bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratumoral lymphangiogenesis in oral squamous cell carcinoma and its clinicopathological significance
Authors: Zhao D. , Pan J. , Li XQ. , Wang XY. , Tang C. , Xuan M.
Published: August 2010

Lymphatic metastasis has always been regarded as a major prognostic indicator for disease progression and as a guide for therapeutic strategies to oral squamous cell carcinoma (OSCC), but to date, how tumor cells access and spread via the lymphatics have not been fully elucidated. Whether tumor cells metastasize by expansion and invasion of pre‐existing peritumoral lymphatics or by the induction and invasion of newly formed lymphatics within tumors is controversial. In order to address this issue and find out the clinicopathological significance of intratumoral lymphangiogenesis, we investigated 86 archival specimens from patients with OSCC, quantitating lymph vessels by immunostaining with D2‐40. We also quantified lymphatic invasion and examined the possible associations of all the above parameters with clinicopathological features and outcome. Higher intratumoral lymphatic density (ILD) and peritumoral lymphatic density (PLD) were both significantly associated with the presence of lymph node metastasis at the time of diagnosis and the outcome of the post‐operation biopsy of 77 patients (P = 0.001). Higher ILD was significantly associated with a higher incidence of intratumoral lymphatic invasion, peritumoral lymphatic invasion and recurrence of tumor (P = 0.001 and P = 0.041 and P = 0.001, respectively). Patients with higher ILD exhibited shorter 5‐year cumulative and disease‐free survival (P = 0.001). Thus, lymphangiogenesis indeed occurs in oral squamous cell carcinoma; ILD might be used as an index to inflect the aggression of the disease, to evaluate the status of lymphatic metastasis, to separate patients at higher risk of an adverse clinical outcome.
Quantitative analysis of Langerhans’ cells in oral chronic graft‐vs.‐host disease
Authors: Orti‐Raduan Érika Sinara Lenharo , Nunes Adauto José Ferreira , Oliveira Denise Tostes , Lara Vanessa Soares , De Assis Taveira Luís Antônio
Published: August 2010

Background:  The Langerhans cells (LCs) are scattered throughout the epithelium of skin and mucosa and have been associated with the graft‐vs.‐host disease (GVHD), which is the highest cause of morbidity and mortality in patients who underwent bone marrow transplant (BMT). This study aims at quantifying the LCs in the oral chronic GVHD (cGVHD).

Methods:  Microscopic sections from biopsies carried out in the buccal mucosa of 40 patients who underwent allogenic BMT and developed (20) or not (20) oral cGVHD (Groups 1 and 2, respectively) were utilised. For the control group, free surgical margins of 20 biopsies of non‐inflammatory lesions in the buccal mucosa (Group 3) were used. The sections were studied in routine colouration and immunostained for CD1a.

Results:  Group 1 (with cGVHD) presented a greater number of Langerhans’ cells/mm2 (50.6 ± 37.2) when compared with the other groups (Group 2, 23.11 ± 19.7; Group 3, 16.6 ± 17.3).

Conclusion:  Our results suggest a greater recruitment of LCs in patients transplanted with cGVHD, probably as a result of cytokines secreted by the inflammatory cells.
Oral ulcers in HIV‐positive Peruvian patients: an immunohistochemical and in situ hybridization study
Authors: Delgado W. A. , Almeida O. P. , Vargas P. A. , León J. E.
Published: August 2010

Background:  This study describes the histopathological, immunohistochemical (IHC) and in situ hybridization (ISH) data of 25 cases of oral ulcers in HIV‐positive patients, with clinical and microscopical features similar to ulcers not otherwise specified (NOS)/necrotizing ulcerative stomatitis (NUS).

Methods:  Sex, age and clinical history were obtained from the clinical records. Histological analysis for H&E, Gomori–Grocott and Ziehl–Neelsen stains, IHC analysis to detect infectious agents and to characterize inflammatory cellular infiltrate, and ISH for cytomegalovirus (CMV) and EBER1/2 were performed.

Results:  Twenty‐one patients were men and four were women (mean age of 34.6 years). The tongue was preferentially affected. Microscopically, the lesions showed extensive necrosis, leukocytoclasia, vasculitis with luminal fibrin clots and an intense inflammatory cellular infiltrate predominated by CD68+ atypical large cells, normal‐sized and crescent‐shaped nuclei macrophages, interspersed by CD8+ T lymphocytes. Mast cells were also observed in all samples studied. CD4+ T lymphocytes, CD20+ B lymphocytes and VS38c+ plasma cells were practically absent. CMV and EBER1/2 were identified in scarce cells of 3 and 16 of 25 cases respectively.

Conclusion:  These results show that CD68+ macrophages, followed by CD8+ T lymphocytes, were the predominant inflammatory cells, indicating they are relevant to the pathogenesis of the ulcers, possibly reflecting an abnormal immune response in the oral mucosa. The clinicopathological and immunoprofile features of the present cases are similar to NOS ulcers/NUS in HIV‐positive patients.
Gene expression analysis by oligonucleotide microarray in oral leukoplakia
Authors: Kuribayashi Yuri , Morita Kei‐ichi , Tomioka Hirofumi , Uekusa Masaru , Ito Daisuke , Omura Ken
Published: August 2010

Background:  Oral leukoplakias (LP) are the most frequent types of oral pre‐cancerous lesions, but there is no accurate assessment of this malignant transformation or even genetic diagnosis of the oral epithelial dysplasia. We need to identify the new genetic diagnosis system of the epithelial dysplasia.

Methods:  Oligonucleotide microarray was used to analyze expression patterns of 29 952 genes in 10 LP patients. We compared the different gene expressions between mild dysplasia cases and severe dysplasia cases.

Results:  Ninety‐six genes expressed differentially were selected as candidates for up‐regulated in severe dysplasia. Subsequently, we further selected 16 genes with highest differentially expression. By hierarchical clustering analysis, the 10 cases were divided mild dysplasia from severe dysplasia.

Conclusions:  The 16 genes are suggested as biomarker gene sets of efficacy and quickly recognized in the development of oral epithelial dysplasia.
Palliative effect of lafutidine on oral burning sensation
Authors: Toida M. , Kato K. , Makita H. , Long N. K. , Takeda T. , Hatakeyama D. , Yamashita T. , Shibata T.
Published: August 2010

Background:  Lafutidine is a unique histamine H2‐receptor antagonist (H2RA) that has a sensitizing effect on capsaicin‐sensitive afferent neurons (CSAN). This effect may make lafutidine useful for the treatment of burning mouth syndrome (BMS).

Methods:  To evaluate the efficacy and safety of lafutidine in patients with oral burning sensation, a randomized controlled trial was performed. Patients who had been receiving other H2RAs with no sensitizing effect on CSAN were randomly assigned to receive lafutidine 10 mg twice daily for 12 weeks, instead of the previous H2RAs, plus gargling with azulene sulfonate sodium (ASS) (lafutidine group, n = 36) or to continue to receive the previous H2RAs plus ASS gargling (control group, n = 35). The intensity of burning sensation was scored by means of a visual analog scale (VAS).

Results:  Thirty‐four patients in the lafutidine group and 30 in the control group completed the study. In the lafutidine group, the rate of improvement in the VAS score as compared with the baseline value was significant after 4, 8, and 12 weeks of treatment (P < 0.05). The improvement rate was consistently higher in the lafutidine group than in the control group; the differences between the groups were significant (P < 0.05) after 4, 8, and 12 weeks of treatment. Only two mild abdominal adverse events occurred in the lafutidine group, but neither required the termination of treatment.

Conclusion:  Oral lafutidine is very safe and effective for reducing the intensity of oral burning sensation and may therefore be a viable option for the treatment of BMS.
Keratinocyte growth factor colocalized with perlecan at the site of capsular invasion and vascular involvement in salivary pleomorphic adenomas
Authors: Maruyama Satoshi , Cheng Jun , Yamazaki Manabu , Liu Airu , Saku Takashi
Published: August 2010

Background:  Capsular invasion is often observed in daily pathologic diagnosis of pleomorphic adenomas, although neither actual information about its occurrence nor molecular mechanisms leading to their invasive activities have been reported. In this study, our aim was to elucidate the mode and the frequency of capsular invasion in this tumor and to characterize the tumor cell arrangement at the site of capsular invasion.

Methods:  The mode and frequency of capsular invasion of salivary pleomorphic adenomas were histopathologically examined in 104 surgical specimens of pleomorphic adenoma, and stromal characteristics, and tumor cell arrangements at the sites of capsular invasion were immunohistochemically investigated.

Results:  A total of 353 areas with capsular invasive changes were collected from 104 cases. The mode of capsular invasion was classified into two types: type I: intracapsular invasion (247 areas, 70%) and type II: capsular penetration (106 areas, 30%). Myxoid stroma, which was perlecan‐immunopositive (+), was shared by both type I and type II sites, while tumor cell foci containing ductal structures were predominant in type II sites. These foci were composed of KGF+ and FGFR2+ cells. In addition, apparent vascular involvement was recognized in 31 tumors (29.8%).

Conclusion:  The results suggest that pleomorphic adenoma cells are able to invade into the capsule and involve blood vessels when they are situated in perlecan‐rich milieu, which accelerate KGF signaling.
Immunoexpression of keratins in the calcifying cystic odontogenic tumor epithelium
Authors: Crivelini Marcelo Macedo , Felipini Renata Callestini , Coclete Gilberto Aparecido , Soubhia Ana Maria Pires
Published: August 2010

Ameloblastomatous epithelium containing clusters of ghost cells is the typical histopathology of calcifying cystic odontogenic tumor (CCOT). This paper aimed to assess keratins AE1‐AE3, K7, K10/13, K14, K18, K19, vimentin, laminin, and collagen IV in 08 CCOTs to discuss their histopathogenesis. Similarity to the immunoprofile of the stratified squamous epithelium was seen in the with the basal layer expressing K14 and the upper cells expressing K10/13. When compared to the immunoprofile of the normal odontogenic epithelium, of odontogenic tumor epithelia and of the ghost cells described in the literature, it was possible to suggest that the CCOT epithelium differentiates towards squamous type.
Malignancy grading is no better than conventional histopathological grading in small squamous cell carcinoma of tongue and floor of mouth: retrospective study in 128 patients
Authors: Weijers M. , Snow G. B. , Dick Bezemer P. , Van Der Waal I.
Published: August 2010

There is an ongoing debate about the predictive value of histopathological parameters in oral cancer. In the past decades, the emphasis was on the possible added value of the so‐called malignancy grading system. In a retrospective study on 128 previously untreated patients with a T1 or T2 squamous cell carcinoma of the tongue and the floor of the mouth, the value of the classical Broders’ grading system and the malignancy grading system were compared with regard to various outcome measures such as regional metastasis, local recurrence and 5‐year survival. The results show that neither of the histological grading systems has a strong predictive value and that none is superior to the other.
Oral health and related quality of life status in patients from UK and Turkey: a comparative study in Behcet’s disease
Authors: Mumcu G. , Niazi S. , Stewart J. , Hagi‐Pavli E. , Gokani B. , Seoudi N. , Ergun T. , Yavuz S. , Stanford M. , Fortune F. , Direskeneli H.
Published: August 2010

Background:  The aim of this study was to evaluate and compare oral health‐related quality of life (oral QoL) in patients from UK and Turkey with Behcet’s disease (BD).

Methods:  Thirty‐one BD patients from UK (F/M: 18/13, mean age: 41.8 ± 11.5 years) and Turkey (F/M: 18/13, mean age: 41.5 ± 10.3) who were matched according to age and gender were included in the study. All patients had active oral ulcers. Oral QoL was assessed by Oral Health Impact Profile‐14 (OHIP‐14). Oral health was evaluated by dental and periodontal indices.

Results:  No significant difference was found in OHIP‐14 scores between patients from UK (22.7 ± 14.4) and Turkey (20.4 ± 14.3) (P = 0.709). The OHIP‐14 score correlated with the healing time of oral ulcers in UK (r = 0.4, P = 0.04) and the number of oral ulcers in Turkey (r = 0.4, P = 0.012). The number of oral ulcers per month was significantly higher in UK (3.3 ± 2.8) compared with that in Turkey (1.5 ± 2.5) (P = 0.014). However, the number of filled teeth and frequency of tooth brushing were significantly lower in patients from Turkey compared with those in UK (P = 0.000). Similarly, the duration since the last dental visit (5.1 ± 7.2 months) was significantly lower in UK compared with that in Turkey (28.6 ± 23.7 months) (P = 0.000).

Conclusions:  Oral QoL was similar in patients from UK and Turkey with active oral ulcers. However, the number of oral ulcers was observed to be higher in UK. As expected, a lower utilization rate of dental services might have led to a poorer oral health in patients from Turkey.
Odontogenic keratocyst expresses vascular endothelial growth factor: an immunohistochemical study
Authors: Mitrou G. K. , Tosios K. I. , Kyroudi A. , Sklavounou A.
Published: August 2010

Background:  Vascular endothelial growth factor (VEGF) expression may act as a sensitive measure of the angiogenic potential of a lesion. Furthermore, VEGF has been implicated in the pathogenesis of cystic tumors and inflammatory odontogenic cysts. Thus, we studied the expression of VEGF in the epithelium of odontogenic keratocyst (OK) in association with cell proliferation and apoptosis.

Methods:  Forty‐two cases of OK, 26 cases of dentigerous cyst (DC), and 15 cases of residual cyst (RC) were retrospectively examined by immunohistochemistry for VEGF, Ki67/Mib‐1 and anti‐caspase‐3. For VEGF and caspase‐3, the intensity of immunostaining was qualitatively assessed, while for the evaluation of Ki67 the average number of positively stained nuclei in 10 high‐power microscopic fields (×400) was calculated.

Results:  The VEGF expression was stronger in OK when compared with DC (P < 0.007). The rate of nuclear Ki67 expression in OK was significantly higher than that in DC (P < 0.001) and RC (P < 0.001). Cytoplasmic caspase‐3 expression was statistically more intense in RC than in OK (P = 0.001) or DC (P < 0.001). A statistically significant correlation was seen in OK for Ki67 (P < 0.001) and VEGF (P = 0.023), but not for caspase‐3. Multiple regression analysis revealed a linear relationship between VEGF and Ki67.

Conclusions:  The VEGF was expressed in the epithelium of OK, DC, and RC with a variable intensity, and in OK VEGF expression was related to Ki67. It is suggested that VEGF expression by the odontogenic epithelium is not induced solely by inflammation.
Arecoline and oral keratinocytes may affect the collagen metabolism of fibroblasts
Authors: Xia Li , Tian‐You Ling , Yi‐Jun Gao , Dong‐sheng Tang , Wen‐Hui Li
Published: August 2010

Background:  The characteristic of oral submucous fibrosis (OSF) is related with the disturbance of synthesis and degradation of extracellular matrix. Arecoline, the areca nut (betel nut) component of betel quid, plays a major role in pathogenesis of OSF. But the exact mechanism how arecoline influences the collagen metabolism is unclear.

Methods:  Oral keratinocytes and fibroblasts were cocultured and keratinocytes were pre‐treated by arecoline. Fibroblasts alone, fibroblasts stimulated by arecoline, fibroblasts cocultured with keratinocytes and fibroblasts cocultured with keratinocyte pre‐treated by arecoline were included as the four groups in the present study. The concentration of collagen, the content and activity of matrix metalloproteinase (MMP) and the concentration of tissue inhibitor of metalloproteinase (TIMP) were assessed.

Results:  The collagen production of fibroblasts decreased when cocultured with keratinocytes; when cocultured with keratinocytes pre‐treated by arecoline, fibroblasts produced more soluble collagen than non‐pretreated coculture group. MMP‐9 was produced only in coculture groups. There was no significant difference in the two coculture groups. The activation ratio of pro‐MMP‐2 in arecoline pre‐treated keratinocytes‐fibroblasts coculture group was significantly higher than that of non‐coculture groups, but no significant difference existed in the two coculture groups. TIMP‐1 produced by arecoline pre‐treated keratinocytes‐fibroblasts coculture group was significantly higher than those by the other three groups.

Conclusion:  TIMP‐1 and the interaction of oral keratinocytes and fibroblasts play important role in pathogenesis of OSF.
Differential gene expression profiles of whole lesions from patients with oral lichen planus
Authors: Tao Xiao‐An , Li Chun‐Yang , Xia Juan , Yang Xi , Chen Xiao‐Hua , Jian Yu‐Tao , Cheng Bin
Published: August 2010

Background:  The molecular biological properties of oral lichen planus (OLP) are largely unknown. The aim of this study was to identify the genes responsible for its pathogenesis at the genome scale using DNA microarray technology.

Methods:  The RNA samples extracted from the specimens of nine OLP patients and nine controls were analyzed with Affymetrix GeneChip. Real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) analysis was applied to confirm GeneChip results.

Results:  A total of 985 differentially expressed genes (629 up‐regulated and 356 down‐regulated) were identified. These genes were involved in many function classifications and biochemical pathways. The results of quantitative RT‐PCR analysis of FOXP3, VEGFA, ANGPT1, MMP1, and SCGB2A2 were consistent with their changes demonstrated by GeneChip.

Conclusions:  This study showed the gene expression profiles of OLP, which were quite distinct from that of healthy controls. These results presented a global view of physiopathologic processes in lesions, which will give important clues to understand pathogenesis and identify new therapeutic targets of OLP.
Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct carcinomas
Authors: Ko Young Hyeh , Roh Ji Hyeon , Son Young‐Ik , Chung Man Ki , Jang Jeon Yeob , Byun Hayoung , Baek Chung‐Hwan , Jeong Han‐Sin
Published: August 2010

J Oral Pathol Med (2010) 39: 349–355

Objective:  Defects in the mitotic checkpoint lead to aneuploidy and might facilitate tumorigenesis. However, the ploidy status in salivary duct carcinoma (SDC) has been reported to play limited role in prediction of prognosis. Thus, we need more reliable markers to reflect the rapid tumor progression in SDCs. We aimed here to investigate the expression of mitotic checkpoint proteins benzimidazole 1 homolog beta (BUB1B) and mitosis arrest‐deficient 2 like 1 (MAD2L1) in SDCs and to determine their possible role as surrogate prognostic markers.

Methods:  We analyzed the clinical courses, pathologic findings and immunohistochemical profiles of mitotic checkpoint proteins (BUB1B and MAD2L1) in 27 pathologically confirmed SDCs. The expression status of BUB1B and MAD2L1 was compared with clinicopathologic factors and other molecular markers, such as TGF‐beta, c‐erb‐B2, androgen receptor, vascular endothelial growth factor, and epidermal growth factor receptor, for prognostic significance.

Results:  High BUB1B expression was detected in 25.9% of subjects, and high MAD2L1 expression was in 55.6% of subjects. However, survival analysis revealed that mitotic checkpoint expression did not have prognostic significance in SDCs, nor did the other studied markers. Rather, the clinical variable of N classification at diagnosis (in N+ status, hazard ratio 5.19, 95% CI 1.26–21.32 for disease‐free survival and hazard ratio 7.18, 95% CI 1.09–46.99 for overall survival) was strongly associated with survival and prognosis based on the Cox proportional hazard model.

Conclusions:  Mitotic checkpoint proteins appeared to play a limited role in predicting prognosis in SDCs. Further study is required to elucidate the exact role of mitotic checkpoint proteins in SDCs.
Fatty‐acid‐binding protein 5 promotes cell proliferation and invasion in oral squamous cell carcinoma
Authors: Fang Lei‐Ya , Wong Tung‐Yiu , Chiang Wei‐Fan , Chen Yuh‐Ling
Published: August 2010

J Oral Pathol Med (2010) 39: 342–348

Background:  Oral squamous cell carcinoma (OSCC) is one of the most malignant neoplasms worldwide, and the molecular mechanism of oral tumorigenesis is still unclear. Fatty‐acid‐binding protein 5 (FABP5) was found in our previous study to be upregulated in oral squamous cell carcinomas by proteomic analysis. The implications of FABP5 overexpression in oral cancer progression have not yet been elucidated.

Materials and methods:  In this study, the recombinant adeno‐associated virus vectors were used to deliver and increase the expression of FABP5 in human OSCC cell lines. U6 promoter‐driven short‐hairpin RNA (shRNA)‐triggered RNA interference was used to block FABP5 gene expression. Transwell Matrigel invasion assay, MTS cell proliferation assay, reverse transcription‐polymerase chain reaction, Western blot, and gelatin zymography analysis were used to investigate the effects of FABP5 on cell invasion, growth, and matrix metalloproteinase (MMP) production.

Results:  Overexpression of FABP5 in oral cancer cells increased cell proliferation and invasiveness by increasing the expression of MMP‐9. Silencing FABP5 with shRNA significantly suppressed cell proliferation, MMP‐9 activities, and invasiveness.

Conclusion:  Our study provides the first evidence that FABP5 expression modulated MMP‐9 production and the invasive behavior of oral cancer cells and suggests that FABP5 may provide novel targets for therapeutic intervention.
Oral cancer over four decades: epidemiology, trends, histology, and survival by anatomical sites
Authors: Zini Avraham , Czerninski Rakefet , Sgan‐Cohen Harold D.
Published: August 2010

J Oral Pathol Med (2010) 39: 299–305

Background:  Oral cancer is one of the few life‐threatening oral diseases. The subtypes and different sites of oral cancer has different etiology epidemiology and survival rate. Prevalence of the various anatomical oral sites provided potential baseline for improvement of clinical approach.

Methods:  Incidence and survival rates were derived from the Israel National Cancer Registry and included all registered data between 1970 and 2006. Oral cancer included the lips, tongue, buccal mucosa, gums, vestibulum, floor of the mouth, and palate.

Results:  Most prevalent oral cancer subtype was squamous cell carcinoma (SCC) among men above the age of 55 years. Females had a higher incidence of SCC in lateral border of tongue, gums and buccal mucosa. Lymphoma and sarcoma were the most prevalent under the age of 20. Melanomas and metastatic disease revealed the lowest survival rate, while invasive or infiltrating basal cell carcinoma in the lips had the highest rate. The highest oral survival rate was for the lip, and the lowest was for the tongue and gums.

Conclusions:  Early detection of oral cancer is important for all the medical health team. Decrease in lip carcinoma may be a result of occupational or awareness changes and should be studied. Non‐epithelial tumors under the age of 20 should be considered as a differential diagnosis. A basic oral examination should be included in all routine medical examinations, with emphasis on high‐risk patients and high‐risk oral sites.
Oxidative Protein Folding in the Secretory Pathway and Redox Signaling Across Compartments and Cells
Authors: Margittai Éva , Sitia Roberto
Published: August 2010

The endoplasmic reticulum (ER) is central for many essential cellular activities, such as folding, assembly and quality control of secretory and membrane proteins, disulfide bond formation, glycosylation, lipid biosynthesis, Ca2+ storage and signaling. In addition, this multifunctional organelle integrates many adaptive and/or maladaptive signaling cues reporting on metabolism, proteostasis, Ca2+ and redox homeostasis. We are beginning to understand how these functions and pathways are integrated with one another to regulate homeostasis at cell, tissue and organism levels. The mechanisms underlying the introduction of the proper set of disulfide bonds into secretory proteins (oxidative folding) are strictly related to redox homeostasis, ER stress sensing and signaling and provide a good example of the integration systems operative in the early secretory compartment.
ALLO‐AGGRESSION IN CHICKENS
Authors: Simonsen Morten
Published: August 2010

Simonsen, M. Allo‐aggression in chicken. Serological identification of the major genetic locus. Acta path, microbiol. scand. Sect. C, 83: 1–14, 1975.

The B‐group is the conventional name for the major histocompatibility system (MHS) of the chicken and was first described as a blood group locus. It actually comprises an unknown number of linked loci, at least one of which (AA) governs allo‐aggression as manifested, and studied here by the GVH reaction. The gene product(s) of the AA locus would appear to be expressed not only in T cells but also for example in the nucleated erythrocytes, which fact would then in principle permit their detection by haemagglutination. In practice such detection requires that a number of other haemagglutinating antibodies, directed against other antigens of the same B haplotype be first removed, because the unabsorbed antiserum against one given haplotype seems to agglutinate the RBC of almost any unrelated chicken in the world. A strategy is described which allows a planned absorption of the irrelevant specificities from sera against entire haplotypes; hence lead to successful typing for the AA locus. Some observations suggest an extreme degree of linkage disequilibrium in White Leghorns with respect to the genes determining the Bl haplotype, which appears to be a common haplotype in that particular race.
DEMONSTRATION OF DELAYED‐TYPE HYPERSENSITIVITY IN GUINEA‐PIGS BY THE AGAROSE PLATE TECHNIQUE
Authors: Bræendstrup O. , Magnusson M. , Maxild J. , Werdeiin O.
Published: August 2010

A recently developed method for demonstration of antigen‐dependant migration inhibition, the agarose plate technique, and skin tests were used to demonstrate delayed hypersensitivity towards Mycobacterium tuberculosis and Nocardia farcinica in guinea‐pigs. Peritoneal exudate cells from animals immunized with M. tuberculosis and N. farcinica displayed immunologically specific inhibition of migration after stimulation with tuberculin and N. farcinica sensitin, respectively. The slight cross reactivity between the two antigens demonstrated by skin tests was also observed with the agarose technique. Previous skin testing did not influence migration inhibition of peritoneal exudate cells. Migration inhibitory activity of supernatants of tuberculin stimulated lymph node cells from guinea‐pigs which had been immunized with M. tuberculosis was demonstrated on peritoneal exudate cells from non‐immunized animals.
THE EFFECT OF AZATHIOPRINE ON MONONUCLEAR BLOOD CELLS CULTURED IN VITRO
Authors: Ødegaard Arne
Published: August 2010

The effect of Azathioprine (AZP), an immunosuppressive drug, on the function of blood monocytes and lymphocytes cultured in vitro, was studied. An attempt was made to correlate the effect of the drug on various functions of mononuclear phagocytes with the effect on the rosette forming ability of lymphocytes. The experiments indicate that AZP in concentrations below the level of cytotoxicity suppressed the rosette forming ability of lymphocytes as well as the digestive capacity of macrophages.
INTERACTION OF CONCANAVALIN A WITH HUMAN NEUTROPHIL GRANULOCYTE FUNCTION IN VITRO
Authors: Koch Christian
Published: August 2010

The ingestion of Staphylococcus aureus by human neutrophil granulocytes was inhibited by the addition of concanavalin A (Con A). Intracellular killing of the bacteria and reduction of nitroblue‐tetrazolium (NBT) was enhanced, however, indicating stimulation of oxydative metabolism by Con A. This stimulation may in part be due to agglutination of the cells, since NBT reduction was less prominent when agglutination was prevented. The effects of Con A were different from those of metabolic inhibitors of glycolysis, and the decreased ingestion is probably caused by specific binding of Con A to cell membrane glycoproteins leading to derangement in normal membrane function.
HUMAN IgM INTERACTING WITH STAPHYLOCOCCAL PROTEIN A
Authors: Grov Arne
Published: August 2010

IgM from 7 sera of patients with macroglobulinemia has been examined for interaction with staphylococcal protein A. Three of the IgM proteins were fixed to a protein A‐Sepharose column. They gave a direct co‐precipitation and the “star‐phenomenon”, but no direct precipitation in agar. The primary protein A reactive sites were localized to the Fc‐region, but co‐precipitation and “star”‐formation were also dependent on other molecular configurations. Two of the sera examined contained both protein A reactive and protein A non‐reactive IgM in different ratio.
DIFFERENT RATES OF DISAPPEARANCE OF COMMON ENTEROBACTERIAL ANTIGEN AND TYPE‐SPECIFIC E. COLI O‐ANTIGEN IN RAT PERITONEAL MACROPHAGES
Authors: Thomsen Ole frøkjær , Hjort Tage
Published: August 2010

Common enterobacterial antigen (CA) and type‐specific E. coli O‐antigen were studied in rat peritoneal macrophages by means of immunofluorescence technique. At different time intervals after intraperitoneal injection of killed or viable E. coli O4, macrophages were harvested from the peritoneal fluid and the number of macrophages in which CA or E. coli O4‐antigen, respectively, could be demonstrated was recorded. During the first few days, equal numbers of peritoneal macrophages were found to contain CA and E. coli O4‐antigen, but on days 7—14 and onwards during the remaining experiment, i.e. throughout 8 weeks, CA was detected in fewer macrophages than E. coli O4‐antigen, indicating a lesser degree of persistence of CA than of E. coli O4‐antigen in the macrophages after phagocytosis of the bacteria. The results correspond with those previously obtained in experimental pyelonephritis in rats.
HISTOCHEMICAL DEMONSTRATION OF ACID β‐GLUCURONIDASE AND CARBOXYLIC ESTER HYDROLASE ACTIVITY IN SENSITIZED LYMPHOCYTES DURING LYSIS OF ALLOGENEIC FIBROBLASTS
Authors: Poulsen Poul Brix , Güttler Flemming
Published: August 2010

Sensitized spleen cells were incubated with 51Cr‐labelled target fibroblasts. The interaction of lymphoid cells and target cells was stopped by fixation in formalin vapour. Target cell lysis was evaluated by the release of 51Cr and the cultures were stained for acid β‐glucuronidase and carboxylic ester hydrolase. The sensitized lymphoid cells aggregated around cultured donor‐type, fibroblasts and showed a marked staining for β‐glucuronidase activity within a six‐hour incubation period. Spleen cells of unimmunized mice were negative or weakly positive for β‐glucuronidase. Staining for carboxylic ester hydrolase activity was observed only in spleen cells of allo‐immunized mice. The staining was less intense as compared with the staining for β‐glucuronidase. These observations add further support to the suggestion that lysosomal hydrolases might have a bearing on cell‐mediated target cell injury.
COMPARISON BETWEEN THYMUS‐DEPENDENT AND THYMUS‐INDEPENDENT LYMPHOCYTES AS STIMULATOR CELLS IN ALLOGENEIC MIXED LYMPHOCYTE CULTURE
Authors: Häyry Pekka , Kontiainen Sirkka , Nordling Stig , Andersson Leif C.
Published: August 2010

Resting and activated DBA/2 T and non‐T spleen lymphocytes were compared with a view to their ability to stimulate CBA spleen T lymphocytes in one‐way mixed lymphocyte culture. Resting T and non‐T cells were obtained by fractionation of spleen lymphocytes in preparative free flow cell electrophoresis. Activated T and non‐T cells were obtained by stimulation of DBA/2 spleen cells with phytohaemagglutinin and E. coli lipopolysaccharide, respectively, and by fractionation of the activated cells (blasts) in one‐g velocity sedimentation. Both resting and activated DBA/2 T and non‐T cells induced MLC responses of the same order of magnitude, provided that the culture conditions were adjusted in such a way that both types of stimulator cells survived equally well.
URINARY EXCRETION OF GRANULOCYTE‐SPECIFIC ANTINUCLEAR FACTORS IN RHEUMATOID ARTHRITIS
Authors: Wiik Allan , Henriksen Kirsten , Faber Viggo
Published: August 2010

Sera and 24‐hour urine samples were obtained from 36 patients with rheumatoid arthritis. On the basis of precedent serum studies the patients were divided into two groups, group A consisting of 20 patients showing varying titres of IgG granulocyte‐specific antinuclear factors, almost exactly corresponding to the titres in the 16 group B patients, but differing as to the complement‐fixing properties of the specific antibodies which were restricted to group A only. In five group A patients and one group B patient, an increased excretion of total protein in the urine and an abnormal agarose electrophoresis pattern of the concentrated proteins suggested kidney damage which could not be accounted for by previous or recent medication or clinically explicable nephropathy. IgG granulocyte‐specific antinuclear factors were present in urines from 12 group A patients and 3 group B patients. A direct relation between high titres of complement‐fixing granulocyte‐specific antinuclear factors and presence of the specific antibodies in the urine was demonstrated. In one group A patient with a classical Felty's syndrome, a renal biopsy disclosed immune complex deposition, thovigh clinical and laboratory signs of glomerulopathy were absent. It is suggested that complement‐fixing granulocyte‐specific antinuclear factors may occupy a position comparable to that of complement‐fixing anti‐DNA in systemic lupus erythematosus as regards the induction of immune complex deposition and eventually glomerulitis.
ANTIBODY RESPONSE TO HAPTEN‐PROTEIN CONJUGATES IN CARRIER PRIMED MICE
Authors: Sarvas Heikki
Published: August 2010

Priming mice with a protein (bovine serum albumin or ovalbumin) prepared them for a markedly enhanced anti‐hapten response to the conjugate of a hapten NIP (4‐hydroxy‐3‐iodo‐5‐nitrophenacetyl) and the protein. The enhancing effect of this preimmunization was carrier‐specific and dependent on the priming dose of the carrier. Thus, on day 6, anti‐NIP titers were 6 to 240 times (p<0.01‐<0.001) higher in groups primed with 0.01 to 10 mg of BSA and challenged with NIP‐BSA than in groups not primed with the carrier. The optimum dose (0.1 to 1 mg) of BSA for an enhanced anti‐NIP response also resulted in the highest secondary anti‐BSA titers. The enhancing effect of the carrier priming was observed only at the beginning of the anti‐NIP response. Corresponding findings were obtained when ovalbumin was used for preimmunization and as the carrier in the challenge. This dose‐response relationship in mice was different from that found earlier in chickens. Small doses of carrier induced optimal priming in chickens. Priming with higher doses which induced high titers of anti‐carrier antibody had a suppressive effect on the anti‐hapten response in these birds.
FURTHER STUDIES OF THE CROSS‐REACTION BETWEEN KLEBSIELLA TYPE 12 AND TYPE 13 CAPSULAR POLYSACCHARIDES IN SERA FROM HYPERIMMUNIZED RABBITS
Authors: Eriksen Jorunn
Published: August 2010

A cross‐reaction between Klebsiella types 12 and 13 polysaccharides was demonstrated in hyperimmunized rabbit sera. In most of the sera, the cross‐reaction could only be demonstrated by passive haemagglutination and not by precipitation. Immunization with Klebsiella type 13 induced antibodies of both the IgM and IgG class, but the antibodies cross‐reacting with Klebsiella type 12 polysaccharide were only IgM antibodies. In Klebsiella type 12 sera, the antibody activity was mainly, or only, demonstrated in the IgM class, none or only traces being found in IgG. Klebsiella type 12 antigen seemed to inhibit or delay production of IgG antibodies.
JOINT FLUID IMMUNE COMPLEXES INVOLVING GRANULOCYTE‐SPECIFIC ANTINUCLEAR FACTORS IN RHEUMATOID ARTHRITIS
Authors: Wiik Allan
Published: August 2010

Joint fluids from nine patients with rheumatoid arthritis and three patients with osteoarthrosis were fractionated by Sephadex G‐200 gel filtration at pH 7.35. Most rheumatoid joint fluids contained macromolecular and intermediate size aggregates of IgG, whereas osteo‐arthrosis joint fluids did not. The aggregates regularly comprised IgG granulocyte‐specific antinuclear factors, but only rarely any naturally occurring antibodies to, rabbit red cells. Inhibitors of granulocyte‐specific antinuclear factor reactions were removed from one rheumatoid joint fluid by gel filtration at neutral pH. IgM antinuclear factors of low molecular size were detected in five rheumatoid joint fluids. Three aggregates containing rheumatoid joint fluids were also fractionated at pH 4.5. This caused dissociation of the aggregates in one case and incomplete dissociation in the two other. The low molecular size IgM antinuclear factors disappeared, probably indicating pronounced sensitivity of these antibodies to lowering of the pH. The data suggest participation of granulocyte‐specific antinuclear factors in rheumatoid joint fluid immune complexes. These antibodies may thus gain pathophysiological activity by contributing to immune complex mediated inflammation.
THE BCG‐INDUCED RESISTANCE TO LISTERIOSIS
Authors: Bennedsen J. , Larsen S. Olesen
Published: August 2010

BCG immunization schedules for the demonstration of resistance to listeriosis in C3H mice were re‐evaluated in a series of experiments. A two‐step procedure was found to be superior to a one‐step vaccination schedule. Reactivation with BCG five days before challenge caused a significant depression of the multiplication of Listeria monocytogenes in the spleen. A saline extract of tubercle bacilli was able to reactivate the BCG immunization in the “same way, even though a transient non‐immunogenic effect of the same extract was also demonstrated. In the two‐step procedure the vaccination dose was found to play a minor role, whereas the reactivation was dose‐dependent.
REJECTION PATTERNS OF THREE HUMAN MALIGNANT TUMOURS TRANSPLANTED IN THYMUS GRAFTED NUDE MICE
Authors: Povlsen C. O. , Rygaard J.
Published: August 2010

Nude mice suffering from congenital thymic aplasia will accept human malignant tumours. This study concerns the effect of grafting of neonatal thymus in nude mice subsequently transplanted with human malignant tumours serially grown in nude mice. Three different human tumours —a malignant melanoma, a Burkitt's lymphoma and an epidermoid carcinoma—were rejected by nude mice supposed to be fully immunologically competent following thymus grafting. The rejection process in its various stages was studied by transplanting the malignant melanoma to nude mice, still in the process of immunological reconstitution. There was a considerable variation in the development of immunological competence following thymus grafting. Rejection time varied from 14 to 132 days after thymus transplantation. The rejection process differed microscopically from a classical cell‐mediated immune response in a striking paucity of lymphocytes. A histological grading of the time course of the rejection process is set forth and discussed.;
DRUG EFFECTS ON HUMAN LEUCOCYTE MIGRATION AND MIGRATION INHIBITORY ACTIVITY FROM LYMPHOCYTES STIMULATED WITH CONCANAVALIN A
Authors: Bendtzen Klaus
Published: August 2010

The in vitro effect of a number of drugs on human peripheral blood leucocyte migration and migration inhibitory factors produced by lymphocytes stimulated with concanavalin A was studied. Using the indirect leucocyte migration agarose technique, migration was not influenced by cyclophosphamide, diethylstilbestrol or puromycin. Theophylline (2 μg/ml) marginally inhibited, and methylprednisolone (2.5 μg/ml) markedly stimulated, cell migration under agarose. Production of leucocyte migration inhibitory activity (‐LMIA) was inhibited by theophylline (20 and 200 μg/ml) and abolished by methylprednisolone (2.5 μg/ml), cyclophosphamide (2.5 and 25 μg/ml), diethylstilbestrol (0.01 μg/ml) and puromycin (0.1 to 10 μg/ml). The influence of LMIA on migrating cells was inhibited by puromycin (1 and 10 μg/ml) and by high concentrations of diethylstilbestrol (0.1 μg/ml).
SMOOTH‐MUSCLE ANTIBODIES AND ANTIBODIES TO CYTOMEGALOVIRUS AND EPSTEIN‐BARR VIRUS IN LEUKAEMIAS AND LYMPHOMATA
Authors: ANDERSEN P. , MØLGAARD J. , ANDERSEN IRENE , ANDERSEN H. K.
Published: August 2010

By means of the indirect immunofluorescent method, smooth‐muscle antibodies (SMA) were detected significantly more often in patients with malignant diseases (11.7 per cent) than in normal controls (3.3 per cent) (0.02 p>0.01). SMA occurred in 23.8 per cent of patients with Hodgkin's disease, in 13.3 per cent of patients with myeloproliferative diseases and in 4.7 per cent of patients with lymphoproliferative diseases. Other tissue antibodies were rare and they were found to occur at the same frequency in patients and controls. The occurrence of cytomegalovirus (CMV) antibodies did not differ significantly in patients and controls and, in both groups, the frequency of these antibodies increased with increasing age. The frequency of Epstein‐Barr‐virus (EBV) antibodies increased also with increasing age both in patients and controls, but these antibodies were found more frequently in patients than in controls (p = 0.03). No relationship between the occurrence of SMA and viral antibodies was de monstrated. Thus, the development of SMA in patients with malignancies could not be shown to be due to CMV or EBV infection.
MACROPHAGE PROLIFERATION AND ACTIVATION DURING TOXOPLASMA GONDII INFECTION IN MICE: RELATIONSHIP TO LYMPHOCYTE STIMULATION
Authors: REIKVAM ÅSMUND
Published: August 2010

Macrophage proliferation and activation as well as lymphocyte stimulation in the peritoneal cavities of mice were investigated during the course of a Toxoplasma gondii (Beverly strain) infection. Macrophage proliferation had started already after day one and reached a first peak on day 2 (3H‐thymidine labelling index ˜6 per cent). This proliferation was not accompanied by any notable lymphocyte stimulation. An equally high L.I. for macrophages was found after injection of 0.9 per cent saline. From day 3‐4 and peaking on day 7‐11, a considerable blastoid transformation of lymphocytes occurred (maximum L.I. for lymphoid cells ˜20 per cent on day 7). In parallel with this blastoid response, a substantial macrophage proliferation took place (L.I. ˜8 per cent). Large numbers of activated macrophages also appeared during this period. DNA synthesizing cells were found even among the most highly activated macrophages. The results indicated that the early and the late macrophage proliferations were stimulated by different mechanisms.
INFLUENCE OF HYDROCORTISONE ON UPTAKE AND ELIMINATION OF32P‐LABELLEDE. COLIBY RAT POLYMORPHONUCLEAR NEUTROPHILS (PMN)IN VITRO
Authors: BAARDSEN A.
Published: August 2010

Hydrocortisone was tested for inhibition of uptake and of elimination ofE. coliby monolayers of rat peritoneal PMN.32P was used as label of the bacteria and their degradation products eliminated from the phagocytes. The cellular uptake was reduced by hydrocortisone (1‐2 mg per ml) both in the presence and absence of serum, while the elimination of bacterial label was reduced by 0.5 mg per ml and higher concentrations of the drug.
THE IMPACT OF HLA‐A, B OR HLA‐D IDENTITY ON THE MIF PRODUCTION IN MLC
Authors: STENBJERG STENER , MYGIND KIRSTEN , JØRGENSEN FRITZ
Published: August 2010

The relative influence on MIF release in MLC of different parts of the HLA region was studied in 1) MLCs between cells from HLA‐A and B identical (probably HLA‐D unidentical) unrelated persons and 2) MLCs between cells from HLA‐D identical, HLA‐A and B unidentical unrelated persons. It was found that the HLA‐D part of the region has the major effect on the MIF production. Studies of MIF activity in supernatants from mitomycin treated cultures lent some evidence to the hypothesis that there is an extreme linkage disequilibrium between the HLA‐D alleles and hypothetical separate MIF alleles. Examination of families with crossover between the HLA‐A, B and HLA‐D part of the region is required for confirmation of these findings.
RESTITUTION OF STREPTOZOTOCIN INDUCED DIABETES MELLITUS IN NUDE MICE WITH PANCREATIC GRAFTS FROM THE RAT
Authors: BUSCHARD KARSTEN , RYGAARD JORGEN
Published: August 2010

Transplants of 1‐3 rat pancreases have proven to restitute streptozotocin induced diabetes in athymic nude mice. One out of 9 diabetic nude mice showed restitution following subcutaneous implantation of 1 rat pancreas. Three out of 6 nude mice were restituted by 2‐3 grafts. Implants of rat submandibular gland did not restitute nude mice similarly treated with streptozotocin. The model seems of interest in studies of inter‐species transplantation of pancreas.
A LEUCOCYTE MIGRATION STUDY ON THE CELL‐MEDIATED IMMUNITY AGAINST ADULT HUMAN ORAL MUCOSA AND STREPTOCOCCAL ANTIGENS IN PATIENTS WITH RECURRENT APHTHOUS STOMATITIS
Authors: Donatsky O.
Published: August 2010

In vitro demonstration of cell‐mediated immunity (CMI) against adult human oral mucosa antigen (AHOM) and streptococcal antigens was accomplished by means of the leucocyte migration test (LMT) in patients with recurrent aphthous stomatitis (RAS). If antigenic extracts of AHOM, Streptococcus sanguis strain 2A or Streptococcus pyogenes strain M5 were used in the LMT experiments, the distribution of migration indices (MI) over patients with RAS differed significantly from the distribution over the controls. In patients with other oral lesions, these MI‐distributions did not differ significantly from those among the controls. Extracts of other tissues such as kidney and uterus tissues or of other bacterial antigens such as Brucella abortus and Escherichia coli did not reveal any significant differences between the LMT responses in RAS and controls. The present findings show that CMI against AHOM antigen and streptococcal antigens are features characteristic of RAS. Furthermore, the results indicate that common antigenic determinants might be shared by AHOM and streptococci.
STUDIES ON THE TREPONEMA PALLIDUM IMMOBILIZING ACTIVITY IN NORMAL HUMAN SERUM
Authors: HEDERSTEDT BENGT
Published: August 2010

It was shown that T. pallidum immobilized in vitro by normal serum had lost its infectivity in rabbits. This finding suggested that the immobilizing activity of normal serum might play a role in the natural resistance of man against infections with T. pallidum. However, the results of serological studies of acquired early syphilis in man and of experimental syphilis in cynomolgus monkeys did not present evidence that the immobilizing activity of normal serum protected against syphilis infection.
STUDIES ON THE TREPONEMA PALLIDUM IMMOBILIZING ACTIVITY IN NORMAL HUMAN SERUM
Authors: HEDERSTEDT BENGT
Published: August 2010

The immobilizing IgM antibody of normal serum and the IgG antibody of syphilis serum reacted with different antigens of T. pallidum. The normal serum antibody to T. pallidum cross‐reacted with antigens of various mammalian tissues.
THE INABILITY OF A DIABETOGENIC VIRUS TO INDUCE DIABETES MELLITUS IN ATHYMIC (NUDE) MICE
Authors: BUSCHARD KARSTEN , RYGAARD JØRGEN , LUND EBBA
Published: August 2010

The effect of a known diabetogenic M‐strain encephalomyocarditis(EMC)‐virus in athymic nude mice (lacking the thymus‐dependent lymphocyte system), and in heterozygous littermates and homozygous normal mice of the background strain (C57/B16) was investigated. While by 3 weeks 4 out of 4 surviving virus‐inoculated littermates and 9 out of 9 inoculated normal mice developed diabetes mellitus, none of the 7 surviving virus‐inoculated nude mice became diabetic. Virus was isolated from all inoculated animals, including non‐diabetic nude mice. It is concluded that it is the response of the thymus‐dependent lymphocyte system evoked by the virus rather than the virus itself that leads to damage to the insulin producing cell.