Biomedical subjects

Prem Puri

Publications and source records attributed to Prem Puri.

At least 55 records · Page 3Linked to original sources

PubMed2004

Increased expression of EGFR and TGF-alpha in segmental renal dysplasia in duplex kidney.

Renal dysplasia (RD) is a disorganised development of renal parenchyma that results in a deficit of functional renal tissue. It is known that the epidermal growth factor (EGF) and the transforming growth factor-alpha (TGF-alpha) enhance renal cell proliferation, migration and differentiation during kidney development through binding to the same EGF receptor (EGFR). The aim of the study was to analyse the expression of TGF-alpha and EGFR in the dysplastic kidney. The specimens of dysplastic upper poles duplex kidneys were surgically resected from 19 patients. Indirect immunohistochemistry was performed using the ABC method employing antibodies against EGFR and TGF-alpha, and gene expression using primers specific to the human genes. There was absent or weak EGFR and TGF-alpha immunoreactivity in normal kidney tissue. In dysplastic kidneys, there was strong TGF-alpha and EGFR immunoreactivity in the epithelium of primitive tubules and strong EGFR immunoreactivity in the connective tissue around the primitive tubules. Our findings of markedly increased local expression of EGFR and TGF-alpha in primitive tubules suggest that EGFR and TGF-alpha may play an important role in altering renal morphogenesis resulting in renal dysplasia.

Child↗

PubMed2004

Insulin-like growth factor-1 expression in reflux nephropathy.

BACKGROUND: Reflux nephropathy (RN) is recognised as a major cause of end-stage renal failure in children and young adults. Insulin-like growth factor-1 (IGF-1), a peptide growth factor produced by collecting ducts, and its receptor, insulin-like growth factor-1 receptor (IGF-1R), are present in the glomeruli and basolateral membrane of renal proximal tubular cells. Exogenous IGF-1 has been shown to enhance proliferation and reduce apoptosis of tubular cells following renal injury. METHODS: We designed this study to investigate the expression of IGF-1 in RN. The kidney specimens from 15 children with RN were obtained at the time of nephrectomy. Control material included normal kidney specimens obtained from adult patients during partial nephrectomy for an incidentaloma. Single-label immunofluorescence histochemistry was carried out using polyclonal antibodies to IGF-1 and IGF-1R employing laser scanning confocal microscopy. Double-label immunofluorescence histochemistry was carried out using monoclonal antibodies to vimentin and clusterin to assess tubulointerstitial fibrosis. IGF-1 and IGF-1R gene expression were evaluated by in situ hybridisation (ISH). The TUNEL method was utilised to assess tubular apoptosis. RESULTS: In the normal kidney there was strong IGF-1 and IGF-1R immunoreactivity in the proximal tubules, whereas IGF-1 and IGF-1R immunoreactivity was markedly reduced in RN specimens. Strong IGF-1 and IGF-1R mRNA expression was observed in the proximal tubules in normal kidneys, whereas IGF-1 and IGF-1R mRNA expression was undetectable in RN. Renal tubulointerstitial expression of vimentin and clusterin was markedly increased in RN kidneys. Decreased IGF-1 and IGF-1R expression in RN strongly correlated with severity of tubular apoptosis in RN compared with controls. CONCLUSION: These data suggest that the downregulation of IGF-1 and IGF-1R may play an important role in the pathogenesis of RN, at least in part by increasing interstitial collagen deposition and tubular apoptosis.

Adolescent↗

PubMed2004

Upregulated expression of EGF and TGF-alpha in the proximal respiratory epithelium in the human hypoplastic lung in congenital diaphragmatic hernia.

Newborn infants with congenital diaphragmatic hernia (CDH) still have a high mortality rate. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) are peptide growth factors involved in the fetal lung growth and development. The EGF and TGF-alpha have been reported to promote pulmonary branching activity and alveolar type-II pneumocyte proliferation. Epidermal growth factor and TGF-alpha immunoreactivity and mRNA expression in the bronchial and bronchiolar epithelium is maximal during early fetal life and barely detectable in the proximal airways of neonatal lung. The purpose of this study was to determine protein and gene expression of EGF and TGF-alpha in CDH lung in order to elucidate the potential role of these growth factors in the pathogenesis of pulmonary hypoplasia in CDH. Lung tissue specimens were obtained from archival lung tissue from 11 patients with CDH and 5 controls. Indirect immunohistochemistry was performed using ABC method with anti-EGF and anti-TGF-alpha antibodies. In situ hybridization was performed using EGF and TGF-alpha specific digoxigenin-labeled oligonucleotide probes. The most striking difference between hypoplastic CDH lung and control lung was the strong EGF and TGF-alpha mRNA expression and immunoreactivity in the bronchial and bronchiolar epithelium in CDH lung. The upregulated protein and gene expression of EGF and TGF-alpha in the proximal airways in the CDH hypoplastic lung suggests persistence of fetal stage of pulmonary airway development in CDH.

Epidermal Growth Factor↗

PubMed2004

Genetic polymorphisms of angiotensin system genes in congenital diaphragmatic hernia associated with persistent pulmonary hypertension.

BACKGROUND/PURPOSE: The renin-angiotensin system plays an important role in pulmonary artery remodelling. Several polymorphisms of genes encoding for components of the renin angiotensin system such as the angiotensin converting enzyme (ACE), the angiotensinogen (AGT) gene, and the angiotensin II type 1 receptor (ATIR) have been associated with the development of pulmonary hypertension. The aim of this study was to investigate the ACE I/D genotype, the M235 T polymorphism of the AGT gene and the A1166 C polymorphism of AT1R in the lungs of congenital diaphragmatic hernia (CDH) complicated by persistent pulmonary hypertension (PPH) in the newborn. METHODS: Genomic DNA was extracted from archival paraffin-embedded lung tissue from 13 newborns with CDH complicated by PPH and from 9 controls. Genotyping for the I/D-ACE, the M235 T-AGT, and the A1166 C-ATIR gene polymorphisms were determined by a polymerase chain reaction-based method with appropriate restriction digest when required. RESULTS: In controls, ACE genotype distribution of DD, ID, and II was 11%, 33%, and 55%, respectively, whereas in CDH it was 70%, 15%, and 15%, respectively. The ACE-DD genotype was significantly higher in CDH compared with controls (P <.05). In CDH samples, the prevalence of AGT-MM genotype was lower (8% v. 33%; P <.05), whereas the AGT-TT genotype was higher (61% v. 22%; P <.05) compared with controls. There were no differences in allele frequencies of AT1R between CDH patients and controls. CONCLUSIONS: These data suggest that D allele of the ACE gene insertion/deletion polymorphism and angiotensinogen M235 T polymorphism may be associated with PPH in newborns with congenital diaphragmatic hernia.

Alleles↗

PubMed2004

Pathogenesis of Hirschsprung's disease and its variants: recent progress.

The enteric nervous system (ENS) is a complex network of interconnected neurons within the wall of the intestine that controls intestinal motility, regulates mucosal secretion and blood flow, and also modulates sensation from the gut. The cells that form the ENS in mammals are derived primarily from vagal neural crest cells. During the past decade there has been an explosion of information about genes that control the development of neural crest. Molecular-genetic analysis has identified several genes that have a role in the development of Hirschsprung's disease. The major susceptibility gene is RET, which is also involved in multiple endocrine neoplasia type 2. Recently, genetic studies have provided strong evidence in animal models that intestinal neuronal dysplasia (IND) is a real entity. HOX11L1 knockout mice and endothelin B receptor-deficient rats demonstrated abnormalities of the ENS resembling IND type B in humans. These findings support the concept that IND may be linked to a genetic defect.

Animals↗

PubMed2004

Variant Hirschsprung's disease.

Conditions that clinically resemble HD despite the presence of ganglion cells on suction rectal biopsy results, can be diagnosed by providing an adequate biopsy and employing a variety of histological techniques. Intestinal neuronal dysplasia is a distinct clinical entity that can be clearly proven histologically. Patients with IND not only have abnormalities of submucosal and myenteric plexuses but also defective innervation of the muscle. Internal sphincter achalasia, which is histologically characterized by nitrergic nerve depletion, can be diagnosed on anorectal manometry and successfully treated by internal sphincter myectomy. The outcome of smooth muscle disorders is generally fatal. The need for surgical intervention should be weighed carefully and individualized because most explorations have not been helpful and are probably not necessary.

Biopsy, Needle↗

PubMed2004

The significance of serum erythropoietin levels in assessing the severity of renal damage in children with reflux nephropathy.

PURPOSE: Erythropoietin (EPO) is the principal factor regulating red blood cell production in humans. It has been shown that EPO gradually decreases with the progression of diabetic nephropathy and may be used as a marker of severity of disease. In vitro studies have shown that interleukin-10 (IL-10) acts synergistically with EPO to increase stimulation of erythroid differentiation and proliferation. We evaluate serum levels of EPO and IL-10 in children with reflux nephropathy (RN). MATERIALS AND METHODS: Serum level of EPO and IL-10 were measured in 32 girls and 22 boys with RN, and in 22 boys and 10 girls who served as healthy controls. Renal scarring was evaluated with Technetium dimercapto-succinic acid scan. RN was severe (less than 20% uptake) in 16 children, moderate (20% to 40% uptake) in 25 and mild RN (greater than 40% uptake) in 13. Because anemia may further stimulate EPO production we also compared the index Hb (hemoglobin) x EPO in all patients. IL-10 and EPO were measured with standard enzyme-linked immunosorbent assay technique. The unpaired t test was used for statistical analysis. RESULTS: There were no statistically significant differences in the serum levels of EPO in children with RN (6.11 +/- 0.51 mIU/ml) compared to controls (6.42 +/- 0.46 mIU/ml) (p >0.5). Similarly the index Hb x EPO was 75.25 +/- 5.65 in children with RN compared to 73.76 +/- 5.48 in controls. Mean EPO levels were similar for mild, moderate and severe RN. There was no difference in the serum levels of IL-10 in children with RN (23.14 +/- 2.32 pg/ml) compared to controls (22.67 +/- 4.13 pg/ml) (p >0.5). CONCLUSIONS: Although EPO has been reported to be a marker of progressive renal disease in diabetic nephropathy, our data indicate that serum levels of EPO do not reflect the severity of renal parenchymal damage in children with RN.

Child↗

PubMed2004

Tumor necrosis factor-alpha gene polymorphism in reflux nephropathy.

PURPOSE: Interstitial scarring contributes to the progression of renal failure in reflux nephropathy. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the disease susceptibility and pathogenesis of several inflammatory diseases promoting interstitial infiltration of inflammatory cells. We evaluate the frequency of TNF-alpha gene polymorphism in patients with reflux nephropathy. MATERIAL AND METHODS: Renal scarring was evaluated with technetium dimercapto-succinic acid renal scan. Genotyping was performed on 104 patients with reflux nephropathy and 30 controls for the TNF-alpha gene polymorphisms using polymerase chain reaction and restriction digest. This polymorphism involved a guanidine to adenosine transition at position -308 and was designated as TNF1 (-308G) and TNF2 (-308A). RESULTS: The allele frequencies of TNF1 and TNF2 were 18.8% and 81.2% in patients with reflux nephropathy and 76.7% and 23.3% in controls, respectively. The genotype distribution of TNF-alpha-AA was significantly higher (66.4% vs 10%, p <0.05), while the TNF-alpha-GG was lower (13.4% vs 60%, p <0.05) in patients with reflux nephropathy compared to controls. CONCLUSIONS: This study demonstrates for the first time the association of the cytokine TNF-alpha gene polymorphism in patients with reflux nephropathy. Our data suggest that patients with vesicoureteral reflux and TNF-alpha AA genotype may have increased susceptibility to reflux nephropathy.

Adolescent↗

PubMed2004

Interstitial cells of Cajal in the human normal urinary bladder and in the bladder of patients with megacystis-microcolon intestinal hypoperistalsis syndrome.

OBJECTIVE: To investigate the distribution of c-kit-positive interstitial cells of Cajal (ICCs) in normal bladder and bladders from patients with megacystis-microcolon-intestinal peristalsis syndrome (MMIHS, a rare congenital and generally fatal cause of functional intestinal obstruction in the newborn), the most characteristic feature of which is abdominal distension caused by a distended unobstructed urinary bladder. PATIENTS AND METHODS: Full-thickness bladder specimens were obtained from four infants with MMIHS and four controls, and processed as paraffin-wax and frozen sections. Sections were assessed using single immunohistochemistry with monoclonal and polyclonal anti-c-kit antibodies. Anti-alpha-smooth muscle actin (SMA) antibody was used to investigate the contractile apparatus in smooth muscle cells of the urinary bladder. Specimens were examined using light and confocal scanning microscopy. RESULTS: There were many c-kit positive ICCs in the normal urinary bladder, appearing as small, long, bipolar cells with only two long and several short processes. In contrast, ICCs were absent in the MMIHS bladder. alpha-SMA immunoreactivity was lower in MMIHS urinary bladder than in control sections. CONCLUSION: This study shows for the first time the presence of c-kit-positive ICCs in the normal human urinary bladder. The lack of ICCs in the MMIHS bladder may contribute to the voiding dysfunction in this disease.

Colon↗

PubMed2004

The role of nitric oxide in bladder urothelial injury after bladder outlet obstruction.

OBJECTIVE: To investigate the role of nitric oxide (NO) in the pathogenesis of injury to the bladder mucosa after bladder outlet obstruction (BOO). MATERIALS AND METHODS: The response of bladder mucosa to BOO consists of thickening with fibrous connective tissue; NO is a multipurpose messenger important in blood vessel relaxation, neuronal communication and inflammatory activities of macrophages, and is synthesized by NO synthase (NOS), with three distinct isoforms; inducible (iNOS), endothelial (eNOS) and neuronal (nNOS). Fifteen male guinea pigs had a silk ligature placed around the bladder neck to induce BOO; controls included five sham-operated animals. The animals were killed at 2, 4, 6, 8 and 12 weeks after BOO. NADPH-diaphorase staining was used as a nonspecific method to determine NOS isoform distribution. Single- and double-label immunofluorescence histochemistry for iNOS, eNOS, nNOS and macrophage colony stimulating factor (M-CSF) were used, with laser scanning confocal microscopy to assess the results. The relative amount of iNOS mRNA was evaluated using reverse-transcription-polymerase chain reaction (RT-PCR), and a standard method to determine the degree of apoptosis. RESULTS: Bladder mucosa had a markedly increased intensity of NADPH-diaphorase staining 2 weeks after BOO. iNOS immunoreactivity was markedly greater in the bladder mucosa 2 weeks after BOO than in controls. The immunolocalization of iNOS and M-CSF was identical in bladder mucosa after BOO. RT-PCR showed stronger iNOS mRNA expression in the obstructed bladder mucosa 2 weeks after BOO than in controls. eNOS and nNOS expression was detected only 8 weeks after BOO, with markedly more immunoreactivity 12 weeks after initiating BOO. Increased eNOS and nNOS immunoreactivity strongly correlated with the induction of apoptosis in the bladder mucosa. CONCLUSION: There was overexpression of iNOS by activated macrophages in the early stages of BOO. This overexpression did not induce apoptosis in the iNOS-expressing cells of bladder mucosa in the early stages. After long-term BOO bladder mucosa showed strong eNOS and nNOS immunoreactivity, correlating with apoptosis. Thus we suggest that eNOS and nNOS, by triggering cell death, may be important in eliminating hyperplastic urothelial cells, reflecting the plasticity of the bladder response to obstructive stimuli.

Animals↗

PubMed2003

Increased expression of mast cells in reflux nephropathy.

End-stage renal disease is characterized by interstitial infiltrate of inflammatory cells in association with tubular atrophy and interstitial fibrosis. Mast cells (MCs) secrete a large number of fibrogenic factors and have been implicated in chronic inflammatory processes with fibrous tissue deposition. The aim of this study was to investigate the distribution of MCs in kidneys with reflux nephropathy (RN) and to determine the relationship between MCs and the interstitial fibrotic process in RN. Kidney specimens from 12 patients (aged 2-13 years) with severe RN secondary to primary high-grade vesicoureteral reflux, obtained at the time of nephrectomy, and 5 controls were examined. Sections were investigated histochemically by acid toluidine blue (TB) and immunohistochemically with antibodies for anti MC-tryptase, MC-chymase, c- kit (CD117), and fibronectin. Double staining for fibronectin and MC-tryptase was performed and examined using confocal scanning microscopy. TB histochemistry showed a marked increase of MCs in RN specimens compared with controls. MC-tryptase, chymase, and c- kit immunopositive MC infiltration was significantly higher in RN samples (14.2+/-9.6) than controls (1.3+/-0.8), ( P<0.05). In all the sections there were more MC-tryptase-positive cells than MC-chymase-positive MCs. Double staining showed increased immunoreactivity of MCs and fibrosis in the renal interstitium of kidneys with RN. The number of infiltrating tryptase-positive MCs was correlated with the degree of interstitial renal scarring. This study demonstrates for the first time the increased expression of MCs in RN, suggesting that MCs may be involved in the development of scarring in RN.

Case-Control Studies↗

PubMed2003

Increased levels of circulating adhesion molecules in neonates with congenital diaphragmatic hernia complicated by persistent pulmonary hypertension.

The aim of this study was to determine circulating levels of adhesion molecules in serum from patients with congenital diaphragmatic hernia (CDH) to investigate the relationship between soluble ICAM-1, ELAM-1, and VCAM-1 liberated by activated vascular endothelium and the development of persistent pulmonary hypertension (PPH) in patients with CDH. We measured serum levels of ICAM-1, ELAM-1, and VCAM-1 in 20 high-risk neonates with CDH at the time of diagnosis (11 with PPH and 9 without PPH) and 7 age-matched controls using ELISA system. We further examined the lungs of 5 patients with CDH complicated by PPH who died during resuscitation and stabilization, and three control lung specimens for the expression of adhesion molecules using immunohistochemistry. The mean serum ICAM-1 levels in CDH patients with PPH (227.0+/-98.9 ng/ml) were increased compared with levels in CDH patients without PPH (140.29+/-37.4 ng/ml; p<0.05) and controls (130.0+/-23.8 ng/ml; p<0.05). Mean serum ELAM-1 levels in CDH patients with PPH (116.5+/-19.2 ng/ml) were significantly increased compared with levels in CDH patients without PPH (79.3+/-27.9 ng/ml; p<0.01) and controls (58.4+/-14.5 ng/ml; p<0.001). Mean serum VCAM-1 levels in CDH patients with PPH (1596.9+/-460.4 ng/ml) were significantly higher compared with levels in CDH patients without PPH (1069.3+/-444.6 ng/ml; p<0.01) and controls (838.0+/-171.2 ng/ml; p<0.001). But serum adhesion molecule levels in CDH patients without PPH were no different from controls statistically. Pulmonary vascular endothelial cells from CDH lung with PPH had strong expression of adhesion molecules compared with controls. Up-regulated expression of adhesion molecules on the endothelium of pulmonary vessels and high circulating levels of adhesion molecules in CDH patients with PPH suggest that adhesion molecules may play a role in the development of PPH in CDH.

Case-Control Studies↗

PubMed2003

Abnormal vasculature in intestinal neuronal dysplasia.

Intestinal neuronal dysplasia (IND) is an intestinal motility disorder, which clinically resembles Hirschsprung's disease (HD). Adventitial fibromuscular dysplasia (AFMD) consists of proliferation of smooth muscle cells and collagen fibers in the adventitia of blood vessels. The purpose of this study was to investigate vascular abnormalities in large bowel biopsies from patients with isolated HD, IND associated with HD and isolated IND. Large bowel biopsies from patients presenting with isolated HD ( n=23), IND associated with HD ( n=11), isolated IND ( n=16) and normal bowel as controls ( n=6) were investigated using acetylcholinesterase (AChE) histochemistry, van Gieson staining and alpha-smooth muscle actin (alpha-SMA) immunohistochemistry. Increased AChE activity around submucosal vessels was found in 9/16 (56%) cases with isolated IND, 3/11 (27%) cases of IND associated with HD, 5/23 (21%) isolated HD cases and 0/6 controls. AFMD was found in 10/16 (62%) of the isolated IND cases, 4/11 (362) of the cases with IND associated with HD and 4/23 (17%) cases of HD without IND using van Gieson staining. None of the control specimens revealed AFMD. Increased alpha-SMA immunoreactivity filaments were demonstrated in the submucosal vessel wall in 9/16 (56%) of isolated IND and 2/11(18%) of IND associated with HD cases. Normal alpha-SMA immunoreactivity around submucosal vessels was seen in isolated HD and controls. Abnormal submucosal vasculature is a common histological finding in isolated IND and IND associated with HD and may be a useful additional diagnostic feature in these patients.

Adolescent↗

PubMed2003

Unilateral spermatic vessel ligation in prepubertal rats decreases microvascular blood flow to ipsilateral testis postpubertally.

High ligation of spermatic vessels (HLSV) and low ligation of spermatic vessels (LLSV) have been described in the surgical treatment of high undescended testis. Testicular capillary blood flow utilizing laser Doppler flowmetry after these maneuvers has not been studied thus far; hence, this study was designed. Thirty male rats, aged 30 days, were randomized into three groups: group I, sham surgery; group II, unilateral HLSV ligation and division of main spermatic vessels high in the left retroperitoneal space; and group III, unilateral LLSV ligation and division of main spermatic vessels close to the left testis. Thirty days later, both testes were explored through scrotal incision and capillary blood flow was measured by laser Doppler flowmeter continuously and simultaneously from both testes. The right testis, the vessels of which were not disturbed in any group, served as the control. The mean decrease in the testicular blood flow between the right testis and left testis was 4.8, 92.9, and 74.2 PFU in groups I, II, and III respectively. There was a significant ( p<0.05) decrease in ipsilateral blood flow in group-II and group-III rats; however, upon comparing group II with group III, there was no significant difference between them. Both HLSV and LLSV in rats significantly decrease the capillary blood flow of ipsilateral testis. Although LLSV group had less reduction in capillary blood flow to the ipsilateral testis than HLSV group, the difference was not statistically significant.

Animals↗

PubMed2003

Increased expression of ICAM-1 and VCAM-1 in the lung of nitrofen-induced congenital diaphragmatic hernia in rats.

Recently, increased expression of inflammatory cytokine, tumor necrosis factor (TNF)-alpha, has been reported in both humans and animal models with CDH and the decreased TNF-alpha expression in CDH lung after antenatal dexamethasone (Dex) treatment. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 are induced by several inflammatory cytokines such as TNF-alpha. The aim of this study was to investigate pulmonary ICAM-1 and VCAM-1 expression in CDH lung in rats and to determine the effect of antenatal glucocorticoid. CDH model was induced in pregnant rats following administration of nitrofen on day 9.5 of gestation. In control animals, the same dose of olive oil was given without nitrofen. Dex (0.25 mg/kg) was given on day 18.5 and 19.5 of gestation. RT-PCR was performed to evaluate the relative amount of ICAM-1 and VCAM-1 mRNA expression. Fluorescein immunohistochemistry using anti-ICAM-1 and anti-VCAM-1 antibody was performed using light and confocal microscopy. ICAM-1 and VCAM-1 mRNA expression and ICAM-1 and VCAM-1 immunoreactivity were markedly increased in CDH lung compared to controls. Dex downregulated the expression of both adhesion molecules in the hypoplastic lung. Increased ICAM-1 and VCAM-1 mRNA expression in hypoplastic lungs would suggest that the increased local synthesis of pulmonary adhesion molecules may induce respiratory distress in CDH. Decreased expression of adhesion molecules in CDH lungs after Dex treatment suggests that antenatal glucocorticoids therapy may improve pulmonary immaturity and associated respiratory distress in nitrofen-induced CDH lung.

Animals↗

PubMed2003

ICAM-1 expression is upregulated in reflux nephropathy.

Reflux nephropathy (RN) is a major cause of end-stage renal failure in children and young adults. Intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein, has a role in the regulation of interaction among immune cells. It has been demonstrated that increased levels of tubular ICAM-1 correlate with an extent of tubular damage in diabetic nephropathy. We hypothesized that ICAM-1 local synthesis is altered in reflux nephropathy and therefore designated this study to investigate ICAM-1 expression in RN. The kidney specimens from six patients with severe reflux nephropathy secondary to primary vesicoureteral reflux were obtained at the time of nephrectomy. Control materials included normal kidney specimens obtained from three adult patients during partial nephrectomy for an incidentaloma. Fluorescent immunohistochemistry was carried out using monoclonal antibodies to ICAM-1 utilizing confocal laser scanning microscopy. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of ICAM-1. In the control kidneys, there was lack of ICAM-1 immunoreactivity in the interstitium and proximal tubules and moderate immunoreactivity in the glomerulus. In the refluxing kidney there was strong ICAM-1 immunoreactivity in the glomerulus, interstitium and proximal tubules. The RT-PCR showed strong ICAM-1 mRNA expression in the refluxing kidneys and absent or weak ICAM-1 expression in the controls. Our findings of increased expression of ICAM-1 in the severe reflux nephropathy kidney suggests that ICAM-1 may play a role in the pathogenesis of renal parenchymal damage associated with RN.

Adult↗

PubMed2003

Increased c-Met tyrosine kinase expression in segmental renal dysplasia.

Renal dysplasia (RD) is a disorganized development of renal parenchyma that results in a deficit of functional renal tissue. It has been suggested in the animal model that increased expression of HGF receptor, c-Met tyrosine kinase in the epithelial cells during kidney development may induce a growth of dysplastic epithelia and result in RD. The aim of this study was to investigate the immunoreactivity of c-Met tyrosine kinase in the dysplastic kidney in order to further understand the pathogenesis of RD. Specimens of dysplastic upper pole kidney were obtained from 19 patients during upper pole partial nephrectomy for non-functioning upper moiety of duplex kidney. In the dysplastic kidney, there was strong c-Met immunoreactivity in the epithelium of primitive tubules. In contrast, c-Met immunoreactivity was barely detectable in the normal kidney. Markedly increased expression of HGF receptor, c-Met tyrosine kinase in renal dysplasia suggests that HGF may be involved in the development of renal dysplasia.

Child↗

PubMed2003

Is contralateral exploration necessary in girls with unilateral inguinal hernia?

BACKGROUND/PURPOSE: Routine contralateral groin exploration in girls with unilateral inguinal hernia (UIH) continues to be controversial. The aim of this study was to determine the incidence of contralateral hernia development in girls after UIH repair. METHODS: Between 1972 and 2000, 391 girls underwent repair of UIH. Ninety-one (23%) of the 391 girls underwent routine contralateral exploration during UIH repair and were excluded from the study. The median age at operation in the remaining 300 girls was 3.3 years (range, 1 month to 14 years). Two hundred ten (70%) girls had right-sided and 90 (30%) had left-sided UIH. Familial history of hernia was identified in 8 (3%) patients. The follow-up ranged from 1.5 to 14 years. Mann-Whitney U test was used for intergroup comparison. RESULTS: A contralateral hernia developed in 24 (8%) of the 300 patients who had unilateral repair of inguinal hernia. Median time from operation to occurrence of the contralateral hernia was 3 years (range, 1 to 4 years). Age at operation, side of hernia, and familial history did not influence the development of contralateral hernia. CONCLUSIONS: These data suggest that the low incidence of contralateral hernia development in girls undergoing UIH repair does not justify routine contralateral groin exploration.

Adolescent↗