Biomedical subjects

Marc Grynpas

Publications and source records attributed to Marc Grynpas.

8 recordsLinked to original sources

PubMed2005

Nephrolithiasis and nephrocalcinosis in rats with small bowel resection.

Intestinal resection (IR) may lead to hyperoxaluria and nephrolithiasis. A rat model of IR was developed, in which kidney stones form. We describe the urine chemistries and histopathologic features. Rats underwent resection of 40-45 cm of distal ileum (n=16) or sham resection (SR) (n=8), and were then fed a 1% Na oxalate, 0.02% Ca diet. After 1 week on the diet, 24 h urine samples were obtained for stone chemistries. At 4-7 months after surgery, kidneys were examined grossly and by light microscopy. The extent and location of crystallization was assessed by polarized light. Histochemistry and infrared spectroscopy were used to determine crystal composition. IR rats had higher urine oxalate excretion (P<0.01) and concentration (P<0.001) than SR rats, and lower urine citrate excretion; only IR rats formed kidney stones (12/15 surviving rats). Tissue calcification was found only in kidneys from IR rats, located in the cortex (83% of kidneys), medulla (73%) and papillary tip (47%). Crystals, composed of CaOx, apatite, and calcium carbonate, filled collecting duct lumens, and were associated with tubular obstruction, and interstitial inflammation. Crystals in the papillary interstitium incited inflammation with tubular destruction and development of progressive papillary erosion. This new rat model of nephrolithiasis and nephrocalcinosis resembles the pattern of urinary abnormalities and tissue calcification that may be seen in humans with small bowel resection. The model allows further studies of the mechanisms of renal crystal formation, and possible therapeutic interventions.

Animals↗

PubMed2005

Crystal-associated nephropathy in patients with brushite nephrolithiasis.

BACKGROUND: We have biopsied the renal cortex and papillae of patients who form brushite renal stones asking if this unusual stone type is associated with specific tissue changes. We contrasted these with biopsies of 15 calcium oxalate stone formers, three stone formers with intestinal bypass, and four normal subjects. METHODS: We studied all ten brushite stone formers treated with percutaneous nephrolithotomy (PNL) during the past 3 years using digital video imaging of renal papillae, and obtained cortical and papillary biopsies. Biopsies were analyzed by light and electron microscopy, microinfrared spectroscopy, and electron diffraction. RESULTS: Apatite crystals plugged scattered terminal collecting ducts whose cells were injured or dead, and surrounding interstitium inflamed and fibrotic. White papillary deposits of interstitial apatite particles, so called Randall's plaque, were also present. Glomerular changes and cortical tubular atrophy and interstitial fibrosis were moderate to severe. CONCLUSION: Brushite stone formers combine the interstitial plaque of calcium oxalate stone formers with the collecting duct apatite plugs found in stone formers with intestinal bypass. Collecting duct injury and interstitial fibrosis are severe. Prominent cortical fibrosis, tubule atrophy, and glomerular pathology seem secondary to the collecting duct plugging. We believe crystallization obstructs and destroys terminal collecting duct segments thereby damaging nephrons, perhaps via intranephronal obstruction, and producing a hitherto unrecognized renal disease.

Adolescent↗

PubMed2005

A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia.

Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder characterized by pleiotropic developmental anomalies of the limbs, teeth, face and eyes that was shown recently to be caused by mutations in the gap junction protein alpha 1 gene (GJA1), encoding connexin 43 (Cx43). In the course of performing an N-ethyl-N-nitrosourea mutagenesis screen, we identified a dominant mouse mutation that exhibits many classic symptoms of ODDD, including syndactyly, enamel hypoplasia, craniofacial anomalies and cardiac dysfunction. Positional cloning revealed that these mice carry a point mutation in Gja1 leading to the substitution of a highly conserved amino acid (G60S) in Cx43. In vivo and in vitro studies revealed that the mutant Cx43 protein acts in a dominant-negative fashion to disrupt gap junction assembly and function. In addition to the classic features of ODDD, these mutant mice also showed decreased bone mass and mechanical strength, as well as altered hematopoietic stem cell and progenitor populations. Thus, these mice represent an experimental model with which to explore the clinical manifestations of ODDD and to evaluate potential intervention strategies.

Abnormalities, Multiple↗

PubMed2005

A visual analog scale for measuring dental fluorosis severity.

BACKGROUND: To date, no continuous scale exists for measuring the severity of dental fluorosis (DF). OBJECTIVES: The authors developed and validated a visual analog scale (VAS) for DF. They tested the scale in clinical (DF-endemic area) and laboratory settings. METHODS: Dentists and nondentists (23 per group) were asked to grade the DF severity in photographs of 23 anterior teeth with different DF levels (using a 100-millimeter VAS) to create a VAS for DF. Statistical analysis was performed to validate the new scale. The authors used clinical and laboratory (unerupted third molars) analyses to assess the usefulness of the VAS. RESULTS: The authors used an intraclass correlation coefficient (ICC) to assess the interexaminer (ICC = .79: good agreement) and intraexaminer (.88 < ICC < .97: excellent agreement) reliability during creation of the scale. They used the Spearman rank correlation (r(s)) to validate the VAS against the gold standards (that is, the Thylstrup-Fejerskov index [TFI] and Dean's index [DI]) (the results showed excellent or good correlation for 45 examiners). Two dentist examiners clinically tested the new VAS, and the results showed excellent (r(s) = .922, P < .001) correlation and excellent ICC between the examiners (ICC = .96), as well as good ICC between the TFI and the VAS for DF (ICC = .6). The laboratory study showed better correlation between fluoride concentration and the VAS for DF than between fluoride concentration and the TFI. CONCLUSION: Because of its simplicity, precision and utility in statistical applications, the VAS for DF can be useful in DF studies.

Adolescent↗

PubMed2004

Relationship among MRTA, DXA, and QUS.

Dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) are the accepted modalities for the evaluation of fracture risk in the clinical setting. However, neither method provides a direct measurement of bone mechanics. In this study, we investigated a prototype device, known as a mechanical response tissue analyzer (MRTA), which provides direct mechanical measurements of mechanical properties of bone. A total of 56 healthy volunteers (20 men and 36 women) between the ages of 18 and 83 were recruited. The MRTA was used to measure the cross-sectional bending stiffness (EI) of the ulna bone. Axial speed of sound (SOS) at the ulna bone was determined by QUS; bone mineral content (BMC) and bone mineral density (BMD) were determined by DXA. Correlations, regression analysis, and analyses of variance (ANOVAs) were used to compare the three modalities. These analyses revealed that although there are strong linear relationships among the data collected by the various technologies, the bone properties reflected by MRTA are not fully explained by DXA and QUS. We conclude that the total information conveyed by MRTA measurements is unique. Further research is needed to delineate the different qualities of bone strength that are captured by MRTA, but not by DXA or QUS.

Absorptiometry, Photon↗

PubMed2003

Tissue mineralization is increased following 1-year treatment with high doses of bisphosphonates in dogs.

Suppression of bone turnover using anti-resorptive agents such as bisphosphonates prevents bone loss but also may increase tissue mineralization. This may make the bone more prone to initiate microcracks. The objective of this study was to determine whether suppression of remodeling caused by treatment of dogs for 1 year with five times the clinical dose of either alendronate or risedronate is associated with increased tissue mineralization and whether it changes the nature of the mineral crystal. Thirty-five dogs were divided into three weight-matched groups and treated daily for 1 year with a subcutaneous injection of saline (CON, n = 12), oral risedronate (RIS, 0.5 mg/kg/day, n = 11), or oral alendronate (ALN, 1.0 mg/kg/day, n = 12). Density fractionation, peripheral quantitative computerized tomography (pQCT), and quantitative backscattered electron microscopy (qBSE) were used to evaluate changes in mineral content of bone tissue from the vertebrae or ribs. Infrared microspectroscopy (IR) and X-ray diffraction were used to assess the quality of the mineral and some aspects of collagen structure in the thoracic vertebrae and iliac crest. Following 12 months of treatment, there was a significant shift toward higher density bone in both ALN (P = 0.04) and RIS (P = 0.002) by density fractionation methods. IR, pQCT, and qBSE did not detect any significant differences in mineralization, probably because of their lower sensitivity and/or because of the smaller region of interest they sample. No significant differences were found in the maturity of the mineral crystals or in their length or size. We conclude that treatment for 1 year with high doses of bisphosphonates which suppress bone remodeling up to 90% increases tissue mineralization, but does not change the nature of the mineral crystal.

Alendronate↗

PubMed2003

Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle.

Our purpose here is to test the hypothesis that Randall's plaques, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative biopsies of plaques in kidneys of idiopathic-calcium-stone formers and patients with stones due to obesity-related bypass procedures and obtained papillary specimens from non-stone formers after nephrectomy. Plaque originates in the basement membranes of the thin loops of Henle and spreads from there through the interstitium to beneath the urothelium. Patients who have undergone bypass surgery do not produce such plaque but instead form intratubular hydroxyapatite crystals in collecting ducts. Non-stone formers also do not form plaque. Plaque is specific to certain kinds of stone-forming patients and is initiated specifically in thin-limb basement membranes by mechanisms that remain to be elucidated.

Adult↗

PubMed2002

Spaceflight affects bone formation in rhesus monkeys: a histological and cell culture study.

Using analyses of iliac crest cell and tissue, back-scattered electron imaging, and biochemical techniques, we characterized the effects of a 14-day spaceflight (Bion 11) on bone structure and bone formation in two 3- to 4-yr-old male rhesus monkeys compared with eight age-matched Earth-control monkeys. We found that postflight bone volume was 35% lower than preflight values in flight monkeys. This was associated with reduced osteoid (-40%) and mineralizing (-32%) surfaces and decreased bone formation rate (-53%). Moreover, flight monkeys exhibited trends to lower values of mineralization profile in iliac bone (back-scattered electron imaging) and to decreased osteocalcin serum levels (P = 0.08). The initial number of trabecular bone cells yielded in cultures did not differ in flight and control animals before or after the flight. However, osteoblastic cell proliferation was markedly lower in postflight vs. preflight at 9 and 14 days of culture in one flight monkey. This study suggests that a 14-day spaceflight reduces iliac bone formation, osteoblastic activity, and/or recruitment in young rhesus monkeys, resulting in decreased trabecular bone volume.

Animals↗