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Biomedical subjects

L A Fitzpatrick

Publications and source records attributed to L A Fitzpatrick.

At least 91 records · Page 5Linked to original sources
PubMed1995

Antithetic effects of ryanodine and ruthenium red on osteoclast-mediated bone resorption and intracellular calcium concentrations.

In the process of bone remodeling, osteoclasts are responsible for resorption of bone. High levels of intracellular calcium decrease the bone resorbing activity of osteoclasts and increase detachment of osteoclasts from the bone surface. The regulatory role of intracellular calcium in bone resorption is not clearly understood. To understand this phenomenon, we studied the effects of the intracellular calcium modulators ryanodine and ruthenium red on bone resorption using the disaggregated osteoclast pit assay. Changes in intracellular calcium concentrations after treatment with these compounds were detected with the fluoroprobe fura2. With ryanodine, a significant, dose-dependent decrease in bone resorption was detected. This inhibition of bone resorption was reversible upon the removal of ryanodine. Ryanodine increased intracellular calcium concentrations, suggesting that the mechanism of inhibition by ryanodine was via alterations in intracellular stores of calcium. After treatment with ruthenium red, osteoclasts resorbed significantly more bone compared to vehicle-treated cells. This increase in bone resorption correlated with a decrease in intracellular calcium concentrations. The addition of parathyroid hormone or ruthenium red to osteoclast cultures containing ryanodine did not attenuate the decrease in bone resorption caused by ryanodine, suggesting that the mechanism of ryanodine inhibition of bone resorption may involve the "locking" of a calcium channel in an open position.

Analysis of Variance↗
PubMed1995

Matrix proteins associated with bone calcification are present in human vascular smooth muscle cells grown in vitro.

Atherosclerotic lesions are composed of cellular elements that have migrated from the vessel lumen and wall to form the cellular component of the developing plaque. The cellular elements are influenced by various growth-regulatory molecules, cytokines, chemoattractants, and vasoregulatory molecules that regulate the synthesis of the extracellular matrix composing the plaque. Because vascular smooth muscle cells (VSMC) constitute the major cellular elements of the atherosclerotic plaque and are thought to be responsible for the extracellular matrix that becomes calcified in mature plaques, immunostaining for collagenous and noncollagenous proteins typically associated with bone matrix was conducted on VSMC grown in vitro. VSMC obtained from human aorta were grown in chambers on glass slides and immunostained for procollagen type I, bone sialoprotein, osteonectin, osteocalcin, osteopontin, decorin, and biglycan. VSMC demonstrated an intense staining for procollagen type I, and a moderately intense staining for the noncollagenous proteins, bone sialoprotein and osteonectin, two proteins closely associated with bone mineralization. Minimal immunostaining was noted for osteocalcin, osteopontin, decorin, and biglycan. The presence in VSMC of collagenous and noncollagenous proteins associated with bone mineralization suggest that the smooth muscle cells in the developing atherosclerotic plaque play an important role in the deposition of the extracellular matrix involved in calcification of developing lesions.

Biglycan↗
PubMed1995

Role of calcium channels in parathyroid hormone secretion.

Experimental evidence exists for the presence of parathyroid cell membrane calcium channels that respond to plasma calcium. In previous reports, the effects of various calcium channel agents on PTH secretion have revealed conflicting results. To resolve some of these inconsistencies, we have compared the pure calcium channel agonist, (+)202-791, and its antagonistic enantiomer (-)202-791 with other calcium channel agents--verapamil, nifedipine, and (+)Bay-K-8644. The agonist (+)202-791 enhanced 45Ca+2 uptake and decreased PTH secretion, while the antagonist (-)202-791 decreased 45Ca+2 uptake and increased PTH secretion. The calcium channel appears coupled to a G-protein as indicated by pertussis toxin treatment of the cells. The enantiomers (+/-)202-791 had little effect on intracellular cAMP production suggesting that the calcium channel may not be responsible for the previously observed calcium-mediated changes in cAMP. The antagonist (-)202-791 increased the phosphorylation of a 60-kd protein. The enantiomers (+/-)202-791 did not alter the effect of depolarizing concentrations of potassium on PTH secretion. Our results suggest that calcium channels provide a pathway for the movement of calcium across the plasma membrane and that this pool of calcium regulates, at least in part, PTH secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

The importance of bone biopsy in managing renal osteodystrophy.

A case is presented in which bone biopsy results helped to resolve not only difficult issues in the clinical management of the patient's renal osteodystrophy but also disruptive psychosocial problems surrounding her clinical course. The outcome was a satisfactory resolution based on rational medical treatment and directed supportive care. The presentation highlights important principles in the procurement, processing, and interpretation of the bone biopsy, while also addressing the importance of accurate diagnosis in facilitating the overall long-term management by the entire renal team.

Aged↗
PubMed1995

Nifedipine, but not verapamil, acutely elevates parathyroid hormone levels in premenopausal women.

BACKGROUND: Calcium channel antagonist therapy in humans has been associated with changes in anterior pituitary, thyroid and adrenal hormone secretion. Human studies assessing effects of calcium channel antagonists on calciotropic hormones have been few and typically involved small numbers of subjects studied for short periods of time. Few of these previously published studies have included women. The endocrine effects of calcium channel antagonists in women have become increasingly important as more women are taking these agents for diseases such as hypertension, angina, Raynaud's phenomenon and migraine. OBJECTIVE: To assess both acute and chronic effects of calcium channel antagonists on calciotropic hormones in women. DESIGN: A four-week prospective, randomized trial. SUBJECTS: Twenty-nine premenopausal women, randomly assigned to receive either 240 mg of sustained release verapamil or 30 mg of sustained release nifedipine daily. LABORATORY END-POINTS: Total and ionized serum calcium, phosphate, creatinine, parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP) and calcitonin, measured at baseline, after 24 hours, and 28 days of treatment. RESULTS: Total and ionized calcium, phosphate, creatinine, PTHrP and calcitonin levels were not altered significantly after 24 hours or 28 days in any of the subjects, when compared to baseline. There were no significant differences in PTH levels after 24 hours or 28 days of verapamil treatment. There was a significant increase in serum PTH levels after 24 hours of nifedipine therapy; however, these differences were not evident after 28 days of therapy. CONCLUSIONS: The short-term administration of nifedipine results in increased release of parathyroid hormone; however, long-term administration has no significant effect on the concentrations of calciotropic hormones.

Adult↗
PubMed1995

Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features.

OBJECTIVE: Osteomalacia associated with adult acquired Fanconi's syndrome is thought to result from hypophosphataemia and relative 1,25-dihydroxyvitamin D deficiency. We have followed the clinical and diagnostic features of patients with osteomalacia associated with adult Fanconi's syndrome, with particular emphasis on their responses to treatment with calcium, phosphate and vitamin D. DESIGN: Retrospective Mayo Clinic case-note review from 1975 to 1994 and prospective follow-up study, combined with literature review. PATIENTS: Eleven patients (7 male, 4 female) were identified who satisfied criteria for diagnosis of osteomalacia and adult Fanconi's syndrome. Twenty-five additional patients were identified in a literature review from 1954 to the present. METHODS: Clinical history and physical examination, serum and urine bone and mineral parameter, X-ray radiography and iliac crest bone histomorphometry. RESULTS: All patients presented with typical symptoms of osteomalacia, including lower extremity or low back bone pain, and all had fractures, pseudofractures, and/or bone demineralization on X-ray radiography. Osteomalacia and Fanconi's syndrome were diagnosed concurrently in 10 patients, whereas osteomalacia preceded diagnosis of Fanconi's syndrome by 5 years in one patient. Pre-treatment bone biopsies in 9 of the 11 patients demonstrated increased osteoid surface, volume and width. In the one patient labelled with tetracycline prior to biopsy, mineralization lag time was prolonged at 111 days (normal 19.2 +/- 1.0 days). Hypophosphataemia, inappropriately low 1,25-dihydroxyvitamin D levels, renal insufficiency, and chronic acidosis due to bicarbonate leak and uraemia, contributed to the osteomalacia in these patients. Secondary hyperparathyroidism was present in two patients. Eight of the 11 patients with osteomalacia associated with Fanconi's syndrome had monoclonal disorders, including multiple myeloma or lymphoma, many of them manifest by light-chain proteinuria. Over a mean patient follow-up period of 46 months (range 1-239 months), patients responded symptomatically to calcium, phosphate, and vitamin D replacement typically within 1-6 months. In 8 patients in whom follow-up data were available, post-treatment serum phosphate and 1,25-dihydroxyvitamin D levels improved in the setting of stable mild renal insufficiency; only one patient developed end-stage renal failure after 20 years, suggesting that these patients do not invariably progress rapidly to renal failure. CONCLUSIONS: Regardless of the underlying cause, osteomalacia associated with adult acquired Fanconi's syndrome appears to respond well to calcium, phosphate, and vitamin D replacement. These patients do not appear to necessarily require 1,25-dihydroxyvitamin D replacement.

Adult↗
PubMed1995

Artificial insemination of Bos indicus heifers: the effects of body weight, condition score, ovarian cyclic status and insemination regimen on pregnancy rate.

Effects of body weight, condition score, ovarian cyclic status and insemination regimen on pregnancy rates were investigated in 164 Bos indicus heifers synchronised with norgestomet-oestradiol and pregnant mare serum gonadotrophin (PMSG). Oestrus detection techniques were also compared. Heifers were inseminated at either a fixed time (group 1, n = 83) of 48.0 +/- 0.2 h (mean +/- SEM) after implant removal or at 8.9 +/- 0.5 h after oestrus was detected (group 2, n = 81). Group 2 heifers that were not detected in oestrus by 72 h after implant removal were inseminated at that time. Oestrus was detected for the purpose of insemination using heatmount detectors. Tail-paint and oestrogen treated, chin-ball harnessed steers were used to compare the efficiency of oestrus detection. The probability of ovarian cyclicity increased with increasing body weight and condition score (P < 0.001). A higher proportion of heifers that were acyclic at the commencement of treatment, compared with cyclic heifers, were detected in oestrus at the time of insemination in the fixed-time inseminated group (P < 0.01). Analysis of covariance revealed that intervals from implant removal to oestrus were influenced by ovarian cyclic status (P < 0.01) and insemination group (P < 0.05). A higher pregnancy rate (% +/- SEM) was obtained in acyclic compared with cyclic heifers in the group 1 heifers (50.0 +/- 10 vs 28.1 +/- 6; P = 0.055) but not among the group 2 heifers (45.8 +/- 10 vs 49.1 +/- 7; P = 0.787). The probability of pregnancy was found to be associated negatively with body weight (P = 0.01) while a higher pregnancy rate was obtained in the group 2 compared with group 1 heifers (48.2% vs 34.9%; P = 0.093). The efficiency of oestrus detection was highest using heatmount detectors compared with tail-paint and chin-ball harnessed steers (90.7% vs 37.0% and 23.5%, respectively; P < 0.0001). We conclude that pregnancy rates can be increased in extensive environments when insemination follows oestrus detection using heatmount detectors compared with a fixed-time insemination. The fertility of heifers inseminated at a fixed time is influenced by ovarian cyclic status due to its influence on oestrus-to-insemination intervals.

Analysis of Variance↗
PubMed1995

Oestrus detection techniques and insemination strategies in Bos indicus heifers synchronised with norgestomet-oestradiol.

Oestrus was synchronised in 57 Bos indicus heifers using norgestomet-oestradiol and pregnant mare serum gonadotrophin. Oestrus was detected by observations made at six-hourly intervals, using oestrogen-treated and chin-ball harnessed steers, heatmount detectors, tail-paint and visual observation. Heifers were inseminated once at either a fixed time of 49.2 +/- 0.4 h (mean +/- SE; n = 29) after implant removal or 12.6 +/- 1.5 h (n = 28) after oestrus was detected. The mean (+/- SE) time to the onset of oestrus was 47.1 +/- 1.9 h, while 90% of heifers recorded in oestrus were detected within 66 h of implant removal. Heatmount detectors were significantly more efficient at detecting oestrus than chin-ball harnessed steers, tail paint or visual observation (P < 0.001). A higher pregnancy rate was obtained in heifers inseminated after oestrus detection compared with heifers inseminated at a fixed-time (57.1 vs 34.5%; P = 0.043) and a higher pregnancy rate was obtained in heifers classified as easy to inseminate compared with heifers classified as difficult to inseminate (57.8 vs 0%, P < 0.001). We conclude that heatmount detectors are an efficient means of detecting oestrus in synchronised B indicus heifers and that pregnancy rates can be increased when insemination follows oestrus detection compared with a fixed-time insemination regimen.

Animals↗
PubMed1995

Spontaneous oscillations of intracellular calcium in single bovine parathyroid cells may be associated with the inhibition of parathyroid hormone secretion.

PTH secretion is tightly regulated by extracellular calcium ([Ca2+]e) and in turn regulates calcium homeostasis through its action on target tissues. We investigated the mechanism and physiological significance of intracellular calcium ([Ca2+]i) levels in relation to the secretion of PTH in single bovine parathyroid cells. [Ca2+]i was recorded using digital imaging microscopy, and secretion of PTH was correlated in the same cell using the reverse hemolytic plaque assay. In individual parathyroid cells, oscillations of [Ca2+]i were present in response to specific stimuli. Like secretory activity, response to [Ca2+]e concentrations was heterogeneous. Oscillations of [Ca2+]i occurred spontaneously in 22% of cells at inhibitory concentrations of [Ca2+]e. Oscillations were present only in high [Ca2+]e (> or = 1.8 mM) and not noted at lower concentrations of [Ca2+]e. The interval and amplitude of [Ca2+]i oscillations were 42 +/- 2 sec, and 20 +/- 1 nM (mean +/- SE), respectively. Oscillations were rapidly abolished when [Ca2+]e was removed by EGTA, and this effect was reversible. Addition of Mg2+ or polycationic antibiotics such as neomycin resulted in an [Ca2+]i spike, but oscillations were absent. Lanthanum, which blocks Ca2+ influx through calcium channels in various cells, rarely caused oscillations even in the presence of high concentrations of [Ca2+]e. To test the role of cAMP in [Ca2+]i oscillations, we added the beta-agonist isoproterenol. The addition of isoproterenol, however, did not cause oscillations. The number of cells that released PTH was significantly lower in cells with oscillations compared with cells without oscillations. We suggest that spontaneous [Ca2+]i oscillations are due to the influx of [Ca2+]e through ion channels rather than release from [Ca2+]i stores and may be a specific intracellular signal associated with inhibition of PTH secretion.

Animals↗
PubMed1995

Hormone concentrations in the caudal vena cava during the first ovarian follicular wave of the oestrous cycle in heifers.

Changes in pulsatile secretion of LH, FSH, oestradiol and progesterone were related to the growth phase, early plateau phase and regression phase of the first ovarian dominant follicle of the oestrous cycle in Bos indicus heifers. Relationships between these hormones during the three phases were also investigated. Accurate measurements of episodic ovarian steroid secretion were obtained by catheterizing the caudal vena cava via the lateral saphenous vein; the tip of the catheter was positioned just cranial to the ovarian vein using transrectal ultrasonography. Pulsatile secretion of oestradiol was increased only during the growth phase of the dominant follicle and was associated with high frequency release of LH pulses. However, mean concentrations of oestradiol were reduced when the dominant follicle attained its maximum diameter. Between the growth and plateau phases, as the amount of progesterone released increased and oestradiol released decreased, LH pulse frequency and mean concentration of LH decreased. Pulses of LH released were followed within 15 min by increases in mean concentrations of oestradiol (P < 0.001); however, there was no apparent relationship between LH and progesterone release (P = 0.19). Although there was little evidence of pulsatile release of FSH, mean concentrations of FSH were increased by 0.2 ng ml-1 (P = 0.04) during the plateau phase, which was on average 2.1 days before the day of emergence of the second dominant follicle of the oestrous cycle. This increase in FSH, in conjunction with the decrease in secretion of oestradiol, may be an indication of the loss of functional dominance by the first dominant follicle of the oestrous cycle.

Animals↗
PubMed1995

Sequential changes in ovarian follicular dynamics in Bos indicus heifers before and after nutritional anoestrus.

This study examined the effects of live mass on ovarian follicular dynamics in heifers before and after the onset of nutritional anoestrus. The effects of decreased live mass on secretion of progesterone, LH and FSH were also investigated. Ovarian characteristics were monitored in 16 postpubertal Brahman heifers using daily transrectal ultrasonography. After two normal oestrous cycles, 11 heifers (treatment group) were allocated to a restricted diet, until the cessation of their oestrous cycles, that resulted in a decrease in live mass of 0.8 kg day-1. Heifers were then fed an ad libitum diet, resulting in increasing live mass until resumption of oestrous cycles. Five heifers (control group) were fed an unrestricted diet throughout the experimental period. The concentrations of progesterone in plasma were monitored twice a week and the concentrations of LH and FSH were determined on day 6 after ovulation, before initiation of dietary restriction, after a 17% decrease in live mass and after the onset of anoestrus in the treatment group. Onset of anoestrus was preceded by linear decreases in the size of ovarian follicles and corpora lutea, and in the persistence of the first dominant follicles of oestrous cycles. These changes were proportional to the decrease in live mass (P < 0.001). The frequency of pulses of LH or mean concentration of FSH on day 6 of the oestrous cycle were not changed after a 17% decrease in live mass, and did not increase following the onset of anoestrus, although concentrations of progesterone were < 0.2 ng ml-1, suggesting that release of LH was suppressed at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1995

Physiological effects of undernutrition on postpartum anoestrus in cows.

The focus of this review is the physiological effects of undernutrition on ovarian follicle growth and the occurrence of ovulation in postpartum cows. Evidence suggests that moderate levels of underfeeding, before or after calving, may interfere with the mechanism(s) of final follicle maturation and ovulation, whereas more pronounced nutritional deficiencies may affect the mechanism(s) regulating dominant follicle size and the dynamics of dominant follicle growth and regression. Severe undernutrition may result in the absence of follicles > 5 mm in diameter. These changes are consistent with likely effects of reduced LH or FSH secretion that have been associated with inhibition of both tonic and surge release of GnRH from the hypothalamus. As yet, there is no direct evidence for local effects of undernutrition on ovarian function in cows, and studies examining this tissue often ignore dynamic interdependencies between the hypothalamus, anterior pituitary gland, and the ovaries, and possible nutritional modulation of ovarian feedback mechanisms that affect gonadotrophin secretion. Further research is required to elucidate nutritional effects on the positive feedback regulation of gonadotrophin secretion and on the expression of behavioural oestrus. Further studies are also needed to determine whether nutritional or metabolic state may influence ovarian function directly in a manner that affects the duration of postpartum anoestrus and fertility in postpartum cows.

Anestrus↗
PubMed1994

Relation of coronary calcium determined by electron beam computed tomography and lumen narrowing determined by autopsy.

Coronary calcium determined by electron beam computed tomography (CT) has not been systematically evaluated regarding prediction of histopathologic atherosclerotic disease. Furthermore, gender specificity has not been examined. The 3 major epicardial arteries were dissected from 13 consecutive hearts (5 women and 8 men) after autopsy. Each artery was straightened and scanned using CT in contiguous 3 mm thick cross sections. After imaging, histologic sections were prepared at corresponding intervals and luminal area obstruction determined by planimetry. Electron beam CT scans were analyzed to determine coronary calcium area (i.e., tomographic area with CT density > 130 Hounsfield units). A total of 522 histologic specimens were examined and paired with corresponding CT scans (182 in women, 340 in men). Receiver-operating characteristic (ROC) analysis was used to define site specificity of calcium area for luminal area narrowing by atherosclerosis. ROC curve areas for segmental CT calcium and prediction of atherosclerosis representing mild, moderate, or severe disease were, respectively, 0.712, 0.843, and 0.857 for women and 0.732, 0.793, and 0.841 for men. Curves relating false-positive rate (1-specificity) to predefined degrees of atherosclerotic narrowing versus calcium area were curvilinear. In both women and men, calcium areas on the order of 1 mm2/coronary segment were necessary to predict at least mild atherosclerosis with a false-positive rate of 0% (i.e., 100% specificity), whereas a calcium area > 3 mm2 was necessary to predict the same result for severe disease. In conclusion, coronary artery calcium area as determined by electron beam CT has the potential to predict segmental histopathologic coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Paracrine interactions among parathyroid cells: effect of cell density on cell secretion.

Cell-cell interactions are important in the regulation of endocrine cell secretion. To investigate the possibility that cell communication may alter the regulation of parathyroid cell secretion, we utilized the reverse hemolytic plaque assay (RHPA) to measure parathyroid hormone (PTH) release from individual cells. Bovine parathyroid cells were dispersed and plated with protein A-conjugated erythrocytes at cell densities ranging from 0.9 to 36 x 10(2) cells/cm2 in 0.2 mM calcium. Cell populations were greater than 98% homogenous as determined by immunocytochemistry and in situ hybridization for PTH mRNA. Plaques were developed and data analyzed for the amount of PTH per cell released (plaque area in microns 2 x 10(4)) and the determination of cell recruitment (% plaques formed). A positive correlation existed between parathyroid cell density and the amount of PTH released. As the distance between cells increased, the plaque area (amount of PTH released per cell) decreased (ranging from 1.0 x 10(4) microns 2 at 0.9 x 10(2) cells/cm2 versus 1.6 x 10(4) microns 2 at 36 x 10(2) cells/cm2). The percentage of cells releasing PTH (recruitment) also decreased (16% at 0.9 x 10(2) cells/cm2 versus 47% at 36 x 10(2) cells/cm2). These data suggest that parathyroid cells in close proximity are stimulated to secrete more hormone than those at lesser densities. In addition, parathyroid cells are recruited to secrete PTH when plated at high density. Factor(s) released by the parathyroid cell may increase cell responsiveness and stimulate secretion in a paracrine fashion.

Animals↗
PubMed1994

Effects of transforming growth factor beta (TGF beta) and 1,25 dihydroxyvitamin D3 on the function, cytochemistry and morphology of normal human osteoblast-like cells.

Individually, transforming growth factor beta (TGF beta) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) alter the growth and differentiation of normal and transformed osteoblast-like (OB) cells. Although recent evidence suggests interactions between TGF beta and 1,25(OH)2D3 may occur, little is known of the individual or combined effects of these hormones on the expression of the osteoblast phenotype at the cytochemical and biochemical levels in normal human OB (hOB) cells. Primary cultures of hOBs were treated with TGF beta (0.001-10 ng/ml) and 1,25(OH)2D3 (0.1 pM-100 nM) either alone or in combination. TGF beta and 1,25(OH)2D3 stimulated spindle-shaped cells to become stellate in appearance and increased the number of cytoplasmic processes. TGF beta increased 3H-thymidine incorporation and 1,25(OH)2D3 reduced this effect. Conversely, procollagen type-I synthesis and secretion were increased in a dose-dependent manner in the presence of TGF beta but were not significantly affected in the presence of 1,25(OH)2D3. TGF beta and 1,25(OH)2D3 each marginally increased alkaline phosphatase (ALP) activity, but the combination synergistically increased ALP activity in a dose- and time-dependent manner at the cytochemical and biochemical level (three to tenfold over vehicle controls; n = 12). In contrast, TGF beta reduced 1,25(OH)2D3-stimulated osteocalcin secretion. These data suggest that TGF beta stimulates hOB cells to actively produce collagen matrix and proliferate. The combination of TGF beta and 1,25(OH)2D3, however, produces a synergistic increase in ALP activity and maintenance of collagen synthesis. 1,25(OH)2D3 stimulation may induce cells to advance to an endstage where cell proliferation is reduced and osteocalcin expression is promoted. Interactions between TGF beta and 1,25(OH)2D3 may represent important steps in the regulation of osteoblast differentiation and matrix production.

Alkaline Phosphatase↗
PubMed1994

Age- and gender-related changes in the distribution of osteocalcin in the extracellular matrix of normal male and female bone. Possible involvement of osteocalcin in bone remodeling.

With increasing age, bone undergoes changes in remodeling that ultimately compromise the structural integrity of the skeleton. The presence of osteocalcin in bone matrix may alter bone remodeling by promoting osteoclast activity. Whether age- and/or gender-related differences exist in the distribution of osteocalcin within individual bone remodeling units is not known. In this study, we determined the immunohistochemical distribution of osteocalcin in the extracellular matrix of iliac crest bone biopsies obtained from normal male and female volunteers, 20-80 yr old. Four different distribution patterns of osteocalcin within individual osteons were arbitrarily defined as types I, II, III, or IV. The frequency of appearance of each osteon type was determined as a percent of the total osteons per histologic section. The proportion of osteons that stained homogeneously throughout the concentric lamellae (type I) decreased in females and males with increasing age. The proportion of osteons that lack osteocalcin in the matrix immediately adjacent to Haversian canals (type III) increased in females and males with age. Osteons staining intensely in the matrix adjacent to Haversian canals (type II) increased in females and was unchanged in aging males. Osteons that contained osteocalcin-positive resting lines (type IV) increased in bone obtained from males with increasing age but were unchanged in females. Sections of bone immunostained for osteopontin (SPP-I), osteonectin, and decorin did not reveal multiple patterns or alterations in staining with gender or increasing age. We suggest that the morphology of individual bone remodeling units is heterogeneous and the particular morphologic pattern of osteocalcin distribution changes with age and gender. These results suggest that differences in the distribution of osteocalcin in bone matrix may be responsible, in part, for the altered remodeling of bone associated with gender and aging.

Adult↗
PubMed1994

Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis.

Coronary atherosclerosis is frequently associated with calcification of arterial plaque. To understand the mechanisms responsible for the formation of atherosclerotic calcification, we examined human coronary arteries for the presence and extent of mineral. In sections stained specifically for mineral, staining was diffuse and present in all atherosclerotic plaques. Hydroxyapatite was not detected in normal coronary artery sections. Distribution of hydroxyapatite coincided with a similar distribution of calcium detected by a radiodense pattern using contact microradiography of the same sections before cytochemical staining. By energy-dispersive x-ray microanalysis, the chemical composition of calcified sites was identical to hydroxyapatite (Ca10[PO4]6[OH]2), the major inorganic component of bone. Osteopontin is a phosphorylated glycoprotein with known involvement in the formation and calcification of bone and is regulated by local cytokines. Human coronary artery segments (14 normal and 34 atherosclerotic) obtained at autopsy were evaluated immunohistochemically using polyclonal antibodies generated against human osteopontin. Immunohistochemistry for osteopontin indicated intense, highly specific staining in the outer margins of all diseased segments at each calcification front; staining was evident throughout the entire plaque. Conversely, arterial segments free of atheroma and calcification and sections treated with nonimmune serum had no evidence of positive staining. Osteopontin, a protein involved in mineralization is specifically associated with calcific coronary atheroma and may play an important role in the onset and progression of this disease in human coronary arteries. The deposition of noncollagenous proteins such as osteopontin may regulate the presence or absence of calcification and ultimately alter vessel compliance.

Adult↗