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G Lajoie

Publications and source records attributed to G Lajoie.

At least 19 recordsLinked to original sources
PubMed2001

Predicting progression in IgA nephropathy.

Immunoglobulin A (IgA) nephropathy is one of the most common primary types of glomerulonephritis to progress to end-stage renal disease. Its variable and often long natural history makes it difficult to predict outcome. We investigated the association of the rate of renal function decline based on the slope of creatinine clearance over time with demographic, clinical, laboratory, and histological data from 298 patients with biopsy-proven IgA nephropathy with a mean follow-up of 70 months. Using univariate analysis, urinary protein excretion at baseline and Lee pathological grading, as well as mean arterial pressure (MAP) and urinary protein excretion during follow-up, were associated with the rate of deterioration in renal function. Of these, only MAP and urinary protein excretion during follow-up were identified as independent factors by multiple linear regression analysis. The combination of best accuracy of prediction and shortest observation time using these two parameters was reached between the second and third years of follow-up. A semiquantitative method of estimating the rate of progression by using these factors was developed. These results indicate that MAP and severity of proteinuria over time are the most important prognostic indicators of IgA nephropathy. The potential relevance of the algorithm in patient management is shown.

Adolescent↗
PubMed2001

Approach to the diagnosis of thin basement membrane nephropathy in females with the use of antibodies to type IV collagen.

CONTEXT: Thin basement membrane nephropathy is recognized by a diffusely thin glomerular basement membrane (GBM) ultrastructurally. In contrast to Alport syndrome (AS), there is no GBM thickening, lamellation, or granular inclusions. Morphologically, there is overlap between thin basement membrane nephropathy and AS in female patients in whom there might be only thin GBM and no pathognomonic findings of AS. OBJECTIVE: To determine if the use of antibodies to collagen IV is helpful in making the distinction between thin basement membrane nephropathy and AS in female patients with primarily thin GBMs. DESIGN: We examined renal biopsies from 9 adult female patients with thin GBMs for the presence of alpha1, alpha3, alpha4, and alpha5 chains of type IV collagen by immunofluorescence. RESULTS: In 2 patients with segmental GBM staining, no suggestion for AS was found on physical examination or in their family history. In the remaining 7 patients with normal GBM staining, 4 had family members with end-stage renal disease of unknown etiology, raising the suspicion of X-linked or autosomal-recessive AS. Three patients were presumed to have thin basement membrane nephropathy. CONCLUSION: Segmental GBM staining for alpha3, alpha4, and alpha5 chains of type IV collagen raises the suspicion of AS in the presence of adequate controls and other supporting evidence. Normal GBM staining for alpha3, alpha4, and alpha5 chains of type IV collagen, however, does not exclude AS.

Adult↗
PubMed2000

Evaluation of the metal binding properties of the histidine-rich antimicrobial peptides histatin 3 and 5 by electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) was used to investigate metal ion interactions with salivary peptides histatin 3 (H3) and histatin 5 (H5). Conformational changes of these peptides in the presence of metal ions were studied using circular dichroism spectroscopy. H3 and H5 formed high affinity complexes with Cu(2+) and Ni(2+) and, to a lesser extent, with Zn(2+). Both peptides show the potential for multiple binding sites for Cu(2+) and Ni(2+) and only a single strong binding site for Zn(2+). The binding of a third Cu(2+) ion to H3 seems to enable the binding of a fourth ion to H3. The binding of a second and third Ni(2+) ion to H5 has a similar effect in enabling the binding of a fourth ion. None of the metal ions examined stabilized a regular secondary structure for either peptide. Subtle changes in overall conformation are seen with the addition of Cu(2+) to both H3 and H5.

Amino Acid Sequence↗
PubMed2000

Chitinase genes responsive to cold encode antifreeze proteins in winter cereals.

Antifreeze proteins similar to two different chitinases accumulate during cold acclimation in winter rye (Secale cereale). To determine whether these cold-responsive chitinases require post-translational modification to bind to ice, cDNAs coding for two different full-length chitinases were isolated from a cDNA library produced from cold-acclimated winter rye leaves. CHT9 is a 1,193-bp clone that encodes a 31.7-kD class I chitinase and CHT46 is a 998-bp clone that codes for a 24.8-kD class II chitinase. Chitinase-antifreeze proteins purified from the plant were similar in mass to the predicted mature products of CHT9 and CHT46, thus indicating that there was little chemical modification of the amino acid sequences in planta. To confirm these results, the mature sequences of CHT9 and CHT46 were expressed in Escherichia coli and the products of both cDNAs modified the growth of ice. Transcripts of both genes accumulated late in cold acclimation in winter rye. Southern analysis of winter rye genomic DNA indicated the presence of a small gene family homologous to CHT46. In hexaploid wheat, CHT46 homologs mapped to the homeologous group 1 chromosomes and were expressed in response to cold and drought. We conclude that two novel cold-responsive genes encoding chitinases with ice-binding activity may have arisen in winter rye and other cereals through gene duplication.

Amino Acid Sequence↗
PubMed2000

Tumor necrosis factor receptor p55-deficient mice respond to acute Yersinia enterocolitica infection with less apoptosis and more effective host resistance.

Tumor necrosis factor (TNF) has generally been regarded as a protective cytokine in host defense against bacterial infections. In the present study, we evaluated the role of TNF in the acute phase of infection by Yersinia enterocolitica by using mice rendered genetically deficient in TNF receptor p55 (TNFRp55(-/-)). Unexpectedly, TNFRp55(-/-) mice showed more effective resistance to the bacteria, reflected in enhanced bacterial clearance and less tissue damage, than did control C57BL/6 mice. C57BL/6 mice showed evidence of extensive apoptosis in the spleen accompanied by a selective decrease in the CD4(+)-T-cell population of splenocytes, whereas TNFRp55(-/-) mice were spared these changes. The splenocytes from TNFRp55(-/-) mice also maintained a robust gamma interferon IFN-gamma response to mitogenic stimulation, while the comparable response in C57BL/6 mice was impaired. In addition, splenocytes harvested from infected mice demonstrated lower production of interleukin-10 IL-10 in TNFRp55(-/-) mice than in C57BL/6 mice. These findings suggest that Yersinia can induce TNFRp55-mediated apoptosis of splenocytes in the acute phase of the infection and that alteration of T-cell-generated cytokines can dramatically alter the early events in host defense against this pathogen.

Acute Disease↗
PubMed1999

Outcome of kidney transplantation from high-risk donors is determined by both structure and function.

METHOD: Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both). RESULTS: Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). CONCLUSION: Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.

Aged↗
PubMed1999

Calciphylaxis precipitated by ultraviolet light in a patient with end-stage renal disease secondary to systemic lupus erythematosus.

Calciphylaxis is a rare and severe calcification syndrome described mainly in patients with end-stage renal disease (ESRD) undergoing dialysis or with a renal transplant. This life-threatening condition is characterized by the abrupt onset of painful ischemic skin ulcers and necrosis. Secondary local and systemic infection may supervene and, without timely and appropriate interventions, calciphylaxis may be fatal. A precipitant or challenging agent is believed to be necessary to initiate the process. We describe a case of a woman with ESRD receiving continuous ambulatory peritoneal dialysis who developed calciphylaxis in the setting of severe hyperparathyroidism after receiving UV photoradiation therapy. We suggest that the UV light served as the challenging agent in the precipitation of this devastating condition.

Adult↗
PubMed1998

NMR studies of the antimicrobial salivary peptides histatin 3 and histatin 5 in aqueous and nonaqueous solutions.

Conformational studies of the salivary peptides histatin 3 (H3) and histatin 5 (H5) were performed by NMR and circular dichroism (CD) in aqueous and nonaqueous solutions. Histatin 5 has no defined structure in H2O but adopts a more helical conformation in dimethyl sulfoxide and aqueous trifluoroethanol. This is in agreement with the CD analysis, which shows no secondary structure in H2O but increasing helical content in the presence of trifluoroethanol. CD analysis shows that H3 has less propensity to form a helical structure than H5 in similar conditions. The NMR analysis of H3 in H2O at pH 7.4 reveals that its conformational mobility is less than that of H5 as indicated by the observation of backbone cross peaks alphaN (i, i + 1) and NN (i, i + 1) and the slow exchanging amide protons in the C-terminus. However, H3 remains essentially unordered as suggested by the lack of longer range nuclear Overhauser effects (NOEs) in the NOESY spectrum. H3 becomes much more ordered in a mixture of 50:50 H2O-dimethyl sulfoxide as indicated by the numerous NOEs, including several side chain to side chain and side chain to backbone connectivities. Our data suggest that in these conditions H3 contains a turn in the region of K13 to K17 and possibly a 3(10) helix at the C-terminus. This study demonstrates that H3 and H5 are both conformationally mobile and that each adopt different types of conformations in aqueous and nonaqueous solutions.

Amino Acid Sequence↗
PubMed1996

Mast cells in acute cellular rejection of human renal allografts.

Mast cells (MCs), few in the normal kidney, are found in increased number in the renal parenchyma in diseases associated with persistent chronic inflammation. MCs are not easily identified in routinely processed archival tissue sections with histochemical stains. A more reliable method of detection was provided with the introduction of MC tryptase-specific monoclonal antibodies. To determine the possible role of MCs in renal allograft rejection, we studied 28 biopsy specimens from renal allografts that had been in place for various lengths of time (from 3 days to 40 months) in patients whose primary diagnosis was acute interstitial rejection; the specimens were associated with varying degrees of interstitial fibrosis, edema, and hemorrhage. The specimens were graded on a semiquantitative scale (from 0 to 3+) for the severity of rejection, the degree of interstitial fibrosis, interstitial edema, and interstitial hemorrhage. Eosinophils, plasma cells, and MCs were quantitatively evaluated in these biopsy specimens. MCs were detected by use of a commercially available anti-MC tryptase monoclonal antibody, which proved to be an excellent tool to detect MCs in routinely processed paraffin sections. A positive correlation was found between the number of MCs and the time since transplantation (R = 0.841, P < 0.005) and between the number of MCs and the severity of interstitial fibrosis (R = 0.489, P < 0.005), as well as with interstitial edema (R = 0.517, P < 0.005). MCs were increased in number in patients with moderate (n = 18; mean, 18.00 MCs per 10 high power fields [HPFs]) and severe (n = 5; mean, 12.20 MCs per 10 HPFs) acute rejection compared with patients with mild (n = 5; mean, 2.44 MCs per 10 HPFs) acute rejection and normal kidneys (n = 6; mean, 1.75 MCs per 10 HPFs). These results suggested that MCs might play a role in the process of acute rejection of renal allografts and in the development of interstitial fibrosis.

Acute Disease↗
PubMed1995

Renal thrombotic microangiopathy associated with multicentric Castleman's disease. Report of two cases.

Castleman's disease (also called giant lymph node hyperplasia or angiofollicular lymph node hyperplasia) is a clinicopathological entity of unknown etiology. Two histologic patterns of lymph nodes are classically recognized: the hyaline-vascular and plasma-cell variants. Recently, multicentric Castleman's disease has emerged as a separate clinical entity manifested primarily by generalized lymphadenopathy and systemic manifestations, such as thrombocytopenia, hemolytic anemia, hepatosplenomegaly, altered liver function tests, central nervous system alterations, and autoimmune manifestations. A number of renal alterations have been described in association with the two pathological variants of Castleman's disease, but thrombotic microangiopathy has been previously reported only once in a patient with Castleman's disease. No renal biopsy was performed in that patient, although there was evidence of renal dysfunction. We report two cases of biopsy-proven renal thrombotic microangiopathy associated with multicentric Castleman's disease. In addition to having lymph node pathology characteristic of Castleman's disease, both patients presented with generalized lymphadenopathy and systemic manifestations, including acute renal failure, hypergammaglobulinemia, anemia, thrombocytopenia, and hypoalbuminemia. Autoantibodies were present in both patients, including antiphospholipid antibodies in one patient. The renal biopsies, examined by light, immunofluorescence, and electron microscopy, were diagnostic for renal thrombotic microangiopathy. The simultaneous development of two rather uncommon syndromes, multicentric Castleman's disease and renal thrombotic microangiopathy, suggests a possible link between Castleman's disease and renal thrombotic microangiopathy. Furthermore, we propose that the production of autoantibodies, in particular antiphospholipid antibodies, may lead to the development of thrombotic microangiopathy in some patients with multicentric Castleman's disease.

Adult↗
PubMed1995

Proliferative activity of cyst epithelium in human renal cystic diseases.

Increased proliferative activity of the renal tubular epithelium is thought to be a prerequisite for renal cyst formation by many investigators. However, in humans, the exact in vivo proliferation rate of epithelial cells lining these cysts is not known. In this study, which used immunohistochemical methods with an antibody to proliferating cell nuclear antigen (PCNA), the proliferation index (PI) (percentage of PCNA positive cell nuclei among epithelial cells lining the renal cysts) was determined in 10 cases of autosomal dominant polycystic kidney disease (ADPKD), 8 cases of autosomal recessive polycystic kidney disease (ARPKD), and 8 cases of acquired cystic kidney disease (ACKD). Cysts with proximal and distal nephron phenotype and cysts with markedly thickened basement membranes, as well as cysts lined by atrophic (flattened), "regular" (cuboidal or cylindrical), and hyperplastic epithelium, were evaluated separately. The overall PI of cyst epithelium (excluding hyperplastic cysts) was 2.58 in ADPKD, was 10.5 in ARPKD, and was 3.61 in ACKD. Overall, there were only minor differences in the PI between the various types of cysts. Cysts with hyperplastic epithelium in ACKD (unlike in ADPKD) showed a high PI (9.1). For comparison, the PI of two renal cell carcinomas occurring in two ACKD cases was also determined (13.70 and 8.67%). The PI of tubular epithelium in normal kidneys was only 0.22 to 0.33%, depending on the tubule segment. In contrast, in polycystic kidneys, those noncystic segments of the nephron from which the cysts are thought to originate (distal nephron (specifically collecting duct)) in ARPKD, primarily distal in ADPKD, proximal and distal in ACKD, had PI values similar to those of the cyst epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

A comparative study of DNA quantitation in breast carcinoma with image cytometric analysis and in vitro fine-needle aspiration with flow cytometric analysis.

The DNA ploidy status of 53 fresh primary breast carcinomas was analyzed in a comparative study of flow cytometric (FCM) and image cytometric (ICM) analyses. Samples for FCM analysis were obtained with an in vitro fine-needle aspiration technique. Touch imprints from the same tumors were analyzed by three independent observers by ICM analysis. An ICM comparative study of "sequential" and "visually selected" nuclei also was performed. There was an overall concordance of 0.85 in the classification of diploid and nondiploid tumors by FCM and ICM analyses. In most discordant cases, a nondiploid population was identified by FCM analysis alone. This is attributed to the superior resolution of and sampling/preparatory method used for FCM analysis. There was an overall concordance of 0.91 in the classification of diploid and nondiploid tumors by ICM analysis. Selective analysis of atypical nuclei resulted in increased sensitivity in the detection of DNA aneuploid populations by ICM analysis.

Biopsy, Needle↗
PubMed1992

Hepatoid adenocarcinoma of the papilla of Vater.

An adenocarcinoma of the papilla of Vater showing hepatoid differentiation similar to that described for hepatoid adenocarcinoma of the stomach is reported. The tumor was a poorly differentiated adenocarcinoma with clear cells containing occasional hyaline droplets and exhibiting bile secretion. Alpha-fetoprotein (AFP), alpha 1-antitrypsin (alpha 1-AT) and carcino-embryonic antigen (CEA) were demonstrated by immunoperoxidase staining. This appears to be the first report of a hepatoid adenocarcinoma at this location.

Adenocarcinoma↗
PubMed1990

Crystal and molecular structure of two geometrically restricted chemotactic tripeptides, analogues of formyl-methionine-leucine-phenylalanine.

The crystal structures of HCO-Met-Leu-Phe-OC(CH3)3, (CH25H39N3O5S), fMLP-OtBu, and HCO-Met psi [CSNH]-Leu-Phe-OCH3, (C22H33N3O4S2), fMS LP-OMe, have been determined by single crystal X-ray diffraction, and their conformational properties investigated by molecular mechanics energy calculations. Crystals of fMLP-OtBu are monoclinic, space group P2(1), a = 12.027(4), b = 9.492(3), c = 12.660(4) A, beta = 101.99(3) degrees, Z = 2; those of fMS LP-OMe are orthorhombic, space group P2(1)2(1)2(1), a = 7.130(1), b = 12.097(2), c = 31.060(5) A, Z = 4. The first compounds fMLP-OtBu is the t-butyl ester of the tripeptide fMLP that represents one of the most potent compounds in inducing the lysozyme release from human neutrophils that reflects the chemotactic activity. From the crystal structure, it is shown that the orientation of the phenylalanine side chain is largely affected by the presence of the bulky group. fMSLP-OMe was shown to be inactive after thionation of the methionine residue in the original tripeptide. Nevertheless, the crystal structure does not reveal any influence of the presence of the thionated peptidic bond on the backbone conformation. The X-ray results have been used to generate parameters for empirical energy calculations. Subsequently, a strategy based on random generation of conformations followed by energy-minimization was applied to investigate the conformational space of thiopeptides, in comparison with normal peptides. From molecular free energy calculations, it is shown that the main influence of the introduction of a thioamide bond on the molecular structure is to prevent the existence of C7(eq) conformations involving the thiomethionine residue. Consequently, a larger number of conformers are found to form intramolecular hydrogen bonds involving the formyl group, reducing its availability to interact with the receptor. For the first time, the theoretical prediction of the existence of C7eq conformations for fMLP is made. The resulting conformers are compared to previously active structures of these chemotactic agents.

Amino Acid Sequence↗
PubMed1989

Some remarkable effects of thiopeptide and derived linkages on lysozyme release from neutrophils by esters of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe-OR).

A variety of recently synthesized analogues of the chemotactic agent f-Met-Leu-Phe-OR modified in the backbone were tested for their ability to induce the release of lysozyme from human neutrophils. In sharp contrast to the effects of thiopeptide linkages on the biological activity of Leu5-enkephalin as previously reported, the presence of single thioamide bonds at either one of the endo-positions of the chemotactic peptide, abolished activity. Thioamide-derived linkages such as amidoximes and cyanamidines were generally also detrimental to activity, except in the cases of the cyanamidoformyl derivatives which showed enhanced activity and two amidoxime esters, one O-acetylated and the other O-esterified intramolecularly, which retained moderate activity. The mechanistic significance of these results is discussed in terms of conformational effects on receptor recognition.

Humans↗
PubMed1984

Synthesis and biological activity of monothionated analogs of leucine-enkephalin.

The synthesis of the four regioisomers of monothionated Leu-enkephalins (Leu-Enk) from previously reported protected precursors is described. The Tyr1-thio analog was obtained as a 1:1 mixture of the L- and D-Tyr diastereomers. The pure compounds were tested for opiate-like activity by using the guinea-pig ileum (GPI) and mouse vas deferens (MVD) preparations, by assessing analgesic effects following intra-cerebroventricular administration and by examining their ability to displace [3H]-D-Ala2, D-Leu5-enkephalin (DADLE) and [3H]-dihydromorphine from rat brain homogenates. The results demonstrate that depending on the backbone position of the thioamide function, activity can be decreased or increased. In the smooth muscle preparations as well as in the opiate binding tests, the activity of D,L-Tyr1-thio-Leu-Enk and Gly3-thio-Leu-Enk was reduced. The activity of the latter analog was also diminished in the analgesia test. In all biological assays, Phe4-thio-Leu-Enk was either equally or slightly less potent than the parent compound. However, introduction of the sulfur atom in position 2 of Leu-Enk increased the potency of the compound in all assays, the MVD assay being the most sensitive. The results are interpreted in terms of the thioamide (amide) function in receptor recognition processes, the probable behavior of thiopeptides toward physiologically relevant peptidases and the structural divergences between tissue-specific receptors.

Amino Acids, Sulfur↗
PubMedDate not supplied

Cell proliferation in the developing human kidney.

In a previous study, utilizing antibodies to proliferating cell nuclear antigen (PCNA), we determined the proliferation index (PI) (percentage of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both adult and pediatric kidneys was very low (below 0.5 in all examined cell populations). In our present study, we investigated cell proliferation in the developing human kidney with an antibody to PCNA. Histologically normal kidneys were collected from 25 fetuses (spontaneous abortions and stillborns) ranging from 10 wk of gestation to term. Immature mesenchyme (blastema), immature early tubules, ampulla of ureteric bud, proximal tubules, Tamm-Horsfall protein (THP)-positive tubules, distal tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature early tubules remains high (33-43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases starting from the second trimester. The PI of THP-positive tubules, distal tubules, collecting ducts, and glomeruli starts out relatively high (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as term approaches (1.8, 1.3, 1.2, and 1.4, respectively). Interestingly, as soon as proximal tubules become differentiated (appearance of light microscopic features of proximal tubular epithelium with TP lectin positive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to show changes of the PI in various renal cell populations during human nephrogenesis. These changes in the PI relate to the stage of differentiation of the developing nephron segments.

Cell Division↗