Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Crystallization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,747 records · Page 97Linked to original sources

Fourier transform infrared microscopy identification of crystal deposits in tissues: clinical importance in various pathologies.

The presence of crystal deposits in tissues is associated with various pathologies. Sometimes their identification is useful for understanding the etiology or the mechanism of the disorder. The authors applied Fourier transform infrared microscopy (FTIRM) to the molecular characterization of crystal deposits in tissue and compared the results with those provided by histologic studies using polarized light microscope and histochemical reactions. Twenty-five biopsies were investigated. In 10 cases, the results were in good agreement. In 15 cases only FTIRM could precisely identify the crystals. In three cases, this technique allowed to characterize dihydroxyadenine crystals revealing an adenine phosphoribosyltransferase deficiency previously undiagnosed in patients presenting severe chronic renal failure. In three cases, crystal deposition was related to drug therapy. In other cases, crystal identification was useful to understand the mechanism of the pathology responsible for tissue damage and crystal deposition.

Adenine↗

Circulating Charcot-Leyden crystals in the hypereosinophilic syndrome.

A patient who had malignant melanoma associated with the hypereosinophilic syndrome died of cardiovascular thrombotic lesions. Widespread tissue eosinophilia was accompanied by numerous Charcot-Leyden crystals in the tumor as well as in various organs, including the renal tubules. A unique observation, not previously described, is the finding of Charcot-Leyden crystals in the thrombi and vessels, including the renal glomeruli. While little is known of the significance of Charcot-Leyden crystals, it is speculated that the circulating crystals injure the endothelium and trigger intravascular coagulation, resulting in thrombosis. A search for the crystals in blood and/or urine may be of additional aid in the evaluation of the extent of the thrombotic process. A special staining method is proposed to facilitate recognition of the crystals, since these are virtually not visualized by routine stain. With the use of such a staining method, future observations in other cases of the hypereosinophilic syndrome may elucidate the role of Charcot-Leyden crystals in the pathogenesis of the thrombotic cardiovascular lesions of this syndrome.

Adult↗

Calcium oxalate crystals in the thyroid. Their identification, prevalence, origin, and possible significance.

Calcium oxalate crystals are not encountered in normal animal tissues, except for the human thyroid, where they were found in 79 of 100 routine consecutive autopsies. They appear during childhood, and numbers of crystals increase with age. In diffuse hyperplasia, prevalence was higher, but crystals were fewer than expected. In adenomas and carcinomas, crystals were decreased except for three cases with a striking focal increase. None was found in 22 adult primate thyroids. After Clorox digestion of human thyroids, calcium oxalate dihydrate was identified by x-ray diffraction and infrared spectroscopy. Origin, tissue and species localization are discussed in relation to ascorbate metabolism, thyroperoxidase, and calcitonin. Possible metabolic roles are suggested. Calcium oxalate crystals injected in animals and humans initiate a foreign body reaction with giant cells. In Hashimoto's thyroiditis, crystals disappear but occasionally remain with giant cell reaction. In subacute thyroiditis, granulomas are related more to colloid than to crystals.

Adolescent↗

Visualization of RNA crystal growth by atomic force microscopy.

The crystallization of transfer RNA (tRNA) was investigated using atomic force microscopy (AFM) over the temperature range from 4 to 16 degrees C, and this produced the first in situ AFM images of developing nucleic acid crystals. The growth of the (110) face of hexagonal yeast tRNAPhe crystals was observed to occur at steps on vicinal hillocks generated by multiple screw dislocation sources in the temperature range of 13.5-16 degrees C. Two-dimensional nucleation begins to dominate at 13.5 degrees C, with the appearance of three-dimensional nuclei at 12 degrees C. The changes in growth mechanisms are correlated with variations in supersaturation which is higher in the low temperature range. Growth of tRNA crystals was characterized by a strong anisotropy in the tangential step movement and transformation of growth modes on single crystals were directly observed by AFM over the narrow temperature range utilized. Finally, lattice resolution images of the molecular structure of surface layers were recorded. The implications of the strong temperature dependence of tRNAPhe crystal growth are discussed in view of improving and better controlling crystallization of nucleic acids.

Crystallization↗

Reduced secretion of proinflammatory cytokines of monosodium urate crystal-stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients?

BACKGROUND: In gouty arthritis, monosodium urate (MSU) crystals interact with monocytes and neutrophils to produce inflammatory reactions associated with acute synovitis. In patients with end-stage renal disease (ESRD), gouty arthritis is a rare condition despite often severe hyperuricaemia. We wondered whether differences in the secretion of proinflammatory cytokines by MSU crystal-stimulated monocytes might be one explanation for the low incidence of gouty arthritis in patients with ESRD compared with healthy controls. METHODS: Thirteen patients with ESRD on intermittent haemodialysis treatment, six patients with chronic renal failure not yet on dialysis, and 15 age- and sex-matched healthy controls were examined. Monocytes, purified from peripheral blood mononuclear cells (PBMC) by immunomagnetic bead separation, were incubated for 18 h in the presence of MSU crystals, Escherichia coli lipopolysaccharide (LPS) or medium alone. The supernatants were studied for the presence of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) using cytokine-specific enzyme-linked immunosorbent assays. RESULTS: Monocytes from patients with ESRD produced significantly lower amounts of IL-1beta, IL-6 and TNF-alpha after stimulation with MSU crystals or LPS than did monocytes from healthy subjects. Cytokine production was not significantly different between ESRD patients on haemodialysis and chronic renal failure patients not yet on dialysis. Artificial MSU crystals were stronger stimuli than tophus-derived 'natural' MSU crystals. CONCLUSION: We demonstrate that monocyte-associated immunosuppression in ESRD leads to reduced secretion of proinflammatory cytokines in response to stimuli such as MSU crystals. This may be one of the factors preventing many ESRD patients from the manifestation of acute gout despite often severe hyperuricaemia.

Adult↗

Crystallization of and preliminary crystallographic data for allosteric L-lactate dehydrogenase from Bifidobacterium longum.

L-Lactate dehydrogenase from Bifidobacterium longum aM101-2 was overexpressed in Escherichia coli and then purified. The enzyme was crystallized from a polyethylene glycol 6000 solution by the hanging drop vapor diffusion method. Crystals grown in the presence of NADH (type II), both NADH and oxamate (type III), and NADH, oxamate, and FBP (type IV) were analyzed. All three crystal forms belong to the orthorhombic system, space group P2(1)2(1)2. The cell dimensions of the type II crystals were a = 106.2 A, b = 131.6 A, and c = 63.8 A. Those of the type III and type IV crystals were a = 106.4 A, b = 131.4 A, and c = 63.8 A. The type III crystals diffract X-rays to beyond 2.5 A spacing. The type II and type III crystals were stable as to X-ray irradiation.

Allosteric Site↗

Hydrolysis of cholesteryl oleate liquid crystals by hormone-sensitive lipase.

Cholesteryl oleate liquid crystals were prepared by sonication as a model of lipid droplets accumulated in foam cells derived from macrophages. These liquid crystals were spherical and showed an anisotropic cross image. Hormone-sensitive lipase from bovine adipose tissue hydrolyzed these liquid crystals optimally at pH 6.8. The Km for the liquid crystals was about 8 times that for vesicles or emulsified cholesteryl oleate. The Vmax for the liquid crystals was the same as that for the emulsified substrate and 6 times that for the vesicle substrate. Phospholipid inhibited cholesteryl oleate hydrolysis in a concentration-dependent fashion, phosphatidylserine being especially inhibitory. The effect of phospholipids on the activity changed upon their incorporation into the cholesteryl oleate liquid crystals, phosphatidylethanolamine increasing the activity to about twice that of the control. These results suggest that hormone-sensitive lipase hydrolyzes cholesteryl oleate liquid crystals as a model of endogenous lipid droplets and its activities are affected by phospholipids.

Animals↗

Crystal-storing histiocytosis associated with lymphoplasmacytic neoplasms. Report of three cases mimicking adult rhabdomyoma.

Massive crystal deposition is rare in lymphoplasmacytic (LPc) or plasma cell neoplasms. We report three cases in which the accumulation of crystals in histiocytes closely reproduced the histologic features of adult rhabdomyoma. The patients, all female, aged 18, 77, and 78 years, presented with tumor of cervical lymph nodes (two cases) or the otolaryngic mucosa (two cases). In addition, two patients had monoclonal serum or urine immunoglobulin (IgM-kappa-1, unknown-1), and one had renal and bone marrow involvement on biopsy. This last patient died of acute renal failure at 5 months, another was alive without disease at 8 years, and the remaining one was lost to follow-up. Lymph nodes, mucosae, and kidney showed a neoplastic LPc infiltrate masked by sheets of large benign histiocytes containing sheaves of crystals. Paraffin-section immunohistochemistry demonstrated monoclonal staining of the LPc cells in all cases (IgM-kappa-2, IgA-kappa-1) and of the crystals (IgM-kappa) in one case. In all patients, the crystal-containing cells were positive for KP-1 (CD68), but not for desmin, muscle-specific actin, or myoglobin. These findings suggest that, in any case of adult rhabdomyoma in which the histologic findings are not typical, a crystal-storing histiocytosis should be ruled out: recognition of the atypical LPc component and the histiocytic immunophenotype of the crystal-storing cells will help prevent a serious misdiagnosis.

Adolescent↗

Calcium pyrophosphate dihydrate gout and other crystal deposition diseases.

The number of crystal or birefringent particles associated with arthritis is increasing, and a uniform taxonomy is needed. The term gout has been proposed as a generic term for these diseases based on historical, clinical, and crystallographic reasons. Calcium pyrophosphate dihydrate gout follows monosodium urate gout in frequency, and its spectrum of clinical manifestations continues to grow. Familial calcium pyrophosphate dihydrate gout was described for the first time in kindreds studied in England and Tunisia; new Jewish and Spanish kindreds were also reported. Type I collagen was shown to nucleate nativelike calcium pyrophosphate dihydrate crystals, and pyrophosphate elaboration was explored in cartilage explants in an attempt to reproduce the in vivo metabolic or endocrine disorders associated with calcium pyrophosphate dihydrate gout. The effect of pyrophosphatase and different cofactors such as magnesium in dissolving calcium pyrophosphate dihydrate crystals was investigated. High-resolution electron microscopy was used to study the interrelation between apatite and other basic calcium phosphate crystals in apatite gout. Raman microscopy was applied for the first time to identify crystals in biologic specimens. A simple and specific technique for basic calcium phosphate crystal identification is necessary to understand the relationship between different calcium phosphate crystals and osteoarthritis. Several reports about children and young patients with primary oxalate gout described the effect of oxalate on eyes, periodontal tissues, and bone. Multicenter studies showed poor results of renal transplantation, but favored combined liver and renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcinosis↗

What is the relation between crystals and osteoarthritis?

The nature of the relation between osteoarthritis and the various forms of calcium crystals that are found within osteoarthritic joints continues to challenge and confound researchers. The most basic question is whether such crystals are directly relevant to the development of osteoarthritis, or are merely a byproduct or marker of the disease itself. The past year has produced several studies that elucidate important aspects of the molecular and cellular mechanisms of calcium pyrophosphate dihydrate and apatite crystal formation. Such studies may yield novel targets for therapeutic intervention in crystal-associated osteoarthritis. Other recent studies have provided further understanding of the mechanisms by which crystals induce inflammation. Arthroscopic assessment of patients with knee osteoarthritis refractory to traditional therapy suggests that the combined absence of chondrocalcinosis on plain films and identifiable crystals on compensated polarized light microscopy of synovial fluid from arthrocentesis may not be adequate to exclude clinically relevant crystalline deposition and inflammation. Clinical criteria are needed to identify patients with occult crystalline disease who, by virtue of crystal-induced inflammation, require more aggressive anti-inflammatory therapy than those with noninflammatory osteoarthritis.

Animals↗

Calcium crystal effects on the cells of the joint: implications for pathogenesis of disease.

In the past three years, there has been considerable progress in delineating the mechanism of calcium-containing crystal-induced cell activation: (1) the identification of Ca2+ influx and p42/44 mitogen-activated protein kinase activation as the signal transduction pathways; (2) induction of nuclear transcription factors of cyclic adenosine monophosphate (cAMP) response element binding protein, activator protein-1, and nuclear factor kappaB; (3) the differential role of crystal endocytosis and dissolution in crystal-induced metalloproteinase synthesis and mitogenesis; (4) crystal upregulation of matrix metalloproteinases, including MMP-13 but downregulation of tissue inhibitor of metalloproteinase-1 and -2, thus magnifying the degenerative effect of crystals. Phosphocitrate, a specific inhibitor of biologic effect of calcium crystals, reverses the degenerative effects of crystals.

Calcium Phosphates↗

Signaling mechanisms involved in crystal-induced tissue damage.

The association of crystal deposition with osteoarthritis and joint destruction is well established. Recent advances in understanding the mechanisms whereby calcium crystals contribute to cartilage damage are highlighted in this review. In vitro studies have shown that when calcium-containing crystals come in contact with cells they cause an influx in Ca 2+ concentration and activation of p42/44 mitogen-activated protein kinases. This is followed by induction of proto-oncogenes (c- fos, c- jun ) and induction of the nuclear transcription factors activator protein-1 and nuclear factor-kappaB, which in turn lead to crystal-induced modulation of normal gene expression. Some of the downstream effects known to date include increased mitogenesis, up-regulation of members of the matrix metalloproteinase family, down-regulation of tissue inhibitor of metalloproteinase-1 and -2 in fibroblasts, induction of neutrophil chemotactic chemokines such as interleukin-8, activation and degranulation of neutrophils, and inhibition of neutrophil apoptosis. Because no known drug prevents or treats the consequences of basic calcium phosphate crystal deposition, an improved understanding of the molecular mechanisms leading to crystal-induced joint degeneration is essential to the development of a rational approach to target the consequences of crystal deposition.

Animals↗

Minipump induced hyperoxaluria and crystal deposition in rats: a model for calcium oxalate urolithiasis.

PURPOSE: Unraveling the mechanisms leading to clinically active calcium oxalate (CaOx) stone disease and the development of effective medical therapies to treat it have been hampered by the lack of appropriate animal models. To address this problem we developed a model of hyperoxaluria and calcium oxalate crystal deposition by implanting osmotic minipumps subcutaneously into male rats, that is minipump induced hyperoxaluria and crystal deposition in rats. MATERIALS AND METHODS: Male Harlan-Sprague Dawley rats (225 to 290 gm) were implanted subcutaneously with 1-week 2 ml osmotic minipumps containing 1.5 M potassium oxalate (360 microM KOx/24 hours, [KOx-trt], 11) or phosphate buffered saline (PBS-trt, 9) on days 1 and 7. The 24-hour urine collections were performed on days 0, 4, 7, 11 and 14. Data were analyzed by ANOVA and Tukey's HSD. Urinary crystals were analyzed by light microscopy. Kidneys were harvested on day 14 and processed for light and polarizing microscopy, and RNA analysis.RESULTS Mean overall creatinine excretion +/- SEM (PBS-trt 107 +/- 7 and KOx-trt 123 +/- 6 microM/24 hours, p >0.07) and day 14 serum creatinine (PBS-trt 83 +/- 4 and KOx-trt 83 +/- 5 microM, p >or=0.9) were similar in the 2 treatment groups. Overall urinary volume (PBS-trt 11.3 +/- 0.8 and KOx-trt 18.0 +/- 1.5 ml/24 hours, p <or=0.001) and oxalate (OX) excretion (PBS-trt 9.2 +/- 0.6 and KOx-trt 44 +/- 4.2 microM/24 hours, p <or=0.001) were higher in KOx-trt vs PBS-trt rats. In KOx-trt rats OX excretion on day 0 was significantly less than on any day after implantation (p <or=0.01). All KOx-trt rats excreted calcium oxalate dihydrate crystals by day 4 and had intrarenal deposits of birefringent crystals by day 14. Overall the morphology of kidneys of OX rats was normal, although localized regions of inflammation and tubular debris were occasionally observed. Reverse transcriptase-polymerase chain reaction and Northern blot analysis revealed that the expression of 3 distress molecules tumor necrosis factor receptor, osteopontin and kidney injury molecule were up-regulated in KOx-trt kidneys. CONCLUSIONS: The model of minipump induced hyperoxaluria and crystal deposition in rats reliably induces hyperoxaluria, CaOx crystalluria and CaOx crystal deposition. These characteristics make it an appropriate model for investigations of the effects of OX on renal physiology as well as investigating the efficacy of new therapeutics.

Animals↗

Why biomolecules prefer only a few crystal structures.

We have shown that, in determining the biomolecule-crystal symmetry, the occupation of low-site-symmetry Wyckoff positions is crucial, which contrasts with the overwhelming majority of nonmolecular, inorganic crystals where atoms mainly reside in high-symmetry Wyckoff positions. We consider the general relation between the symmetry of an isolated molecule and the possible symmetries of biomolecular crystals it can generate. We reveal that the improper symmetry operations (inversion and mirror symmetries) are prohibited in the chirally pure biomolecular crystals. Next, we show that the low (C1) symmetry of large biological molecules substantially decreases the space in a crystal where the molecules can reside. The space "forbidden" for molecule centers is found to be in the R vicinity of the higher-symmetry Wyckoff positions on symmetry lines, where R is the molecule characteristic size. The remaining free space and hence the probability for the structure to exist are shown to be drastically increased when replacing any rotation axis by a screw one. Based on the proposed model, we have explained the peculiar distribution of biomolecular crystals over the space groups, which can be obtained from biomolecule-crystal databases.

Amino Acids↗

Isolation of Medicago truncatula mutants defective in calcium oxalate crystal formation.

Plants accumulate crystals of calcium oxalate in a variety of shapes, sizes, amounts, and spatial locations. How and why many plants form crystals of calcium oxalate remain largely unknown. To gain insight into the regulatory mechanisms of crystal formation and function, we have initiated a mutant screen to identify the genetic determinants. Leaves from a chemically mutagenized Medicago truncatula population were visually screened for alterations in calcium oxalate crystal formation. Seven different classes of calcium oxalate defective mutants were identified that exhibited alterations in crystal nucleation, morphology, distribution and/or amount. Genetic analysis suggested that crystal formation is a complex process involving more than seven loci. Phenotypic analysis of a mutant that lacks crystals, cod 5, did not reveal any difference in plant growth and development compared with controls. This finding brings into question the hypothesized roles of calcium oxalate formation in supporting tissue structure and in regulating excess tissue calcium.

Calcium↗

Formation of quinol co-crystals with hydrogen-bond acceptors.

The crystal structures of eight new co-crystals of quinol with pyrazine, piperazine, morpholine, pyridine, piperidine, 4,4'-bipyridine, N-methylmorpholine and N,N'-dimethylpiperazine are reported. Quinol forms 1:1 co-crystals with pyrazine, piperazine and N,N'-dimethylpiperazine, but 1:2 co-crystals with morpholine, 4,4'-bipyridine, N-methylmorpholine, pyridine and piperidine. This difference can be rationalized in most cases by the presence of, respectively, two or one strong hydrogen-bond acceptor(s) in the guest molecule. The exception to this generalization is 4,4'-bipyridine, which forms a 1:2 co-crystal, possibly to optimize crystal packing. All structures are dominated by hydrogen bonding between quinol and the guest molecules. A doubly bridging motif, which connects pairs of quinol and guest molecules via NH...O or CH...O interactions, is present in all but the sterically hindered N,N'-dimethylpiperazine and N-methylmorpholine co-crystals.

Crystallization↗

Expression, purification and crystallization of enterococcus faecium streptogramin A acetyltransferase.

The streptogramin A acetyltransferase from Enterococcus faecium (SWISS-PROT P50870) has been overexpressed in Escherichia coli, purified and crystallized. Crystallization conditions were screened using the hanging-drop vapor-diffusion method and resulted in two distinct crystal forms. Form I crystals diffract to 2.5 A and belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 68.6, b = 102.6, c = 107.5 A. Form II crystals diffract to 2.7 A and belong to space group F222, with unit-cell parameters a = 185.8, b = 185.8, c = 186.5 A. Rotation-function and packing analyses for both crystal forms indicate that the asymmetric unit may contain one and two copies of the trimeric enzyme for crystal forms I and II, respectively.

Acetyltransferases↗

L-Isoaspartate 115 of porcine beta-trypsin promotes crystallization of its complex with bdellastasin.

Bdellastasin is a 59-amino-acid, cysteine-rich, antistasin-type inhibitor of sperm acrosin, plasmin and trypsin, isolated from the medicinal leech Hirudo medicinalis. The complex formed between bdellastasin and porcine beta-trypsin has previously been crystallized in the presence of PEG in a tetragonal crystal form of space group P4(3)2(1)2 and has now been found to crystallize under high-salt conditions in the enantiomorphic space group P4(1)2(1)2. These structures have been solved and refined to 2.8 and 2.7 A resolution, respectively. Bdellastasin turns out to have an antistasin-like fold exhibiting a bis-domainal structure. In the second new crystal form, the flexible N-terminal subdomain is rotated with respect to the C--terminal subdomain by about 90 degrees, fitting into a cavity formed by symmetry-related trypsin molecules. The canonical inhibitor-proteinase interaction is restricted to the primary binding loop comprising residues Leu31-Lys36 of bdellastasin. During the refinement, a bound sodium ion occupying the calcium-binding site of the porcine beta-trypsin component was discovered. This sodium ion is coordinated in a tetragonal-pyramidal manner, with the geometry of the enclosing loop slightly changed compared with the loop in the presence of calcium. In the crystal form of space group P4(3)2(1)2, the electron density for residue 115 of porcine beta-trypsin clearly indicates the presence of a beta-isomerized L-aspartic acid, which is placed in spatial proximity to segment Thr144--Gly148 of a symmetry-related trypsin molecule. This is the first structurally observed example of an L-isoaspartate in beta--trypsin originating from Asn. A comparison with other known crystal structures of porcine beta-trypsin-macromolecular inhibitor complexes suggests that the deamidation, isomerization and racemization of Asn115 is the key step in crystallization.

Animals↗