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In our own study, hemolytic I E. coli i were isolated more frequently from patients with IBD, 7 of 15, compared with healthy controls, 1 of 9; this difference did, however, not reach statistical significance (p = 0.18), Paper V. The clonal nature of I E. coli i isolated from IBD patients contradicts the possible assumption that IBD through an impaired immune system allows an overgrowth of I E. coli i at random. This indicates that a patient with IBD with a concomitant I Salmonella i , I Campylobacter i or I C. difficile i infection probably has a higher risk of a positive stool sample simply because of more frequent submission of stool samples from IBD patients compared to patients with acute gastroenteritis alone [16]. Increased levels of antibodies towards I E. coli i antigens in IBD patients, Paper VII, supports a more direct interaction of I E. coli i with the immune system in IBD patients, even though IBD medications will also influence the serologic response, Paper VIII. Increased levels of antibodies towards I E. coli i antigens in IBD patients further support a more direct interaction of I E. coli i with the immune system in IBD patients, Paper VII, even though IBD medications will also influence the serologic response, Paper VIII. Recently, through metagenomics in a pediatric population comparing IBD patients with their healthy siblings, a strong correlation to IBD has been found with the abundance of bacterial virulence genes, enriched specifically in the UC microbiome with I E. coli i abundance, suggesting that I E. coli i is a central driver in UC pathogenesis [113]. [Extracted from the article]

Viral cardiac diseases have a significant impact on global health, and RNA viruses play a crucial role in their pathogenesis. This literature review aims to provide a comprehensive understanding of the complex relationship between RNA viruses and cardiac diseases, focusing on the molecular processes and clinical implications of these interactions. The paper begins by discussing the various RNA viruses that have been linked to cardiac infections. Subsequently, the study explores the mechanisms through which RNA viruses can cause cardiac injury, including direct viral invasion, immune‐mediated responses, and molecular mimicry. The review extensively examines the intricate interplay between the host immune system and RNA viruses, shedding light on both protective and harmful immune responses. Additionally, it investigates the role of viral persistence and chronic inflammation in the long‐term effects on cardiac health. The thorough analysis presented not only enhances our scientific understanding of how RNA viruses contribute to the development of cardiac diseases but also highlights potential avenues for future research and breakthroughs in this field. Given the significant global health threat posed by viral cardiac disorders, unraveling the molecular foundations of these diseases is essential for advancing diagnostic capabilities and therapeutic interventions. [ABSTRACT FROM AUTHOR]

The first WHO classification for central nervous system tumours was published in 1979, where several morphological subtypes of meningioma were defined.41 In short, the classification of meningiomas did not change substantially from 2000 to 2016 besides the sedimentation of brain invasion as a stand-alone criterion for WHO grade 2 meningiomas in 2016.42 According to the 2016 classification, nine histological subtypes constitute a WHO grade 1 meningioma, three constitute a WHO grade 2 meningioma (atypical, chordoid and clear cell meningioma) and three constitute a WHO grade 3 meningioma (anaplastic, papillary and rhabdoid). Taken together, our studies on WHO grade 3 meningiomas show that the disease is very different from benign meningioma: the WHO grade 3 meningioma will likely be the cause of death, and in most patients, the disease course is long-stretched with repeated surgeries and worsening performance status. In analysis #3, we hypothesized that the gene expression in WHO grade 3 meningiomas from patients with a primary meningioma would differ from the gene expression from patients with a secondary malignant meningioma. Analysis 3: WHO grade 3 meningiomas from patients with primary malignant meningioma ( I n i = 27) were compared to grade 3 meningiomas from patients with secondary malignant meningioma ( I n i = 24). Analysis #2: WHO grade 1 meningiomas from controls ( I n i = 51) were compared to WHO grade 1 meningiomas from patients with later grade 3 meningioma recurrence ( I n i = 9). [Extracted from the article]

This paper gives an account of the history of veterinary bacteriology including clinical veterinary bacteriology as well as the area of veterinary public health in Denmark from the 1880s to 2022. We describe key persons, including B. Bang, C.O. Jensen, K.A. Jensen and others who made important contributions to the development of these areas of microbiological expertise, and we discuss how challenges ranging from bovine tuberculosis to bacterial antimicrobial resistance have been met. Further, we describe progress in research on important bacterial pathogens both with regard to animal clinical aspects and zoonotic food‐related aspects. Finally, we describe current issues in relation to One Health and research organization. [ABSTRACT FROM AUTHOR]

The Swedish scientist Örjan Ouchterlony published four ground‐breaking papers 1948–1966 in Acta Pathol Microbiol Scand where he described a new method of antigen–antibody reactions in gel. He described and defined the ‘reaction of identity’ and ‘reaction of partial identity’ when he used related antigens and ‘reaction of non‐identity’ when he used non‐related antigens. His results inspired scientists in other countries to further develop and modify the ‘Ouchterlony method’ which became useful for both scientific and clinical purposes. This survey describes how the methods were discovered and how they became modified and improved and how they were used, but also underlines that the original Ouchterlony method is still used. [ABSTRACT FROM AUTHOR]

Surgeons, who documented what they had seen and felt in the abdomen of the patient, made the earliest descriptions of Crohn's disease (CD). Dalziel wrote the first pathology description in 1913. Crohn and his coworkers reinvented what Dalziel had written about and called it by a different name, 'regional enteritis'. Later others elaborated on the histologic features, at first the lymphoid follicles, later the granulomas. Some thought the latter were comprised of lymphatic endothelial cells and that endothelial plugs obstructed the lymphatics. Tonelli and others recognized that lymphedema was important and caused by obstructions to lymphatic vasculature. Some lymphatics they described contained lymphocyte plugs and others granulomas. Immunohistochemistry (IHC) has now shown that endothelial cells are not the cause of lymphatic obstruction, but rather CD68‐positive macrophages, concluding that the 'lymphocyte thrombi' are passive, caught upstream of granuloma‐obstructed lymphatics. Numerous authors recognized that transmural edema was the most significant change in Crohn's disease and that this was later followed by fibrosis and contracture of the diseased segment. Key descriptive papers spoke of the segmental lymphedema. Most recently, attention has been given to attachments of the intralymphatic CD68+ granulomas to a focal point where endothelial damage occurred, damage suggesting infectious penetration of the mucosa, necrosis of lymphatic endothelium and then granulomatous response, both inside and outside the lymphatics, of submucosa, muscularis, and subserosa. D2‐40 IHC outlines the endothelium, and anti‐CD68 shows the granulomas. IHC adds a valuable perspective when reviewing CD resections. [ABSTRACT FROM AUTHOR]

As one of the malignant tumors with high incidence rate and high mortality, lung cancer seriously threatens the life safety of patients. Research shows that microorganisms are closely related to lung cancer. The microbiome is symbiotic with the host and plays a vital role in the functions of the human body. Microbiota dysbiosis is correlated with development of lung cancer. However, the underlying mechanisms are poorly understood. This paper summarizes the composition characteristics of the gut-lung axis microbiome and intratumoral microbiome in patients with lung cancer. We then expound five potential carcinogenic mechanisms based on microorganisms, such as genotoxicity, metabolism, inflammation, immune response, and angiogenesis. Next, we list three high-throughput sequencing methods, and finally looks forward to the prospect of microorganisms as novel targets for early diagnosis and treatment of lung cancer. [ABSTRACT FROM AUTHOR]

This study is an attempt to shed light on why the connective tissue mast cell (MC) is preserved in all species with a blood circulatory system, i.e., the vertebrates since >500 million years, which suggests that the MC performs as yet not understood indispensible life‐promoting actions. The literature survey focuses on data in published papers on MC functions in immunological and nonimmunological reactions, host protection, pregnancy, inflammation, and wound healing. All data are thus accessible to the reader. The MC is a secretory cell with a unique mediator profile. A distinctive role for MCs is defined not only by their extensive mediator composition but also by their prominent ability to affect the vasculature to expedite selective cell recruitment and permeability changes and to set the stage for an appropriate acquired response. MCs, harboring a wide range of surface membrane receptors, are activated by the major female sex hormones as well as by diverse potentially adverse stimuli. MC activation/degranulation creates a presumably unique triad tissue response in physiological and pathological situations alike: extracellular matrix degradation and tissue remodeling, de novo cell proliferation, and de novo angiogenesis. As shown in the literature, MC‐activation is crucial for successful female reproduction in the mouse, implying one of possibly several yet unidentified physiological roles of MCs. Moreover, the activated MC aids newborns to survive to reproductive age owing to its key beneficial actions in inflammation and wound healing. Thus, a not previously described life‐perpetuating loop spanning generations are apparently formed, which, hypothetically, could contribute to the continued survival of the vertebrates. [ABSTRACT FROM AUTHOR]

Our histological and hormonal findings suggest that cryptorchidism may be more than a simple anomaly of testicular position as cryptorchidism may be associated with an endocrinopathy (as a possible subtle hypofunction of the hypothalamic-pituitary-gonadal axis) that may contribute to impairment of testicular development in both testes, even when one testis descend to the scrotum. A more recent study, including 319 boys treated for unilateral cryptorchidism with simultaneous biopsy of the contralateral scrotal testis, found that 48% of the cryptorchid testes and 21% of contralateral testis had no Ad spermatogonia [237]. Twenty-tree boys with congenital cryptorchidism having at least one non-palpable testis had a significantly higher frequency of reduced G/T and AdS/T than those with palpable testes (ascending testes and congenital palpable). However, comparison data from the general population also include men with a history of cryptorchidism, and as 2.5% of boys in the western world undergo surgery for cryptorchidism and about 5% exhibit cryptorchidism in at least some years, findings similar to the general population does not exclude the impact of cryptorchidism on azoospermia. CRYPTORCHIDISM Cryptorchidism, "undescended testis", "retentio testis", and "maldescended testis" are terms synonymously used to define incomplete descensus of the testis from an intraabdominal position into the scrotal sac [1]. [Extracted from the article]

The Swedish COVID‐19 response has received excessive attention, despite not having distinctively different goals or features than other countries. The overall response has included almost all sectors of society and cannot be described here. Instead, this paper provides a general, brief description of the response from a public health perspective, but hopefully it gives a somewhat more nuanced picture of the efforts to combat COVID‐19 in Sweden. [ABSTRACT FROM AUTHOR]

Cholera, a devastating diarrheal disease that caused several global pandemics in the last centuries, may share some similarities with the new COVID‐19. Cholera has affected many populations in history and still remains a significant burden in developing countries. The main transmission route was thought to be predominantly through contaminated drinking water. However, revisiting the historical data collected during the Copenhagen 1853 cholera outbreak allowed us to re‐evaluate the role of drinking‐water transmission in a city‐wide outbreak and reconsider some critical transmission routes, which have been neglected since the time of John Snow. Recent empirical and cohort data from Bangladesh also strengthened the dynamic potentiality of other transmission routes (food, fomite, fish, flies) for transmitting cholera. Analyzing this particular nature of the cholera disease transmission, this paper will describe how the pattern of transmission routes are similar to COVID‐19 and how the method of revisiting old data can be used for further exploration of new and known diseases. [ABSTRACT FROM AUTHOR]

Until recently, diagnostics of brain tumors were almost solely based on morphology and immunohistochemical stainings for relatively unspecific lineage markers. Although certain molecular markers have been known for longer than a decade (combined loss of chromosome 1p and 19q in oligodendrogliomas), molecular biomarkers were not included in the WHO scheme until 2016. Now, the classification of diffuse gliomas rests on an integration of morphology and molecular results. Also, for many other central nervous system tumor entities, specific diagnostic, prognostic and predictive biomarkers have been detected and continue to emerge. Previously, we considered brain tumors with similar histology to represent a single disease entity. We now realize that histologically identical tumors might show alterations in different molecular pathways, and often represent separate diseases with different natural history and response to treatment. Hence, knowledge about specific biomarkers is of great importance for individualized treatment and follow‐up. In this paper we review the biomarkers that we currently use in the diagnostic work‐up of brain tumors. [ABSTRACT FROM AUTHOR]

This study describes a case of primary myoepithelial carcinoma of the skin and reviews the available literature on this topic. Myoepitheliomas and carcinomas arise most frequently from myoepithelial cells within the salivary glands but are found in many anatomical locations. We documented a case of an 80-year-old man with a 2 × 2 × 1 cm tumour located on the scalp. This tumour emerged over a period of 2 months. The tumour was radically excised, and histological examination revealed a cutaneous myoepithelial carcinoma. At an 18-month follow-up, no recurrence of the tumour was found. A systematic literature search identified 23 papers that reported 58 cases of cutaneous myoepitheliomas and myoepithelial carcinomas. All cases are reviewed in the presented paper. This case report and literature review serves to increase awareness regarding myoepithelial carcinomas. These tumours exhibit high metastatic potential, and it is thus very important to perform radical surgery. [ABSTRACT FROM AUTHOR]

Chemokines are cytokines that are involved in the movement of leukocytes and the occurrence of immune responses. It has recently been noted that these cytokines play a role in the movement of cancer cells to different parts of the body and create a suitable environment [i.e. (pre) metastatic niche] for their growth and proliferation. We studied the role of chemokines in the metastasis of cancer cells, as well as their involvement in the proliferation and growth of these cells. Relevant literature was identified by a PubMed search (2005–2017) of English language papers using the terms ‘chemokine,’ ‘metastasis niche,’ and ‘organotropism.’ Based on the nature of cancer cells, the expression of chemokine receptors on these cells leads to metastasis to various organs, which ultimately causes changes in different signaling pathways. Finally, the targeting of chemokines on cancer cells could prevent the metastasis of cancer cells toward different organs. [ABSTRACT FROM AUTHOR]

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000–2017) of English‐language literature using the terms ‘oxidative stress,’ ‘reactive oxygen species,’ ‘hematopoietic stem cell,’ and ‘leukemia.’ The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long‐term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject. [ABSTRACT FROM AUTHOR]

Aim of the current study was to evaluate the inter‐observer agreement between pathologists in the diagnosis of celiac disease (CD), in the qualified context of a multicenter study. Biopsies from the “PreventCD” study, a multinational‐ prospective‐ randomized study in children with at least one‐first‐degree relative with CD and positive for HLA‐DQ2/HLA‐DQ8. Ninety‐eight biopsies were evaluated. Considering diagnostic samples with villous atrophy (VA), the agreement was satisfactory (κ = 0.84), but much less when assessing the severity of these lesions. The use of the recently proposed Corazza‐Villanacci classification showed a moderately higher level of agreement (κ = 0.39) than using the Marsh‐Oberhuber system (κ = 0.31). 57.1% of cases were considered correctly oriented. A number of >4 samples per patient was statistically associated to a better agreement; orientation did not impact on κ values. Agreement results in this study appear more satisfactory than in previous papers and this is justified by the involvement of centers with experience in CD diagnosis and by the well‐controlled setting. Despite this, the reproducibility was far from optimal with a poor agreement in grading the severity of VA. Our results stress the need of a minimum of four samples to be assessed by the pathologist. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs), and similar environmental contaminants, have been linked to virus outbreaks and increased viral induced mortality since the 1970s. Yet the mechanisms behind this increased susceptibility remain elusive. It has recently been illustrated that the innate immune viral detection system is tightly regulated by small non‐coding RNAs, including microRNAs (miRNAs). For virus infections miRNA‐155 expression is an important host response against infection, and deregulation of this miRNA is closely associated with adverse outcomes. Thus, we designed a targeted in vitro study using primary chicken fibroblasts, first exposed to a mixture of PCBs (Arochlor‐1250) before being stimulated with a synthetic RNA virus (poly I:C), to determine if PCBs have the potential to deregulate miRNA‐155. In this paper, we provide the first data for the deregulation of miRNA‐155 when a host is exposed to a mixture of PCBs before a virus infection. Thus, we provide important evidence that PCBs can be involved in the deregulation of important miRNA pathways involved in the immune system; thereby demonstrating novel insights into the mechanism of PCB toxicity on the immune system. [ABSTRACT FROM AUTHOR]

Primary extratesticular seminomas exceptionally occur in the epididymis or in the paratesticular region/spermatic cord. Some old papers included poor histological description or insufficient photographic documentation, reducing the number of faithful cases: an up‐to‐date systematic review is lacking. We report the 4th primary seminoma of the paratesticular region/spermatic cord in a 35‐year‐old man, including the first echographic description. We provide review of the literature and etiopathogenetic discussion. Ultrasound examination showed a right paratesticular, solid, heterogeneous mass (iso‐hypoechoic with hyperechoic striae; peri‐ and intra‐lesional vascular signals) with no testicular involvement: the paratesticular origin was confirmed by pathological examination. Despite careful gross examination and extensive sampling, the 6.5‐cm extratesticular tumor revealed only one microscopic focus with minimal invasion (<2 mm) of the atrophic testicular parenchyma. Intratubular germ cell neoplasia or morphologic features of a regressed testicular tumor (fibrosis/scar, necrosis, hyalinization, calcification, inflammation) were not found. Primary seminomas of the paratesticular region/spermatic cord occurred at an older mean age and presented as bigger lesions if compared to the 9 primary epididymal seminomas reported in literature. Clinical‐pathological correlation and accurate sampling are mandatory for a correct diagnosis. [ABSTRACT FROM AUTHOR]

This paper gives an update on the local distributions of HCV genotypes in Aydin province of Turkey, provides a comparison with the previous records, and discusses the potential causal reasons shaping the evolving genotype profiles. Patient files from 2011 to 2016 were retrospectively analyzed, and newly detected cases were documented. Out of 286 patients, male and female ratios were determined to remain nearly the same (~50%). Genotype 1 was still the most common (90.2%), followed by genotype 3 (5.9%), genotype 2 (2.1%), and genotype 4 (1.4%) in frequency. There were international patients (4.50%). One patient had genotyped 2+3 together. Genotypes 4 and 2+3 were detected for the first time, and the patients with genotype 4 were interestingly all male and also domestic individuals. However, these patients traveled or lived abroad in the past due to occupational reasons, thereby likely acquired the infection while abroad. HCV surveillance system is currently inadequate and some infected patients may go undetected in the province. Remapping the regional distribution of HCV genotypes from time‐to‐time is required for identifying the local dynamics and causes leading to it. This process enhances the clinical preparation and readiness for the better management of the disease. [ABSTRACT FROM AUTHOR]

Immune Thrombocytopenic Purpura ( ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/ GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins ( PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients. [ABSTRACT FROM AUTHOR]

Bacterial resistance is a growing phenomenon which led the scientific community to search for new therapeutic targets, such as biofilm. A bacterial biofilm is a surface-associated agglomerate of microorganisms embedded in a self-produced extracellular polymeric matrix made of polysaccharides, nucleic acids, and proteins. Scientific literature offers several reports on a biofilm's role in infections regarding various body districts. The presence of a bacterial biofilm is responsible for poor efficacy of antibiotic therapies along with bacterial infections in ear, nose, and throat ( ENT) districts such as the oral cavity, ear, nasal cavities, and nasal sinuses. In particular, bacterial biofilms are associated with recalcitrant and symptomatically more severe forms of chronic rhinosinusitis. As of today, there are no therapeutic options for the eradication of bacterial biofilm in ENT districts. Hyaluronic acid is a glycosaminoglycan composed of glucuronic acid and N-acetylglucosamine disaccharide units. Its efficacy in treating rhinosinusitis, whether or not associated with polyposis, is well documented, as well as results from its effects on mucociliary clearance, free radical production and mucosal repair. This review's aim is to evaluate the role of bacterial biofilms and the action exerted on it by hyaluronic acid in ENT pathology, with particular attention to the rhinosinusal district. In conclusion, this paper underlines how the efficacy of hyaluronate as an anti-bacterial biofilm agent is well demonstrated by in vitro studies; it is, however, only preliminarily demonstrated by clinical studies. [ABSTRACT FROM AUTHOR]

The article provides information on history and current knowledge of pathological factors and virulence of several strains of bacteria Escherichia coli. Topics discussed include increased resistance towards antimicrobials with virulence gene, shigatoxin produced by E. coli O117:K1:H7 strain, and urinary tract infection.

Chronic lymphocytic leukemia ( CLL) is the most common leukemia in adults. Its clinical course is typically indolent; however, based on a series of pathobiological, clinical, genetic, and phenotypic parameters, patient survival varies from less than 5 to more than 20 years. In this paper, we show for the first time that the expression of the interferon-inducible DNA sensor IFI16, a member of the PYHIN protein family involved in proliferation inhibition and apoptosis regulation, is associated with the clinical outcome in CLL. We studied 99 CLLs cases by immunohistochemistry and 10 CLLs cases by gene expression profiling. We found quite variable degrees of IFI16 expression among CLLs cases. Noteworthy, we observed that a reduced IFI16 expression was associated with a very poor survival, but only in cases with ZAP70/ CD38 expression. Furthermore, we found that IFI16 expression was associated with a specific gene expression signature. As IFI16 can be easily detected by immunohistochemistry or flow cytometry, it may become a part of phenotypic screening in CLL patients if its prognostic role is confirmed in independent series. [ABSTRACT FROM AUTHOR]

Presents an overview of articles featured in the 2003 special issue of "APMIS," on dendritic cells (DC). Papers on the aspects of dendritic cell biology; Role of DC in the balance between T-cell immunity and tolerance; Functions and activities of DC.

In this paper, an antimycobacterial component of extracellular metabolites of a gut bacterium Raoultella ornithinolytica from D. veneta earthworms was isolated and its antimycobacterial action was tested using Mycobacterium smegmatis. After incubation with the complex obtained, formation of pores and furrows in cell walls was observed using microscopic techniques. The cells lost their shape, stuck together and formed clusters. Surface-enhanced Raman spectroscopy analysis showed that, after incubation, the complex was attached to the cell walls of the Mycobacterium. Analyses of the component performed with Fourier transform infrared spectroscopy demonstrated high similarity to a bacteriocin nisin, but energy dispersive X-ray spectroscopy analysis revealed differences in the elemental composition of this antimicrobial peptide. The component with antimycobacterial activity was identified using mass spectrometry techniques as a glycolipid-peptide complex. As it exhibits no cytotoxicity on normal human fibroblasts, the glycolipid-peptide complex appears to be a promising compound for investigations of its activity against pathogenic mycobacteria. [ABSTRACT FROM AUTHOR]

In this paper, we have focused on the metastatic behavior of EGC and its particularities. The main factors that are currently considered as predictors of the metastatic behavior and that are used in the therapeutic decision (endoscopic resection vs surgical removal) are the tumor size (upper or bellow 2 cm), depth of infiltration, angiolymphatic invasion, the presence or absence of ulceration, and histologic type (undifferentiated vs differentiated carcinomas). However, most of the metastatic cases were published as case reports or case series. This is the reason why a proper estimation of metastatic risk in EGC is not well known. To date, 79 cases presenting bone metastases, three reports of brain metastases, and one EGC that was associated with skin metastasis were published. However, occult metastasis, lymph node micrometastasis, and skip metastasis can also occur and should be identified. Making a synthesis of the literature data that is correlated with our experience, we finally proposed the inclusion of the six Japanese subgrouping system, tumor size, angiolymphatic invasion, and micrometastasis as components of the pTNM staging system, which should be particularly adapted for EGC. [ABSTRACT FROM AUTHOR]

The shift from illness to disease has had a profound impact on modern medicine - particularly in the realm of cancer screening. In screening, it is not patients with illness who seek help from the healthcare system; it is asymptomatic healthy individuals who are invited into the healthcare system to be examined for pathology. The underlying assumption of screening is that abnormalities and pathology always progress. If this were true, it would always make sense to look for disease even when people feel well. The million (or more accurately multi-billion) dollar question is whether the fundamental assumption that disease invariably leads to illness is valid. This is the question that the present paper will try to explore and answer. [ABSTRACT FROM AUTHOR]

Archaea are non-bacterial prokaryotes associated with oral microbiota in humans, but their roles in oral pathologies remain controversial. Several studies reported the molecular detection of methanogenic archaea from periodontitis, but the significance of this association has not been confirmed yet. An electronic search was therefore conducted in MEDLINE-Pubmed to identify all papers published in English connecting archaea and periodontal infections. Data analysis of the selected studies showed that five genera of methanogenic archaea have been detected in the subgingival microbiota, Methanobrevibacter oralis being the most frequently detected species in 41% of periodontitis patients and 55% of periodontal pockets compared to 6% of healthy subjects and 5% of periodontally-healthy sites (p < 10−5, Chi-squared test). Based on the five determination-criteria proposed by Socransky (association with disease, elimination of the organism, host response, animal pathogenicity and mechanisms of pathogenicity), M. oralis is a periodontal pathogen. The methanogenic archaea load correlating with periodontitis severity further supports the pathogenic role of methanogenic archaea in periodontitis. Therefore, detection and quantification of M. oralis in periodontal pockets could help the laboratory diagnosis and follow-up of periodontitis. Determining the origin, diversity and pathogenesis of archaea in periodontal infections warrants further investigations. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one by Carlssons Bokförlag on the introduction of bacteriology into Swedish medicine and another by Bodil Persson on the men and women.

The involvement of the vascular system in malignancy encompasses not only angiogenesis, but also systemic hypercoagulability and a pro-thrombotic state, and there is increasing evidence that pathways of blood coagulation and angiogenesis are reciprocally linked. In fact, cancer atients often display hypercoagulability resulting in markedly increased thromboembolism, which requires anti-coagulant treatment using heparins, for example. Clinical trials reveal that treatment with various low-molecular-weight heparins (LMWHs) improves the survival time in cancer patients receiving chemotherapy compared with those receiving unfractionated standard heparin (UFH) or no heparin treatment, as well as in cancer patients receiving LMWH as thrombosis prophylaxis during primary surgery. This anti-tumor effect of the heparins appears to be unrelated to their anti-coagulant activity, but the mechanisms involved are not fully understood. Tumor growth and spread are dependent on angiogenesis and it is noteworthy that the most potent endogenous pro- and anti-angiogenic factors are heparin-binding proteins that may be affected by systemic treatment with heparins. Heparin and other glycosaminoglycans play a role in vascular endothelial cell function, as they are able to modulate the activities of angiogenic growth factors by facilitating the interaction with their receptor and promoting receptor activation. To date, preclinical studies have demonstrated that only LMWH fragments produced by the heparinase digestion of UFH , i.e. tinzaparin, exert anti-angiogenic effects in any type of tissue in vivo. These effects are fragment-mass-specific and angiogenesis-type-specific. Data on the effect of various LMWHs and UFH on endothelial cell capillary tube formation and proliferation in vitro are also presented. We hope that this paper will stimulate and facilitate future research designed to elucidate whether the anti-angiogenic or anti-tumor effects of commercial LMWHs in their own right are agent specific and whether anti-angiogenic properties increase the anti-tumor properties of the LMWHs in the clinic. [ABSTRACT FROM AUTHOR]

Lukinmaa S, Nakari UM, Eklund M, Siitonen A. Application of molecular genetic methods in diagnostics and epidemiology of food-borne bacterial pathogens. 2004:112;908–29.Salmonella enterica,CampylobacterandYersiniaspecies, Shiga toxin-producingEscherichia coli(STEC),Listeria monocytogenesandClostridium perfringensare the bacterial pathogens constituting the greatest burden of food-borne disease in Finland. Several molecular genetic methods have been applied to diagnose, discriminate and survey these bacteria. PCR, PCR-RFLP and PFGE are the most widely and successfully used. However, these methods are unable to replace conventional and internationally standardised phenotyping. Electronic database libraries of the different genomic profiles will enable continuous surveillance of infections and detection of possible infection clusters at an early stage. Furthermore, whole-genome sequence data have opened up new insights into epidemiological surveillance. Laboratory-based surveillance performed in a timely manner and exploiting adequate methods, and co-operation at local, national and international levels are among the key elements in preventing food-borne diseases. This paper reviews different applications of molecular genetic methods for investigating enteric bacterial pathogens and gives examples of the methods successfully used in diagnostics and epidemiological studies in Finland. [ABSTRACT FROM AUTHOR]

Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular, the role of DCs in the generation of regulatory T cells is highlighted. [ABSTRACT FROM AUTHOR]

During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity and in selected patients to tumor regression. However, the majority of clinical trials are still in phase I, and interpretations are hampered by pronounced variation in study design related to technical aspects of DC preparation, treatment and schedule, monitoring of immune response, and clinically relevant endpoints, including toxicity and response evaluation. This paper aims to review the technical aspects and clinical impact of vaccination trials, focusing on the generation of DC-based vaccines, evaluation of immunologic parameters and design of clinical trials necessary to meet the need for good laboratory and clinical practice. [ABSTRACT FROM AUTHOR]

Human tissue kallikreins are fifteen homologous genes encoding for secreted serine proteases and residing tandemly on chromosome 19q13.4. These enzymes are highly expressed in a variety of tissues and participate in diverse physiological processes. Human tissue kallikreins were found to be associated with several malignancies, especially endocrine-related cancers, including prostate, ovarian, breast and testicular cancer. In testicular germ cell tumors, some tissue kallikrein genes, including KLK5, KLK10, KLK13 and KLK14, were found to be significantly down-regulated. Tissue-specific splice variant forms of some kallikreins have been identified in the testis. In this paper, the expression of KLK5, KLK10, KLK13 and KLK14 in testicular cancer and their possible roles during testicular cancer development, as well as their clinical applications are briefly reviewed. [ABSTRACT FROM AUTHOR]

Human germ cell tumours (GCTs) constitute a heterogeneous group of tumours that can be classified into four major subgroups. One of these subgroups encompasses (immature) teratomas and yolk sac tumours of patients under the age of 5 years. In this paper we review the various clinical, histological and cytogenetical aspects of these infantile GCTs. The primordial germ cell (PGC) has been suggested to be the cell of origin for GCTs. Infantile GCTs, however, have been suggested to originate from PGCs at a different stage of maturation than adult GCTs. The cytogenetic constitution of infantile GCTs also appears to differ from the adult GCTs and includes recurrent losses of 1p and 6q. Recently, two cases of infantile GCT were detected with constitutional 12q13 translocations. These exceptional cases may be instrumental in the search for candidate genes related to infantile and/or adult GCT development. [ABSTRACT FROM AUTHOR]