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Biomedical subjects

D D Lee

Publications and source records attributed to D D Lee.

At least 55 records · Page 3Linked to original sources
PubMed1989

Use of cultured embryonic chicken osteoblasts as a model of cellular differentiation and bone mineralization.

When chicken embryonic progenitor cells were selected and grown in culture as previously described, by 30 days cellular differentiation could be demonstrated by expression of in vivo levels of osteocalcin, alkaline phosphatase (APase), type I collagen and phosphoproteins (PP). Ultrastructural analysis revealed that the cultures were similar morphologically to young osteoid in vivo with structural features including well-developed, orthogonally arranged collagen fibrils with 64-70 nm periodicity and electron opaque areas consisting of very poorly crystalline hydroxyapatite. Analysis of collagen synthesis versus collagen accumulation in the matrix indicated a temporal inconsistency between the time of synthesis and accumulation, suggesting that accumulation was largely controlled at the level of fibril formation. Analysis of PP accumulation demonstrated a 10-fold increase in total phosphoamino acid content over the 30 day time course. PP synthesis analyzed by [3H]-Ser(P) and [14C]-Thr(P) incorporation showed an induction similar to that seen for APase. Experiments undertaken to characterize the nature of PP synthesized by the cultures identified a unique 66 kD protein. This protein was purified from chick tibial and calvarial bone and a polyclonal antibody was raised in rabbits. Ultrastructural immunocytochemistry using this antibody and the protein A-gold technique revealed specific immunolabelling over regions of mineralizing matrix in vitro, a reaction identical to that observed for the distribution of this 66 kD PP in vivo during embryonic tibial bone development in the chicken.

Animals↗
PubMed1989

The three-dimensional spatial relationship between the collagen fibrils and the inorganic calcium-phosphate crystals of pickerel and herring fish bone.

High-voltage (1.0 mega-volt) electron stereomicroscopy has been used to examine the spatial relationship between the inorganic crystals and the collagen fibrils of pickerel and herring bone. Stereomicrographs of cross sections of the collagen fibrils encompassing regions of initial to full mineralization showed that the calcium phosphate crystals are located within the collagen fibrils. In all stages of mineralization, calcium-phosphate deposits were not observed associated or within membrane-bound structures. Serial cross sections of the fully mineralized collagen fibrils were three-dimensionally reconstructed using the computer graphic imaging process. Findings from this study suggest that there exist a local "bulging" along the fibrils corresponding to the 680 A periodicity in which additional mass of minerals were observed to be accommodated within the collagen fibril structure at this sites.

Animals↗
PubMed1989

Relaxation therapy lowers blood pressure more effectively in hypertensives with raised plasma norepinephrine and blunts pressor response to anger.

The effects of relaxation therapy on blood pressure and neural responses to "social stress"-anger instigation were determined in 30 male patients with mild primary hypertension. "Social stress"-anger induced increases in systolic and diastolic blood pressures (both p less than 0.01) and plasma norepinephrine (p less than 0.05) before therapy. Diastolic blood pressure before and during anger challenge were related to simultaneous plasma norepinephrine (r = 0.56, p less than 0.01 and r = 0.39, p less than 0.05). Relaxation reduced resting diastolic blood pressure (p less than 0.01), the reduction of blood pressure was related to baseline plasma norepinephrine (p less than 0.05). The pressor response of systolic blood pressure to anger challenge (p less than 0.02) was blunted by relaxation therapy. These findings suggested that noradrenergic control of blood pressure was amplified during stress and relaxation therapy was effective in lowering blood pressure and neutralizing the response to "social stress" anger instigation.

Adult↗
PubMed1988

Effects of celiprolol on plasma renin, aldosterone, norepinephrine and epinephrine in primary hypertension.

Celiprolol is a newly developed cardioselective beta-blocking agent with mild beta 2-agonist and weak alpha 2-antagonist properties. To evaluate the acute (2.5 hours) and chronic (2 weeks) effects of celiprolol (400 mg once a day) on plasma renin, aldosterone, norepinephrine and epinephrine, 20 patients with mild to moderate primary hypertension were studied in a double-blind placebo-controlled crossover trial. Two and one-half hours after the first dose of both placebo and celiprolol, supine and standing measurements of blood pressure showed a significant reduction, whereas plasma norepinephrine increases were comparable with baseline values. Placebo and celiprolol produced similar changes on supine blood pressure and plasma norepinephrine. In 9 patients celiprolol decreased plasma renin (from a mean +/- standard deviation of 1.09 +/- 0.35 to 0.77 +/- 0.52 ng/ml/hr, p less than 0.05) and aldosterone (from 9.2 +/- 3.7 to 6.7 +/- 3.9 ng/dl, p less than 0.05) acutely both supine and standing, but placebo did not change these parameters. Celiprolol increased pulse rate supine (but not standing) as compared with baseline values. After 2 weeks of celiprolol therapy, blood pressure was decreased both supine and standing compared with placebo in 18 patients (140 +/- 18/88 +/- 8 vs 149 +/- 18/94 +/- 7, 136 +/- 18/91 +/- 6 vs 142 +/- 20/97 +/- 9 mm Hg, respectively, each p less than 0.05), without a change of pulse rate when supine and with a reduction when standing. There were no significant changes of plasma renin, aldosterone, norepinephrine and epinephrine levels during chronic therapy compared with placebo.

Adult↗
PubMed1988

Behavioral vs beta-blocker therapy in patients with primary hypertension: effects on blood pressure, left ventricular function and mass, and the pressor surge of social stress anger.

We compared the relative effects of relaxation therapy, conventional hygienic techniques, and a beta-receptor blocker, atenolol, on control of arterial pressure, left ventricular mass, and diastolic function in patients with mild primary hypertension. Furthermore, we related these effects to baseline neural tone and its changes and assessed the efficacy of relaxation or the pressor surge of "social stress" anger. In group I left ventricular mass index was related to both systolic and diastolic blood pressure (r = 0.46; p less than 0.05). Plasma norepinephrine was related to age (r = 0.33; p less than 0.01). Slope was inversely related to both plasma norepinephrine (r = -0.29; p less than 0.05) and age (r = -0.31; p less than 0.05). Relaxation therapy reduced both supine systolic and diastolic blood pressures, 4.5% and 7.6%, respectively, but did not affect plasma norepinephrine. Hygienic informational therapy reduced plasma norepinephrine by 18%, (p less than 0.05) and did not change blood pressure. Blood pressure responders to nondrug therapy (i.e., diastolic blood pressure reduction of 7% or more) had a 7% reduction of left ventricular mass index (p less than 0.02). On the other hand, atenolol reduced systolic and diastolic blood pressure by 10% and 15%, respectively, (p less than 0.01) and improved left ventricular function by 17% (p less than 0.05) without a significant change in left ventricular mass index. Finally, relaxation therapy but not hygienic therapy reduced systolic blood pressures 4% and 6%, respectively (p less than 0.01), both before and during social stress anger.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Collagen expression, ultrastructural assembly, and mineralization in cultures of chicken embryo osteoblasts.

A newly defined chick calvariae osteoblast culture system that undergoes a temporal sequence of differentiation of the osteoblast phenotype with subsequent mineralization (Gerstenfeld, L. C., S. Chipman, J. Glowacki, and J. B. Lian. 1987. Dev. Biol. 122:49-60) has been examined for the regulation of collagen synthesis, ultrastructural organization of collagen fibrils, and extracellular matrix mineralization. Collagen gene expression, protein synthesis, processing, and accumulation were studied in this system over a 30-d period. Steady state mRNA levels for pro alpha 1(I) and pro alpha 2 collagen and total collagen synthesis increased 1.2- and 1.8-fold, respectively, between days 3 and 12. Thereafter, total collagen synthesis decreased 10-fold while mRNA levels decreased 2.5-fold. In contrast to the decreasing protein synthesis after day 12, total accumulated collagen in the cell layers increased sixfold from day 12 to 30. Examination of the kinetics of procollagen processing demonstrated that there was a sixfold increase in the rate of procollagen conversion to alpha chains from days 3 to 30 and the newly synthesized collagen was more efficiently incorporated into the extracellular matrix at later culture times. The macrostructural assembly of collagen and its relationship to culture mineralization were also examined. High voltage electron microscopy demonstrated that culture cell layers were three to four cells thick. Each cell layer was associated with a layer of well developed collagen fibrils orthogonally arranged with respect to adjacent layers. Fibrils had distinct 64-70-nm periodicity typical of type I collagen. Electron opaque areas found principally associated with the deepest layers of the fibrils consisted of calcium and phosphorus determined by electron probe microanalysis and were identified by electron diffraction as a very poorly crystalline hydroxyapatite mineral phase. These data demonstrate for the first time that cultured osteoblasts are capable of assembling their collagen fibrils into a bone-specific macrostructure which mineralizes in a manner similar to that characterized in vivo. Further, this matrix maturation may influence the processing kinetics of the collagen molecule.

Animals↗
PubMed1988

Labetalol blunts morning pressor surge in systolic hypertension.

Twenty-four-hour ambulatory blood pressure, including the acceleration phase, and left ventricular mass were evaluated in 16 patients with isolated systolic hypertension (standing blood pressure greater than or equal to 160 mm Hg systolic and less than or equal to 95 mm Hg diastolic). After a 4-week, single-blind, placebo period, each patient underwent 24-hour ambulatory blood pressure monitoring and echocardiography. Labetalol therapy was then initiated at 100 mg twice a day in a single-blind manner and increased weekly by 100 mg twice a day until blood pressure control was obtained or a maximum dosage of 400 mg twice a day was reached. Blood pressure control was achieved at a mean daily dose of 363 +/- 46 mg of labetalol. Measurements were repeated at the end of an 8-week maintenance phase. Labetalol therapy significantly reduced the mean 24-hour systolic ambulatory blood pressure from 154 +/- 8 (mean +/- SEM) mm Hg at baseline to 142 +/- 6 mm Hg (p greater than 0.01) and controlled the early morning surge in systolic ambulatory blood pressure. Minor reductions in diastolic blood pressure and heart rate were statistically but not clinically significant. Left ventricular mass was not changed. Labetalol monotherapy provides effective 24-hour control of systolic blood pressure, including the acceleration phase, in patients with isolated systolic hypertension.

Blood Pressure↗
PubMed1988

Noradrenergic hyperactivity in primary hypertension; central and peripheral markers of both behavioral pathogenesis and efficacy of sympatholytic and relaxation therapy.

The effects of clonidine or relaxation therapy were determined in two separate groups of patients with primary hypertension. Ten patients were treated with clonidine monotherapy for 3 months. There were concurrent reductions of blood pressure, plasma and CSF norepinephrine, all p less than 0.01. The changes of blood pressure and norepinephrine were correlated, p less than 0.05 and 0.01, respectively. Thirty patients received hygienic instructions, and 17 of them had relaxation training in addition. Relaxation lowered blood pressures, p less than 0.01, the reduction of blood pressure was related to baseline plasma norepinephrine, p less than 0.05, and greater in patients with "raised" plasma norepinephrine, p less than 0.02. Plasma norepinephrine was lowered after hygienic therapy, p less than 0.05, the change was not significant after relaxation training. Arterial pressure elevation appears to be related to raised plasma norepinephrine. This noradrenergic hyperactivity is a marker for blood pressure responsiveness to sympatholytic therapy with clonidine or relaxation techniques.

Adult↗
PubMed1988

Primary hypertension: left ventricular mass and function, sympathetic nervous system activity, and therapy.

Left ventricular (LV) mass is a predictor of morbidity in patients with hypertension. To elucidate the mechanisms of left ventricular hypertrophy (LVH) in primary hypertension, we examined the relationships of LV mass, arterial blood pressure, and plasma norepinephrine--as a marker of sympathetic nervous system tone--in three populations of patients with mild or moderate hypertension. We found linking of neural tone with (a) arterial blood pressure in mild and moderate hypertension, (b) LV mass in moderate hypertension, and (c) diastolic function in mild hypertension, suggesting that neural tone is a factor in both the pathogenesis and the sequelae of hypertension. Additionally, elevated norepinephrine level may reflect subtle loss of diastolic function before hypertrophy is manifest. Both nondrug and drug therapy may regress LV mass after blood pressure reduction with disparate effects on neural tone.

Adult↗
PubMed1987

Unusual case of an ectopic spleen.

A rare case of a very unusual position of a normally functioning spleen in the posterior aspect of the right lobe of the liver is reported. A 6-year-old boy was evaluated with echocardiography for congenital heart disease of coexisting atrial and ventricular septal defects with pulmonary hypertension. Other associated cardiac abnormalities on this child included a right-sided aortic arch, drainage of the azygous vein into the superior vena cava and an Eisenmenger complex. At the time of echocardiography, absence of the spleen in its normal location was noted. This prompted further investigation into localizing the spleen using 99mTc-sulfur colloid and heat denatured 99mTc-RBC scintigraphy. Both scans demonstrated the spleen to lie posterior to the right hepatic lobe.

Child↗
PubMed1987

Neurohumoral mechanisms and left ventricular hypertrophy: effects of hygienic therapy.

To determine the effects of hygienic (non-drug) therapy on blood pressure (BP) control and its relationship to sympathetic tone and left ventricular mass (LVM) in primary hypertension, plasma norepinephrine (NE) and renin activity (PRA), LVM, and nutritional and behavioral status were assessed in 76 borderline to mild hypertensives. Pretherapy plasma NE was related to diastolic blood pressure (DBP) and PRA (r = 0.24, P less than .05 and r = 0.37, P less than .01, respectively). Plasma NE of high renin patients (221 +/- 52) (mean +/- SD) was greater than that of normal renin patients (159 +/- 61, ng/l, P less than .01). LVM was related to systolic blood pressure (SBP) (P less than .001), DBP (P less than .01) and urinary sodium (P less than .05), and inversely related to PRA (P less than .01). Septal wall thickness was related to hostility (r = 0.42, P less than .05). After seven weeks of hygienic therapy, DBP was reduced by 6 mmHg (P less than .01). The change in SBP was related to baseline plasma NE (P less than .05) and inversely related to LVM (P less than .05). These results suggest that raised sympathetic tone may be a pathogenic factor in primary hypertension and that hygienic therapy lowers BP more effectively in patients with raised sympathetic tone and low LVM.

Adult↗
PubMed1987

Cervical myelopathy attributable to pseudogout. Case report with radiologic, histologic, and crystallographic observations.

A 77-year-old woman complained of numbness in her hands and feet, progressive unsteadiness, weakness, and loss of proprioception of six months' duration. A myelogram revealed stenosis of the spinal canal at the levels of C2-3, T6-7, L2-3, and L3-4. On computerized tomography scan, a large dorsal, epidural, soft tissue mass and focal calcification of the ligamentum flavum were seen at C3. Laboratory studies ruled out gout, collagen disease, vitamin B12 deficiency, syphilis, parathyroid, and thyroid disease. At decompressive laminectomy, a nodular mass in the ligamentum flavum (C2-4) was found and removed. Three months after operation, the neurologic symptoms had improved. Histologic examination of the elastic ligament revealed deposits of birefringent crystals, which were identified by X-ray diffraction as calcium pyrophosphate dihydrate (CCPD). Only about six cases of myelopathy attributable to deposits of CPPD appear to have been previously reported.

Aged↗
PubMed1986

The solid, calcium-phosphate mineral phases in embryonic chick bone characterized by high-voltage electron diffraction.

The solid mineral phases of calcium-phosphate (Ca-P) in the long bones from embryonic chicks between the ages of 9 and 13 days have been examined by high voltage (1.0 MV) electron microscopy and electron microdiffraction. The study was undertaken to identify the chemical and crystallographic nature of the inorganic mineral phase(s) prepared under conditions which significantly reduce artifacts of specimen preparation and microscopic examination of the tissues. Electron microdiffraction patterns of solid mineral phase particles in the osteoid matrices of the subperiosteal region of tibiae were principally those of poorly crystalline hydroxyapatite. In rare instances (less than 1% of the estimated volume of the mineral phase present in the zone of early mineralization), relatively large single crystals were observed within clusters of hydroxyapatite. From calculations of both interplanar spacings and measurements of angular displacement of diffraction reflections from single crystal microdiffraction patterns, two distinct phases other than hydroxyapatite were identified: brushite and beta-tricalcium phosphate. A third phase, resembling an apatite, remains unidentified. The results suggest that very small amounts of nonapatitic phases of Ca-P exist in chicken bone tissue. No temporal relationship could be established between the nonapatitic and apatitic phases. There is at present no evidence from this study to support the concept that nonapatitic phases are precursors of a final apatitic phase in bone.

Animals↗
PubMed1986

Detection and localization of silicon and associated elements in vertebrate bone tissue by imaging ion microscopy.

The growing long bones from normal embryonic chicks and young rats have been examined in situ by imaging ion microscopy, a highly sensitive technique for elemental detection and localization. In tibial diaphyses from chick and rat, treated with anhydrous ethylene glycol, embedded in Spurr medium, and dry sectioned 1-2 microns thick, analyses revealed the presence of silicon, calcium, magnesium, carbon, and oxygen. Silicon localization was principally extracellular in the tissues. Comparison of single element maps of silicon and calcium indicated that silicon specifically appeared in putative uncalcified osteoid regions of tibiae. Detection and imaging of silicon by ion microscopy support results of earlier work by Carlisle, who demonstrated the element in osteoid of rat and mouse bone by electron probe microanalysis. The current data offer the possibility for characterizing more completely silicon interaction in vertebrate calcified tissues.

Animals↗
PubMed1985

Microbeam electron diffraction and lattice fringe studies of defect structures in enamel apatites.

A microbeam diffraction method in transmission electron microscopy has been applied to lattice structural studies of human and shark enamel apatite crystals. The technique allows diffraction patterns to be obtained from very small regions of the specimen (40 nm in diameter) and transfers minimal energy to the sample during analysis. The presence of crystal defects, nonisolated dislocations with the dislocation line positioned perpendicular to the 100-type planes, was observed in the central part of the crystals. Further experiments with acid-etching of crystals containing such defects showed an initial preferential dissolution at the site of these atomic imperfections. The relative abundance of the crystal defects was approximately the same in both human enamel and shark enameloid.

Animals↗
PubMed1985

Yeast adhesion in the pathogenesis of endocarditis due to Candida albicans: studies with adherence-negative mutants.

Two spontaneous cerulenin-resistant mutants of Candida albicans, 4918-2 and 4918-10, were unable to adhere in vitro in fibrin-platelet clots. Because in vitro adherence correlates well with colonization of nonbacterial thrombotic endocarditis on traumatized valvular endocardium, 50% infectious dose studies were performed with a rabbit model of endocarditis. Wild-type C. albicans required 10(3.6) +/- 0.12 cfu in comparison with 10(5.73) +/- 0.31 and 10(7.3) +/- 0.21 cfu for mutants 4918-2 and 4918-10, respectively. The relative avirulence of mutant strains in producing endocarditis was not attributed to accelerated clearance of these strains from the bloodstream. In fact, clearance of wild-type and mutant strains was almost identical. In the same animals renal candidiasis was observed with all strains of C. albicans, although the number of cfu per gram of kidney was higher after infection with wild-type C. albicans. Thus, strains of C. albicans with reduced ability to adhere in vitro to a fibrin-platelet matrix are relatively avirulent in the rabbit endocarditis model.

Adhesiveness↗
PubMed1985

In vitro concatemerization of bacteriophage T7 DNA: role of DNA synthesis and gene 6 exonuclease.

The replication of bacteriophage T7 DNA in vivo proceeds via the synthesis of complex concatemeric intermediates which are joined via the 160 base pair terminal redundancies at either end of the phage chromosome. To gain some insight into the mode of generation of these structures, we have examined the role of DNA synthesis in the formation of concatemeric bacteriophage T7 DNA in vitro. Incubation of mature T7 DNA with T7-infected cell extracts and a deoxynucleoside [32P]triphosphate resulted in the incorporation of significant radioactivity into the DNA. Highest levels of incorporation were at the termini of the DNA and decreased toward the middle of the molecule. Incorporation was dependent upon the presence of the activity of the gene 6 exonuclease and correlated with the generation of concatemeric DNA. A model explaining the role of exonucleolytic degradation and DNA synthesis in the generation of concatemeric DNA is presented.

Carbon Radioisotopes↗