bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide exchange in MHC molecules
Authors: Jensen Peter E. , Weber Dominique A. , Thayer Wesley R , Westerman Larry E. , Dao Chinh T
Published: April 2006

Summary: Major histocompatibihty complex (MHC)‐encoded glycoproteins bind peptide antigens through non‐covalent interactions to generate complexes that are displayed on tbe surface of antigen‐presenting cells (APC) for recognition by T ceils, Peptide‐binding site occupancy is necessary for stable assembly of newly synthesized MHC proteins and export from the endoplasmic reticulum (ER), The MHC class II antigen‐processing pathway provides a mechanism for presentation of peptides generated in the endosomal pathway of APC, The chaperone protein, invariant chain, includes a surrogate peptide that stahilizes newly synthesized class II molecules during transport to endosomal compartments. The invariant chain‐derived peptide must be replaced through a peptide exchange reaction that is promoted by acidic pH and the MHC‐encoded co‐factor HLA‐DM, Peptide exchange reactions are not required for presentation of antigens by MHC class I molecules because they bind antigens during initial assembly in the ER, However, exchange reactions may play an important role in editing the repertoire of peptides presented by both class II and class I molecules, thus influencing the specificity of immunity and tolerance.
The impact of the non‐classical MHC proteins HLA‐DM and HLA‐DO on loading of MHC class II molecules
Authors: Kropshofer Harald , Hämmerling Günter J. , Vogt Anne B.
Published: April 2006

Summary: Peptide binding to classical major histocompatibility complex (MHC) class II molecules is known to be determined by the properties of the class ii peptide binding groove but recently it turned out to be co‐controlled by the activity of the non‐classical MHC molecules HLA‐DM and HLA‐DO: HLA‐DM functions as a mediator of peptide exchange. In addition, HLA‐DM is a chaperone for MHC class II molecules in endosomal and lysosomal loading compartments because it stabilizes the empty MHC class Ii peptide binding groove and keeps it receptive for peptide loading until appropriate peptide ligands are captured. Since HLA‐DM favors the generation of high‐stability peptide‐MHC class Ii complexes by releasing low‐stability peptide ligands, DM activity affects the peptide repertoire presented on the ceil surface of antigen‐presenting cells. HLA‐DO is expressed mainly in B cells and binds tightly to HLA‐DM thereby modulating its activity Together, HLA‐DM and HLA‐DO are critical factors in shaping the MHC class Il‐associated self or foreign peptide repertoire of antigen presenting cells and, hence, govern initiation or prevention of an immune response.
Fc receptor signaling and trafficking: a connection for antigen processing
Authors: Amigorena Sebastian , Bonnerot Christian
Published: April 2006

Summary: Most hematopoietic cells express a wide variety of receptors for tbe Fc portion of immunoglobulins (FcR) belonging to the immun‐noreceptor family. FcRs are multichain complexes composed of ligand‐binding a chains, which determine Ig binding, and signal tranduction subunits, bearing a conserved immunoreceptor tyrosine‐based activation motif (ITAM). Besides signaling, most FcyRs also efficiently internalize antigen‐antibodies complexes and thus induce efficient processing of antigens into peptides presented by major histocompatibility complex (MHC) class II molecules. Importantly, ITAMs and cyiosolic effectors of cell signaling also determine FcyR's endocytic transport and antigen presentation capacities.
Evolution of the mammalian MHC: natural selection, recombination, and convergent evolution
Authors: Yeager Meredith , Hughes Austin L.
Published: April 2006

Summary: The genes that encode molecules involved in antigen presentation within the class I and class II regions of the mammalian major histocompatibility complex (MHC) include several that are highly polymorphic. There is evidence that this polymorphism is maintained by positive selection, most likely overdominant selection, relating to their role in presenting foreign peptides to T cells. This selection can maintain allelic lineages for much longer periods of time than neutral polymorphisms are expected to last, but sharing of polymorphic amino acid motifs among species of different mammalian orders is due to independent (or convergent) evolution rather than common ancestry. It has been suggested that interallelic recombination (gene conversion) plays a role in enhancing polymorphism, but there is evidence of striking differences among loci with respect to the rate at which such recombination has contributed to current polymorphism. Recent attempts to interpret linkage relationships in the MHC region as evidence of ancient genomic duplications are not supported by phylogenetic analysis. Rather, natural selection may have played a role in the linkage of other genes to those of the MHC.
Allorecognition in colonial tunicates: protection against predatory cell lineages?
Authors: Magor Brad G. , De Tomoso Anthony , Rinkevich Baruch , Weissman Irving L.
Published: April 2006

Summary: The MHC molecules have been historically perceived as transplantation antigens, though it is now recognized that their primary, if not sole, role is in eliminating parasites and in surveillance and clearance of aberrant self. Indeed, pregnancy in mammals would represent the closest to a natural transplantation process that occurs in vertebrates. However, among the immediate ancestors to the vertebrates, natural intraspecific allorecognition processes are common. Among members of the colonial tunicate Botryllus schlosseri, two individuals that share a single allele of the highly polymorphic fusibility/histocompatibility (Fu/HC) locus are able to fuse with one another. Could this Fu/HC he related to the MHC such that the MHC really did have its origins as a transplantation antigen?

Presently we review the genetics and biology of natural transplantation processes in colonial tunicates, comparing it with alloreeognition as mediated through the vertebrate T‐cell receptor, killer cell inhibitory receptor/Ly49, and MHC. Experimental approaches to determining if the molecules regulating allorecognition in tunicates have any ancestral relationship to the vertebrate MHC are discussed, as is a genomic approach to isolating novel mediators of allorecognition. We also explore the biological basis for allorecognition in colonial tunicates and recent work that highlights the costs of not maintaining a system for allorecognition.
Gene organisation determines evolution of function in the chicken MHC
Authors: Kaufman Jim , Jacob Jansen , Shaw Jain , Walker Brain , Milne Sarah , Beck Stephan , Salomonsen Jan
Published: April 2006

Summary: Some years ago, we used our data for class I genes, proteins and peptide‐binding specificities to develop the hypothesis that the chicken B‐F/B‐L region represents a “minimal essential MHC”, In this view, the B locus contains the classical (highly expressed and polymorphic) class I α and class II β multigene families, which are reduced to one or two members, with many other genes moved away or deleted from the chicken genome altogether. We found that a single dominantly expressed class I gene determines the immune response to certain infectious pathogens, due to peptide‐binding specificity and cell‐surface expression level. This stands in stark contrast to well‐studied mammals like humans and mice, in which every haplotype is more‐or‐less responsive to every pathogen and vaccine, presumably due to the multigene family of MHC molecules present. In order to approach the basis for a single dominantly expressed class I molecule, we have sequenced a portion of the B complex and examined the location and polymorphism of the class I (B‐F)α, TAP and class II (B‐L) β genes. The region is remarkably compact and simple, with many of the genes expected from the MHC of mammals absent, including LMP, class II α and DO genes as well as most class III region genes. However, unexpected genes were present, including tapasin and putative natural killer receptor genes. The region is also organised differently from mammals, with the TAPs in between the class I genes, the tapasin gene in between the class II (B‐L) β genes, and the C4 gene outside of the class I α and class II β genes. The close proximity of TAP and class I α genes leads to the possibility of co‐evolution, which can drive the use of a single dominantly expressed class I molecule with peptide‐binding specificity like the TAP molecule. There is also a single dominantly expressed class II β gene, but the reason for this is not yet clear. Finally, the presence of the C4 gene outside of the classical class I α and class II β genes suggests the possibility that this organisation was ancestral, although a number of models of organization and evolution are still possible, given the presence of the Rfp‐γ region with non‐classical class I α and class II β genes as well as the presence of multigene families of B‐G and rRNA genes.
Toward an evolutionary genomics of the avian Mhc
Authors: Edwards Scott V. , Hess Chris M. , Gasper Joe , Garrigan Dan
Published: April 2006

Summary: We review recent developments in the ongoing study of the evolution of the Mhc gene family in birds, with emphasis on class II B genes and results from songbirds obtained in our laboratory. Southern blots suggest a surprising diversity in Mhc class II gene number among various songbird species (Passeriformes). We have sequenced ∼30 kb contigs from Mhc‐bearing cosmid clones from two species, red‐winged blackbirds (Agelaius phoeniceus) and bouse finches (Carpodacus mexicanus), whose demography, lifetime reproductive success, epizootics, parasitology and mate choice are among the best studied for natural populations of birds. Of three genes cloned from these species, only one appears strongly polymorphic, and one (from the house finch) is likely a pseudogene. All are similar in structure to those in chickens, albeit with introns intermediate in length between chickens and mammals. Phylogenetic analysis of available class II B peptide‐binding region exons suggests that the overwhelming longterm force operating on avian genes sampled thus far has been post‐speciation gene duplication and/or concerted evolution. These and other results suggest that the evolution of class II B genes in birds conforms to a mixture of several models of multigene family evolution proposed for the mammalian Mhc, incorporating ongoing homogenization, duplication and pseudogene formation. Large‐scale sequencing studies in these and other species, though still in their infancy, will prove invaluable for studying the comparative structures of avian Mhcs, as well as patterns of selection, mutation and linkage disequilibrium at several scales.
Comparative genome organization of the major histocompatibility complex: lessons from the Felidae
Authors: O'Brien Stephen J. , Yuhki Naoya
Published: April 2006

Summary:The mammalian major histocompatibility complex (MHC) has taught both immunologists and evolutionary biologists a great deal about the patterns and processes that have led to immune defenses. Driven principally by human and mouse studies, comparative MHC projects among other mammalian species offer certain advantages in connecting MHC genome characters to natural situations. We have studied the MHC in the domestic cat and in several wild species of Felidae. Our observations affirm class I and class II homology with other mammalian orders, derivative gene duplications during the Felidae radiation, abundant persistent trans‐species allele polymorphism, recombination‐derived amino acid motifs, and inverted ratios of non‐synonymous to silent substitutions in the MHC peptide‐binding regions, consistent with overdominant selection in class I and II genes. MHC diversity as quantified in population studies is a powerful barometer of historic demographic reduction for several endangered species including cheetahs, Asiatic lions, Florida panthers and tigers. In two cases (Florida panther and cheetah), reduced MHC variation may be contributing to uniform population sensitivity to emerging infectious pathogens. The Felidae species, nearly all endangered and monitored for conservation concerns, have allowed a glimpse of species adaptation, mediated by MHC divergence, using comparative inferences drawn from human and mouse models.
Comparative organization and function of the major histocompatibility complex of domesticated cattle
Authors: Lewin Harris A. , Russell George C. , Glass Elizabeth J.
Published: April 2006

Summary: This review focuses on recent advances in research on the bovine major histocompatibility complex (BoLA), with specific reference to the genetic organization, polymorphism and function of the class II genes. The BoLA region is unlike the MHC of humans and mice in that a large inversion has moved several class II genes, including the TAP/LMP cluster, close to the centromere of bovine chromosome 23. Therefore, dose linkage of MHC genes and other genes associated with the MHC in humans and mice does not appear to be required for normal immunological function. In cattle, polymorphism in the class IIa genes influences both the magnitude and the epitope specificity of antigen‐specific T‐cell responses to foot‐and‐mouth disease virus peptides. Disease association studies have demonstrated that BoLA alleles affect the subclinical progression of bovine leukemia virus (BLV) infection. This association is strongly correlated with the presence of specific amino acid motifs within the DRB3 antigen‐binding domain. In addition to the practical significance of these findings, the association between BoLA and BLV provides a unique model to study host resistance to retrovirus infection in a non‐inbred species. These studies contribute to our understanding of the evolution of the MHC in mammals, to the development of broadly effective vaccines, and to breeding strategies aimed at improving resistance to infectious diseases.
Cattle MHC: evolution in action?
Authors: Ellis Shirley A. , Ballingall Keith T
Published: April 2006

Summary: Because major histocompatibility complex (MHC) genes play a major role in the development of acquired immune responses, it is essential to obtain comparative information on their organisation, expression and possible functional dichotomies in different species. In human, three classical, polymorphic class I genes (HLA‐A, B‐ and ‐C) and four expressed A/B class II gene pairs (HLA‐DM, ‐DP, ‐DQ and ‐DR) are each present on all haplotypes. With the exception of the HLA‐DRB loci, it has been assumed that a similar rigid organisational situation exists in other mammalian species. However, extensive analysis of the bovine MHC (BoLA) at both the genomic and transcriptional levels has revealed a degree of genetic fluidity not described in other species. None of the four (or more) classical class I genes identified is consistently expressed, and haplotypes differ from one another in both the number and composition of expressed class I genes. Similarly, in the class II region, the number of DQ genes varies between haplotypes in both number and composition. These variations in both class I and II (which appear to reflect differences at the genomic level) are likely to play an important role in cattle immune responses. The observed phenotypic differences in cattle demonstrate very clearly the dynamic nature of the MHC region. This review addresses the functional impact of such variation in different breeds and populations, and its significance in terms of MHC evolution.
Monomorphism and polymorphism at Mhc DRB loci in domestic and wild ruminants
Authors: Mikko Sofia , Røed Knut , Schmutz Sheila , Andersson Leif
Published: April 2006

Summary: Genetic polymorphism at Mhc class II DRB loci was investigated in samples of musk‐ox from Canada and Greenland; moose from Sweden, Norway, Canada, and Alaska, roe deer from Norway and Sweden; reindeer from Svalbard and Norway; fallow deer from Norway and Sweden; and red deer from Norway. The results were compared with published data on cattle, bison, goal, sheep, and red deer. Cattle‐specific primers amplified a single DRB locus in all species except fallow deer and red deer, in which two loci were found. Single strand conformation polymorphism analysis and DNA sequence analysis were employed to detect genetic polymorphism. Complete monomorphism was found in musk‐ox and fallow deer. Limited polymorphism was found in the moose, roe deer, and reindeer from Svalbard, whereas intermediate to extensive DRB diversity was present in reindeer from Norway and in bison, sheep, goat, cattle, and red deer. The restricted Mhc diversity in moose, roe deer, and fallow deer is notable in relation to the dramatic population expansion of moose and roe deer in Sweden during this century and since fallow deer is used for meat and game production with good results and without any marked disease problems. The results question the view that species or populations with restricted Mhc diversity have poor resistance to infectious diseases. A phylogenelic tree analysis revealed a clustering of DRB sequences within species rather than within allelic lineages across species. The results suggest trans‐species persistence of polymorphic sequence motifs rather than of allelic lineages.
Genome sequencing analysis of the 1.8 Mb entire human MHC class I region
Authors: Shiina Takashi , Tamiya Gen , Oka Akira , Takishima Nobusada , Inoko Hidetoshi
Published: April 2006

Summary: The human MHC class I region spans 1.8 Mb from the MICB gene to the HLA‐F gene at the telomeric end of the HLA region. There are fewer genes recognized in this region than in the class II or class III region, probably because this region remained uncharacterized for genomic organization. Based on the 1,796,938 bp genomic sequence of the entire class I region determined in our laboratory, the complete gene structure of this region has finally emerged. This region embraces as many as 118 genes (73 known and 45 new genes) with a gene density of one gene every 15.2 kb, which is comparable to that of the gene‐rich class III region. The GC content is fairly uniform throughout the class I region, being 45.8% on average, which corresponds to the isochore HI. By investigation of genetic polymorphisms in 26 out of 758 microsatellite repeats identified in the class I region, we could reduce the critical region for Behçet's disease (associated with B5 1) and psoriasis vulgaris (associated with Cw6) to approximately 50 kb segments, between MICA and HLA‐B and between TCF19 and S, respectively. Thus, systematic large‐scale genomic sequencing provides an efficient way of identifying genes and of mapping disease‐susceptible genes in the genome.
The functionality of HLA‐G is emerging
Authors: Le Bouteiller Philippe , Blaschitz Astrid
Published: April 2006

Summary: In view of the recently published data, the HLA‐G class Ib gene appears to be a functional locus. This is based on the following observations: 1) HLA‐G is capable of presenting nonamer peptides and of exerting antigen‐presenting functions; 2) HLA‐G is a ligand for at least three natural killer (NK) and other cell inhibitory receptors of the immunoglobulin superfamily, namely leukocyte immunoglobulin‐like receptor‐1 /immunoglobulin‐like transcript (ILT)‐2, ILT‐4 and p49; 3) in addition to the extravillous cytotrophoblast cells, HLA‐G proteins have been detected in endothelial cells of placental chorionic villi, as well as in amniotic fluid and in some medullary thymic epithelial cells; 4) major histocompatibility complex (MHC) class Ib genes that share the unique characteristics of HLA‐G, including a high expression in placenta, have been reported in other mammalian species. In addition to the classical MHC class I roles (antigen presentation and ligarion to NK receptors inducing inhibitory and/or activatory signals), HLA‐G is likely to exert other, novel functions: first, HLA‐G was shown to be involved in the control of HLA‐E expression by furnishing the appropriate class I leader sequence nonamer peptide; second, we hypothesize that HLA‐G could be a regulator of placental angiogenesis; third, soluble HLA‐G isoforms may act as specific immunosuppressors during pregnancy. Such functional properties, although incompletely understood, are likely to be important in the outcome of human pregnancies but also in normal adult life.
Recombination within the human MHC
Authors: Carrington Mary
Published: April 2006

Summary: Recombination (crossing over) in the human MHC is thought to have played a role in generation of novel alleles at various HLA loci. It is also responsible for the diversity observed at the haplotype level, although the functional consequences of this activity are not clear. Historic and family studies of recombination have provided estimations of recombination fractions across the MHC and identified potential hotspots for recombination in the class II region. Other characteristics of recombination in the human MHC such as haplotype specificity in recombination frequency and localized sequence motifs involved in recombination have been considered, but have been difficult to address given the constraints of human population studies, Single‐sperm typing holds promise in overcoming some of the limitations inherent in the study of recombination in human populations. Both family‐based and sperm typing analyses of recombination, along with our knowledge of linkage disequilibrium patterns in the MHC, may provide novel information regarding the evolution of HLA haplotypes chat will be difficult to obtain by other means.
The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases
Authors: Price Patricia , Witt Campbell , Allock Richhard , Sayer David , Garlepp Michael , Kok Chee Choy , French Martyn , Mallal Simon , Christiansen Frank
Published: April 2006

Summary: An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the dearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150–200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA‐A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA‐B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin‐dependent diabetes mellitns (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis co the central MHC between HLA‐B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1‐associated diseases are more closely associated with HLA‐DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen‐independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co‐factor in the diverse immunopathological conditions associated with the 8.1 AH.
Gene conversion can create new MHC allees
Authors: Högstrand Kari , Böhme Jon
Published: April 2006

Summary: It is possible to measure gene conversion of MHC genes with the help of a semi‐nested PCR assay. Several considerations are of utmost importance when such an assay is set up. Using this assay, we have found that gene conversion occurs in MHC class II genes in mouse sperm, but not in somatic cells tested. Although this gene conversion occurs in germline cells, it is already completed in spermatogonia, and consequently is a mitotic event unlinked to meiosis. The frequency of gene conversion events in MHC class II genes varies strongly from one allele to another, with the highest detected frequencies as high as 1/40,000 for an individual heterozygous for both donor and acceptor sequences. Deletions or insertions in one gene relative to the other seem to lower the efficiency of gene conversion considerably. Stretches within MHC genes amenable to gene conversion are located in CpG clusters, whereas MHC genes not involved in gene conversion have background CpG levels. DNA damage, either chemical or radiation induced, increases the frequency of gene conversion of MHC class II genes in cultured cells of the fibroblastoid lineage. The effect of chemical DNA damage seems roughly dose dependent, whereas irradiation has a maximal effect at low doses.
Major histocompatibility complex class I genes in primates: co‐evolution with pathogens
Authors: Vogel Thorsten U. , Evans David T. , Urvater Julie A. , O'Connori David H. , Hughes Auslin L. , Watkins David I.
Published: April 2006

Summary: The major histocompatibility complex (MHC) is the most polymorphic genetic system known, playing a central role in the cellular immune response to pathogens. The relationship between the MHC of humans and non‐human primates has increased our understanding of MHC evolution and how polymorphism of this gene family may have been generated. We will review MHC class I evolution in great apes and Old World and New World primates and discuss new data from the simian immunodeficiency virus/rhesus monkey animal model that demonstrate the role of MHC class I alleles in selecting for new populations of viruses. This suggests that certain pathogens co‐evolve with the MHC class I molecules they encounter in a population.
Major histocompatibility complex class II polymorphisms in primates
Authors: Bontrop Rondd E. , Otting Nel , de Groot Natasja G. , Doxiadis Gaby G. M.
Published: April 2006

Summary: In the past decade, the major histocompatibility complex (MHC) class II region of several primate species has been investigated extensively. Here we will discuss the similarities and differences found in the MHC class II repertoires of primate species including humans, chimpanzees, rhesus macaques, cotton‐top tamarins and common marmosets. Such types of comparisons shed light on the evolutionary stability of MHC class II alleles, lineages and loci as well as on the evolutionary origin and biological significance of haplotype configurations.
Fibrous dysplasia: A nosologic problem in the diagnosis of fibro‐osseous lesions of the jaws
Authors: Eversole L. R. , Sabes William R. , Rovin Sheldon
Published: April 2006

Abstract. A total of 841 reviewed cases and 75 reported cases of fibro‐osseous lesions of the jaws, excluding the giant cell group, are analyzed with regard to clinical, radiographic, and histologic features. Precise criteria for the differential diagnosis of fibrous dysplasia, ossifying fibroma, gigantiform cementoma, chronic diffuse sclerosing osteomyelitis, focal sclerosing osteomyelitis, and periapical cementoma have been presented with emphasis on radiographic and behavioral features.
The effect of proteolytic enzymes on the induction of heterotopic bone formation by demineralized dentin in guinea pigs
Authors: Bang Gisle , Johannessen Jan Vincents
Published: April 2006

Abstract. Of a total of 80 allogenic demineralized guinea pig dentin samples, 60 were treated with collagenase or trypsin, leaving a group of 20 controls. The dentin was then either subjected to amino acid analysis and transmission electron microscopy, or implanted in the abdominal muscles of 12 male guinea pigs for four weeks. Amino acid analyses of the CH3COOH extracts of dentin matrix proteins revealed a marked difference between the collagenase‐ and trypsin‐treated samples, suggesting the extraction by trypsin of a non‐collagenous protein or of peptides derived from such a protein. Both collagenase and trypsin reduced the ability of demineralized dentin to induce bone formation, but whereas the former resulted in enhanced resorption of the dentin implants, the trypsin‐treated dentin did not. If the host mesenchymal cells need to be exposed to the inducing factor for a certain minimal length of time for induction of bone formation, enhanced resorption would hinder the induction process. While electron microscopy of control specimens exhibited collagen fibrils with distinct cross‐striations, the samples exposed to collagenase treatment displayed disarranged and swollen fibrils with loss of cross‐striation. Many of the collagen fibrils of the trypsin‐treated dentin had, however, retained their cross‐striation. The present results indicate that (he bone‐inducing capacity of dentin matrix may be caused by a non‐collagenous protein.
Studies on levamisole, a potentially useful drug in the treatment of Behçet's syndrome
Authors: Sampson Derek
Published: April 2006

Abstract The anthelmintic drug, levamisole, was shown to amplify the response of human peripheral blood lymphocytes to vegetable mitogens. A similar enhancement of blast formation in the mixed lymphocyte culture was also demonstrated. High concentrations of the drug led to depression of both of these responses. These observations led to studies in a rat breast cancer model in which immunopotentiation was demonstrated in vivo, and this effect was associated with tumor regression. As in the human in vitro studies, high doses of the drug were not associated with augmentation of the immune response and in this circumstance no inhibition of tumor growth was observed. Assuming that potentiation of immune responsiveness is of benefit to patients suffering from Behçet's syndrome, the development of clinical trials employing levamisole appears justified, as long as the drug dosage is carefully monitored.
Electron microscopy of cells displaced into the dentinal tubules due to dry cavity preparation
Authors: Eda Shigeo , Saito Toshio
Published: April 2006

Using dogs' teeth, cells displaced into the dentinal tubules due to dry cavity preparation were observed using electron microscopy. In order to obtain adequate fixation a new local‐perfusion method was employed. Most of the cells which moved into the dentinal tubules were odontoblast nuclei and partly neutrophilic leukocytes and erythrocytes. Not only odontoblast nuclei but also cytoplasmic organelles, such as mitochondria, rough endoplasmic reticulum, free ribosomes, and lysosomes were displaced into the tubules. The weavings of dentinal fibers in the tubules were observed in some areas.
Tyrosine‐rich crystalloids in adenoid cystic carcinoma: histochemical and ultrastructural observations
Authors: Gould A. R. , Van Arsdall L. R. , Hinkle S. J. , Harris W. R.
Published: April 2006

Tyrosine‐rich crystalloids are described in an example of an adenoid cystic carcinoma arising in an oral minor salivary gland of the hard palate. This represents the first reported case of an adenoid cystic carcinoma of oral minor salivary gland in which tyrosine‐rich deposits have been identified. The tyrosine deposits appear refractile but not birefringent at the light microscopic level; and histochemical findings indicate a relatively simple, homogeneous chemical composition rich in tyrosine. Their ultrastructural nature is that of a finely granular, but otherwise patternless, highly electron‐dense material. The electron microscopic features of the neoplasm are similar to previous reports. Based upon the findings of this and previous investigations, it is not as yet possible to state whether the tyrosine‐rich deposits truly represent a crystalline or amorphous solid.
Benign lymphoepithelial lesion in a patient with Sjögren's disease and an IgG paraprotein
Authors: Basu M. K. , Price J. D. , Matthews J. B.
Published: April 2006

Clinical and laboratory investigations were performed on a patient presenting with xerostomia and swelling of the parotid gland. Lymphoid infiltration of the salivary glands (parotid and labial) and paraproteinaemia were found. Immunoperoxidase studies of labial and parotid glands revealed that local immunoglobulin synthesis was essentially polyclonal although monoclonal staining of Russell bodies within the labial tissue suggested that at least some of the serum paraprotein was being synthesised locally. The implications of these findings are discussed in terms of diagnosis and treatment.
Fibrous histiocaytomas of the oral and maxillofacial regions
Authors: Thompson S. H. , Shear M.
Published: April 2006

Fibrous histiocytomas of the oral and maxillofacial regions arc rare. The present study analyzes a sample of 63 cases from the literature together with 7 personally observed cases. Age, sex, site, size, clinical behaviour, treatment and survival were evaluated and related to a histological classification based on that of Rosai (1981). Lesions were assessed for histological criteria which would place them in one of 2 groups: fibrous histiocytoma (FH) or pleomorphic fibrous histiocytoma (PFH). Within these 2 histological groups the cases were subdivided into clinically benign, aggressive or malignant lesions. Thirty‐nine cases (56.0%) were classified as FH and 31 eases (44.0%) as PFH. The mean age of male patients with PFH was significantly higher than female patients with FH (t = 3.05; d.f. 37; p < 0.0025). Lesions in the PFH group involved bone more frequently than those in the FH group (Yale's Chi2 = 16.66; d.f. 1; p < 0.00025). Lesions involving bone for both histological groups were more likely to be aggressive or malignant than soft‐tissue lesions (Yale's Chi2 = 29.9; d.f. 1; p < 0.00025). Soft‐tissue lesions were usually less than 5 cm in greatest diameter. Radiographic features of malignancy for lesions with bone involvement is of prognostic importance regardless of the histological appearance of the lesion. The majority of the lesions under study were from the deep tissues of the oral and maxillofacial regions.
Stereologic analysis of the lymphoid stroma in parotid adenolymphoma
Authors: Nikai H. , Schroeder H. E.
Published: April 2006

In 2 parotid adenolymphomas, the composition of lymphoid stroma was analysed, using Stereologic point‐counting methods at the electron microscopic level. In the 2 lesions, the stroma was almost identical with respect to organization and composition. Most areas of the stroma showed accumulation of mixed cell populations. On average, the latter were comprised of 5.1 % fibroblastic/relicular cells, 2.7% macro‐phages, 68.9% small and 18.8% medium/large lymphocytes, 0.5% blastforming T‐lymphocytes, 2.3% blastforming 13‐lymphocylcs, and 1.6% plasma cells. Polymorphonuclear leukocytes and mast cells were extremely rare. Areas corresponding to the mantle zone of lymphoid follicles were found to contain 83.0% small and 15.8% medium/large lymphocytes. The present data seem to be in accordance with the speculation that the lymphoid stroma of adenolymphoma represents an immune reaction.
Clinical utilization of sialochemistry in Sjögren's syndrome
Authors: Stuchell R. N. , Mandki I. D. , Baukmasii H.
Published: April 2006

Sialochemistry was performed on the stimulated parotid secretion of a group of patients with Sjögren's syndrome (SS) having a Grade 4 iymphocytic infiltrate of their minor labial salivary glands and a normal control group. Parameters examined included flow rate, and concentration of sodium, potassium, chloride, urea, calcium, phosphate, total protein, IgA, IgG. albumin, amylase and lactoferrin. Although all SS patients had virtually no parotid secretion in the absence of stimulation, with a gustatory stimulation, 40% of the patients with SS had a relatively normal parotid flow rate, when compared with the control group. The SS patients, regardless of flow rate, exhibited a highly significant (p < 0.01) elevation in the concentration of sodium, chloride, IgA, IgG, and lactoferrin and a significant (p < 0.05) increase in albumin concentration, when compared with the control group. The phosphate level was significantly lower (p < 0.01) in SS patients than in the control group. The elevated IgA in SS was almost all 1 IS, in contrast to parotitis where 7S was a major contributor. In view of the variation in flow rate in SS patients chemical quantitation of selected salivary components can be a valuable aid in the differential diagnosis of this disease and in monitoring patients over time.
Calcifying epithelial odontogenic tumour: a case showing features of malignancy
Authors: Basu M. K. , Matthews J. B. , Sear A. J. , Bkowne R. M.
Published: April 2006

A case of malignant calcifying epithelial odontogenic tumour is reported in a 75–year‐old man. Evidence of local tissue invasion and lymph‐node metastasis is presented. Immunoperoxidase studies of the neoplastic cells and tumour amyloid were negative for a variety of antigens, including the epithelial markers CEA and keratin. The histological and clinical findings are discussed.
Cellular effects of human leukocyte hydrolases III: inflammatory exudate and synovial fibroblasts
Authors: Cogen R. B. , Taubman S. B.
Published: April 2006

Experiments were undertaken to determine whether lysosomal enzymes obtained from human polymorphonuclear leukocytes (PMN) might adversely affect the viability of human synovial fibroblasts. The effects of the PMN granule enzymes were additionally determined in the presence of an inflammatory exudate. These in vitro results indicated that as a result of these experimental conditions, the lysosomal enzymes, although present in relatively high concentration, were incapable of cell destruction and could only release cells from their growth surfaces; as could other proteases. However, even this effect was not expressed in the presence of naturally occurring inhibitors widely distributed in body fluids, such as scrum; and most importantly which arc also present in inflammatory exudates. This was in spite of the relatively high dilution of serum and inflammatory exudate used. So that, in effect, the relatively dilute inhibitors present in both serum and inflammatory exudates prevented the relatively concentrated lysosomal enzymes from exerting any discernible effects on either the cells, or the intercellular substance under these experimental conditions. This possibly suggests that the role of PMN granule enzymes as mediators of the cellular destruction observed in many inflammatory diseases, needs further elucidation.
Epidemiological and diagnostic aspects of oral squamous cell carcinoma
Authors: Binnie W. H. , Rankin K. V.
Published: April 2006

Available data in United Stales on morbidity, mortality and survival is reviewed and trends discussed. Oral squamous cell carcinoma is a small problem in numerical terms, but is a highly lethal disease. The diagnosis is not difficult for the competent pathologist but problems arise in the diagnosis and prognosis of potentially malignant conditions. Our understanding of the behavior of dysplastic lesions is limited and any attempts to determine individuals “at risk” should be encouraged.
Mucoepidermoid carcinoma: ultrastructural and histogenetic aspects
Authors: Dardick I. , Daya D. , Hardie J. , van Nostrand A. W. P.
Published: April 2006

Ultrastructural examination of 6 mucoepidermoid carcinomas (4 from parotid salivary gland and 2 from lung) was used to investigate tumor cell types, their interrelationship, histogenetic aspects and factors involved in the multiplicity of histological patterns in this tumor. On the basis of light‐microscopic cellular features, mucoepidermoid carcinomas are generally thought to be formed by 3 principal cell types, mucinous, squamous and intermediate. However, low‐magnification electron micrographs reveal that there arc 2 basic tumor‐cell types interpreted as modified luminal epithelial and myoepithelial cells. Both cell types may independently show a range of line structural modification and organizational arrangement, Luminal epithelial cells have varying degrees of mucin production and lumen, formation in some regions, while modification of these cells is one mechanism for squamoid and frankly squamous appearances in other areas. Preferential proliferation of the second type of tumor cell aligned on the outer aspect of luminal epithelial cells is responsible for the development of isomorphic regions composed of intermediate cells. Squamous metaplasia can also occur in relationship to these latter cells. Based on these observations and recent ultrastructural and histochemical studies of salivary gland tumors, it is suggested that, in addition to the excretory duct, neoplastically altered cells in the acinar‐intercalated duct region must be considered as a potential source for the development of mucoepidermoid carcinomas.
Proliferation of mast cells in normal and DMBA‐treated mouse skin
Authors: Farnoush A. , Mackenzie I. C.
Published: April 2006

To examine the pattern of proliferation of mast cells in the skin of Swiss Webster mice, single or multiple pulses of ‐3H‐thymidine. autoradiography and selective staining techniques were combined to detect DNA synthesis. A very low labelling index was found for the mast cells of normal skin but alteration of the mast‐cell population using the chemical carcinogen dimethylbenzanthracene led to increased labelling of mast cells. A series of studies of experimentally altered skin showed a pattern of mast cell labelling which suggested derivation of new mast cells by local self‐replication. The labelling pattern indicated that mast cells labelled after 1 h divided to produce 2 daughter cells and that the rate of increase in the number of labelled mast cells following repeated labelling for up to 20 days was linear. These data do not suggest major recruitment of mast cells from a distant source during this period.
Leiomyosarcoma of the mandible: diagnosis as aided by immunohistochemical demonstration of desmin and laminin
Authors: Miettinen M. , Lehto V.‐P. , Ekblom P. , Tasanen A. , Virtanen I.
Published: April 2006

A mandibular spindle‐cell sarcoma originally diagnosed as malignant fibrous histiocytoma displayed a whorl‐like histological structure and cellular pleomorphism. By electron microscopy the tumor cells showed prominent basal laminae around the tumor cells and bundles of myofilaments with attachment plaques. In support of the ultrastructural observations, immunofluorescence (IF) microscopy with antibodies to laminin, the major component of basal lamina, gave a bright pericellular staining of the tumor cells. IF microscopy using antibodies against intermediate filament (IMF) proteins revealed the presence of desmin, the muscle‐type of IMF protein, in most tumor cells. On the other hand, staining for myoglobin was negative. The data are consistent with the diagnosis of leiomyosarcoma rather than malignant fibrous histiocytoma, and suggest that expression of desmin and laminin can be useful markers of smooth‐muscle derivation of Sarcomatous tumors.
The oral carriage of yeasts and coliforms in patients on cytotoxic therapy
Authors: Samaranayake L. P. , Calman K. C. , Ferguson M. M. , Kaye S. B. , MacFarlane T. W. , Main B. , Welsh J. , Willox J.
Published: April 2006

The oral carriage of yeasts and coliforms in a healthy adult population and a group of patients with malignancies, undergoing cytotoxic therapy was investigated. A quantitative increase in the intra‐oral carriage of Candida species and coliforms was observed during cytotoxic therapy. The most frequent yeast and the coliform isolated were Candida albicans and Escherichia coli, respectively. Thus, the oral cavity may constitute a reservoir of potentially pathogenic flora in patients on cytotoxic therapy.
Altered H‐antigen reactivity as an early indicator of malignant transformation in oral epithelium
Authors: Auclair P. L.
Published: April 2006

This study was undertaken to determine whether or not the blood group H‐antigen reactivity of oral epithelium has value in predicting malignant transformation. Tissue from 3 groups of patients was studied retrospectively, using an immunoperoxidase technique. Two biopsy specimens from each patient, obtained at different times but from the same site, were examined for the presence of H‐antigen. Group 1 consisted of 16 patients in which the initial biopsy was histologically benign, but the subsequent biopsy revealed epidermoid carcinoma. The initial biopsies in Groups II (17 patients) and III (17 patients) revealed epithelial dysplasia. Whereas the subsequent biopsy in Group II revealed carcinoma, the subsequent biopsy in Group III remained non‐invasive. Normal epithelium from 64 patients was also studied.

The results showed that in normal epithelium, H‐antigen‐negative cells are rarely seen, but 81% of the initial benign specimens of Group I showed antigen‐negative areas. Therefore, it was concluded that altered H‐antigen reactivity in histologically benign epithelium may serve to predict eventual malignant transformation, and that immunologic de‐differentiation precedes histologic dedifferentiation. A comparison between the initial biopsy specimens of Groups II and III yielded nearly identical results and showed that it was not possible, on the basis of the H‐antigen reactivity, to predict which dysplastic lesions would progress to epidermoid carcinoma.
Histopathologic studies of DMBA‐induced mouse submandibular‐gland tumors with or without cryoprobe treatment
Authors: Takai Y. , Hyun K‐H. , Murase N. , Hosaka M. , Mori M.
Published: April 2006

Histopathologic observations of 9,10‐dimethyl‐1,2‐benzanthracene (DMBA)‐induced tumors in the mouse submandibular glands arc reported using cryoprobe treatment. The experimental animals were divided into 2 groups; one received a carcinogen injection into the normal submandibular gland, and the oilier was injected with DMBA on the Mill day following cryosurgery of the gland using a 60°C cryoprobe. Pathologic findings were classified as premalignant lesions or squamous‐cell carcinomas with varying degrees of keratinization, fibrosarcoma and mixed carcinoma. There was also one case each of malignant pleomorphic adenoma and cystic adenoma. Tumor incidence was nearly the same in the 2 groups. Most of the carcinomas and sarcomas in the submandibular gland were induced during the 12th and 17th weeks. DMBA application during the proliferating stage which followed the cryosurgery did not enhance epithelial‐tumor induction. During submandibular gland carcinogenesis, alterations in the granular convoluted tubule cells suggests they were the initial target cells undergoing malignant transformation. Squamous‐cell carcinomas with varying degrees of keratinization were induced following squamous metaplasia in duct‐like structures or multicystic lesions.
Ultrastructural and histochemical studies of granular‐cell ameloblastoma
Authors: Nasu M. , Takagi M. , Yamamoto H.
Published: April 2006

Four cases of granular‐cell ameloblastoma were studied by light and electron microscopy, histochemistry and electron enzymehistochemistry. Microscopically, granular cells commonly occurred in a follicular pattern, but, in one case, they were in a plexiform pattern. The high activity of acid phosphatase and electron microscopic features revealed that the cytoplasmic granularity was ascribed to the high content of lysosomes. It was speculated that granular‐cell ameloblastoma occurs due to the altered dysfunction of tumor cells, and the age factor is related to the pathogenesis of this tumor.
Malignant endothelial neoplasm arising in the area of lymphangioma: immunohistochemical and ultrastructural observation
Authors: Nagata M. , Semha I. , Ooya K. , Urago A. , Yonezawa S. , Sakae K.
Published: April 2006

This report presents a rare malignant endothelial neoplasm which arose at the site of a pre‐existing lymphangioma. The lymphangioma was located on the right buccal miicosa, and the malignant neoplasm arose 17 years after irradiation of the initial tumor. Clinical, light microscopic and immunohistochcmical (Factor VIII‐related antigen and Ulex europueus Agglutinin‐1) studies were made, together with observations by transmission and scanning electron microscopy. These studies provide evidence that this malignant neoplasm was well‐differentiated and had not yet lost the characteristics of normal lymphatic cells.