PubMed Health⌕ Search

Biomedical subjects

B A Alman

Publications and source records attributed to B A Alman.

At least 19 recordsLinked to original sources
PubMed2002

Eosinophilic granuloma. A different behaviour in children than in adults.

Localised Langerhans-cell histiocytosis of bone (eosinophilic granuloma) is a benign tumour-like condition with a variable clinical course. Different forms of treatment have been reported to give satisfactory results. However, previous series all contain patients with a wide age range. Our aim was to investigate the effect of skeletal maturity on the rate of recurrence of isolated eosinophilic granuloma of bone excluding those arising in the spine. We followed up 32 patients with an isolated eosinophilic granuloma for a mean of five years; 17 were skeletally immature. No recurrences were noted in the skeletally immature group even after biopsy alone. By contrast, four of 13 skeletally mature patients had a recurrence and required further surgery. This suggests that eosinophilic granuloma has a low rate of recurrence in skeletally immature patients.

Adolescent↗
PubMed2001

Tcf-3 expression and beta-catenin mediated transcriptional activation in aggressive fibromatosis (desmoid tumour).

Aggressive fibromatosis harbours mutations resulting in beta-catenin protein stabilization. Primary cell cultures demonstrate constitutive tcf activation in aggressive fibromatosis. Expression and co-immunoprecipitation studies suggest that beta-catenin binds and activates tcf-3 in this tumour. This is the first demonstration of tcf-3 activation by beta-catenin stabilization in a human neoplastic process.

Cytoskeletal Proteins↗
PubMed2001

Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or beta-catenin genes, resulting in beta-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in beta-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to beta-catenin stabilization in aggressive fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion.

Animals↗
PubMed2001

Local complications after limb-salvage surgery for pediatric bone tumours: a pictorial essay.

The prognosis for patients with bone sarcoma treated with LSS has improved considerably over the past 2 decades, but this has also lead to an increase in the number of complications requiring treatment. Imaging plays an important role, not only in assessing the primary tumour, but also in identifying postsurgical complications. Plain radiography demonstrates the majority of the complications associated with LSS and remains the mainstay of follow-up imaging. Complications such as fractures are common and warrant frequent plain film follow-up. Imaging with scintigraphy, MRI and CT should be tailored to the patient's clinical history, type of surgery and suspected complications. A baseline postoperative bone scan examination can be helpful for comparisons with subsequent scans for the detection of complications. Sonography should be considered if infection is suspected. Finally, tumour recurrence may be frequent enough to consider more extensive use of MRI.

Adolescent↗
PubMed2000

Prominent expression of mRNA for proinflammatory cytokines in synovium in patients with juvenile rheumatoid arthritis or chronic Lyme arthritis.

OBJECTIVE: To examine the cytokine profiles in synovium of patients with juvenile rheumatoid arthritis (JRA) or Lyme arthritis, 2 chronic inflammatory arthritides that affect children. METHODS: We used in situ hybridization with specific riboprobes to determine the expression of mRNA for proinflammatory or antiinflammatory cytokines in synovial samples from 5 patients with early, untreated JRA, 15 patients with late, treated JRA, and 9 patients with chronic Lyme arthritis. For comparison, synovia were examined from 6 patients with rheumatoid or psoriatic arthritis, and from 9 patients with various orthopedic conditions. RESULTS: Among the children with early, untreated JRA, a median of 3 to 8% of inflammatory cells in synovial samples expressed mRNA for the proinflammatory cytokines interleukin 1beta (IL-1beta), tumor necrosis factor-alpha(TNF-alpha), or interferon-gamma (IFN-gamma). Although a median of 3.9% of the cells expressed mRNA for the antiinflammatory cytokine IL-10, none had IL-4 mRNA. Most of the patients with late, treated JRA, chronic Lyme arthritis, rheumatoid, or psoriatic arthritis had mRNA for each of these proinflammatory cytokines in about 1% of the cells, whereas mRNA for the antiinflammatory cytokines was less frequent. The inflammatory cell density was much less in the synovium of patients with various orthopedic conditions, but about 1% of the infiltrating cells expressed mRNA for at least one of the proinflammatory cytokines. CONCLUSION: Patients with early or late JRA or chronic Lyme arthritis have expression of mRNA in synovial tissue primarily for proinflammatory cytokines, with less expression of antiinflammatory cytokines.

Adult↗
PubMed1999

Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis (also called desmoid tumor) occurs as a sporadic lesion or as part of Familial Adenomatous Polyposis, which is caused by germ line mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the regulation of the cellular level of beta-catenin, which is a mediator in Wnt signaling. Mutational analysis of the beta-catenin and APC genes was performed in 42 sporadic aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had a point mutation in beta-catenin at either codon 45 or codon 41 (producing a stabilized beta-catenin protein product). Immunohistochemistry showed an elevated beta-catenin protein level in all tumors, regardless of mutational status. Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the six tumors in which this was tested. The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of aggressive fibromatosis. This is the first demonstration of somatic beta-catenin mutations in a locally invasive, but non metastatic lesion composed of spindle cells, illustrating the importance of beta-catenin stabilization in a variety of cell types and neoplastic processes. Moreover, this tumor has one of the highest reported frequencies of beta-catenin mutations of any tumor type.

Base Sequence↗
PubMed1999

Expression of osteocalcin and its transcriptional regulators core-binding factor alpha 1 and MSX2 in osteoid-forming tumours.

Osteosarcoma, fibrous dysplasia, and myositis ossificans contain osteoid-producing cells that are not necessarily morphologically typical osteoblasts. Nevertheless, these pathologic cells may share differentiation steps with osteoblasts at the molecular level. Osteocalcin, a bone-specific extracellular matrix protein, is a marker of mature osteoblasts. Osteocalcin is upregulated by the transcription factor core-binding factor alpha 1, which is responsible for commitment to the osteoblastic lineage, and is downregulated by MSX2, a homeobox-containing transcription factor expressed during the early proliferative phase of osteoblast differentiation. Semiquantitative reverse transcription-polymerase chain reaction was used to compare expression levels of osteocalcin, core-binding factor alpha 1, and MSX2 in 34 osteosarcoma, five fibrous dysplasia, and five myositis ossificans specimens, as well as in seven normal cortical bone samples. Despite normal or elevated levels of core-binding factor alpha-1 expression in most specimens, osteocalcin expression was low or undetectable in most cases of osteosarcoma (25 of 34) and myositis ossificans (4 of 5). Single-strand conformation polymorphism and sequencing did not identify any mutations in the DNA-binding domain of core-binding factor alpha 1. However, a high level of MSX2 expression was demonstrated in these lesions, which may inhibit osteocalcin transcription. The presence of moderate levels of osteocalcin in fibrous dysplasia may contribute to the characteristic disconnected appearance of trabeculae in that entity because osteocalcin is a negative regulator of bone formation.

Bone Neoplasms↗
PubMed1999

Pelvic obliquity after fusion of the spine in Duchenne muscular dystrophy.

Spinal fusion, ending caudally at L5 rather than at the sacrum, is recommended for selected patients with scoliosis due to Duchenne muscular dystrophy. We present a retrospective review of 48 patients operated on for this condition. Patients having spinal curvature with a Cobb angle of less than 40 degrees and with less than 10 degrees between a line tangential to the superior margins of both iliac crests and a line perpendicular to the spinous processes of L4 and L5, were fused to L5 (38 patients); patients not meeting these criteria were fused to the sacrum (10 patients). Spinal and sitting obliquity increased in patients fused to L5, rather than to the sacrum, but the severity of the worsening obliquity was significantly greater in patients in whom the apex of the curve was below L1. Two of the ten latter patients required revision procedures for worsening obliquity when their pulmonary function deteriorated to less than 25% of predicted values. We recommend fusion to the sacrum for scoliosis in Duchenne muscular dystrophy, especially for patients with an apex to their curve below L1.

Adolescent↗
PubMed1998

Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis is a monoclonal proliferation of spindle (fibroblast-like) cells. A subset of lesions contain somatic truncating adenomatous polyposis coli (APC) gene mutations, and all of the lesions contain an elevated beta-catenin protein level. A major function of APC is to regulate beta-catenin protein level. Beta-catenin has a dual function in the cell: it is a member of the adherens junction, and it binds transcription factors in the tcf-lef family, transactivating transcription. Cell cultures from aggressive fibromatoses containing an APC mutation were studied. Transient transfection of the full-length APC gene caused decreased proliferation and beta-catenin protein level in these cultures. To determine whether beta-catenin protein level was responsible for the change in proliferation rate, stable transfections of deltaN89beta-catenin (a stabilized form that is not degraded by APC, but retains all other functions) were achieved in half of the cultures derived from each tumor, whereas the other half were transfected with an empty vector. Transfection of the full-length APC gene in cultures that were stably transfected with deltaN89beta-catenin did not result in a change in proliferation. The type I promotor of p56lck contains an HMG consensus region, to which members of the tcf-lef family can bind. p56lck was expressed in cultures not transfected with the full-length APC gene and in cultures transfected with the full-length APC gene and deltaN89beta-catenin, but not in cultures transfected with only the full-length APC gene. These data show that APC truncating mutations give aggressive fibromatosis cells a proliferative advantage through beta-catenin and suggest that beta-catenin acts to transactivate transcription.

Apoptosis↗
PubMed1997

Differential collagen I gene expression in fetal fibroblasts.

PURPOSE: Fetal wound healing is characterized by the regeneration of normal dermis and the absence of scar. Transforming growth factor beta-1 (TGF-beta1) is a ubiquitous cytokine with potent fibrogenic effects in both postnatal and fetal wounds. Supplementing fetal wounds with TGF-beta1 results in increased fibrosis consisting primarily of collagen I. We hypothesized that the lack of scar formation in fetal wounds may be caused by differential collagen I gene (COL1A1) expression. The authors examined basal collagen Ia gene expression in human fetal, newborn, and adult dermal fibroblasts after stimulation with exogenous TGF-beta1. METHODS: Subconfluent human dermal fibroblasts from fetal, newborn, and adult cell lines were incubated for 24 hours, then stimulated by incubation for 4 hours with 1 ng/mL of human recombinant TGF-beta1, or with media alone for basal collagen gene expression, and then placed in guanidium isothyocyanate buffer. To quantitate COL1A1 gene expression, total cellular RNA was extracted and subjected to northern and slot blot hybridization analysis with Dig-labeled COL1A1 probes. The membrane was exposed to x-ray film for 15 minutes and developed. RESULTS: Scant COL1A1 gene transcript was detected in control fetal fibroblasts. Brief stimulation with of TGF-beta1 upregulated the COL1A1 gene transcription in fetal fibroblasts. Gene expression for COL1A1 in both postnatal cell lines appeared similar in treated and untreated cells. Housekeeping control (GAPDH) confirmed no difference in total amount of RNA at the start or end of the experiment. CONCLUSION: COL1A1 gene expression is notably absent in unstimulated fetal fibroblasts, but is upregulated by TGF-beta1. In contrast, postnatal fibroblasts demonstrate significant constitutive COL1A1 gene expression at baseline and unchanged after TGF-beta1 stimulation. This differential regulation may contribute to the ability of fetal wounds to regenerate without scar and explain the effect of exogenous TGF-beta1 to increase fibroplasia in fetal dermal incisional wounds.

Adult↗
PubMed1997

Aggressive fibromatosis (desmoid tumor) is a monoclonal disorder.

Aggressive fibromatosis (also called deep fibromatosis or desmoid tumor) is a proliferation of cytologically benign-appearing fibrocytes, often resulting in significant functional loss. The nature of the lesion is controversial: some evidence suggests that it is a reactive process, whereas other evidence supports a neoplastic etiology. The pattern of X chromosome inactivation, using a technique based on polymerase chain reaction (PCR) amplification of a hypervariable CAG repeat region flanking Hhal restriction sites of the human androgen receptor gene, was determined in four cases in which cryopreserved tumor and adjacent normal tissue were available. All four tumors demonstrated a monoclonal pattern, while the adjacent normal tissues demonstrated a polyclonal pattern. This demonstrates that aggressive fibromatosis is proliferation of cells derived from a single clone with a growth advantage, and thus is likely a neoplastic process.

Arm↗
PubMed1997

Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors).

Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling. beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). Six cases of aggressive fibromatosis of the extremities from patients without familial adenomatous polyposis, or a family history of colon cancer, were studied. Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Western blot and Northern dot blot showed that all six tumors had a higher level of beta-catenin protein than surrounding normal tissues, despite containing similar levels of beta-catenin mRNA. Immunohistochemistry localized beta-catenin throughout the cell in tumor tissues, although it localized more to the periphery in cells from normal tissues. Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues. In some cases, this is caused by a somatic mutation resulting in a truncated APC protein.

Adenomatous Polyposis Coli Protein↗
PubMed1996

Activating mutations of Gs protein in monostotic fibrous lesions of bone.

Activating mutations of the alpha chain of the heterotrimeric signal transducer Gs disrupt the inherent guanosine triphosphatase activity of the alpha chain, stimulate adenylyl cyclase, and can result in independent cell proliferation. Such mutations are identified in a number of endocrine disorders, including McCune-Albright syndrome, which is a triad of endocrinopathy, café au lait spots, and polyostotic fibrous dysplasia. The mutation in this syndrome is a missense point mutation in exon 8 that results in the substitution of either histidine or cysteine for arginine at position 201. Monostotic fibrous dysplasia is a nonhereditary isolated bone lesion. Other isolated bone lesions that share some cytologic and clinical similarities to fibrous dysplasia are osteofibrous dysplasia and aggressive fibromatosis involving bone. Four cases of monostotic fibrous dysplasia, four cases of aggressive fibromatosis involving bone, and one case of osteofibrous dysplasia were studied to determine if a mutation was present in exon 8 of the alpha chain of Gs. A missense mutation was present in all of the fibrous dysplasias. The other fibrous lesions and uninvolved tissue did not contain a mutation. Somatic activating mutations of Gs differentiate fibrous dysplasia from the other lesions and may be responsible for the loss of control of local proliferation and growth factor expression.

Adolescent↗
PubMed1996

Regulation of proliferation and platelet-derived growth factor expression in palmar fibromatosis (Dupuytren contracture) by mechanical strain.

Palmar fibromatosis (Dupuytren contracture) causes fibrosis of specific palmar fascial bands. These bands are subjected to repetitive mechanical strain in situ. Primary cell cultures were derived from (a) palmar fibromatosis from eight patients, (b) uninvolved palmar fascia (Skoog's fibers) from four of these patients, and (c) normal palmar fascia from four additional patients. The cells were plated onto collagen-coated membranes either subjected to cyclic strain (25% maximal strain at 1 Hz) or without strain. Bromodeoxyuridine incorporation showed an increase in proliferation in all cultures subjected to strain. This increase was highest for palmar fibromatosis (10 to 40% nuclear incorporation, p = 0.02). Skoog's fibers and fascia from the normal individuals showed a trend (not significant) toward increase with strain (8 to 25%, p = 0.15 for Skoog's fibers, and 8 to 15%, p = 0.45 for normal fascia). Cyclic strain increased the expression of platelet-derived growth factor-A relative to glyceraldehyde-3-phosphate dehydrogenase in palmar fibromatosis (2.2 to 3.5, p = 0.05) and Skoog's fibers (0.8 to 2.0, p = 0.04). The expression of platelet-derived growth factor-B relative to glyceraldehyde-3-phosphate dehydrogenase was enhanced by cyclic strain only in the fibromatosis tissue (0.7 to 2.1, p = 0.04). The normal fascia did not express platelet-derived growth factor. Platelet-derived growth factor neutralizing antibody decreased bromodeoxyuridine incorporation in fibromatosis cultures subjected to cyclic strain to near levels for those grown in the absence of strain (38 to 16%, p = 0.05). Conditioned medium from fibromatosis cells grown under stain showed a trend toward increased proliferation in additional fibromatosis cultures compared with conditioned medium from fibromatosis cells grown without strain (9 to 15% nuclear incorporation, p = 0.20). The observed palmar fibromatosis contracture can be partially explained on the basis of the cell's response to cyclic strain, which may be mediated by platelet-derived growth factor.

Antibody Specificity↗
PubMed1996

Molecular genetic and immunohistochemical analysis of the tumor suppressor genes Rb and p53 in palmar and aggressive fibromatosis.

This pilot project analyzed the tumor suppressor genes p53 and Rb in 13 cases of aggressive fibromatoses and six cases of palmar fibromatoses (Dupuytren contracture). Immunohistochemistry, reverse transcription polymerase chain reaction, polymerase chain reaction followed by single-strand confirmation polymorphism analysis, and Southern blot to detect gene rearrangements were used. No abnormalities were detected in p53. The aggressive fibromatoses demonstrated a lack of Rb immunohistochemical staining and decreased mRNA for Rb. No structural mutation in the coding sequence of the Rb gene was detected. The decreased level of Rb gene expression, despite a normal coding sequence, may indicate increased proliferation and may suggest potential treatment schemes.

Blotting, Southern↗
PubMed1996

Function of dislocated hips in children with lower level spina bifida.

We reviewed 52 children, born between 1974 and 1985 with spina bifida affecting L3 and L4, who had dislocated hips. Their motor function was stable and they were able to walk at the time of dislocation. They were interviewed and examined physically and radiologically. Physical function was measured by the Rand Health Insurance Study questionnaire (HIS), the Childhood Health Assessment questionnaire (CHAQ), and by determining the functional level of ambulation according to Hoffer et al (1973). In a subgroup of 12 patients with L4 level of involvement from both treatment groups we measured the metabolic energy consumption while walking. Thirty patient (49 hips) had been treated by operative relocation and 22 conservatively. Ten of the hips treated by operation subluxated or redislocated. The function in the two groups (conservative nu operated) was similar (HIS score 7.8 v 8.0, p = 0.45; CHAQ 14 v 13, p = 0.2; level of mobility 0.61 v 0.63, p = 0.5). Patients in whom operation had failed had worse function than did those with successful surgery (HIS score 8.8 v 6.1, p = 0.025) and those with successful surgery had better function than patients treated conservatively (HIS score 8.8 v 8.0, p = 0.15). Function in patients with failed operations, however, was worse than in those who did not have surgical treatment (HIS score 6.6 v 7.8, p = 0.07). In the 12 so examined the operated group had a 30% more energy-efficient gait (0.271 v 0.361 ml O2 kg/m, p = 0.05). Patients with failed operations had worse function than those who were not operated on. The benefit of surgical relocation of the dislocated hips was marginal.

Adolescent↗
PubMed1995

Platelet-derived growth factor in fibrous musculoskeletal disorders: a study of pathologic tissue sections and in vitro primary cell cultures.

Despite the great variability in the clinical behavior of fibrous lesions of the musculoskeletal system, they are composed of cytologically similar fibrocytes. Receptors for estrogen or progesterone, or both, are present in some of these lesions and some increase their rate of growth during periods of high levels of sex steroid hormones. The platelet-derived growth factor-B (PDGF-B) proto-oncogene encodes the B chain of PDGF, a mitogen for fibrocytes. Tissue from aggressive fibromatosis, fibrous dysplasia, plantar fibromatosis, and recurrent plantar fibromatosis was analyzed with use of the polymerase chain reaction and in situ hybridization for the expression of PDGF-B and PDGF beta receptor. Cell culture was used to determine if estrogen and progesterone stimulation modulated the expression of PDGF-B. Aggressive fibromatosis, fibrous dysplasia, and recurrent plantar fibromatosis expressed PDGF-B; plantar fibromatosis, normal plantar fascia, normal fascia lata, and mature scar did not. All of the tissues expressed PDGF beta receptor. The level of expression in aggressive fibromatosis and fibrous dysplasia was four times that in the recurrent plantar fibromatosis. Estrogen and progesterone stimulation in aggressive fibromatosis resulted in an increase in the level of expression. Therefore, the detection of PDGF-B may be an adjunct in the pathologic identification of locally invasive lesions. Its production may be a common mechanism leading to a fibroproliferative response through deregulation of the control of growth by both paracrine and autocrine mechanisms.

Base Sequence↗