Biomedical subjects

D G Hicks

Publications and source records attributed to D G Hicks.

At least 19 recordsLinked to original sources

PubMed2006

Proton radiography of a laser-driven implosion.

Protons accelerated by a picosecond laser pulse have been used to radiograph a 500 microm diameter capsule, imploded with 300 J of laser light in 6 symmetrically incident beams of wavelength 1.054 microm and pulse length 1 ns. Point projection proton backlighting was used to characterize the density gradients at discrete times through the implosion. Asymmetries were diagnosed both during the early and stagnation stages of the implosion. Comparison with analytic scattering theory and simple Monte Carlo simulations were consistent with a 3+/-1 g/cm3 core with diameter 85+/-10 microm. Scaling simulations show that protons>50 MeV are required to diagnose asymmetry in ignition scale conditions.

Journal Article↗

PubMed2006

Dissociation of liquid silica at high pressures and temperatures.

Liquid silica at high pressure and temperature is shown to undergo significant structural modifications and profound changes in its electronic properties. Temperature measurements on shock waves in silica at 70-1,000 GPa indicate that the specific heat of liquid rises SiO(2) well above the Dulong-Petit limit, exhibiting a broad peak with temperature that is attributable to the growing structural disorder caused by bond breaking in the melt. The simultaneous sharp rise in optical reflectivity of liquid SiO(2) indicates that such dissociation causes the electrical and therefore thermal conductivities of silica to attain metalliclike values of 1-5 x 10(5) S/m and 24-600 W/m x K, respectively.

Journal Article↗

PubMed2004

Shock compressing diamond to a conducting fluid.

Laser generated shock reflectance data show that diamond undergoes a continuous transition from optically absorbing to reflecting between Hugoniot pressures 600<P(H)<1000 GPa. The data are consistent with diamond having a thermal population of carriers at P(H) approximately 600 GPa, undergoing band overlap metallization at P(H) approximately 1000 GPa and melting at 800<P(H)<1000 GPa. The results agree well with an equation of state model that predicts that elemental carbon remains solid throughout the interior of Neptune.

Journal Article↗

PubMed2004

Multi-MeV proton source investigations in ultraintense laser-foil interactions.

A study of the properties of multi-MeV proton emission from thin foils following ultraintense laser irradiation has been carried out. It has been shown that the protons are emitted, in a quasilaminar fashion, from a region of transverse size of the order of 100-200 microm. The imaging properties of the proton source are equivalent to those of a much smaller source located several hundred microm in front of the foil. This finding has been obtained by analyzing proton radiographs of periodically structured test objects, and is corroborated by observations of proton emission from laser-heated thick targets.

Journal Article↗

PubMed2003

Shock-induced transformation of Al2O3 and LiF into semiconducting liquids.

Shock compression of sapphire (Al2O3) and lithium fluoride (LiF) to pressures above 5 Mbar has been observed to transform these transparent, wide band-gap insulators into partially degenerate liquid semiconductors with optical reflectivities of several percent. Reflectivities rise steadily with shock pressure up to 45% in sapphire at 20 Mbar and 20% in LiF at 13 Mbar. Using a simple model, the electron scattering length was inferred to be approximately the interatomic distance. In addition, several equation-of-state points at these pressures were measured.

Journal Article↗

PubMed1999

Osteonecrosis of the temporomandibular joint: correlation of magnetic resonance imaging and histology.

PURPOSE: The aims of this study were to investigate whether osteonecrosis affects the mandibular condyle and to determine whether this condition could be diagnosed with magnetic resonance imaging (MRI). MATERIALS AND METHODS: The study was based on 50 temporomandibular joints in 44 patients in whom MRI and surgery were performed for painful internal derangements. At the time of surgery, a core biopsy specimen was obtained from the marrow of the mandibular condyles, and the histological observations were correlated to T1-(proton density) and T2-weighted MR images. RESULTS: Histological evidence of osteonecrosis was found in nine joints (18%). Bone marrow edema, which may be a precursor of osteonecrosis, was found in nine other joints. The MRI was 78% sensitive and 84% specific for the diagnosis of osteonecrosis of the mandibular condyle. However, the positive predictive value was only 54% because of a number of false-positive MRI diagnoses. CONCLUSION: Osteonecrosis can affect the mandibular condyle, and this condition can be diagnosed with MRI. A combination of edema and sclerosis of the bone marrow was the most reliable MRI sign of osteonecrosis. The cause, its clinical significance, and the need for treatment are unknown.

Adult↗

PubMed1999

Histopathology of the palmar beak ligament in trapeziometacarpal osteoarthritis.

Eighteen cadaver hands were studied to investigate the relationship between degeneration of the palmar beak ligament and articular disease of the trapeziometacarpal joint. Eight of 18 joints had chondromalacia alone; 10 contained areas of eburnation in the palmar aspect of the joint. Beak ligament degeneration correlated closely with the presence of articular degeneration; all joints with eburnation demonstrated frank detachment of the ligament from its metacarpal insertion site. Histologically, the collagen fibers of the beak ligament were disorganized at the metacarpal attachment. The normal insertional zone of fibrocartilage was often unrecognizable on the metacarpal side and, in more degenerative specimens, an intervening synovial recess appeared at the palmar beak of the metacarpal. The trapezial insertion of the beak ligament showed no degenerative change. Increasingly severe cartilage disease was associated with progressive and selective degeneration of the collagen framework of the beak ligament at its insertion onto the thumb metacarpal. These localized histopathologic findings further support the existence of an anatomically distinct intra-articular beak ligament essential to the normal function of the trapeziometacarpal joint and suggest an etiologic relationship to osteoarthritic disease.

Aged↗

PubMed1998

Treatment of multifocal lymphoma of bone with intensified ProMACE-CytaBOM chemotherapy and involved field radiotherapy.

Primary bone involvement is an unusual extranodal presentation of non-Hodgkin lymphoma (NHL). The optimal treatment for this entity has not been determined. While solitary bone lymphomas can be eradicated with local radiation in 50% of patients, distant relapses occur frequently, and the treatment of patients with multifocal osseous disease, or those presenting with associated soft tissue invasion or adenopathy is even less satisfactory. Over a 4-year period, nine patients with multifocal bone lymphoma were treated with intensified versions of the ProMACE-CytaBOM regimen and involved-field radiation. Seven patients had diffuse large cell histology and two patients had diffuse mixed type. Seven patients survived event-free at a median follow-up of 2.3 years (range .5-3.5). In most survivors, there was little or no change in the abnormal radiographic bone findings despite the clinical response to therapy. In one patient, magnetic resonance imaging (MRI) established that bone infarction rather than relapse of lymphoma was the cause of a new lytic bone lesion that developed during treatment.

Adult↗

PubMed1998

Bone morphogenetic protein-7 in growth-plate chondrocytes: regulation by retinoic acid is dependent on the stage of chondrocyte maturation.

Although the bone morphogenetic proteins stimulate chondrogenesis, little is known regarding their expression and regulation in growth-plate chondrocytes. The expression of bone morphogenetic protein-7 was examined in chick growth-plate chondrocyte cultures. Low basal levels of bone morphogenetic protein-7 mRNA and protein expression were stimulated by increasing doses of all-trans retinoic acid, a metabolite of vitamin A. The addition of 10 microM retinoic acid resulted in approximately a 6-fold increase in bone morphogenetic protein-7 mRNA levels. In contrast, other growth regulators, including basic fibroblast growth factor, transforming growth factor-beta, vitamin D, bone morphogenetic protein-6, bone morphogenetic protein-7, and parathyroid hormone-related peptide, did not alter bone morphogenetic protein-7 transcript levels. The increase in bone morphogenetic protein-7 transcripts, although present at 6 hours, was maximal following a 12-hour exposure to retinoic acid. Retinoic acid induction of bone morphogenetic protein-7 transcript levels was dependent on protein synthesis because the induction could be blocked by cyclohexamide. In maturationally distinct subpopulations of chondrocytes separated by countercurrent centrifugal elutriation, retinoic acid markedly induced bone morphogenetic protein-7 mRNA levels in the least differentiated chondrocytes but had no effect in the most terminally differentiated hypertrophic chondrocytes. Immunohistochemical localization of bone morphogenetic protein-7 demonstrates its expression throughout the developing and adolescent growth plate consistent with the constitutive pattern of expression seen in isolated chondrocytes. The addition of exogenous bone morphogenetic protein-7 to chondrocyte cultures stimulated maturation in undifferentiated chondrocyte populations. The data support a role for bone morphogenetic protein-7 as an autocrine regulator of chondrocyte maturation in the growth plate. Regulation of bone morphogenetic protein-7 by retinoic acid may be important in normal growth and development as well as in pathologic conditions of an excess or deficiency of vitamin A.

Animals↗

PubMed1998

Interleukin-10 inhibits cytokine synthesis in monocytes stimulated by titanium particles: evidence of an anti-inflammatory regulatory pathway.

The anti-inflammatory mediator interleukin-10 was investigated as a potential inhibitor of proinflammatory cytokine release in human peripheral blood monocytes activated with titanium particles. It inhibited the secretion of both tumor necrosis factor-alpha and interleukin-6 in a dose-dependent manner, with complete inhibition observed at 2 ng/ml. Co-culture experiments were performed to determine whether this cytokine may have functional importance as an inhibitor of the inflammatory response. When unstimulated lymphocytes and monocytes were co-cultured with titanium-stimulated monocytes, they significantly suppressed the secretion of both interleukin-6 and tumor necrosis factor-alpha. The inhibitory effect of these co-cultured cells could be partially blocked with the addition of an interleukin-10 neutralizing antibody. Interleukin-10 levels were measured in monocyte cultures treated with titanium particles as well as in fresh monocyte cultures treated with conditioned medium from titanium-stimulated monocytes. The latter experiments demonstrated marked stimulation of interleukin-10 secretion in conditioned medium-treated cultures, an effect that was related to the presence of tumor necrosis factor-alpha in the conditioned medium. The addition of titanium to conditioned medium-treated cultures markedly reduced the secretion of interleukin-10, suggesting that the most responsive cells are unstimulated monocytes exposed to agents released from activated monocytes. Altogether, the expression and responsiveness to interleukin-10 suggest a potential role for anti-inflammatory cytokines in regulation of the inflammatory response to wear debris.

Cells, Cultured↗

PubMed1998

MR imaging of rabbit hip cartilage with a clinical imager and specifically designed surface coils.

RATIONALE AND OBJECTIVES: The authors' purpose was to develop a magnetic resonance (MR) imaging technique for examining the hip joint of a rabbit with a clinical MR imager. MATERIALS AND METHODS: Fourteen hips of 10 male New Zealand white rabbits were examined on a 1.5-T MR imager with a specially designed surface coil. Field of view was 3-8 cm, matrix was 256-512 x 192-256, section thickness was 0.9-2.0 mm, and spacing was 0.3-0.5 mm. The hips were sectioned and evaluated by means of light microscopy. Measurements of cartilage thickness from MR images were correlated with those from histologic specimens. RESULTS: The resolution obtainable with a 1.5-T imager was adequate for imaging articular cartilage when a débrided rabbit hip specimen was placed in the center of a 3.5-cm single-loop coil. Rabbit hip cartilage had a trilaminar appearance on MR images. The coefficient of correlation between cartilage-thickness measurements was .81. CONCLUSION: MR imaging of rabbit hip cartilage can be performed on 1.5-T clinical MR imaging unit. Limitations due to the field strength can be overcome with efficiently designed surface coils.

Acetabulum↗

PubMed1998

The potential role of transforming growth factor beta in fracture healing.

As shown in previous studies, the transforming growth factor beta superfamily of growth factors is involved in many aspects of skeletal development and regulation, including fracture repair and bone regeneration. Several studies have shown transforming growth factor beta messenger ribonucleicacid and protein expression in cells comprising fracture callus. In healing fractures in a chick model, differential isoform expression of the transforming growth factor betas was observed by in situ hybridization, with more prominent expression of the transforming growth factor beta 2 and transforming growth factor beta 3 isoforms. Small amounts of transforming growth factor beta 1 were present in early callus and increased in expression later during chondrogenesis and endochondral ossification. These findings resemble those reported in rat and human fracture callus. Transforming growth factor beta 4 expression was not significant in the chick fracture model. Transforming growth factor beta can function as a morphogen when injected subperiosteally, inducing cartilage and bone formation that morphologically resembles many of the events occurring in fracture callus. Exogenous transforming growth factor beta has been used in several critical size defect models of bone regeneration and fracture healing, with most of the studies showing increased bone or callus formation and increased mechanical stability. Numerous variables, including markedly different dose ranges and differing isoforms, dosing regimens, delivery methods, animal models, and various times and endpoint measures for analysis, make it difficult to comparatively assess the effects of transforming growth factor beta on bone healing. Additional study is necessary to satisfactorily determine the role of transforming growth factor beta in normal fracture healing and its potential for use in augmenting this process.

Animals↗

PubMed1998

Leiomyomatosis peritonealis disseminata, endometriosis, and multicystic mesothelioma: an unusual association.

A 32-year-old, previously healthy woman with a diffuse, complex tumoral process is described. While she was being evaluated for primary infertility, a laparoscopic procedure revealed a disseminated peritoneal process associated with bilateral ovarian lesions. A clinical diagnosis of stage III ovarian cancer was made and total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. Pathologic studies showed an admixture of leiomyomatosis peritonealis disseminata (LPD) endometriosis, and an extensive multicystic mesothelial proliferation. Although endometriosis is known to occur in conjunction with either LPD or multicystic mesothelioma, to our knowledge this is the first report of all three lesions occurring simultaneously.

Adult↗

PubMed1998

Cytokine and matrix metalloproteinase expression in pigmented villonodular synovitis may mediate bone and cartilage destruction.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is characterized by hypervascular proliferative synovium containing multinucleated giant cells, macrophages, and hemosiderin. The destruction of articular cartilage and erosion of periarticular bone is thought to be mediated by matrix metalloproteinases (MMPs). Expression of MMPs in some tumors appears to be stimulated through local production of cytokines, and several specific cytokines (TNF alpha, IL-1, and IL-6) play an important role in the stimulation of osteoclastic bone resorption. The role of cytokine secretion and regulation of MMP production in PVNS has not been investigated. DESIGN: In the present study, ten specimens from eight patients (ages 19 to 80) were evaluated histologically according to a modified Mirra classification and immunohistochemically (IHC) for the expression of MMP-9 (92 kDa gelatinase B), tumor necrosis factor alpha (TNF alpha), interleukin 1-beta (IL-1 beta), and interleukin 6 (IL-6). Localization of IL-6 and TNF alpha production was confirmed by in situ hybridization (ISH) for mRNA. RESULTS: All specimens, regardless of location (six knees, one ankle, one subtalar joint), showed diffuse and intense immunoreactivity for cytokines in the giant cells and synovial cells, and less intense and diffuse staining in the activated macrophages. Staining in the fibroblastic elements was minimal. In situ hybridization for TNF alpha and IL-6 mRNA mirrored the immunohistochemistry results, although the IL-6 staining was weaker than that for TNF alpha. Immunoreactivity for MMP-9 was diffuse and strong in giant cells, diffuse and moderate in synovial cells, and focal and moderate to strong in macrophages. In contrast, normal synovium demonstrated focal, moderate immunoreactivity for IL-1 beta, IL-6, TNF alpha and MMP-9 localized in the synovial lining cells. CONCLUSION: These findings suggest that periarticular bone resorption and cartilage destruction which characterize PVNS may be related to the expression of inflammatory cytokines, which in turn stimulate MMP production.

Adult↗

PubMed1997

P-glycoprotein expression in cartilaginous tumors.

BACKGROUND AND OBJECTIVES: Malignant cartilage tumors demonstrate chemotherapeutic resistance through undetermined mechanisms. P-glycoprotein is the protein product of the multiple drug resistance gene 1 (MDR-1) and confers multidrug chemotherapeutic resistance in a variety of malignancies. METHODS: MDR-1 expression was examined in 55 benign and malignant cartilage tumor specimens by immunohistochemistry using C219, C494, and JSB-1 antibodies, and by in situ hybridization with an MDR-1 specific oligonucleotide cDNA probe. RESULTS: Constitutive expression of P-glycoprotein was observed in all benign and malignant cartilage tumor specimens with a similar pattern of immunohistochemical staining present with all three antibodies. In benign tumors and low grade chondrosarcomas, the staining pattern was weak to intermediate and localized to clusters of cells. However, higher grade-tumors (Grade II and III) expressed P-glycoprotein in a higher percentage of cells and with more intense staining. P-glycoprotein expression was absent in normal human articular cartilage, but was focally present in costal and growth plate cartilage. The immunohistochemistry results were confirmed by in situ hybridization in 10 cases. CONCLUSIONS: P-glycoprotein is expressed constitutively in cartilaginous tumors, with greatest expression in high grade malignancies. The findings may account for the resistance of cartilage tumors to chemotherapeutic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Differential regulation of type-II and type-X collagen synthesis by parathyroid hormone-related protein in chick growth-plate chondrocytes.

Parathyroid hormone-related protein is a critical autocrine regulator of endochondral ossification in the growth plate, as demonstrated by the severe disruption of growth-plate structure and function in parathyroid hormone-related protein-deficient transgenic mice. In the present study, the effects of parathyroid hormone-related protein on the synthesis of collagen mRNA and protein were studied in short-term cultures of isolated chick growth-plate chondrocytes. Parathyroid hormone-related protein selectively inhibits type-X collagen protein synthesis with no significant effect on type-II collagen protein synthesis. These effects were present in all maturationally distinct populations of chondrocytes separated by countercurrent centrifugal elutriation. In cultures of resting chondrocytes, the onset of type-X collagen expression was inhibited, while the synthesis of type-X collagen was decreased in cultures of hypertrophic chondrocytes. Synthesis of type-II and type-X collagen mRNA was examined by nonradioactive in situ hybridization with synthetic oligonucleotide cDNA probes, and the level of expression was quantified using digital image analysis. Dose-dependent suppression of type-X collagen gene expression by parathyroid hormone-related protein was observed, with no significant effect on type-II collagen mRNA detected. The results were confirmed by analysis of Northern blots of total chondrocyte mRNA. These experiments demonstrated differential transcriptional regulation of type-II and type-X collagen, with selective suppression of type-X collagen expression, by parathyroid hormone-related protein in growth-plate chondrocytes. In addition, excellent agreement was found between traditional protein and mRNA analyses and microscopic digital image analysis techniques, supporting the use of this convenient and sensitive assay method. Parathyroid hormone-related protein inhibits chondrocyte maturation and is known to stimulate proliferation, suggesting that this autocrine factor may function to regulate premature hypertrophy in the growth plate.

Animals↗

PubMed1997

Osteoclasts constitutively express regulators of bone resorption: an immunohistochemical and in situ hybridization study.

Bone resorption is controlled by the local production of soluble regulatory molecules within the marrow microenvironment that mediate osteoclast recruitment, differentiation, and activation. Under normal conditions osteoclasts are rarely seen; in many pathologic states, however, the number of osteoclasts is dramatically increased, resulting in a net-loss of bone mass. The role of the osteoclasts as autocrine regulators of bone resorption in either normal or pathologic conditions has not been extensively investigated. The expression of IL-1 beta, IL-6, and TNF-alpha was examined in osteoclasts by immunohistochemistry under conditions of normal, reactive, and pathologic bone resorption, including growth plate (3 cases), fracture callus (5 cases), osteomyelitis (3 cases), Paget's disease (6 cases), giant-cell tumor of bone (14 cases), and brown tumor of hyperparathyroidism (2 cases). In each case, osteoclasts demonstrated immunoreactivity for IL-1 beta, IL-6, and TNF-alpha. In areas of active bone resorption, the intensity and uniformity of staining among the various conditions were similar, suggesting constitutive expression of these cytokines by activated osteoclasts. Giant-cell tumors of bone showed cytokine reactivity in over half of the giant cells, whereas stromal cells showed scattered staining. In acute osteomyelitis, inflammatory cells (mainly macrophages) and osteoclasts were intensely positive for all three cytokines. The immunohistochemical findings were confirmed by in situ hybridization using probes specific for IL-6 and TNF-alpha, the pattern of mRNA expression paralleled that of immunoreactivity for these cytokines. These findings support the notion of autocrine/paracrine regulation of bone remodeling by osteoclasts. Because overproduction of these cytokines may enhance bone resorption through the stimulation of osteoclast progenitor cells as well as mature osteoclasts, pathologic bone lesions with a large increase in the number of osteoclasts may be self-perpetuating. Alteration in the synthesis, secretion, or activity of these important regulatory molecules may in turn alter bone remodeling and loss.

Bone Diseases↗

PubMed1996

Effects of lead on growth plate chondrocyte phenotype.

Lead toxicity is a major public health problem in the United States. The skeleton serves as the major reservoir for ingested lead, where it is incorporated into bone matrix during calcification. While lead in bone has been considered inactive, mounting clinical and epidemiological data has shown a strong correlation between lead exposure and adverse effects on stature in children. These epidemiologic data suggest a direct effect of lead on skeletal development, but whether it reflects a systemic effect, a specific effect on osteoblasts, or an effect on the epiphyseal growth plate is as yet unclear. This study examined the effects of lead on parameters of cartilage biology in isolated chondrocytes. Changes in growth plate chondrocyte phenotype were assessed utilizing an established avian growth plate chondrocyte model. Low, sublethal doses of lead caused specific and significant effects on a number of important markers of growth plate chondrocyte phenotype, including suppression of alkaline phosphatase and both type II and type X collagen expression at the protein and mRNA levels, and a decrease in thymidine incorporation. In contrast, proteoglycan synthesis was stimulated relative to controls in lead-treated cultures, suggesting that the alterations in collagen and DNA synthesis and alkaline phosphatase activity are not due to cytotoxity. The data demonstrate important regulatory effects of lead on growth plate chondrocytes in cell culture and suggest an inhibitory effect on the process of endochondral bone formation. The growth plate may be one of the key target tissues accounting for the adverse effects of chronic lead exposure on skeletal development.

Animals↗