Near-haploidy in two malignant fibrous histiocytomas

In order to isolate proteinase genes from parasitic nematodes by polymerase chain reaction (PCR) techniques, we employed a pair of consensus oligonucleotide primers designed to anneal to the active site cysteine (primer ncpC) and asparagine (primer ncpN) coding regions of cysteine proteinases. The primers were biased toward the nucleotide and codon usages of cysteine proteinase genes of nematodes and were based on the consensus nucleotide sequences flanking the active site residues of genes from Haemonchus contortus, Caenorhabditis elegans, and Ostertagia ostertagi. We employed 'touchdown' PCR conditions and were able to amplify novel cysteine proteinase gene fragments from the rodent parasite Strongyloides ratti, the human pathogen S. stercoralis, the canine hookworm Ancylostoma caninum, and from C. elegans. These clones are gene homologs of cathepsin B-like (lysosomal associated) proteases and will facilitate screening of both cDNA and genomic DNA libraries.     

Cytogenetic characterization of ten malignant fibrous histiocytomas

The use of pesticides has extensively grown in the last decades, regardless of the economic level of the countries. This led to great improvements in agriculture but also a threat for human health. Short term effects are quite well known through approval procedures for pesticides. On the other hand, long term effects are not properly assessed. A review of epidemiologic knowledge is presented here. Epidemiologic studies on pesticides have found associations with long-term effects on health mainly in three fields: cancer (especially hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral hazards, Parkinson's disease), and reproductive disorders (infertility, birth defects, adverse pregnancy outcomes, perinatal mortality). These conclusions have been obtained despite difficulties in exposition assessment due to the retrospective nature of the studies. But the continuous development of pesticide use in agriculture, and also in domestic environment, emphasizes the need for epidemiologic studies on long-term effects of pesticides relying on accurate exposure assessment.     

Expression of the tissue metalloproteinase inhibitors TIMP-1 and TIMP-2 in malignant fibrous histiocytomas and dermatofibromas as studied by in situ hybridization and immunohistochemistry

The expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was studied in eight malignant fibrous histiocytomas (MFH) and in eight dermatofibromas (DF) using in situ hybridization methods (ISH). Immunohistochemical stainings were also performed using corresponding antibodies to TIMP-1 and TIMP-2. In ISH the neoplastic cells of MFHs showed a high level of expression for both TIMP-1 and TIMP-2 mRNAs. The cells usually expressed similarly both TIMPs, except for osteoclast-like giant cells, which showed a distinct signal for TIMP-2 but not for TIMP-1. A distinctly lower level of both TIMP-1 and TIMP-2 mRNAs was seen in DFs. Immunohistochemical stainings were concordant with the results obtained by ISH. The findings suggest that the behavior of MFHs and DFs is not directly or solely dependent on the quantity of type IV collagenase inhibitors. The increased TIMP synthesis in MFHs might represent a chaotic response of malignant cells to increased matrix degradation. Alternatively, it may reflect a deranged communication between type IV collagenases and TIMPs in malignant tissues.     

Identification of a novel gene, MASL1, within an amplicon at 8p23.1 detected in malignant fibrous histiocytomas by comparative genomic hybridization

We used comparative genomic hybridization to study malignant fibrous histiocytomas (MFHs) from 19 patients to detect changes in the copy number of DNA sequences, along entire chromosomes. Together with losses and gains in various chromosomal regions, distinct high-level amplifications were found at six loci (4q12-21, 8p21-pter, 8q24.1-qter, 9q12-13, 12p11.2-pter, and 15q11.2-15), suggesting that those regions may contain unknown (proto) oncogenes. We focused on the 8p amplicon, where detailed characterization allowed us to determine that the minimal common amplified region lay between markers D8S1819 and D8S550 at 8p23.1. A novel gene designated MASL1 (MFH-amplified sequences with leucine-rich tandem repeats 1) was isolated from within this narrowly defined region. Expression of the MASL1 gene was enhanced significantly in MFH tumors bearing the 8p amplicon. The primary structure of its deduced product revealed an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, all of which are important structural or functional elements for interactions among proteins related to the cell cycle. These features suggest that overexpression of MASL1 might well be oncogenic with respect to MFH.     

Infrequent somatic mutation of the adenomatous polyposis coli gene in aberrant crypt foci of human colon tissue

BACKGROUND: The authors examined somatic mutations of the adenomatous polyposis coli (APC) gene in 84 human aberrant crypt foci (ACF) to determine whether APC gene mutations were involved in the histologic progression of ACF. METHODS: Mutation cluster regions of the APC gene were subjected to polymerase chain reaction single-strand conformation polymorphism analysis and direct sequencing. RESULTS: Four kinds of deletion were detected in the mutation cluster regions of APC gene in five ACF. APC mutation was detected in 1 of 18 ACF with Stage I abnormalities (6%). Four of 10 adenomatous ACF (40%) harbored the mutation. There were no mutations in 56 hyperplastic ACF. CONCLUSIONS: These results suggest that APC mutations may be involved initially in only a limited number of adenomas in ACF.     

Value of imaging in the assessment of malignant fibrous histiocytoma of the soft tissues

Malignant fibrous histiocytoma (MFH) is a rare and potentially highly malignant sarcoma. The authors report 6 cases of MFH in various sites: two in the chest wall, one in the pelvis, two in the gluteal zones and one on the scalp. Ultrasonography and computed tomography were the main imaging methods used in the assessment of the structure and extension of the tumor. A poor prognosis was noted in four cases: death within a few months in the two thoracic sites, recurrence in the pelvic and scalp lesions, radical surgery allowed recovery in two cases. A review of the literature showed that MRI and CT are complementary in the initial staging and follow-up of these patients.     

Single implant restorations: prosthetically induced soft tissue topography

An aesthetic transition from the smaller diameter of the implant to the prosthetic restoration that resembles the size of the natural tooth has presented an ongoing challenge to the implant restorative dentists. The appearance of the surrounding soft tissue is of major importance, and various techniques have been developed to guide and optimize its topography. The learning objective of this article is to present a cervical contouring concept, whereby the soft tissue topography is optimally determined already in the laboratory phase. Using a custom abutment and provisional crown as components of the transmucosal prosthetic unit (TPU), the topography is transferred to the vital intraoral tissues, which predictably adapt to the enhanced aesthetic configuration. Clinical cases are presented to demonstrate the sequence of the technique in treating the anterior region of the maxilla.     

Morphology and molecular biology of malignant soft tissue sarcomas

Malignant soft tissue tumors are classified and named according to cellular differentiation and thus the non-neoplastic soft tissue they imitate. The topical WHO classification already comprises more than 140 entities and tumor subtypes, but the process of defining new tumor variants will go on. Questions of nomenclature are discussed briefly with laying special emphasis on the non-undisputed concept of malignant fibrous histiocytomas. Without doubt, this diagnosis is made too frequently by which it has become to a collective name for unclassifiable pleomorphic sarcomas. For the time being nobody is able to say whether or not the malignant fibrous histiocytoma will remain an entity. Likely, fibrosarcomas and hemangiopericytomas are defined as exclusion diagnosis, as well. The diagnosis of malignant soft tissue tumors is based on recognizing the cellular line of differentiation. This is frequently possible at light microscopic level, sometimes additional diagnostic methods are required. The most important adjunct method is immunohistochemistry. Because aberrant differentiations and unexpected immunohistochemical reactions are known the use of a panel of antibodies is necessary. In the last years soft tissue tumors has increasingly been characterized by molecular biological methods. The results are of significance for understanding sarcoma pathogenesis and may be used for diagnosis, as well. Chromosome translocations are explained and rhabdomyosarcomas are taken as example for demonstrating the diagnostic significance of molecular biological/cytogenetic findings. Molecular biology may also aid in defining the histopathologic features of an entity as shown for intraabdominal desmoplastic small cell tumors. Eventually, heterogeneity in soft tissue sarcomas is addressed and discussed in view of its importance for diagnosis, classification and therapy as well as for development of sarcoma progression.     

Invasive malignant fibrous histiocytoma in a cow

An invasive malignant fibrous histiocytoma associated with the left cornual process, and causing lysis of the frontal bone, was diagnosed in a cow. The mass compressed the left cerebral hemisphere focally and extended into the frontal sinus and ethmoid and nasal turbinates. It was composed of pleomorphic to spindle-shaped cells with ultra-structural evidence of fibroblastic, myofibroblastic, and fibrohistiocytic differentiation. Trauma and chronic inflammation may be predisposing factors for development of neoplasia in cattle.     

New somatic mutation in the PIG-A gene emerges at relapse of paroxysmal nocturnal hemoglobinuria

We report a detailed longitudinal study of the first patient to be treated (in 1973) for paroxysmal nocturnal hemoglobinuria (PNH) with syngeneic bone marrow transplantation (BMT). The patient subsequently relapsed with PNH in 1983, and still has PNH to date. Analysis of the PIG-A gene in a recent blood sample showed in exon 6 an insertion-duplication causing a frameshift. Polymerase chain reaction (PCR) amplification of the PIG-A exon 6 from bone marrow (BM) slides obtained before BMT showed that the duplication was not present; instead, we found several single base pair substitutions in exons 2 and 6. Thus, relapse of PNH in this patient was not due to persistence of the original clones; rather, it was associated with the emergence of a new clone. These findings support the notion that the BM environment may create selective conditions favoring the expansion of PNH clones.     

Solitary fibrous tumor of soft tissue: a report of 15 cases, including 5 malignant examples with light microscopic, immunohistochemical, and ultrastructural data

We describe 15 soft tissue solitary fibrous tumors (SFTs) occurring in patients 24 to 78 years old (average, 50.6 yr). Ten tumors were benign and arose in the head and neck area (three tumors), thigh (two), vulva (two), upper arm (one), lower leg (one), and retroperitoneum (one). Five tumors were histologically malignant and arose in the thigh (two), abdominal wall (one), buttock (one), and retroperitoneum (one). All of the tumors were grossly well circumscribed. The benign tumors measured from 2 to 10 cm (average, 4.8 cm) and the malignant ones from 3 to 5.5 cm (average, 4.3 cm) in greatest diameter. Microscopically, the benign tumors showed areas of hypercellularity with variable amounts of collagenous and myxoid stroma; one had amianthoid fibers. The malignant tumors were composed of cytologically atypical cells enmeshed in a collagenous or myxoid extracellular matrix. Ultrastructural study of three benign and three malignant tumors showed fibroblastic differentiation; one benign tumor showed myofibroblastic differentiation. Immunohistochemically, all of the tumors examined were immunoreactive for vimentin, and seven of nine were positive for CD34, including all of the malignant ones. There was focal staining for muscle actin in two benign tumors and for Leu-7 in one benign tumor; there was no staining for cytokeratin, desmin, S-100 protein, epithelial membrane antigen, or smooth muscle actin in any of the examined tissues. Follow-up was available for eight patients for 6 to 21 months (average, 12 mo). No tumor recurred locally or metastasized. The SFTs reported herein support the experiences of others who recently described these tumors in the somatic soft tissues. In addition, our series highlights the occurrence of malignant SFTs in the soft tissues. SFTs should be separated from other spindle cell sarcomas, with which they can be confused.     

Lack of point mutation of the APP gene in sporadic Alzheimer's disease in Japanese

We investigated point mutations of the APP gene in 66 patients with sporadic Alzheimer's disease (AD) and 180 normal individuals by use of the PCR (polymerase chain reaction) method. Both the AD patients and the normal individuals were Japanese. We extracted DNA from blood samples using the phenol-chloroform method and amplified exons 16 and 17 of the APP gene by PCR. PCR products were digested by MBO-II (exon 16) and BCL-1(exon 17). Electrophoresis was carried out with 3% agarose gel and the separated fragments were stained with ethidium bromide. In addition we investigated other point mutations of exons 16 and 17 by use of the PCR-SSCP (single stranded conformation polymorphisms) method, and found no fragments that exhibited point mutations in the AD patients and normal individuals. These findings indicate that the presence of point mutation of the APP gene is not a major cause of AD in the Japanese population.     

Cellular UDP-glucose deficiency caused by a single point mutation in the UDP-glucose pyrophosphorylase gene

We previously isolated a mutant cell that is the only mammalian cell reported to have a persistently low level of UDP-glucose. In this work we obtained a spontaneous revertant whose UDP-glucose level lies between those found in the wild type and the mutant cell. The activity of UDP-glucose pyrophosphorylase (UDPG:PP), the enzyme that catalyzes the formation of UDP-glucose, was in the mutant 4% and in the revertant 56% of the activity found in the wild type cell. Sequence analysis of UDPG: PP cDNAs from the mutant cell showed one missense mutation, which changes amino acid residue 115 from glycine to aspartic acid. The substituted glycine is located within the largest stretch of strictly conserved residues among eukaryotic UDPG:PPs. The analysis of the cDNAs from the revertant cell indicated the presence of an equimolar mixture of the wild type and the mutated mRNAs, suggesting that the mutation has reverted in only one of the alleles. In summary, we demonstrate that the G115D substitution in the Chinese hamster UDPG:PP dramatically impairs its enzymatic activity, thereby causing cellular UDP-glucose deficiency.     

Detection of p53 gene mutation in paraffin-embedded asbestos-related lung cancer tissue

The rearrangement of immunoglobulin heavy chain gene (IgH) and T cell receptor gamma gene (TcR gamma) was studied in 30 patients with acute lymphoblastic leukemia (ALL) by the polymerase chain reaction (PCR). 19 cases was found to have rearrangement of IgH gene, 12 of TcR gamma. Most of IgH rearrangement was characterized by one or two specific bands while some had more than two. Rearrangement of TcR gamma gene appeared as one specific band. A slight difference in number, size and lightness of bands was found among the patients. 4 different kinds of rearrangement were observed in the detection of IgH rearrangement in combination with TcR gamma gene. The rearranged patterns of IgH and TcR gamma gene as well as the clinical significance were discussed.     

CT features of calcifications in abdominal malignant fibrous histiocytoma

Driven by the need for a readily available, non-immunological tissue that possesses many of the characteristics of normal human skin, tissue-engineered skin has been developed. For over a decade, laboratory grown or processed skin has been under investigation and, in some cases, available as an alternative to autologous grafts. Apligraf, derived from neonatal foreskin and bovine type I collagen, is the first bi-layered living skin equivalent approved in the US and other countries for use in venous ulcers. Apligraf is effective both in the treatment of refractory venous ulcers and for acute wounds such as surgical excision sites and split thickness donor sites. Apligraf is safe and is not clinically rejected. Its ultimate fate is not known, so it may well work to aid healing in a variety of ways including graft 'take' and as a stimulus for healing.     

What's new in ras genes? Physiological role of ras genes in signal transduction and significance of ras gene activation in tumorigenesis

Ras gene mutations have been found with variable prevalence in different tumor types. While during the past decade a lot of information has been accumulated on the frequency of ras oncogene activation in tumors, the last two years brought considerable progress in elucidating molecular mechanisms of signal transduction for which cellular ras proteins are key elements. They transmit signals from upstream tyrosine kinases to downstream serine/threonine kinases ultimately leading to changes of gene expression cytoskeletal architecture, cell-to-cell interactions and metabolism. These signalling pathways are of interest for the physiological regulation of proliferation and differentiation in normal, as well as in cancer tissue. Mutational activation of cellular ras genes to transforming oncogenes is thought to promote cell growth even in the absence of extracellular stimuli, and may thereby contribute to the initiation and/or progression of tumors.