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Biomedical subjects

M Goyal

Publications and source records attributed to M Goyal.

At least 91 records · Page 5Linked to original sources
PubMed1996

Glomerular epithelial protein 1 and podocalyxin-like protein 1 in inflammatory glomerular disease (crescentic nephritis) in rabbit and man.

The podocyte is the cell responsible in large part for maintaining the glomerular filtration barrier. Glomerular epithelial protein 1 (GLEPP1) is a novel receptor-like transmembrane protein tyrosine phosphatase present on the apical surface of podocyte foot processes. Podocalyxin-like protein 1 (PCLP1) is a transmembrane sialoglycoprotein which is also present on the foot process apical surface as well as on the surface of endothelial cells. GLEPP1 and PCLP1 are thought to play a role in regulating the structure and function of podocyte foot processes. Glomerular injury affecting the podocyte is likely to be reflected by changes in these proteins. GLEPP1 distribution in human renal biopsy with inflammatory glomerular disease and crescent formation was examined by immunocytochemistry. A model of inflammatory glomerular injury induced by guinea pig anti-rabbit basement membrane (anti-GBM) antibody was used to examine the distribution and amount of GLEPP1 and PCLP1 mRNA and protein. A biopsy study was done to determine whether the extent of GLEPP1 depletion from glomeruli at early time points (Day 7) would predict the severity of crescent formation at Day 30. Glomeruli from human renal biopsies with crescentic nephritis showed focal to diffuse disappearance of GLEPP1 protein. No GLEPP1 was present within the cellular crescent. By Day 4 of the rabbit anti-GBM model, before cellular crescents had formed, GLEPP1 protein was reduced from 127 +/- 28 X 10(7) to 30 +/- 5 X 10(7) molecules per glomerulus (p < 0.001), and GLEPP1 mRNA was reduced by 62% (p < 0.05). In contrast, at this time there was no significant reduction of PCLP1 protein from the normal number of 309 X 10(9) molecules per glomerulus and the PCLP1 mRNA level had not decreased. At Day 4, podocyte foot processes were effaced and proteinuria was present. Glomerular culture supernatants from Day 4 rabbits caused a reduction in GLEPP1 but not PCLP1 protein expression by cultured normal glomeruli, showing that a soluble factor was produced at Day 4 which reduced the number of GLEPP1 molecules in glomeruli. There was no detectable proteolysis of GLEPP1 or PCLP1 in glomeruli and no increase in GLEPP1 or PCLP1 excretion in urine. Therefore, the reduction in glomerular GLEPP1 was associated with reduced synthetic capacity. The proportion of glomeruli with reduced GLEPP1 at Day 7 of the model was significantly associated with the percent of glomeruli which had formed crescents at Day 30 (r = 0.86, p < 0.0001). GLEPP1 appears to be a sensitive indicator of glomerular injury during inflammation in man and in the rabbit model. A reduction in amount of GLEPP1 is associated with worse outcome for the glomerulus.

Animals↗
PubMed1996

Fibronectin is the major fibroblast chemoattractant in rabbit anti-glomerular basement membrane disease.

The mechanism for fibroblast recruitment in renal fibrosis due to anti-glomerular basement membrane (anti-GBM) disease is unknown. Since fibroblast recruitment can occur via chemotaxis, assessment of the possible production of fibroblast chemotactic activity by affected renal tissue and its identification could provide important clues. Anti-GBM disease was induced by injection of guinea pig anti-rabbit GBM immunoglobulin G into rabbits previously sensitized to guinea pig immunoglobulin G. On days 4, 7, and 14 after induction, renal tissue was harvested and glomeruli isolated. Overnight serum-free conditioned media from whole cortex and glomeruli were prepared and assayed for fibroblast chemotactic activity. The results show low level activity in both conditioned media from control animals. In contrast, conditioned media from anti-GBM-treated animals at all time points showed significantly elevated fibroblast chemotactic activity peaking on day 4 with subsequent reduction thereafter. The magnitude of increase in cortical conditioned media was significantly higher than that for glomerular conditioned media, suggesting that most of the activity was derived from extraglomerular sources. Gel filtration analysis revealed the activity to be heterogeneous, consisting of at least four major species with estimated molecular weights ranging from 10 to > 100 kd. Acidification of conditioned media failed to increase chemotactic activity significantly, whereas protease digestion abolished it. Treatment of conditioned media with antifibronectin inhibited > 85% of the chemotactic activity, whereas antibodies to platelet-derived growth factor and transforming growth factor-beta did not have a significant effect. These findings taken together suggest that fibronectin-derived peptides represent the predominant fibroblast chemoattractant produced by renal cortex in anti-GBM disease.

Animals↗
PubMed1995

Molecular cloning, expression, and characterization of podocalyxin-like protein 1 from rabbit as a transmembrane protein of glomerular podocytes and vascular endothelium.

Podocytes are responsible in part for maintaining the size and charge filtration characteristics of the glomerular filter. The major sialoprotein of the podocyte foot process glycocalyx is a 140-kDa sialoprotein named podocalyxin. Monoclonal antibodies raised against isolated rabbit glomeruli that recognized a podocalyxin-like protein base upon size, Alcian blue staining, wheat germ agglutinin binding, and distribution in renal cortex were used to expression clone cDNAs from a rabbit glomerular library. On Northern blot the cDNAs hybridized to a 5.5-kilobase pair transcript predominantly present in glomerulus. The overlapping cDNAs spanned 5,313 base pairs that contained an open reading frame of 1,653 base pairs and were not homologous with a previously described sequence. The deduced 551-amino acid protein contained a putative 21-residue N-terminal signal peptide and a 26-amino acid transmembrane region. The mature protein has a calculated molecular mass of 55 kDa, an extracellular domain that contains putative sites for N- and O-linked glycosylation, and a potential glycosaminoglycan attachment sites. The intracellular domain contains potential sites for phosphorylation. Processing of the full-length coding region in COS-7 cells resulted in a 140-kDa band, suggesting that the 55-kDa core protein undergoes extensive post-translational modification. The relationship between the cloned molecule and the monoclonal antibodies used for cloning was confirmed by making a fusion protein that inhibited binding of the monoclonal antibodies to renal cortical tissue sections and then raising polyclonal antibodies against the PCLP1 fusion protein that also recognized glomerular podocytes and endothelial cells in tissue sections in a similar distribution to the monoclonal antibodies. We conclude that we have cloned and sequenced a novel transmembrane core glycoprotein from rabbit glomerulus, which has many of the characteristics of podocalyxin. We have named this protein podocalyxin-like protein 1.

Amino Acid Sequence↗
PubMed1995

Molecular cloning of cDNAs encoding human GLEPP1, a membrane protein tyrosine phosphatase: characterization of the GLEPP1 protein distribution in human kidney and assignment of the GLEPP1 gene to human chromosome 12p12-p13.

Human glomerular epithelial protein 1 (GLEPP1), a receptor-like membrane protein tyrosine phosphatase (PTPase), was cloned and sequenced from a human renal cortical cDNA library. The human nucleotide and derived amino acid sequences were, respectively, 90 and 97% identical to those of rabbit. Human GLEPP1 is predicted to contain 1188 amino acids. The predicted mature protein is 1159 amino acids long and contains a large extracellular domain, a single transmembrane domain, and a single intracellular PTPase domain. Monoclonal and polyclonal antibodies raised against a human GLEPP1 fusion protein recognized a protein with distribution restricted to the glomerulus in human kidney and with an apparent molecular weight of approximately 200 kDa. The GLEPP1 gene was assigned to human chromosome 12p12-p13 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1995

Paediatric post-traumatic endophthalmitis.

AIMS: A retrospective analysis of children with post-traumatic endophthalmitis was performed to determine if microbiological differences exist between this disease in the paediatric population compared with this disease in adults. METHOD: Twelve cases of post-traumatic endophthalmitis in children were analysed to determine characteristics of this disease in youth. Patient ages varied from 18 months to 13 years; the mean age was 8 years. Gram positive organisms were isolated in eight eyes, Gram negative organisms from four eyes, fungus from one eye, and negative cultures in three eyes. The most common isolates were streptococcal species (56.6%) and staphylococcal species (22.2%). Vitrectomy was performed on eight (66.7%) eyes. RESULTS: Visual acuity of 20/200 or better was obtained in eight eyes (66.7%). Three eyes had vision less than 5/200. One eye developed phthisis bulbi. Nine (75%) patients were younger than 10 years of age, and six (66.7%) of these nine obtained a final visual acuity of 20/200 or better. CONCLUSION: Useful vision can be obtained in children with post-traumatic endophthalmitis with early, aggressive treatment. The microbiology of paediatric post-traumatic endophthalmitis differs from adult disease with streptococcal species as the most common infecting organisms.

Adolescent↗
PubMed1995

Fibronectin mRNA in the developing glomerular crescent in rabbit antiglomerular basement membrane disease.

Fibronectin is a multifunctional matrix protein important in wound healing that is markedly increased in glomerular crescents. A previous report established two phases of fibronectin metabolism in crescent formation in an anti-glomerular basement membrane model of crescentic nephritis in the rabbit. Phase I was associated with increased glomerular fibronectin content from plasma. Phase II was associated with increased fibronectin mRNA in glomeruli. To examine the hypothesis that fibronectin is synthesized in the developing crescent, rabbit fibronectin cDNA was cloned, sense and antisense riboprobes were prepared and their specificity under the conditions to be used was validated and in situ hybridization studies were performed in the model. The results showed that the cells in the developing glomerular crescent express an intense fibronectin mRNA signal at Day 7 and that this signal persisted in cells of the crescent at Day 14. This result shows that fibronectin synthesis does indeed take place in cells of the developing crescent in this model and supports the hypothesis that fibronectin may be an important agent regulating crescent formation and fibrosis.

Amino Acid Sequence↗
PubMed1995

Unusual radiological manifestations of Lemierre's syndrome: a case report.

Lemierre's syndrome is an uncommon clinical entity characterized by oropharyngeal infection followed by septic thrombophlebitis of the jugular vein with embolization to the lungs and other organs. The organism is a gram-negative anaerobic bacterium, Fusobacterium necrophorum. We report a case of Lemierre's syndrome in an 8-year-old child who presented with septic arthritis of the left hip joint. Roentgenograms and computed tomography demonstrated gas in the joint and adjacent soft tissues, along with a dislocated hip. Sonography of the neck coupled with the colour Doppler technique did not reveal any abnormality in the jugular veins. A blood culture grew Fusobacterium necrophorum, confirming the diagnosis of Lemierre's syndrome.

Arthritis, Infectious↗
PubMed1994

GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. Identification, molecular cloning, and characterization in rabbit.

Podocytes are specialized epithelial cells with delicate interdigitating foot processes which cover the exterior basement membrane surface of the glomerular capillary. They are in part responsible for the extraordinary charge and size filtration characteristics of the glomerulus. To better understand disease processes affecting the glomerular filter, we searched for proteins with relative specificity to the podocyte using a monoclonal antibody strategy. The first such protein characterized (designated glomerular epithelial protein 1 (GLEPP1)) is a membrane protein-tyrosine phosphatase (PTPase) with a large extracellular domain containing eight fibronectin type III-like repeats, a hydrophobic transmembrane segment, and a single PTPase domain. The GLEPP1 PTPase domain shows homology with two other single domain transmembrane PTPases (PTP beta and Drosophila central nervous system PTP10D). This homology includes 2 cysteines in the PTPase domain not present in intracellular or tandem domain membrane PTPases. GLEPP1 PTPase protein is distributed to the podocyte foot processes themselves. RNase protection assay shows that GLEPP1 mRNA is also present in brain. By analogy with the CD45 PTPase of T cells, we expect that this receptor might play a role in maintaining foot process structure and/or function by regulating tyrosine phosphorylation of podocyte proteins.

Amino Acid Sequence↗
PubMed1994

Identification of M. tuberculosis ribosomal RNA in mouthwash samples from patients with tuberculosis.

It is often not possible to obtain satisfactory sputum samples from patients suspected of having pulmonary tuberculosis. In this study, we asked whether it was possible to identify M. tuberculosis ribosomal RNA (rRNA) in mouthwash samples, and in a prospective clinical study, whether the presence of this rRNA correlated with clinical M. tuberculosis infection. Using a combination of reverse transcriptase and polymerase chain reaction amplification, it was possible to identify M. tuberculosis rRNA in mouthwash samples. M. tuberculosis rRNA was identified in mouthwash samples from patients with active tuberculosis more commonly than in samples from control subjects (P < 0.05). The test was positive in four of ten patients with active pulmonary tuberculosis, one of eight contacts, none of eight past cases of tuberculosis, two of eight patients with other diagnosis and one of five healthy volunteers. M. tuberculosis rRNA was identified in sputum from four of eight patients and in bronchoscopy trap samples from four of five patients with active tuberculosis. However, one of ten sputum samples and two of five bronchoscopy samples from subjects with a clinical diagnosis other than active tuberculosis were positive. These results indicate that although it is technically possible to identify M. tuberculosis on the basis of the presence of rRNA in mouthwash samples, the poor sensitivity and specificity of the technique suggest that it is unlikely to be useful clinically.

Base Sequence↗
PubMed1994

Epidemiology of an outbreak of drug-resistant tuberculosis in the U.K. using restriction fragment length polymorphism.

1. Drug-resistant tuberculosis is a growing health care problem. When a series of cases occur, it is essential to know if patients with multidrug-resistant disease represent one or a number of separate outbreaks. 2. The epidemiology of an outbreak of isoniazid- and streptomycin-resistant tuberculosis in Blackburn was studied by restriction fragment length polymorphism using a probe for the IS6110 DNA sequence. 3. Mycobacterium tuberculosis from four cases of isoniazid- and streptomycin-resistant disease had an identical restriction fragment length polymorphism pattern. This pattern was not shared by drug-sensitive isolates of M. tuberculosis obtained from Blackburn (n = 8) or London (n = 13) or a M. tuberculosis isolate from a fifth Blackburn case which was resistant to isoniazid alone. 4. This methodology confirmed that all four cases of isoniazid- and streptomycin-resistant disease were part of a single epidemiologically related outbreak of drug-resistant disease. This study demonstrates how the epidemiology of an outbreak of multidrug-resistant tuberculosis in the U.K. can be confirmed by restriction fragment length polymorphism.

Adolescent↗
PubMed1994

Evaluation of quantitative magnetic resonance imaging as a noninvasive technique for measuring renal scarring in a rabbit model of antiglomerular basement membrane disease.

Renal function tests are an insensitive means of detecting progressive scarring of the kidney such as occurs in chronic allograft rejection and lupus nephritis. Alternative approaches for the measurement of small progressive changes in renal structure on a repetitive basis are needed. Quantitative magnetic resonance imaging (proton T1 relaxation time) was assessed for this purpose. A rabbit model of antiglomerular basement membrane disease that develops glomerular and interstitial inflammation followed by scarring of the renal cortex was used. Longitudinal studies of cortical T1 showed a marked prolongation of T1 during the initial inflammation and edema associated with glomerular crescent formation (Day 7). The T1 remained prolonged up to Day 120 in animals with significant fibrosis and crescent formation when the wet/dry weight ratio (a measure of edema) had returned to baseline. T1 was a more sensitive index of renal injury than was serum creatinine for all of the end points measured (cortical hydroxyproline per dry weight, percent crescent formation, or histologic fibrosis score). It was concluded from these studies that measurement of renal cortical T1 is quite a sensitive index of renal injury, probably more sensitive than the measurement of serum creatinine, but that this method does not discriminate between edema and scarring.

Animals↗
PubMed1993

Functional outcome of branch retinal vein occlusion after photocoagulation with various laser wavelengths--an automated perimetric analysis.

This study highlights the comparative efficacy of three different laser wavelengths--argon green, argon blue-green, and krypton red--for sector photocoagulation in fresh cases of branch retinal vein occlusion. The mean Logarithm of minimal angle of resolution (LogMAR) improved in the argon green and argon blue-green groups but decreased in the krypton red group. Statistical analysis of the automated visual fields in these eyes showed a mean change in corrected pattern standard deviation value, with increase in all three groups--minimal increase in the argon blue-green group and maximal in the krypton red group, suggesting maximum visual field defect in the krypton laser group. To conclude, the green and the blue-green wavelengths gave results that were decidedly superior to those given by krypton red: further, argon blue-green had an edge over the green wavelength.

Fluorescein Angiography↗
PubMed1993

Comparison of scholastic performances of left handed and right handed students.

An attempt was made to compare the scholastic performance among left and right handed students. Both academic and extra curricular areas were studied among 3608 students from 6th to 12th class, from 10 schools in a rural subdivision of north east Rajasthan. General incidence of left handedness was 8.6% among students, higher in females (12.4%) as compared to males (8.1%). Right handed students performed better in aggregate as well as in individual academic areas (p < 0.05). Left handed students were extreme performers as far as sports and games area was concerned, while right handed students tended to be average performers. Overall handedness affected both the academic and extra-curricular activities except behavior and discipline area (p > 0.05).

Achievement↗