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Biomedical subjects

D G Hicks

Publications and source records attributed to D G Hicks.

At least 37 records · Page 2Linked to original sources
PubMed1996

Extraosseous primary and recurrent giant cell tumors: transforming growth factor-beta1 and -beta2 expression may explain metaplastic bone formation.

Giant cell tumor (GCT) of bone is a locally aggressive neoplasm with a high incidence of recurrence, usually at the site of previous osseous involvement. Primary and recurrent intraosseous lesions typically are lytic and do not show evidence of tumor-associated osteogenesis. Rarely, GCT recurs or is primary within soft tissue, and not infrequently, these extraosseous lesions show metaplastic bone formation that is visible radiographically. The authors report two recurrent and one primary case of extraosseous GCT, all of which exhibited significant deposits of metaplastic bone localized to the periphery of the lesions. In situ hybridization showed messenger RNA (mRNA) for transforming growth factor beta1 (TGF-beta1) and transforming growth factor beta2 (TGF-beta2) in neoplastic stromal cells and osteoclast-like giant cells within the recurrent and primary extraosseous tumors as well as in active osteoblasts on the surfaces of recently formed spicules of metaplastic bone. In situ hybridization also revealed mRNA for TGF-beta1 and TGF-beta2 in primary intraosseous tumors from these cases and from four cases in which neither extraosseous recurrence nor osseous metaplasia was identified. In the microenvironment of the extraosseous soft tissue, production of these osteoinductive growth factors by GCT may have a paracrine effect on mesenchymal progenitor cells, thereby stimulating the osteoblastic differentiation and metaplastic bone formation associated with these lesions.

Adult↗
PubMed1996

Granular histiocytosis of pelvic lymph nodes following total hip arthroplasty. The presence of wear debris, cytokine production, and immunologically activated macrophages.

UNLABELLED: Infiltration of regional lymph nodes by macrophages has been demonstrated after total joint arthroplasty. Although lymph nodes regulate the immune response, neither cytokine production nor the degree of immunological activation of cells within these nodes after total joint arthroplasty has been investigated. Pelvic lymph nodes were obtained from five patients who had had a total of eleven arthroplasties in seven hips three to twenty years before a pelvic staging procedure for adenocarcinoma (of the prostate in four patients and of the endometrium in one). All lymph nodes had polyethylene or metal debris as well as effacement of the normal nodal architecture by a histiocytic infiltrate. These changes were bilateral in the patients who had had an arthroplasty of one hip. Analysis of specimens from pelvic lymph nodes on the side of the involved hip demonstrated intense immunohistochemical staining of histiocytes for the major histocompatibility complex class-II antigen HLA-DR, a marker of histiocyte immune activation. In contrast, staining was absent in specimens from the contralateral lymph nodes as well as in those from seven patients who had had a prostatectomy but not a hip arthroplasty. Immunohistochemical staining for interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 demonstrated a much greater expression of these cytokines in the involved lymph nodes. CLINICAL RELEVANCE: Additions improvements in total joint replacement will be facilitated by a more thorough understanding of the biological response to the components and materials of implants. While local biological factors leading to failure of prostheses are currently under intense investigation, the mechanisms and importance of regional and systemic immune responses to wear debris require further study.

Adenocarcinoma↗
PubMed1996

Mastocytosis presenting as a skeletal disorder.

Mastocytosis is a rare disease of mast-cell proliferation with involvement of the reticuloendothelial systems including skin, bone, gastrointestinal tract, liver, lungs, spleen, and lymph nodes. Systemic mastocytosis is characterized by a combination of symptoms that relate to the mast cells' release of vasoactive substances, such as histamine. These symptoms include urticaria pigmentosa, flushing, syncope with hypotension, headaches, nausea, vomiting, diarrhea, and occasional bronchospasm. The diagnosis of mastocytosis is typically based on the presence of the characteristic extraosseus manifestations. A well recognized roentgenographic feature seen in 70-75% of patients with mastocytosis is diffuse osteolysis and osteosclerosis, affecting primarily the axial skeleton and the ends of the long bones. Rarely, the bony involvement consists of generalized osteoporosis, which may lead to pathologic fracture, or solitary lesions (mastocytomas) which may cause symptoms of localized pain. Four patients with previously diagnosed systemic mastocytosis had unusual skeletal lesions. Clinical and laboratory evaluation of these patients eventually led to the correct diagnosis of systemic mastocytosis. We report these four cases to emphasize the need for thorough evaluation of unusual musculoskeletal findings in association with extraosseus symptoms that are characteristic of mastocytosis. Knowledge of a wide differential diagnosis of unusual skeletal lesions should include systemic mastosytosis.

Adult↗
PubMed1995

Primary lymphoma of bone. Correlation of magnetic resonance imaging features with cytokine production by tumor cells.

BACKGROUND: Primary lymphoma of bone is a rare, aggressive neoplasm that can present with a large, soft-tissue mass despite minimal evidence of cortical destruction on plain radiographs. METHODS: High resolution magnetic resonance imaging (MRI) examinations of four patients with primary lymphoma of bone were reviewed retrospectively, and in each case intramedullary tumors demonstrated "penetrating channels" extending through the cortex. The MRI studies were correlated with the histopathologic assessment of the tumor for each patient. Immunohistochemistry was performed for immunophenotyping and for cytokine expression by tumor cells. The cytokines that were investigated were interleukin-1, interleukin-6, and tumor necrosis factor-alpha, molecules known to regulate osteoclastic activity. RESULTS: The linear cortical foci noted on MRI correlated with the histopathologic findings of tumor-associated cutting cones, in proximity to osteoclastic bone resorption. Immunohistochemical stains showed a B-cell phenotype for each tumor and positive immunoreactivity in tumor cells for cytokine mediators that stimulate osteoclastic activation. CONCLUSIONS: These findings indicate that the tumor cells in these cases produce soluble cytokine mediators that may regulate extensive osteoclastic activity. In primary lymphoma of bone, tumor activation of osteoclastic resorption, with production of tumor tunnels through the cortex, may represent one of the mechanisms by which lymphoma escapes the intramedullary space and forms large, soft-tissue masses without extensive cortical destruction.

Adult↗
PubMed1995

Shared phenotypic expression of osteoblasts and chondrocytes in fracture callus.

Endochondral ossification in fracture healing of rats at 4, 8, 11, 14, and 21 days was analyzed using immunological and molecular probes for markers of the chondrocyte and osteoblast phenotype. These markers were osteocalcin, type I and type II collagen, including the probes homologous to the alternatively spliced forms of alpha 1 type II collagen, type IIA and type IIB. Histologic examination was performed on serial sections of the same tissue blocks to correlate cellular morphology with the immunohistochemical and in situ hybridization findings. At the junction of the cartilaginous and osseous tissue, an overlap of phenotype and morphology was noted. At the 8-day time point, the cells with chondrocyte morphology expressed intracellular message for osteocalcin and type I collagen. Immunohistochemical analysis of these cells also demonstrated intracellular osteocalcin. However, high levels of the type IIA collagen mRNA, which has previously been associated with less differentiated mesenchymal precursor cells, were expressed in both chondrocytes and osteoblasts. At the later time point (21 days) there was a substantial decrease in the number of cells displaying shared phenotypic characteristics. In situ hybridization and immunohistochemistry have permitted identification of an overlapping or shared phenotype in osteoblasts and chondroblasts in fracture callus. The findings raise important questions regarding the possible plasticity of mesenchymal cell phenotypes within the dynamic environment of fracture healing. Additional examination of these issues will further define factors involved in origin, differentiation, and maturation of bone and cartilage cells.

Animals↗
PubMed1995

Rate of degeneration of human acetabular cartilage after hemiarthroplasty.

Biopsy specimens of cartilage and subchondral bone were obtained from the weight-bearing dome of the acetabulum in twelve elderly patients who were having a revision of a hemiarthroplasty of the hip because of pain. Biopsy specimens of acetabular cartilage and subchondral bone were also obtained from eight patients of comparable age who were having a primary hemiarthroplasty for a displaced fracture of the femoral neck; these served as the control specimens. The specimens were stained with hematoxylin and eosin for the initial histological assessment of cartilage structure and cellularity as well as the integrity of the tidemark. Safranin-O and toluidine-blue stains were used to assess proteoglycan content. A histological grading scale was employed for comparative analysis of samples. The joint space of the hip was measured on the radiographs that were made before the revision and was correlated with the histological grade. Review of the histological specimens demonstrated considerable degeneration of acetabular cartilage in the patients who were having a revision of a hemiarthroplasty as compared with that in the age-matched control patients who were having a primary hemiarthroplasty. The progression in the severity of the degeneration correlated directly with the duration of articulation of the implant with the acetabulum. All six of the patients in whom the implant had been in situ for more than five years, and in whom the femoral stem was determined to be stable at the operation, had nearly complete loss of cartilage as seen on histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetabulum↗
PubMed1994

Analysis of type II and type X collagen synthesis in cultured growth plate chondrocytes by in situ hybridization: rapid induction of type X collagen in culture.

Type X collagen is produced by hypertrophic chondrocytes and serves as a highly specific marker for chondrocyte maturation. This study was designed to compare the expression of type II and type X collagen in growth plate sections and in distinct populations of chondrocytes in culture by in situ hybridization. Growth plate sections were treated with type II and type X collagen cDNA probes. Type II collagen mRNA was present throughout the growth plate but greatest in the lower proliferating and upper hypertrophic regions. In contrast, type X collagen was expressed only in the hypertrophic region. Northern analysis confirmed the specificity of the probe for type X collagen mRNA. Chick growth plate chondrocytes were separated by countercurrent centrifugal elutriation into five distinct populations and plated in serum-containing medium. These cultures were examined at varying times after plating for the expression of type II and type X collagen mRNA. At 3 h, type II collagen was present in the majority of the cells in all fractions, and approximately 15-20% of the cells expressed type X collagen mRNA. The cells expressing type X were from the hypertrophic region. At 24 h, however, nearly all cells in culture expressed type X mRNA, and there was a decrease in expression of type II collagen mRNA. Similar results were obtained in cultures in the absence of serum, and SDS-PAGE analysis of collagen synthesis confirmed the expression of type X collagen in all populations of fractionated cells at 24 h at the protein level. Type X collagen is an important marker through which cellular matruation can be evaluated in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hyperostosis cranii ex vacuo: a rare complication of shunting for hydrocephalus.

Hyperostosis cranii ex vacuo is a condition that may develop after successful ventricular shunting for hydrocephalus. It is characterized by diffuse thickening of the skull (particularly the inner table) involving the calvarium and the base. It is a diagnosis that distinguishes marked calvarial thickening from thickening of the skull because of other causes. It is an entity that needs to be considered in patients who have diffuse thickening of the skull, have premature closure of sutures, and who have been treated for hydrocephalus in the past.

Adult↗
PubMed1994

Regulation of osteoclastic activity in infection.

Figure 4 is a diagrammatic representation of five pathways involved in the activation of osteoclastic and osteoblastic cell activity during an infectious process. Pathways 1 and 2 are involved in the recruitment and activation of osteoclasts. These pathways are controlled by systemic hormones and cytokines of the infection/immune axis. As described above, many of the cytokines are synergistic and can evoke very strong stimuli for bone resorption; however, under normal conditions for any given number of bone-resorbing sites, there is always an equivalent compensatory stimulus to enhance bone formation. Pathways 3 to 5 govern the formation stimuli. Thus, for bone to be permanently lost there must be a disruption in the cellular communication that exists between pathways 1 and 2 and pathways 3 to 5. Such a disruption occurs in periodontal disease and osteomyelitis. At present, the molecular mechanisms that create the disruption in cell communication are not known. They may be complex and involve as yet unidentified cell biological principles, or they may be relatively simple reactions involving known factors and enzymes.

Adult↗
PubMed1993

Epithelioid osteosarcoma of bone. Immunocytochemical evidence suggesting divergent epithelial and mesenchymal differentiation in a primary osseous neoplasm.

BACKGROUND: The combination of a primary osteosarcoma of bone with a second carcinomatous cell type has been recognized, although immunohistochemical studies currently have not been performed in an attempt to understand the histogenesis of such a tumor. METHODS: In this report, the authors performed immunohistochemical studies on a primary osseous carcinosarcoma. Using a biotin-streptavidin peroxidase conjugate technique, the expression of keratin, epithelial membrane antigen, and vimentin was analyzed. RESULTS: The epithelial cells expressed cytokeratin and epithelial membrane antigen but did not express vimentin. The mesenchymal cells strongly expressed vimentin, and only rare cells expressed cytokeratin. CONCLUSIONS: The clinical, morphologic, and immunophenotypic data in this instance strongly suggest divergent differentiation of a primitive multipotential uncommitted stem cell in a primary osseous tumor.

Adolescent↗
PubMed1993

Quiz: case report 776. Chondromyxoid fibroma of femur.

CMF is a rare neoplasm of bone, comprising less than 1% of primary bone tumors. The neoplasm was first described in 1948 by Jaffe and Lichtenstein as a separate entity from chondrosarcomas, having slightly different plain film characteristics and a benign clinical course. As of 1985, Kreicbergs, Lonnquist, and Willems estimated that approximately 400 cases have been published. Recently, we encountered a CMF with an unusual clinical presentation. The efficacy of MRI studies is shown.

Adult↗
PubMed1993

Preliminary findings on the effects of sex hormones on bone metabolism in anorexia nervosa.

We performed tetracycline double-labeled bone biopsies and serial bone densitometry on four patients with anorexia nervosa to determine the effects of various conditions of sex hormone replacement and body weight status. We found negligible bone mineral apposition rate in two patients with anorexia nervosa who were taking estrogen and progestin pills while weighing only 79% of normal. However, bone mineral apposition rate was normal in two patients with anorexia nervosa who took no sex hormones and remained amenorrheic while weighing 87% of normal. Histomorphometric analysis revealed a decrease in intracortical trabecular area by 57% and an increase in active osteoblastic surface area by 300%, comparing the subjects who were taking hormone replacement to those who were not. There was no direct evidence of increased resorption in any subject. Six months after biopsy, the two subjects taking sex hormones decreased lumbar bone mineral density by 1.9%, while the two taking no sex hormones remained amenorrheic, but increased bone mineral density by 1.3%. Therefore, we propose that sex hormone therapy in the presence of persistently low body weight might be of limited benefit for bone mineral apposition and density.

Adolescent↗
PubMed1992

Temporomandibular joint: surgically created disk displacement causes arthrosis in the rabbit.

To document a causal relationship between temporomandibular joint disk displacement and arthrosis, the disk was surgically displaced in one temporomandibular joint in each of three rabbits. The rabbits were sacrificed after 4 weeks and the mandibular condyles were studied radiographically and histologically. All three joints that underwent disk displacement had radiographic and histologic evidence of arthrosis, which included erosion of the bone, irregularity and fissure formation of the articular soft tissue cover, disruption of the subchondral layer of cartilage cells, and chondrocyte proliferation. No radiographic or histologic changes occurred in the joints that were untouched. The results suggest that surgically created disk displacement can cause arthrosis in the temporomandibular joint of the rabbit.

Animals↗
PubMed1992

In situ hybridization for Epstein-Barr virus NotI repeats in posttransplant lymphoproliferative disorder.

Epstein-Barr Virus-associated posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. In PTLD, B-cell expansions range from reactive hyperplasias to large cell lymphomas and are often associated with active Epstein-Barr virus (EBV) infection. The lymphoproliferations may infiltrate transplant allografts and therefore may need to be distinguished from acute cellular rejection (ACR). A total of 36 tissue specimens from 11 transplant patients (six kidney, two heart, three liver) with PTLD were studied for EBV content by automated in situ hybridization (ISH) on formalin-fixed or Bouin's-fixed, paraffin-embedded tissue using a synthetic 3' terminally biotin-labeled oligonucleotide DNA probe from the EBV NotI tandem repeat region. The NotI repeat is abundantly transcribed during productive EBV infection and may encode an EBV early antigen. EBV serologies from the 11 patients showed seven primary acute infections and one acute reactivation. Two serologic studies indicated infection of indeterminant onset, and serology was not performed on one patient. Histologically, seven patients presented with polymorphous infiltrates in transplant allograft biopsies, three of which progressed to disseminated monomorphous cell populations and death within 3 to 6 wk. Tissues examined by ISH from all 11 patients showed nuclear staining for EBV in the atypical lymphoid infiltrates (34/36 specimens). The nuclear signal ranged from a stippled pattern of positivity to homogeneous nuclear staining and was localized predominantly in follicular center cells and immunoblasts, although some smaller lymphocytes also contained the viral genome. ISHs performed on 31 allograft biopsies with ACR from 24 transplant patients (six kidney, five heart, 13 liver) without clinical evidence of PTLD and with serological evidence of past EBV infection were negative for the virus. Cell lines containing EBV in the productive state (EB3 and P3HR1) were positive with ISH for NotI, while a latently infected cell line (Raji) was negative. These data indicate that ISH with the NotI probe identifies amplified genome in EBV infections and is useful in discriminating the atypical infiltrate of EBV-associated PTLD from that seen in ACR.

Adolescent↗
PubMed1992

Demonstration of passenger leukocytes in a case of Epstein-Barr virus posttransplant lymphoproliferative disorder using restriction fragment length polymorphism analysis.

Lymphocytic populations of the posttransplant lymphoproliferative disorder in a completely matched renal allograft and a recipient's regional lymph node were examined, using restriction fragment length polymorphism analysis with probe YNH24 to the variable number tandem repeat D2S44. The donor's DNA was found in lymphocytes extracted from both the grafted kidney and the recipient's lymph node 26 days after engraftment. In both these organs, the results of in situ hybridization with a terminally biotin-labeled oligonucleotide probe to the Not I tandem repeat region of the Epstein-Barr virus (EBV) genome, as well as those of Southern blot hybridization to the EBV nuclear antigen region of the EBV genome, were positive. These findings confirmed the presence of the donor's lymphocytes ("passenger leukocytes") in the host nodal tissue in human renal transplantation and implicated EBV as playing a role in the development of posttransplant lymphoproliferative disorder. It is speculated that the EBV proliferative stimulus contributed to the recipient and the donor lymphocyte expansions. Alternatively, the proliferation of both lymphocyte populations could result from a mutual stimulation by minor histocompatibility or other antigens.

Cell Division↗
PubMed1992

Nonradioactive in situ hybridization using digoxigenin-labeled oligonucleotides. Applications to musculoskeletal tissues.

We have optimized a technique for in situ localization of specific mRNAs using digoxigenin-11-dUTP-labeled oligonucleotide probes. DNA probes were synthesized for type I and type II collagen as well as transforming growth factor-beta 1 and 2 (TGF beta 1 and TGF beta 2). Control experiments, such as competitive inhibition, nonsense sequence hybridization, and RNAse digestion all indicated that the technique was highly sensitive and specific. In sections of growth plate, type II collagen mRNA was predominantly expressed in the lower proliferative and upper hypertrophic zone, whereas chondrocytes in articular cartilage stained equally. These techniques then were applied to sections cut from archival pathology specimens of musculoskeletal tissues. Primitive chondrocytes in a chondrosarcoma expressed type I and type II collagen mRNA, but did not stain with the nonsense probe. Sections from an osteosarcoma, an aneurysmal bone cyst, and a neurofibroma also were investigated. The ability to use chemically synthesized oligonucleotide probes, the high resolution, and the short development times possible with this in situ procedure makes this technique appealing for applied research into the gene expression of normal and pathologic cellular events.

Animals↗