor cells at P90. Single RPE transplantation of 60,000 cells in each eye resulted in restoration of near normal mRNA levels for opsin, and S-antigen proteins. Comparisons of mRNA levels of two visual proteins using cDNA probes demonstrated a therapeutic effect of RPE transplantation in preventing a progressive decline in mRNA levels due to retinal degeneration. In contrast, P109 sham-injected controls showed no detectable mRNA levels for these proteins. In vitro protein synthesis in RPE-transplanted retinas implied further competence of these retinas. These data suggest that RPE transplantation not only rescues photoreceptors from degeneration, but more importantly, it allows normal transcription and translation in these cells rendering them capable of participating in the visual and signal transduction cascade.

Animals↗
PubMed1992

Expression of opsin and IRBP genes in mutant RCS rats.

The retinal pigment epithelium of RCS rats bearing the autosomal recessive rdy mutation fails to ingest shed rod outer segment tips. Accumulation of disk debris in the subretinal space of the maturing mutant retina causes a secondary degeneration of photoreceptor cells. Two hypotheses have been offered as possible explanations of the death of photoreceptor cells in this disorder: (1) photoreceptors are starved for amino acids, retinal, oxygen, etc; and (2) that IRBP levels and synthesis may be decreased and interfere with retinal transport and this deficiency is lethal to these cells. To test these hypotheses, we have studied the effect of this mutation on the levels of expression of opsin and IRBP genes, and gene products and on rates of synthesis at various ages in dystrophic RCS p+ rats and compared the results to those obtained with normal Long Evans rats. The mutant rats and normal controls had comparable amounts of opsin and IRBP mRNA transcripts and rates of synthesis up to post-natal day 45 (P45) but opsin transcripts were barely detectable at P60 and thereafter. IRBP mRNA levels were also very low after P62 although somewhat higher than opsin mRNA. Opsin could be detected immunochemically, albeit at lower levels, at all the ages studied up to P310, but IRBP levels fell below detection after P45. We localized opsin and IRBP in the retina by post-embedding EM immunocytochemical procedures and found that opsin is present in the remnants of rod outer segment debris, even at P390, long after detectable opsin synthesis had ceased. These data suggest that expression of opsin and IRBP genes is not influenced by the shape and state of the outer segments, and that the rdy mutation does not influence the expression of the opsin and IRBP in these retinas until the photoreceptor cells are profoundly damaged. Thus, neither hypothesis about the causes of cell death in this disorder is supported.

Aging↗
PubMed1991

Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa.

Thirteen mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa (ADRP) have been produced by transfection of cloned cDNA into tissue culture cells. Three mutants [class I: Phe-45----Leu, Gln-344----termination (deletion of C-terminal positions 344-348), and Pro-347----Leu] resemble wild-type rhodopsin in yield, regenerability with 11-cis-retinal, and plasma membrane localization. Ten mutants [class II: Thr-17----Met, Pro-23----His, Thr-58----Arg, Val-87----Asp, Gly-89----Asp, Gly-106----Trp, Arg-135----Leu, Arg-135----Trp, Tyr-178----Cys, and Asp-190----Gly] accumulate to significantly lower levels, regenerate with 11-cis-retinal variably or not at all, and are transported inefficiently to the plasma membrane, remaining primarily in the endoplasmic reticulum. These data suggest that there are at least two distinct biochemical defects associated with different rhodopsin mutants in ADRP.

Blotting, Western↗
PubMed1991

Differential expression of novel Gs alpha signal transduction protein cDNA species.

The Gs alpha guanine nucleotide-binding signal transduction protein is part of a heterotrimeric complex that is involved in the stimulation of adenylate cyclase upon activation of membrane receptors. We report the characterization of 16 Gs alpha cDNA clones isolated from the human adult retina and fetal eye libraries. Molecular heterogeneity in the 5'-region defines four novel Gs alpha cDNA species which are generated either by alternate splicing or by using alternative promoter. The novel exons upstream of exon 2 interrupt the highly conserved 'region A' in the Gs alpha polypeptide. Non-AUG codons in the novel 5'-exon can initiate translation of these Gs alpha species in vitro. Reverse transcription of total RNA coupled with polymerase chain reaction (RTPCR) using specific primers and in situ hybridization to mRNA in baboon tissue sections with a specific oligonucleotide probe show a high level of expression of these species in retina and brain but not in liver. Differential expression of alternatively spliced Gs alpha species suggests novel signal transducing pathways.

Aged↗
PubMed1991

Arrestin mRNA expression, biosynthesis, and localization in degenerating photoreceptors of mutant rds mice retinas.

The retinal photoreceptors of the mutant rds mouse are unable to form normal outer segments. Eventually the abnormal cells die in the months following birth. The genetic defect in the rds mouse was recently localized to the peripherin gene that encodes a protein in the outer segment disc margin. Although this mutation may explain the morphogenetic defect, i.e., the failure to form outer segments, the reason for subsequent cell death is not clear. Previously, we demonstrated that the capability to synthesize opsin, an outer segment integral membrane protein, is not compromised by the morphogenetic defect although the opsin steady-state content is considerably reduced, since it is not incorporated into an organized outer segment. We have now studied arrestin, a cytoplasmic protein that is part of the phototransduction cascade and appears to shuttle between the inner and outer segment during the light/dark cycle. Since rds mice lack outer segments, it was of interest to determine the effects of the photoreceptor abnormality on arrestin gene expression. Arrestin mRNA levels and protein synthetic rates were high in young rds retinas. When corrected for cell loss, the steady-state arrestin content per cell in the rds retina was comparable to normal. However, in the absence of an outer segment, the total amount of arrestin is concentrated in the remaining inner segment. Consequently, a relatively high level of arrestin is present in the rds inner segment throughout the light/dark cycle. We suggest that the morphogenetic defect indirectly precipitates secondary effects such as the persistent presence of high levels of arrestin or other soluble proteins in the abnormal photoreceptor inner segment, nucleus, and synaptic terminal. This condition, if toxic to the cells, may compromise photoreceptor viability in the rds retina.

Animals↗
PubMed1991

Sequence analysis, expression and chromosomal localization of a gene, isolated from a subtracted human retina cDNA library, that encodes an insulin-like growth factor binding protein (IGFBP2).

The metabolic functions of insulin-like growth factors (IGFs) I and II are modulated by a family of binding proteins which are present in biological fluids and are synthesized by a variety of cell types. A cDNA clone, isolated at random from a subtracted human retina library, has been identified to code for a novel IGF-binding protein (IGFBP2) by its sequence homology to the peptide sequence of IGF binding proteins purified from bovine MDBK and rat BRL-3A cells. The complete nucleotide sequence of the IGFBP2 cDNA is 1406 bp long, contains 66% G-Cs and an open reading frame of 328 amino acids with a putative signal or pro-peptide of 39 residues. The mature polypeptide of 289 amino acids has 18 cysteines, a putative ATP-binding site and an RGD tripeptide. The 1.4 kb IGFBP2 transcript is expressed in several human tissues including fetal eye and fetal brain, but not in the human lymphoblastoid cell line against which the retinal cDNA library was subtracted. In situ hybridization to sections of mouse retina localized the mRNA for IGFBP2 primarily in the outer nuclear layer of photoreceptors. Southern blot analysis of DNA from human x rodent and mouse x rodent somatic cell hybrids assigned the gene for IGFBP2 to human chromosome 2q33-qter and mouse chromosome 1 in a known conserved syntenic region.

Aged↗
PubMed1991

Use of serum prolactin for monitoring the therapeutic response in ovarian malignancy.

Serum prolactin level was estimated in 20 women with ovarian malignancy. High prolactin level was observed in 13 out of 20 women. However, no correlation was seen between prolactin level and the stage of the disease. Serial measurement of prolactin showed a correlation of prolactin level with tumor mass in three patients in which serial tumor mass volume measurements were available. A rise in serum prolactin level was observed in women who had recurrence of the disease. Although the current study is based on a relatively small number of patients, it may be concluded that serum prolactin level might be used as a tumor marker to monitor the therapeutic response in cases of ovarian malignancy.

Adolescent↗
PubMed1991

Analyses of preventable deaths by mechanism of injury among 13,500 trauma admissions.

Preventable deaths (PD) were evaluated by mechanism of injury for 13,500 trauma admissions to eight hospitals over 2 years. There were 42 (3.3%) hospital deaths. Preventable deaths were analyzed by time of death, anatomic site of injury, and mechanism; penetrating (PEN) and blunt with low fall (LF) injuries were considered separately. Preventability of death for patients with probability of survival of less than 0.5, "unexpected deaths," after penetrating and blunt injuries, was determined by consensus of three trauma surgeons. Twelve per cent of deaths were found to be possibly preventable. The incidence of preventable deaths did not differ significantly across groups. Factors in preventable deaths varied by injury cause; delays in operation, PEN (50%), and blunt injury patients (48%); management errors, blunt (52%) and LF (84%); and technical errors, PEN (37.5%). Median times to death were significantly different by cause of injury: PEN, 3 hours; blunt, 13 hours; and LF, 3975 hours. Problems were identified in the hospital care of patients, especially those with LF, leading to sepsis and multiple organ failure.

Accidental Falls↗