bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of antibody production against Hanganutziu‐Deicher (H‐D) antigens with N‐glycolylneuraminic acid in patients with porcine exposure history
Authors: Kobayashi Takaaki , Yokoyama Itsuo , Suzuki Akemi , Abe Mikiko , Hayashi Shuji , Matsuda Haruo , Morozumi Kunio , Breimer Michael E. , Rydberg Lennart , Groth Carl G. , Tibell Annika , Korsgren Olle , Takagi Hiroshi , Nakao Akimasa 
Published: March 2003

Abstract: The significance of non‐αgalactosyl antigens remains unclear in pig‐to‐primate xenotransplantation. Hanganutziu‐Deicher (H‐D) antigens with terminal N‐glycolylneuraminic acid (NeuGc) are widely expressed on endothelial cells of mammalian species, with the exception of humans. As baboons and monkeys also express H‐D antigens, a pig‐to‐non‐human primate experimental model cannot resolve the question of whether H‐D antigens can elicit a potent humoral response in human recipients. The purpose of this study was to elucidate the clinical significance of H‐D antigens by examining the sera from patients who have been previously exposed to porcine tissue.After the digestion of porcine aortic endothelial cells (PAEC) by neuraminidase, NeuGc and N‐acetylneuraminic acid (NeuAc) were quantitated by HPLC. IgG and IgM antibody levels against H‐D antigens were measured by NeuGc‐GM3‐coated ELISA plates in the sera of patients who had undergone ex vivo kidney perfusion 1 to 3 weeks and 2 years previously (n = 2) or had been injected with fetal porcine islets 2 months previously (n = 10).HPLC determined that 9.7×107 NeuAc and 6.3×107 NeuGc residues per cell were released from PAEC by neuraminidase, while 25.7×107 NeuAc and an undetectable level of NeuGc were released from human aortic endothelial cells (HAEC). No significant elevation of IgG or IgM antibody levels against NeuGc‐GM3 was observed in sera from patients with a history of porcine exposure.Considering the active production of antibody against the foreign galactosyl antigens after pig‐to‐human xenotransplantation, some production of antibodies against the equally foreign H‐D antigens would be expected, because large amounts of NeuGc terminated saccharides are present in the pig endothelial cell surface. However, no production of antibodies directed to H‐D antigens could be found in patients exposed to porcine tissue. Further studies are warranted to explain why H‐D antigens do not elicit a significant antibody production.
Plasma perfusion by apheresis through a Gal immunoaffinity column successfully depletes anti‐Gal antibody: experience with 320 aphereses in baboons
Authors: Watts A. , Foley A. , Awwad M. , Treter S. , Oravec G. , Buhler L. , Alwayn I. P. J. , Kozlowski T. , Lambrigts D. , Gojo S. , Basker M. , White‐Scharf M. E. , Andrews D. , Sachs D. H. , Cooper D. K. C. 
Published: March 2003

Abstract: Background: Anti‐Galα1–3Gal (Gal) antibodies (Gal Ab) contribute to the rejection of porcine organs transplanted into primates. Extracorporeal immunoadsorption (EIA) has been developed to eliminate Gal Ab from the circulation. Methods: Between 1995 and 1999 we performed 320 EIAs in baboons using a COBE‐Spectra apheresis unit incorporating a synthetic Gal immunoaffinity column. Three plasma volumes were immunoadsorbed on each occasion. The 221 consecutive EIAs performed in 41 immuno‐suppressed baboons between January 1997 and April 1999 form the basis of this review. Of these 41 baboons, 29 underwent a series of three or four EIAs at daily intervals, seven had multiple series of three EIAs, and the remainder underwent single or double EIAs. Serum Gal Ab levels were monitored by ELISA before and at intervals after the course of EIA. Results: There were two fatal complications, one from a respiratory mishap (unrelated to the EIA) and one from persistent hypotension unresponsive to therapeutic interventions. Seven procedures (3%) were terminated early owing to technical difficulties and/or persistent hypo‐tension. Mean pre‐EIA Gal Ab levels in naïve baboons were 33.1 µg/ml (IgM) and 14.5 µg/ml (IgG). Immediately after three consecutive EIAs, IgM was depleted by a mean of 97.3% and IgG by 99.4%. By 18 to 24 h later, Gal Ab was returning but depletion remained at 80.1% (IgM) and 84.7% (IgG). The subsequent rate of return of Gal Ab depended on the immunomodulatory protocol used. Conclusions: (1) With appropriate monitoring, EIA is an acceptably safe procedure, even in small (< 10 kg) baboons. (2) Three consecutive EIAs are effective in removing > 97% of Gal Ab. (3) In the majority of cases, return of Gal Ab begins within 24 h, irrespective of the immuno‐modulatory protocol.
Xenogeneic milieu markedly remodels endocrine cell populations after transplantation of fish islets into streptozotocin‐diabetic nude mice
Authors: Morrison Carol M. , Yang Hua , Al‐Jazaeri Ayman , Tam Janet , Plisetskaya Erika M. , Wright James R. 
Published: March 2003

Morrison CM, Yang H, Al‐Jazaeri A, Tam J, Plisetskaya EM, Wright JR Jr. Xenogeneic milieu markedly remodels endocrine cell populations after transplantation of fish islets into streptozotocin‐diabetic nude mice. Xenotransplantation 2003; 10: 60–65. © Blackwell Munksgaard, 2003It is unknown whether irrelevant foreign endocrine products secreted by xenografts would be biologically active and potentially harmful to recipients; even if entirely inert, continuous production might result in harmful circulating antigen–antibody complexes. We examined the fate of such a product using a fish (tilapia)‐to‐mouse islet xenograft model. Teleost fish islets, like mammalian islets, are composed primarily of cells producing insulin, glucagon or somatostatin; however, teleost fish have two different populations of somatostatin (SST) producing delta cells, one producing SST‐14, a 14 amino acid SST identical to mammalian SST, which is derived from the pre‐proSST‐I gene which is present in all vertebrates, and the other a “large” (i.e. 22 to 28 amino acid) SST derived from a pre‐proSST‐II gene, which is not found in mammals. In contrast to `large' SST, which has no mammalian homolog, teleost fish insulins, glucagons and SST‐14 exhibit significant biological activity in mammals. Tilapia islets were transplanted under the kidney capsules of streptozotocin‐diabetic nude mice, and mice with functioning grafts were killed at various times after transplantation. Serial sections of graft‐bearing kidneys were stained by immunoperoxidase for insulin, SST‐14, SST‐25 and glucagon positive cells, and the areas of each cell type in the graft were measured using image analysis. Sections of untransplanted tilapia islets (both in situ and after harvest/culture) were also immunostained and measured as controls. Xenotransplantation of fish islets into diabetic nude mice resulted in the rapid degeneration and near total loss of SST‐25+ cells, as well as a marked redistribution of the proportions of the remaining endocrine cell types. The proportions of cell types in the grafts gradually changed from a piscine pattern to that of mammalian islets.
Carboxypeptidase R is an inactivator of complement‐derived inflammatory peptides and an inhibitor of fibrinolysis
Authors: Campbell William , Okada Noriko , Okada Hidechika 
Published: March 2003

Summary:Carboxypeptidase R (CPR) exists in precursor form (proCPR) in plasma in contrast to carboxypeptidase N (CPN), which is present in the active state. CPR plays two important roles, one of which appears to be the control of the inflammatory response by inactivation of anaphylatoxins such as complement‐derived C3a and C5a. Therefore, an increase in CPR activity may facilitate rapid inactivation of these inflammatory mediators generated at the site of bacterial infection. Upregulation of proCPR expression during the inflammatory response initiated for instance by endotoxin (lipopolysaccharide) should play a role in suppressing hyper‐reactivity as seen in septic shock. CPR also functions as an inhibitor of fibrinolysis, where its ability to prevent binding of plasminogen to lysine residues on fibrin clots significantly lengthens tissue plasminogen activator (tPA)‐induced fibrinolysis time. Therefore, upregulation of proCPR production during the inflammatory response may exacerbate thrombosis contributing to the development of disseminated intravascular coagulation as well as other conditions involving thrombosis. Co‐administration of tPA and a specific inhibitor of CPR, such as potato carboxypeptidase inhibitor, which does not affect CPN, may be useful in thrombolytic therapy.This work was supported by a research grant form the Organization for Pharmaceutical Safety and Research.
The immune system: a weapon of mass destruction invented by evolution to even the odds during the war of the DNAs
Authors: Cohn Melvin 
Published: March 2003

Summary: Living systems operate under interactive selective pressures. Populations have the ability to anticipate the future by generating a repertoire of elements that cope with new selective pressures. If the repertoire of such elements were transcendental, natural selection could not operate because any one of them would be too rare. This is the problem that vertebrates faced in order to deal with a vast number of pathogens. The solution was to invent an immune system that underwent somatic evolution. This required a random repertoire that was generated somatically and divided the antigenic universe into combinatorials of determinants. As a result, it became virtually impossible for pathogens to escape recognition but the functioning of such a repertoire required two new regulatory mechanisms: 1) a somatic discriminator between Not‐To‐Be‐Ridded (‘Self’) and To‐Be‐Ridded (‘Non‐self’) antigens, and 2) a way to optimize the magnitude and choice of the class of the effector response. The principles governing this dual regulation are analyzed in the light of natural selection.

Abstract
A. ‘...doth protest too much’
E. Two classes of pathogen must be faced
II. The NTBR–TBR discrimination
A. The three laws of the NTBR‐TBR discrimination
B. The mechanism of the NTBR‐TBR discrimination
C. Facing the “chicken and egg” problem
III. The regulation of effector class
IV. The somatically selected immune repertoire
A. The Protecton is the unit of function
B. The humoral immune system
C. The cell‐mediated immune system
D. The meaning of specificity
V. Why understand when you can cure without it?
VI. Coda: Extracting the postulates used to explain immune behavior
O.K. José! What would it take to change your mind?Mechkonik
On the role of self‐recognition in T cell responses to foreign antigen
Authors: Štefanov́a Irena , Dorfman Jeffrey R. , Tsukamoto Makoto , Germain Ronald N. 
Published: March 2003

Summary:The key role of the thymus in shaping the peripheral T cell receptor (TCR) repertoire has been appreciated for nearly a quarter of a century. For most of that time, a single model has dominated thinking about the physiological role of the positive selection process mediated by TCR recognition of self‐peptides and major histocompatibility complex (MHC) molecules. This developmental filter was believed to populate secondary lymphoid tissues with T cells bearing receptors best able to recognize unknown foreign peptides associated with the particular allelic forms of the MHC molecules present in an individual. More recently, self‐recognition has been suggested to regulate the viability of naïve T cells. Here we focus on new results indicating that a critical contribution of positive selection to host defense is insuring that each peripheral T cell can use self‐recognition to (i) enhance TCR signaling sensitivity upon foreign antigen recognition and (ii) augment the clonal expansion that accompanies limiting foreign antigen display at early points in an infectious process. We also detail new insights into the intracellular signaling circuitry that underlies the effective discrimination between low‐ and high‐quality ligands of the TCR and speculate on how this design might facilitate an additional contribution of self‐recognition to T cell activation in the presence of foreign stimuli.
Odontogenic tumors in Chile: a study of 362 cases
Authors: Ochsenius Germán , Ortega Ana , Godoy Luis , Peñafiel Cristian , Escobar Enrico 
Published: March 2003

AbstractBackground:  Odontogenic tumors are infrequent lesions. Thus, the review of a large number of cases becomes a necessity for both the pathologist and the clinician. Studies on odontogenic tumors have been published in many parts of the world, but there is little information available in the English language literature on the relative frequency of odontogenic tumors in Latin America. The aim of this study was to determine the relative frequency of this heterogeneous group of lesions in a Chilean population, and to compare these data with previous reports.Methods:  We reviewed the records of 28,041 specimens from 1975 to 2000 in the Oral Pathology Referral Institute (IREPO), and using the criteria for histological typification published by the World Health Organization in 1992, we reclassified the odontogenic tumors.Results:  We confirmed a total of 362 odontogenic tumors. The frequency of odontogenic tumors as a percentage of all pathological specimens in our institute was 1.29%. The most frequent histological type was odontomas (44.7%), followed by ameloblastomas (20.4%) and myxomas (8.8%).Conclusions:  Odontogenic tumors are uncommon lesions in the Chilean population and malignant odontogenic tumors are very rare. The relative frequency of various types of odontogenic tumors, as well as the age and gender distribution are similar to those reported in the North American series and different from those found in recently published Asian and African series.
Disturbed tooth eruption in osteopetrotic (op/op) mice: histopathogenesis of tooth malformation and odontomas
Authors: Ida‐Yonemochi Hiroko , Noda Tadashi , Shimokawa Hitoyata , Saku Takashi 
Published: March 2003

AbstractBackground:  Odontoma‐like structures are formed in the jaw bone of osteopetrotic (op/op) mice, which have a congenital deficiency in osteoclastic differentiation due to the absence of functional macrophage colony‐stimulating factor (M‐CSF).Methods:  To clarify the histopathogenesis of tooth malformation and odontoma‐like structures, a 2‐year postnatal process of development of the op/op mandibular incisor was examined radiologically and histologically. At the same time, extracellular matrix (ECM) remodeling around tooth germs was analyzed immunohistochemically.Results:  Abnormal forms of op/op tooth germ were noticeable even at 3 days after birth on a radiogram. Histologically, op/op mice were clearly distinguished by the disappearance of dental follicular space at 3 days. With aging, bone trabeculae, which were not remodeled, penetrated into op/op tooth germs and divided them into several daughter germs, which were recognized as odontomas. In mandibular incisor bodies, the immature ECM components, such as heparan sulfate proteoglycan and tenascin, were preserved diffusely in the dental papilla/pulp, which indicates that maturation of the stroma does not take place in op/op mandibular incisors.Conclusion:  The observation suggests that the disturbed morphogenesis of op/op tooth germs is functionally explained by the disordered immunolocalization of ECM molecules, and that the dental follicular space is essential for normal tooth development because it prevents bone penetration into the tooth germs.
Subcellular localization of beta‐catenin in malignant cell lines and squamous cell carcinomas of the oral cavity
Authors: Gasparoni A. , Chaves A. , Fonzi L. , Johnson G. K. , Schneider G. B. , Squier C. A. 
Published: March 2003

AbstractBackground:  Beta‐catenin, an E‐cadherin‐associated protein involved in cell–cell adhesion and signaling, has been hypothesized to translocate to the nucleus and activate transcription in several human cancers, including oral squamous cell carcinomas (OSCC).Methods:  In the present study, we analyzed the subcellular localization of beta‐catenin in cultures of human oral normal and malignant (cell lines SCC15 and SCC25) keratinocytes and in 24 frozen samples of oral squamous cell carcinomas by a double‐staining technique for nucleic acids and beta‐catenin. Growth potential, as assessed by cell count at different time periods, was established for normal, SCC15 and SCC25 cell lines; oral squamous cell carcinomas were classified according to the histopathological and malignancy indexes.Results:  Beta‐catenin localized at the plasma membrane in the normal and SCC15 cells, not in the SCC25 cells, where it localized mostly in the perinuclear and nuclear areas. In the growth assays, SCC25 cell lines proliferated faster than in normal and SCC15 cells over a period of 6 days (cell numbers were significantly different, P < 0.0001). Carcinoma sections showed a combination of membranous, cytoplasmic and, in few invading epithelial islands of two tumors, nuclear localization of beta‐catenin.Conclusions:  In oral squamous cell carcinomas, nuclear beta‐catenin staining was observed only within invading islands of two carcinomas deep in the underlying connective tissue. On the basis of this study, we conclude that intranuclear beta‐catenin does not appear to be a common finding in oral squamous cell carcinomas and that a clear association between intranuclear beta‐catenin and histopathological and malignancy indexes in vivo could not be established.
Expression of type 2 nitric oxide synthase and p53 in Warthin's tumour of the parotid
Authors: Brennan Peter A. , Umar Tijjani , Smith Graham I. , McCauley Philip , Peters Winston J. , Langdon John D. 
Published: March 2003

AbstractAlthough the pathogenesis of Warthin's tumour is not fully understood, it is generally thought that the tumour arises from heterotopic salivary ducts within pre‐existing lymphoid tissue. Prolonged nitric oxide (NO) production by the enzyme type 2 nitric oxide synthase (NOS2) has been implicated in the pathogenesis of many solid tumours, but not in Warthin's tumour. Since NO and NOS2 are known to be associated with p53, the immunohistochemical expression of both NOS2 and p53 was investigated in 23 cases of Warthin's tumour. Widespread diffuse cytoplasmic immunostaining for NOS2 was found in tumour epithelial cells of all 23 cases studied, and it was additionally expressed in normal salivary duct epithelium. p53 staining was localised to the nuclei of tumour epithelium in 16 cases, with a similar pattern of distribution to tumour NOS2 expression. A significant correlation was found between NOS2 and p53 staining in the tumours (P < 0.001). In contrast to NOS2, p53 was not expressed by normal salivary ductal cells in any of the cases studied. NOS2 is widely expressed by the tumour epithelium of Warthin's, and its association with p53 expression is discussed. The role of NO in the pathogenesis of Warthin's tumour remains to be established.
Deranged expression of the E‐cadherin/β‐catenin complex and the epidermal growth factor receptor in the clinical evolution and progression of oral squamous cell carcinomas
Authors: Bánkfalvi Agnes , Kraßort Melanie , Végh András , Felszeghy Endre , Piffkó Jozsef 
Published: March 2003

AbstractBackground: Deranged expression and function of the E‐cadherin/β‐catenin (E‐cad/β‐cat) complex and the epidermal growth factor receptor (EGFR) have been implicated in the development and progression of carcinomas.Methods: To estimate the role of these molecules in oral cancer, we investigated 75 primary oral squamous cell carcinomas (OSCCs) with adjacent normal and/or dysplastic mucosa, 30 paired metastases and 12 recurrences by immunohistochemistry.Results: All three molecules were constitutionally expressed in the basal/parabasal layers of tumour adjacent ‘normal’ epithelium, in contrast to a significant increase of EGFR and heterogeneous expression of E‐cad/β‐cat in dysplasia. In OSCCs, over‐expression of EGFR correlated significantly with lower tumour grade and poor prognosis, loss of E‐cad was a significant marker for shortened survival, reduced β‐cat staining was a predictive marker for lymph node metastasis.Conclusions: There is a perturbance in intercellular adhesion molecules and EGFR expression/function in oral cancer with major clinical impact. E‐cad and β‐cat seem to inhibit EGFR to enhance the progression of OSCCs.
Transforming growth factor β1 (TGFβ1) expression in head and neck squamous cell carcinoma patients as related to prognosis
Authors: Logullo Angela F. , Nonogaki Suely , Miguel Roberto E. , Kowalski Luiz P. , Nishimoto Inês N. , Pasini Fátima S. , Federico Miriam H. H. , Brentani Ricardo R. , Brentani M. Mitzi 
Published: March 2003

AbstractBackground:  Transforming growth factor β1 (TGFβ1) is a negative growth regulator in keratinocytes, and in vitro studies lead to the concept that loss of TGFβ1 responsiveness is a critical step in epithelial carcinogenesis.Objective:  To investigate the prognostic relevance of TGFβ1 expression in head and neck squamous cell carcinoma (HNSCC).Materials and methods:  TGFβ1 distribution was determined by immunohistochemistry in oral cavity/oropharynx (n = 79), larynx (n = 36) and hypopharynx (n = 25) tumors and in matched normal adjacent mucosa. TGFβ‐type I and II receptors were determined in 20 cases of differentiated oral cavity/hypopharynx tumors. Cases were considered positive if displaying reactivity in >10% of the cells.Results:  TGFβ1‐positive expression was found in 47.2% of larynx, 36.7% of oral cavity/oropharynx and in 24% of the hypopharynx tumors. Reactivity in >60% of the cells was displayed only by 11.4% of HNSCC. All normal controls were positive. TGFβ1‐positive expression did not correlate with clinico pathological parameters. An association with differentiation was verified only in oral cavity/oropharynx tumors (P ≤ 0.001). TGFβ1 was also not related to 5 years survival (Kaplan–Meier). Strong and diffuse expression of TGFβ‐RII was identified in 19/20 cases regardless of TGFβ1 immunoreactivity. Out of 17 TGFβ1‐positive oral cavity/oropharynx tumors, only nine expressed TGFβ‐RI suggesting a disruption of the TGFβ1 pathway. We conclude that TGFβ1 protein immunostaining is not a useful biomarker in assessment of prognosis in HNSCC.
UVB‐induced GM‐CSF production is suppressed by dexamethasone in HaCaT Cells
Authors: Kim Dong Seok , Kim Hye Jin , Choi Kyoung Hee , Chung Jin‐Ho , Kim Kyu Han , Park Kyoung Chan 
Published: March 2003

Background: Epidermal keratinocytes are important sources of a wide variety of cytokines that include the Granulocyte‐macrophage Colony Stimulating Factor (GM‐CSF). Glucocorticoids have been shown to inhibit the production of several cytokines. However, their effect on GM‐CSF synthesis by keratinocytes is still unknown.Methods: The effects of glucocorticoid on GM‐CSF production by keratinocytes were evaluated using ELISA and RT‐PCR analysis.Results: GM‐CSF secretion by HaCaT cells increased with increasing UVB exposure. Dexamethasone suppressed basal release of GM‐CSF. In addition, it strongly inhibited both the UVB‐mediated augmentation of GM‐CSF protein production and mRNA expression. Lincomycin enhanced slightly the inhibitory effect of dexamethasone on GM‐CSF synthesis, while lincomycin itself had no effect on GM‐CSF secretion.Conclusion: Results showed that dexamethasone suppressed basal release and UVB‐induced production of GM‐CSF by keratinocytes.