PubMed Health⌕ Search

Biomedical subjects

G Guay

Publications and source records attributed to G Guay.

At least 19 recordsLinked to original sources
PubMed2001

A family-based study of metabolic phenotypes in calcium urolithiasis.

BACKGROUND: A family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. METHODS: We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent outpatient evaluations simultaneously, including 24-hour urine collection and oral calcium loading. Phenotypes were compared between affected and unaffected sibs from the same sibship. RESULTS: Eighty-three sibships comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176 unaffected sibs, 68 males and 108 females) from 71 families were analyzed. Daily urine calcium excretion was higher in affected compared with unaffected sibs (0.64 +/- 0.33 vs. 0.50 +/- 0.22 mmol Ca(2+)/mmol creatinine, respectively, P < 10(-5)). This corresponded to absolute values of 7.4 +/- 3.9 and 5.1 +/- 2.3 mmol Ca(2+)/day, respectively, for affected and unaffected males, and 5.4 +/- 2.6 and 4.2 +/- 1.9 mmol Ca(2+)/day, respectively, for affected and unaffected female sibs. When analyzed by tertile of onset age of stone passage, the differences in urine calcium were only significant in the first two tertiles (with onset age of stone passage <35 years). The fasting urine Ca(2+)/creatinine ratio was significantly higher in stone formers compared with control sibs (0.46 +/- 0.27 vs. 0.40 +/- 0.27, P = 0.04), as was the postcalcium load Ca(2+)/creatinine ratio (0.57 +/- 0.46 vs. 0.43 +/- 0.41, respectively, P = 0.02). Body mass index was marginally significantly higher in stone forming sibs (P = 0.04). Other urine phenotypes, including oxalate, phosphate, magnesium, citrate, urate, sodium, ammonium, and volume, were not associated with stone passage. CONCLUSION: Increased urine calcium excretion is the only phenotype associated with a kidney stone formation in these French-Canadian families.

Adolescent↗
PubMed2001

Exclusion mapping of major crystallization inhibitors in idiopathic calcium urolithiasis.

PURPOSE: We determined whether genetic variation at 3 loci coding for putative crystallization inhibitors is linked to calcium urolithiasis. MATERIALS AND METHODS: We studied a cohort of 64 French-Canadian sibships including multiple recurrent calcium stone formers, comprising 154 independent pairs of siblings with at least 1 stone episode. Physical and meiotic mapping of the genes coding for osteopontin and uromodulin (Tamm-Horsfall protein) as well as the osteocalcin related gene (ORG or putative nephrocalcin) was performed and microsatellite markers were identified. We used nonparametric linkage analysis in the whole affected sib pair cohort as well as in affected pairs without hypercalciuria, that is concordant for 24-hour urine calcium excretion in the first quartile (mean plus or minus standard deviation 0.053 +/- 0.020 mmol./kg. or 3.4 +/- 1.3 mmol. daily), and in the first and second quartiles (mean 0.064 +/- 0.027 mmol./kg. or 4.9 +/- 2.1 mmol. daily, respectively). RESULTS: Lod scores were less than 0.3 for all 3 loci using these affection statuses. Further analysis enabled the exclusion of uromodulin at (relative risk or lambda = 3.9 and 2.5), osteopontin (lambda = 2.7 and 1.6) and ORG (lambda = 5.5 and 3.7) for affected sib pairs concordant for urine calcium excretion in the lowest and 2 lowest quartiles, respectively. CONCLUSIONS: Loci encoding 3 crystallization inhibitors are unlikely to be major genes involved in calcium stone formation in our population.

Calcium Oxalate↗
PubMed2000

Calcium regulates the association between mitochondria and a smooth subdomain of the endoplasmic reticulum.

Association between the ER and mitochondria has long been observed, and the formation of close contacts between ER and mitochondria is necessary for the ER-mediated sequestration of cytosolic calcium by mitochondria. Autocrine motility factor receptor (AMF-R) is a marker for a smooth subdomain of the ER, shown here by confocal microscopy to be distinct from, yet closely associated with the calnexin- or calreticulin-labeled ER. By EM, smooth ER AMF-R tubules exhibit direct interactions with mitochondria, identifying them as a mitochondria-associated smooth ER subdomain. In digitonin-permeabilized MDCK cells, the addition of rat liver cytosol stimulates the dissociation of smooth ER and mitochondria under conditions of low calcium. Using BAPTA chelators of various affinities and CaEGTA buffers of defined free Ca(2+) concentrations and quantitative confocal microscopy, we show that free calcium concentrations <100 nM favor dissociation, whereas those >1 microM favor close association between these two organelles. Therefore, we describe a cellular mechanism that facilitates the close association of this smooth ER subdomain and mitochondria when cytosolic free calcium rises above physiological levels.

Animals↗
PubMed2000

Evaluation of the calcium-sensing receptor gene in idiopathic hypercalciuria and calcium nephrolithiasis.

BACKGROUND: Calcium urolithiasis is in part genetically determined and associated with idiopathic hypercalciuria. METHODS: We have used a candidate gene approach to determine whether the calcium-sensing receptor (CaR) gene is linked to idiopathic hypercalciuria and calcium urolithiasis in a cohort of French Canadian sibships with multiple affected members (64 sibships from 55 pedigrees yielding 359 affected sibling pairs with > or =1 stone episode). RESULTS: Using nonparametric linkage analysis with various intragenic and flanking markers, we showed that the CaR gene could be excluded as a major gene for hypercalciuric stone formation. We excluded the CaR (lod score <-2) at lambdas values of 1.5, 1.68, and 2.6 for sib pairs concordant for at least one stone passage, at least two stone passages, and at least one stone passage and calciuria above the 75th percentile, respectively. Quantitative trait linkage analyses did not suggest that the CaR gene was linked to biochemical markers of idiopathic hypercalciuria. CONCLUSIONS: This study shows that genetic variants of the CaR gene are not associated with idiopathic hypercalciuria and calcium nephrolithiasis in this population of French Canadians.

Calcium↗
PubMed2000

Biogenesis of multilamellar bodies via autophagy.

Transfection of Mv1Lu mink lung type II alveolar cells with beta1-6-N-acetylglucosaminyl transferase V is associated with the expression of large lysosomal vacuoles, which are immunofluorescently labeled for the lysosomal glycoprotein lysosomal-associated membrane protein-2 and the beta1-6-branched N-glycan-specific lectin phaseolis vulgaris leucoagglutinin. By electron microscopy, the vacuoles present the morphology of multilamellar bodies (MLBs). Treatment of the cells with the lysosomal protease inhibitor leupeptin results in the progressive transformation of the MLBs into electron-dense autophagic vacuoles and eventual disappearance of MLBs after 4 d of treatment. Heterologous structures containing both membrane lamellae and peripheral electron-dense regions appear 15 h after leupeptin addition and are indicative of ongoing lysosome-MLB fusion. Leupeptin washout is associated with the formation after 24 and 48 h of single or multiple foci of lamellae within the autophagic vacuoles, which give rise to MLBs after 72 h. Treatment with 3-methyladenine, an inhibitor of autophagic sequestration, results in the significantly reduced expression of multilamellar bodies and the accumulation of inclusion bodies resembling nascent or immature autophagic vacuoles. Scrape-loaded cytoplasmic FITC-dextran is incorporated into lysosomal-associated membrane protein-2-positive MLBs, and this process is inhibited by 3-methyladenine, demonstrating that active autophagy is involved in MLB formation. Our results indicate that selective resistance to lysosomal degradation within the autophagic vacuole results in the formation of a microenvironment propicious for the formation of membrane lamella.

Animals↗
PubMed1999

Suggestive evidence for a susceptibility gene near the vitamin D receptor locus in idiopathic calcium stone formation.

Calcium is the principal crystalline constituent in up to 80% of kidney stones. Epidemiologic studies have suggested that genetic predisposition plays a major role in the etiology of this condition. This study evaluates by a candidate-gene approach whether the vitamin D receptor (VDR) locus on chromosome 12q12-14 is implicated in idiopathic hypercalciuria and calcium nephrolithiasis in a cohort of 47 French Canadian pedigrees. These comprised 54 sibships with a total of 303 pairs of siblings concordant for > or =1 stone episode. Evidence is provided for linkage to nephrolithiasis with microsatellite marker D12S339 (near the VDR locus, P = 0.01), as well as with flanking markers (D12S1663: P = 0.03 and D12S368: P = 0.01). Inclusion of unaffected sibs in the analyses also supported evidence for linkage. Quantitative trait linkage analysis of urinary calcium excretion yielded linkage to some, but not all, markers. This appears to be the first study to suggest linkage for idiopathic calcium stone formation.

Adult↗
PubMed1998

The 1 alpha-hydroxylase locus is not linked to calcium stone formation or calciuric phenotypes in French-Canadian families.

Calcium urolithiasis is often associated with increased intestinal absorption and urine excretion of calcium, and has been suggested to result from increased vitamin D production. The role of the enzyme 1 alpha-hydroxylase, the rate-limiting step in active vitamin D production, was evaluated in 36 families, including 28 sibships with at least a pair of affected sibs, using qualitative and quantitative trait linkage analyses. Sibs with a verified calcium urolithiasis passage (n = 117) had higher 24-h calciuria (P = 0.03), oxaluria (P = 0.02), fasting and postcalcium loading urine calcium/creatinine (Ca/cr) ratios (P = 0.008 and P = 0.002, respectively), and serum 1,25(OH)2 vitamin D levels (P = 0.02) compared with nonstone-forming sibs (n = 120). Markers from a 9-centiMorgan interval encompassing the VDD1 locus on chromosome 12q13-14 (putative 1 alpha-hydroxylase) were analyzed in 28 sibships (146 sib pairs) of single and recurrent stone formers and in 14 sibships (65 sib pairs) with recurrent-only (> or = 3 episodes) stone-forming sibs. Two-point and multipoint analyses did not reveal excess in alleles shared among affected sibs at the VDD1 locus. Linkage of stone formation to the VDD1 locus could be excluded, respectively, with a lambda d of 2.0 (single and recurrent stone formers) and 3.25 (recurrent stone formers). Quantitative trait analyses revealed no evidence for linkage to 24-h calciuria and oxaluria, serum 1,25(OH)2 vitamin D levels, and Ca/cr ratios. This study shows absence of linkage of the putative 1 alpha-hydroxylase locus to calcium stone formation or to quantitative traits associated with idiopathic hypercalciuria. In addition, there is coaggregation of calciuric and oxaluric phenotypes with stone formation.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1997

AMF-R tubules concentrate in a pericentriolar microtubule domain after MSV transformation of epithelial MDCK cells.

Autocrine motility factor receptor (AMF-R) is localized to an intracellular microtubule-associated membranous organelle, the AMF-R tubule. In well-spread untransformed MDCK epithelial cells, the microtubules originate from a broad perinuclear region and AMF-R tubules extend throughout the cytoplasm of the cells. In Moloney sarcoma virus (mos)-transformed MDCK (MSV-MDCK) cells, microtubules accumulate around the centrosome, forming a microtubule domain rich in stabilized detyrosinated microtubules. AMF-R tubules are quantitatively associated with this pericentriolar microtubule domain and the rough endoplasmic reticulum and lysosomes also co-distribute with the pericentriolar mass of microtubules. The Golgi apparatus is closely associated with the microtubule organizing center (MTOC) within the juxtanuclear mass of AMF-R tubules, and no co-localization of AMF-R tubules with the Golgi marker beta-COP could be detected by confocal microscopy. After nocodazole treatment and washout, microtubule nucleation occurs exclusively at the centrosome of MSV-MDCK cells, and only after microtubule extension to the cell periphery does the microtubule cytoskeleton reorganize to generate the pericentriolar microtubule domain after 30-60 min. AMF-R tubules dispersed by nocodazole treatment concentrate in the pericentriolar region in parallel with the reorganization of the microtubule cytoskeleton. MSV transformation of epithelial MDCK cells results in the stabilization of a pericentriolar microtubule domain responsible for the concentration and polarized distribution of AMF-R tubules.

Animals↗
PubMed1997

Ectasias of the subcapsular sinus in lymph nodes of athymic and euthymic rats: a relation to immunodeficiency.

This paper describes a morphologically unusual feature occurring in lymph nodes of some aged euthymic animals but mostly athymic animals. It initially consists of small alveole-like excrescences of the cortical wall of the subcapsular sinus. With dilatation, an excrescence becomes an ectasia which expands into the cortex. Observations suggest that ectasias enlarge under the influence of an increased pressure of the afferent lymph of a node. Such condition conceivably results from a greater lymph formation due to inflammation of the drained tissue site, combined with an impairment to the flow of lymph from the subcapsular sinus into medullary sinuses. A probable relation of ectasia formation to immunodeficiency is discussed. This formation results in the atrophy of the affected lymphoid cell populations of a node which likely contributes to aggravate the deficiency of the immune system.

Aging↗
PubMed1995

GcvA, a LysR-type transcriptional regulator protein, activates expression of the cloned Citrobacter freundii ampC beta-lactamase gene in Escherichia coli: cross-talk between DNA-binding proteins.

Escherichia coli JRG582 is an ampD ampE deletion derivative of strain HfrH and accordingly it is derepressed for expression of the cloned inducible beta-lactamase gene of Citrobacter freundii, carried on plasmid pNU305. Following chemical mutagenesis of JRG582(pNU305) a cefotaxime sensitive mutant was isolated, CS51(pNU305), which produced low levels of beta-lactamase due to a mutation in the host chromosome. Two recombinant plasmids containing genomic DNA from E. coli HfrH, namely pUB5608 and pUB5611, were isolated as a consequence of their ability to restore the beta-lactam resistant phenotype to CS51(pNU305). This ability was due to direct transcriptional activation of the beta-lactamase gene, ampC, rather than complementation of the CS51 mutation. Transposon mutagenesis and subcloning showed that restoration of ampicillin resistance to CS51(pNU305) was the function of a single gene, which maps at 60.3 min on the E. coli chromosome. The gene encodes a 33 kDa protein with significant homology to members of the LysR family of bacterial activator proteins, in particular the AmpR protein from C. freundii. Homology is especially strong over the N-terminal region which includes the helix-turn-helix DNA-binding motif. This gene was shown to complement the gcvA1 mutation at 60.3 min on the E. coli chromosome, and the DNA sequence agrees exactly with the published sequence of gcvA which encodes the transcriptional activator of the inducible glycine cleavage enzyme system. It is suggested that GcvA can activate transcription of ampC by binding to the AmpR binding region upstream of ampC so as to mimic the activated state of AmpR and hence provides an example of cross-talk between DNA-binding proteins of different inducible enzyme systems.

Amino Acid Sequence↗
PubMed1995

Association of neutrophils with high endothelial venules in the neonatal rat lymph nodes: a probable relation to immunoincompetence.

The endothelium of the high endothelial venules (HEVs) of lymph nodes is normally considered to inhibit an association with neutrophils. The present paper shows that for a few weeks after birth, however, neutrophils are commonly associated with the walls of HEVs, the extent depending on the site of the lymph node. Overall, neutrophils increase in numbers in rat nodes from birth until about day 11, and vanish progressively thereafter. Moreover, neutrophils are more abundant in the nodes of standard neonates than in the nodes of pathogen-free neonates raised in an aseptic milieu. It is concluded that the postnatal recruitment of neutrophils by nodal HEVs relates to the then prevailing state of immaturity of the immune system. An explanation is proposed as to why neonatal HEVs of nodes recruit neutrophils and not only lymphocytes, as is the case later in ontogeny.

Analysis of Variance↗
PubMed1991

Peripheral projections of the chick primary sensory neurons expressing gamma-aminobutyric acid immunoreactivity.

The expression of gamma-aminobutyric acid was studied in sensory neurons and peripheral target tissues of the chick dorsal root ganglia by combining immunocytochemistry and electron microscopy. In the chick embryos, the first immunoreaction was observed at embryonic day 12 in 1.4% of ganglion cell bodies. The intensity of immunostaining gradually increased during development and the percentage of immunostained neurons reached an average of 7.3% after hatching. These immunostained cell bodies could be identified as sensory neurons belonging either to some large neurons of the A1 subclass or to a few small neurons of the B1 subclass. The other neuronal cell bodies, corresponding to the A2 and B2 subclasses, as well as the satellite and glial cells were apparently devoid of any gamma-aminobutyric acid immunostaining. Among the peripheral tissues innervated by the primary sensory neurons, the nerve endings of Achilles' tendon and the paravertebral autonomic ganglia appeared devoid of immunoreactivity. In contrast, immunoreactivity was found within nerve endings located in some neuromuscular spindles of the skeletal muscles and within some Herbst's corpuscles in the subcutaneous tissue of the skin. Thus, the present results provide evidence that gamma-aminobutyric acid may be expressed by neuronal cell bodies belonging to two subclasses of primary sensory neurons and could be a putative neurotransmitter involved in the peripheral sensory innervation of, at least in part, skin and skeletal muscles.

Animals↗
PubMed1990

In vivo differentiation of brown adipocytes in adult mice: an electron microscopic study.

The differentiation of brown adipocyte precursor cells was studied in interscapular brown adipose tissue of adult mice by electron microscopy. Different stages of cell differentiation were characterized in situ. Previous autoradiographic studies suggested that interstitial cells represent the precursor cells of fully differentiated brown adipocytes. The present observations provide morphological evidence for a progressive differentiation of interstitial stem cells into mature brown adipocytes. Four typical stages of development were identified: (1) interstitial cells, (2) protoadipocytes, (3) preadipocytes, and (4) mature brown adipocytes. Interstitial stem cells were small spindle shaped cells, situated between brown adipocytes and characterized by a high nuclear-cytoplasmic ratio, the scarcity of organelles, and the absence of lipid inclusions. Protoadipocytes resembled interstitial cells except that they contained a few tiny lipid droplets in their cytoplasm. Preadipocytes had a larger cytoplasm enclosing many mitochondria and lipid droplets; the smooth endoplasmic reticulum was well developed surrounding the lipid droplets, and was closely associated with the mitochondria. Preadipocytes had the typical structure of growing cells, developing long cytoplasmic processes between and around blood capillaries. Mature brown adipocytes represented the final stage of differentiation. Almost all their cellular volume was occupied by lipid droplets and numerous mitochondria with very dense cristae. Brown adipocytes were also characterized by a tight association with blood capillaries, as expected from metabolically active cells requiring oxygen and substrates. These observations provide direct ultrastructural evidence for a progressive differentiation of interstitial cells into brown adipocytes with a continuum of intermediate cellular types.

Adipose Tissue, Brown↗
PubMed1989

Insulin stimulates in vivo cell proliferation in white adipose tissue.

The effects of insulin on white adipose tissue hyperplasia have been studied by quantitative radioautography in streptozotocin diabetic rats. After 1 mo of diabetes, the majority of the adipocytes were extremely small (less than 15 microM) but contained several tiny triglyceride droplets (pauciadipose cells). At this point, the diabetic animals were infused with insulin (8.5 U.kg-1.day-1) delivered via osmotic minipumps for 0-8 days. Control and diabetic rats were pulse-injected with tritiated thymidine (4 h), and samples of parametrial white adipose tissue (PWAT) were collected for quantitative analysis of mitotic frequencies. One-day insulin treatment increased PWAT weight and adipocyte size without stimulating mitoses. However, after 4 days of insulin replacement, the total tissue labeling index increased greater than 120 times over control values. This marked enhancement of mitotic activity principally occurred in interstitial cells rather than in typical adipocytes, pauciadipose cells, or endothelial cells. After 8 days of insulin infusion, the mitotic activity significantly decreased. The results demonstrate that 1) insulin is able to stimulate cell proliferation in PWAT of adult diabetic rats, 2) it transiently stimulates proliferative activity in adipose tissue after a 2- to 3-day period of induction, 3) the increase in adipocyte size precedes the enhancement of mitotic activity, and 4) the effects of insulin were specific, as in the same rats, under the same experimental conditions, insulin did not increase the cell labeling in brown adipose tissue.

Adipose Tissue↗
PubMed1988

Reduction of postjunctional fold density and depth in dystrophic mice.

A total of 769 neuromuscular junction profiles (on 221 muscle fibers) from 21 normal (C57BL/6J +/+), 6 heterozygous (C57BL/6J dy2J/+) and 22 homozygous dystrophic (C57BL/6J dy2J/dy2J) gastrocnemius were photographed in electron microscopy. The fast and slow twitch muscle fibers were differentiated by the width of the Z lines. The number of secondary postjunctional folds per unit length of synaptic cleft was lower in dystrophic than in normal animals. Intermediate values were obtained in heterozygous animals. The length of the postsynaptic membrane was measured and normalized by dividing it by the length of the cross-section through the synaptic cleft. This normalized length of postjunctional membrane was significantly reduced by 45% in dystrophic animals relative to normal animals and by 41% relative to heterozygous animals. The depth of the secondary folds was also significantly reduced in dystrophic animals relative to normal animals in both fast and slow twitch fibers. These morphometric changes of the postjunctional membrane were observed on NMJs whose nerve terminals were not significantly modified by the dystrophic process and were sometimes observed on apparently normal muscle fibers.

Animals↗
PubMed1988

Beta-adrenergic stimulation of brown adipocyte proliferation.

The mechanisms of brown adipose tissue (BAT) growth were studied by quantitative photonic radioautography using tritiated thymidine to follow mitotic activity. To identify the nature of the adrenergic pathways mediating brown adipocyte proliferation and differentiation, the effects of cold exposure (4 days at 4 degrees C) on BAT growth were compared with those induced by treating rats at 25 degrees C with norepinephrine (a mixed agonist), isoproterenol (a beta-agonist), and phenylephrine (an alpha-agonist). The drugs were continuously administrated via osmotic minipumps (0.375 mumol/h during 4 days) implanted subcutaneously. Cold exposure markedly enhanced the mitotic activity in brown adipocyte precursor cells (interstitial cells and preadipocytes) and endothelial cells forming the numerous capillaries. Norepinephrine mimicked the effects of cold exposure, not only on the mitotic activity, but also on the distribution of the labeling among the various cellular types. Isoproterenol entirely reproduced the effects of norepinephrine both on the labeling index and on the cellular type labeling frequency. In contrast, phenylephrine did not stimulate cell division. These results demonstrate that norepinephrine triggers a coordinated proliferation of brown adipocytes and endothelial cells in warm-exposed rats that is similar to that observed after cold exposure. They also suggest that cold exposure stimulates BAT growth by increasing the release of norepinephrine from sympathetic nerves and that the neurohormone activates mitoses in BAT precursor cells via beta-adrenergic pathways.

Adipose Tissue, Brown↗
PubMed1982

Brown adipose tissue hyperplasia: a fundamental mechanism of adaptation to cold and hyperphagia.

Cold acclimation (4 degrees C) and "cafeteria diets" increased the thermic response of rats to catecholamines. This phenomenon was accompanied by six- to eightfold increases of interscapular brown adipose tissue (IBAT) weight, total tissue cytochrome oxidase activity, and total number of brown adipocytes. Quantitative radioautographic experiments using [3H]thymidine disclosed that cold exposure markedly enhanced the mitotic activity in blood capillaries and small-venule endothelial cells, adipose tissue interstitial cells, and preadipocytes rather than in fully differentiated brown adipocytes. IBAT mitotic index increased 70 times over control values after only 2 days of cold exposure. Thereafter, the proliferative activity progressively decreased. IBAT cell composition was modified during cold acclimation as the percentage of interstitial cells and preadipocytes increased over the other cellular types. Because brown adipose tissue is the principal site of norepinephrine-induced thermogenesis in homeothermal animals, it is suggested that brown adipocyte proliferation from precursor cells represents the fundamental phenomenon explaining the increased capacity of cold-acclimated animals to respond calorigenically to catecholamines.

Adaptation, Physiological↗