Herman Cheung - Academia.edu (original) (raw)

Papers by Herman Cheung

Embryonic Stem Cells - Differentiation and Pluripotent Alternatives, 2011

Gout, Pseudogout and Apatite-Associated Syndromes, 2006

Current Opinion in Orthopaedics, 2006

ABSTRACT Purpose of review: The deposition of calcium-containing crystals in articular tissues is... more ABSTRACT Purpose of review: The deposition of calcium-containing crystals in articular tissues is probably an under-recognized event. Clinical observations indicate that exaggerated and uniquely distributed cartilage degeneration is associated with these deposits. Perhaps the most compelling argument favoring a role for crystals in causing osteoarthritis stems from their in-vitro effects on articular tissues. Recent findings: In contrast to other cytokines, basic calcium phosphate crystal-elicited signal transduction pathways have not been completely studied. In this review, I will highlight some of the recent findings on the roles of intracellular calcium concentrations, mitogen-activated protein kinases and protein kinase C isozymes in the calcium-containing crystal signal transduction pathways. Summary: The ultimate biological effects of calcium-containing crystals on cells are increases in prostaglandin production, matrix metalloproteinase synthesis and secretion, and increased mitogenesis. These effects appear to correlate with calcium deposition disease in vivo. The increased production of matrix-degrading matrix metalloproteinases by synoviocytes results in articular damage and degeneration and the release of additional crystals from the surrounding tissue, while mitogenesis leads to an increase in synoviocytes that could generate more matrix metalloproteinases and prostaglandins. Understanding the crystal-induced cellular response signal transduction mechanisms will allow investigators to design specific therapeutic interventions.

Calcium in Biological Systems, 1985

Current Opinion in Rheumatology, 2005

Calcium-containing crystals can cause the degeneration of articular tissues in two separate pathw... more Calcium-containing crystals can cause the degeneration of articular tissues in two separate pathways. In the direct pathway, crystals directly induce synoviocytes to proliferate and produce metalloproteinases and prostaglandins. The other pathway, the paracrine pathway, involves the interaction between crystals and macrophages/monocytes, which leads to the synthesis and release of cytokines, which can reinforce the action of crystals on synoviocytes and/or induce chondrocytes to secrete enzymes and which eventually causes the degeneration of articular tissues. The purpose of this review is to highlight the recent findings of the biologic effect of these crystals. In the past few years, major advances in the understanding of the biologic effect of crystals and the signal transduction pathway of crystal-induced cell activation offer a unique opportunity to examine the role of crystal in osteoarthritis and cartilage degeneration. Evidence for a causal role of crystals in cartilage degeneration in osteoarthritis is primarily inferential and is based on correlative data. Clinical observations indicate that exaggerated and uniquely distributed cartilage degeneration is associated with these deposits. Measurements of putative markers of cartilage breakdown suggest that these crystals magnify the degenerative process. Studies have shown two potential mechanisms by which crystals cause degeneration. These involve the stimulation of mitogenesis in synovial fibroblasts and the secretion of metalloproteinases by cells that subject these crystals to phagocytosis. New information on how crystals form and how they exert their biologic effects will help in the design of an effective therapeutic approach.

Kidney International, Nov 1, 1983

Bone resorption stimulated by elevated serum 1,25-(OH)2-vitainin D concentrations in healthy men.... more Bone resorption stimulated by elevated serum 1,25-(OH)2-vitainin D concentrations in healthy men. We evaluated whether calcitriol administration to healthy men stimulates bone resorption. We compared serum 1,25-(0H)2-D concentrations, Ca and P04 balances, and urinary hydroxyproline excretion rates in four healthy men adapted to a low Ca diet providing only 4.0 0.2 so mmoles Calday to those in four healthy men eating a comparable diet 4.2 0.9 mmoles Ca/day) during the chronic oral administration of calcitriol. 0.75 jsg every 6 hr. Serum 1,25-(0H)2-D levels averaged 94 16 p during the control studies and 209 35 pM during calcitriol administration. Net intestinal Ca absorption averaged 0.5 0.3 mmoles/day during control and 1.8 0.5 mmoles/ day during calcitriol (P < 0.005), but urinary Ca excretion averaged 8.7 2.0 mmoles/day during calcitriol as compared to 2.9 1.4 mmoles/ day during control (P < 0.005). Thus, mean Ca balance, which averaged -2.4 1.2 mmoles/day during control, was more negative during calcitriol at -6.3 2.4 mmo!es/day (P < 0.05). Average daily P04 balances averaged +7.7 1.5 mmoles/day during control but only tended to be negative during calcitriol at -1 1 5.4 mmoles/day, (NS). Urinary hydroxyproline excretion averaged 0.26 0.03 mmoles/day during control and 0.49 0.06 during calcitriol (P < 0.001). We conclude that elevated serum l.25-(OH)2-D concentrations in healthy men eating low Ca diets stimulate bone resorption.

Kidney Int, 1982

Effects of calcitriol administration on calcium metabolism in healthy men. To evaluate the relati... more Effects of calcitriol administration on calcium metabolism in healthy men. To evaluate the relationship between daily and fasting urinary calcium excretion and serum I ,25-(OH)2-D concentrations, we studied six healthy men during control and during chronic oral calcitriol administration (0.6, 1.2, or 1.8 nmoles every 6 hours for 6 to 12 days) while they ate normal and low calcium diets (calcium content, 19.2 or 4.2 mmoles/day). Daily urinary calcium excretion was directly related to serum l,25-(OH)2-D concentrations but increased more (P < 0.025) while subjects ate the normal calcium diet (slope, 0.081 mmole/day/ pmole/liter; r = 0.94) than when eating the low calcium diet (slope, 0.043 mmole/day!pmole/liter; r = 0.83). During calcitriol and ingestion of the low calcium diet, daily urinary calcium excretion averaged 7.32 2.6 mmoles/day, exceeding the dietary calcium intake (P < 0.02).

A total of 27 papers were presented by a wide spectrum of scientists. There was a strong attendan... more A total of 27 papers were presented by a wide spectrum of scientists. There was a strong attendance by representatives from government, academia, and industrial research centers. The objective of the symposium was to present and discuss recent developments in crystal growth and inhibition processes.

Advances in Crystal Growth Inhibition Technologies, 2002

Crystalline calcium pyrophosphate dihydrate crystals occur frequently in degenerative joints dise... more Crystalline calcium pyrophosphate dihydrate crystals occur frequently in degenerative joints diseases, causing acute attacks of pseudogout. These crystals appear in cartilage and can engender enzymatic damage to cartilage matrix. Currently no reliable method exists to prevent calcium pyrophosphate dihydrate deposition. In this study we investigate the role that phosphocitrate, a naturally occurring compound, may play in preventing calcium phosphate precipitation in cells or cellular compartments. Based on the experimental evidence that phosphocitrate blocks ATP-induced CPPD crystal growth in both articular cartilage vesicles and cartilage explants, we use molecular modeling to analyze how the inhibitory activity of phosphocitrate results from the stereospecific interaction between phosphocitrate and the specific faces of calcium pyrophosphate dihydrate crystal. Our molecular modeling binding studies indicate that phosphocitrate ion is able to bind to (010), (011), (100), (001), (01Ϫ1), and (1Ϫ10) faces of CPPD crystal with the strongest binding energies obtained for the high calcium density planes (010) and (011). We propose that the binding of phosphocitrate to specific faces of CPPD induces morphological changes that may lead to diminished crystal growth or its total cessation. ᭧

Hydroxyapatite is one of the most important minerals in the human body. It constitutes almost the... more Hydroxyapatite is one of the most important minerals in the human body. It constitutes almost the entire mineral phase of bones and tooth enamel. Its ubiquity, however, sometimes may lead to cases of unwanted biomineralization that results in many pathological conditions. Recently, it has been shown in vitro that the growth of hydroxyapatite crystals can be efficiently controlled using phosphocitrate, a naturally occurring compound. Phosphocitrate has been shown also to prevent sticking of cells to hydroxyapatite crystals. However, the molecular mechanism of phosphocitrate interactions with hydroxyapatite crystals was almost entirely unknown due to difficulties in analyzing the X-ray geometry of the unit cell of hydroxyapatite, which exhibits disorder in the hydroxyl ion positions.

The Journal of Physical Chemistry B, 2003

Calcium pyrophosphate dihydrate (CPPD) crystals occur frequently in noninflammatory osteoarthriti... more Calcium pyrophosphate dihydrate (CPPD) crystals occur frequently in noninflammatory osteoarthritic joints; however, they can be phlogistic and membranolytic, causing acute pseudogout attack. So far, the molecular mechanism of crystal-induced membranolysis is still unclear. In this study, using the method of Chemistry at Harvard Macromolecular Mechanics (CHARMM) molecular dynamics, we show that the interactions between the surface of CPPD crystal and the extracellular layer of the hydrated dimyristoyl phosphatidylcholine (DMPC) phospholipid bilayer may lead to decoupling of the external layer from the intracellular side of the membrane. As a result, a local thinning of the layer on the intracellular side of the membrane occurs, which favors water penetration, leading to membranolysis.

Kidney International, 1986

To evaluate the effects of changing rates of fixed acid production on fasting urine Ca/creatinine... more To evaluate the effects of changing rates of fixed acid production on fasting urine Ca/creatinine, we studied five healthy men fed constant diets during control conditions (serum HCO3 27.3 +/- 2.6 SD mEq/liter and blood H+ 40.4 +/- 1.5 microEq/liter) and then during the administration of NH4Cl 3.0 mEq/kg/day (serum HCO3 22.5 +/- 4.9 mEq/liter; P less than 0.025, and H+ 46.8 +/- 2.3 mEq/liter; P less than 0.005). In addition to the expected increase in daily urinary Ca excretion from 5.2 +/- 2.0 to 12.5 +/- 3.0 mmole/day; P less than 0.001 as daily urinary net acid excretion was increased from 48 +/- 32 to 257 +/- 33 mEq/day; P less than 0.001 we observed that fasting urinary net acid/creatinine excretion also increased from 2.9 +/- 1.2 to 11.1 +/- 1.2 mEq/mmole creatinine; P less than 0.001 and fasting urine Ca/creatinine increased from 0.158 +/- 0.111 to 0.456 +/- 0.109 mmole/mmole creatinine; P less than 0.005. The additional Ca appearing in the urine during acidosis ultimately reflected augmented net bone resorption since daily urinary hydroxyproline excretion was increased from 0.232 +/- 0.062 to 0.377 +/- 0.108 mmole/day; P less than 0.01. Since variations in diet composition can cause fixed acid production and thus renal net acid excretion to vary from about zero to 200 mEq/day, such a range could cause fasting Ca/creatinine to vary from 0.09 to 0.37 mmole/mmole (0.03 to 0.13 mg/mg) and should be taken into account in the evaluation of fasting Ca/creatinine.

Kidney International, 1985

We evaluated the effects of hydrochlorothiazide administration in relation to Ca balance, the PTH... more We evaluated the effects of hydrochlorothiazide administration in relation to Ca balance, the PTH and vitamin D endocrine systems, acid-base balance, and bone. We studied six healthy men fed constant diets providing only 5.1 +/- 0.7 SD mmoles Ca/day. Three of the men were also given calcitriol, 0.5 microgram 6-hrly throughout their studies. All subjects were observed during 18 control days and then during 18 days of hydrochlorothiazide (HTZ) administration, 25 mg 12-hrly. Observations during control days 11 through 16 were compared to those during days 7 through 18 of HTZ administration, inclusively. Directional changes during HTZ did not differ among subjects not given or given calcitriol. For all six subjects, control net intestinal Ca absorption, serum 1,25-(OH)2-D concentrations, serum iPTH concentrations, and daily urine cAMP excretion averaged 0.5 +/- 2.2 mmoles/day, 162 +/- 51 pM, 4.3 +/- 2.2 microliter Eq/ml and 4.2 +/- 0.9 mumoles/day, respectively; none changed during HTZ. As expected, HTZ administration was accompanied by a fall in urinary Ca excretion, averaging -1.4 +/- 0.8 mmoles/day; P less than 0.01. HTZ administration was also accompanied by less negative Ca balances, averaging +1.6 +/- 1.0 mmoles/day; P less than 0.025, and by a fall in daily urinary hydroxyproline excretion averaging -0.13 +/- 0.09 mmoles/day; P less than 0.025. We interpret these data to indicate that HTZ administration is accompanied by an inhibition of bone resorption. HTZ administration also raised serum HCO3 concentrations by +2.7 +/- 0.5 mEq/liter; P less than 0.001 and blood pH by + 0.05 +/- 0.02 units; P less than 0.005.(ABSTRACT TRUNCATED AT 250 WORDS)

Kidney International, 1984

Dietary calcium and serum 1,2540H)2-vitamin D concentrations as determinants of calcium balance i... more Dietary calcium and serum 1,2540H)2-vitamin D concentrations as determinants of calcium balance in healthy men. We previously reported that experimental elevations of serum I ,25-(OH)2-vitamin D [1 ,25-(OH)2-Di concentrations produced by the chronic oral administration of calcitriol, 0.75 ig every 6 hr, to healthy human males eating diets providing only 4 mmoles Ca/day stimulate net bone resorption as evidenced by more negative Ca balances and higher rates of urinary hydroxyproline excretion. To determine whether increased dietary Ca intake modifies this response we have compared serum I ,25-(OH)2-D and iPTH concentrations, Ca and P04 balances, and urinary hydroxyproline excretion in three healthy human males adapted to diets providing 22.3 1.3 mmoles Ca/day and three healthy human males adapted to diets providing 9.3 0.7 mmoles Ca/day before and during the continuous oral administration of calcitriol 0.5 sg every 6 hr. For all six subjects, serum I ,25-(OH)2-D levels averaged 89

Kidney International, 1983

Kidney International, 1982