Infiltration Of Mononuclear Inflammatory Cells Research Articles

Ischemia-induced angiogenesis: role of inflammatory response mediated by P-selectin

P-selectin is a 140-kDa glycoprotein expressed on endothelial cells and platelets. P-selectin mediates the tethering and rolling of leukocytes along the endothelium, an early step of leukocyte extravasation. Although inflammation is a requisite process for ischemia-induced angiogenesis, little is known regarding the role of P-selectin in angiogenesis in the setting of tissue ischemia. We examined whether ischemia-induced angiogenesis is altered in P-selectin knockout (P-selectin(-/-)) mice. Angiogenesis was evaluated in a surgically induced hind-limb ischemia model using laser Doppler blood flowmetry (LDBF) and histological capillary density (CD). After left hind-limb ischemia, the ischemic/normal limb LDBF ratio was persistently lower in P-selectin(-/-) mice compared with wild-type (WT) mice. CD was also significantly lower in P-selectin(-/-) mice than in WT mice on Postoperative Day 14. Fewer numbers of total CD45+ inflammatory leukocytes infiltrated into the ischemic tissues in P-selectin(-/-) mice than in WT mice, and immunohistochemical analysis revealed the number of infiltrated leukocytes expressing vascular endothelial growth factor was also decreased in P-selectin(-/-) mice. P-selectin mRNA expression was augmented after hind-limb ischemia in WT mice. In conclusion, P-selectin may play an important role in ischemia-induced angiogenesis by promoting early inflammatory mononuclear cell infiltration. P-selectin would become one possible target molecule for modulating inflammatory angiogenesis.

Post-transplantation nephrotic syndrome

CASE PRESENTATION A 60 year-old Caucasian female who developed chronic renal failure from focal segmental glomerulosclerosis (FSGS) received a living-related renal allograft from her 28year-old son. The patient presented initially at age 48 with signs of nephrotic syndrome (peripheral edema, hypoalbuminemia, and hypercholesterolemia) and a serum creatinine of 1.5 mg/dl (132mmol/l) (normal range 0.6–1.2 mg/dl (52.8–105.6mmol/l)). She was treated with prednisone for six months, followed by cyclosporine A, with only partial remission of proteinuria. Renal function slowly declined over the ensuing decade. At the time of initial presentation, serologic test results were negative or within normal limits for antinuclear antibody, C3 and C4 complement levels, hepatitis B surface antigen, hepatitis C antibody, and serum and urine protein electrophoreses. Her past medical history was significant for hypertension for 25 years, and hypothyroidism. She had no history of childhood urinary tract infections or urinary reflux and she denied regular intake of over-the-counter medications. The patient’s post-operative course was unremarkable and she was discharged seven days post-transplantation with a serum creatinine of 1 mg/dl. Immunosuppressive medications included FK506, mycophenolate mofetil, and prednisone. Four weeks post-transplant, the patient noted worsening lower extremity edema. A 24-hour urine collection contained 4.5 g protein (normal range 0–150 mg/day). Serum albumin was 3.6 g/dl (36 g/l) (normal range 3.5–5.0 g/dl (30–50 g/l)) and serum creatinine was 1.0 mg/ dl (88.4mmol). FK506 levels were within therapeutic range. A renal ultrasound showed no signs of urinary tract outflow obstruction and normal venous and arterial blood flow. A renal biopsy was performed. RENAL BIOPSY FINDINGS Twenty-four glomeruli were sampled for light microscopy, none of which showed segmental or global glomerulosclerosis (Figure 1). Peripheral capillary lumina were fully patent and glomerular basement membranes were uniformly normal in thickness, contour and texture. There was a minimal patchy interstitial mononuclear inflammatory cell infiltrate, involving o5% of the cortical area, with rare foci of mild tubulitis (o5 mononuclear inflammatory cells/ tubular cross-section). There was no significant tubular atrophy or interstitial fibrosis. Features of isometric tubular vacuolization or viral inclusions were not identified. Arterial vessels were unremarkable. Immunofluorescence microscopy showed no staining of peritubular capillaries for C4d and no glomerular staining for IgG, IgM, IgA, C3, C1, fibrinogen, albumin, kappa, or lambda. Electron microscopic examination of two glomeruli revealed diffuse (100%) podocyte foot process effacement and no other significant ultrastructural abnormalities (Figure 2).

In situ expression of T‐helper type 2 immunoregulatory response in myofibroblast of a pediatric bladder inflammatory pseudotumor

Inflammatory pseudotumor (IP) is generally considered to be a non-neoplastic, inflammatory response despite its gross and microscopic features of spindle cell neoplasm. Reported herein is a case arising from the muscularis propria of the urinary bladder in a 14-year-old girl who presented with gross hematuria and impending hypovolemic shock. The tumor consisted of proliferating myofibroblastic cells and various types of inflammatory cells. The immunoregulatory responses and reactions were investigated with regard to infiltration of inflammatory mononuclear cells being a documented finding in IP. Immunhistochemical and in situ hybridization studies for cytokines showed that the myofibroblastic cells were positive for interleukin (IL)-4, IL-5 and negative for interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha expression. The patient has been free of disease since excision of the tumor 34 months ago. Thus, cytokine production in IP suggests that it is reactive in nature and myofibroblasts may be the source of cytokines in the pathogenic process.

Analysis of the mononuclear inflammatory cell infiltrate in the cirrhotic, Dysplastic nodules and hepatocellular carcinomas in patients with chronic hepatitis C infection

Background: Hepatocarcinogenesis is a multistep process entailing the transitions from normal liver_ chronic hepatitis and cirrhotic nodules (CH/CNs) _ dysplastic nodules (DNs) _hepatocellular carcinomas (HCCs). We hypothesized that hepatocarcinogeneis on top of chronic hepatitis C (CH-C) is associated with alterations in the mononuclear inflammatory cell infiltrate (MICs) in response to altered antigenicity of the damaged hepatocytes. Materials and methods: A total of 19 hepatic resection specimens entailing the entire continuum of the lesional steps of the hepatocarcinogenesis (on top of CH-C) were evaluated for MICs using immunohistological methods and mouse monoclonal antibodies (CD3, CD20, CD68 and T-cell intracellular associated antigen, TIA-1). Results: HCCs were: 1) overrepresented in elderly males (56.1 ± 2.0 years, with male to female ratio of 1.8:1), and 2) more common in the right than in left lobe (1.1:1).The transitions from normal liver to the subsequent lesional steps (CH-C/CNs, DNs and HCCs) was associated with statistically significantly (p

Differential Regulation of Gastric Tumor Growth by Cytokines That Signal Exclusively Through the Coreceptor gp130

We have shown that mice with a mutation in gp130 (gp130(757F/F)), the signal transducing receptor for interleukin (IL)-6 family cytokines, have chronic gastric inflammation and develop distal stomach tumors associated with deregulated phosphorylated STAT3 expression. This model recapitulates many characteristics of intestinal-type gastric cancer in humans. To evaluate the role of IL-6 and IL-11 as ligands regulating tumor growth and submucosal invasion, we compared tumor characteristics of gp130(757F/F) mice with gp130(757F/F) mice lacking IL-6 or mature T and B cells. As a result of the gp130(757F/F) mutation, expression of IL-6 and IL-11 was greatly up-regulated concomitant with activation of STAT3 and development of tumors. However, the lack of IL-6 or T and B cells did not impact on tumor growth. While IL-6 did not regulate tumor growth or tumor vascularization, gp130(757F/F)/IL-6(-/-) mice showed approximately 10-20-fold more submucosal tumor invasion, reduced mononuclear inflammatory cell infiltrate, and greater IL-11 and matrix metalloproteinase (MMP)-13 and MMP-9 synthesis than gp130(757F/F) mice. Expression of MMP-13 was largely restricted to tumor-associated stroma, but MMP-9 was also expressed in polymorphonuclear cells and a subset of epithelial cells. In addition, treatment with recombinant IL-11 stimulated expression of MMP-13 and MMP-9 in stomachs of wild-type mice. Increased submucosal invasion in gp130(757F/F)/IL-6(-/-) mice could not be explained by increased vascularization or reduced immunosurveillance but was most likely facilitated by augmented metalloproteinase activity driven by elevated IL-11 levels.

Analysis of the mononuclear inflammatory cell infiltrate in the nontumorigenic, Pretumorigenic and tumorigenic keratinocytic hyperproliferative lesions of the skin

BACKGROUND: The keratinocytic hyperproliferative lesions include non-tumorigenic, pretumorigenic (actinic keratoses, AK), and tumorigenic (squamous cell carcinomas, SCC) conditions. Although mononuclear inflammatory cell infiltrate (MICs) is a constant feature in these lesions, their immunophenotypic characterization is still incomplete. We hypothesized that the development of non-tumorigenic, pretumorigenic, and tumorigenic keratinocytic hyperproliferative lesions is associated with alterations in the mononuclear inflammatory cell infiltrate in response to altered antigenicity of the lesional cells. This study tries to test this hypothesis and to characterize MICs in these lesions. METHODS: Fifty lesions (nontumorigenic lesions, 29; AK, 9 and SCC, 12) were examined using immunoperoxidase staining methods and antibodies targeting histiocytes (CD68), T (CD3), B cells (CD20), and T cells with cytotoxic potential (TIA-1). RESULTS: As compared to the normal skin, the development of the keratinocytic hyperproliferative lesions (normal skin; non-tumorigenic; AK and SCC) was associated with a statistically significant increase( p=

Pathology of End-stage Remodeling in a Family of Cats with Hypertrophic Cardiomyopathy

End-stage hypertrophic cardiomyopathy (ES-HCM), affecting 5-10% of human hypertrophic cardiomyopathy (HCM) patients, is characterized by relative thinning of the ventricular walls and septum with dilation of the ventricular lumen, decreased fractional shortening, and progression to heart failure. C. J. Baty and others recently documented similar progressive changes to ES-HCM in a family of four cats through serial echocardiograms. At the time of heart failure, these cats exhibited changes similar to those exhibited by human ES-HCM patients. Our objectives were to describe the pathologic alterations associated with ES-HCM and investigate the pathogenesis in three of the four cats. Grossly, there was left atrial dilation with relative thinning of the interventricular septum (IVS) and left ventricular free wall (LVFW). The left atrium contained large thrombi in two of the three cats, and all three cats died following thromboembolization of the aortic bifurcation. Histologically, all three cats had subendocardial and myocardial fibrosis, predominantly of the IVS and LVFW, and one cat had acute, multifocal, myocardial infarcts with mononuclear inflammatory cell infiltrates. The pathogenesis of ES-HCM is uncertain, but theories implicate occlusion of the coronary blood flow by thickening of the coronary vessels, coronary vascular thromboembolism or coronary vessel spasm, apoptosis of myocytes, and myocardial hypertrophy beyond the ability of the vasculature to supply blood. Apoptosis assays did not reveal any apoptotic myocytes. Considering the hypercoagulative state of these cats, coronary vascular thromboembolism could be a major contributing factor. We cannot exclude apoptosis or coronary vessel spasm on the basis of the data presented.

Synovitis in a murine model of human factor VIII deficiency

Recurrent joint bleeding is the most common musculoskeletal manifestation of haemophilia and leads to a target joint and synovitis. The pathobiology of haemophilic synovitis (HS) is not well understood. Here the histopathological changes that occur following haemarthrosis were examined in an animal model for human HS. After two haemarthrosis, there was soft tissue and joint swelling and histological changes of acute synovitis included infiltration of the sub-synovial layer by mononuclear cells and neutrophils, thickening of the synovial membrane with villus formation, and hyperplasia of blood vessels. Subacute changes were evident after three haemarthrosis; muscle atrophy was present and an intense mononuclear cell infiltrate filled the sub-synovial space. There was destruction of articular surfaces and loss of cartilage. Seventeen months after three haemarthrosis, chronic joint changes included gross deformity and loss of congruence due to dense fibrotic tissue filling the joint space. The mononuclear inflammatory cell infiltrate and thickened synovial membrane persisted. Pits and erosions of articular surfaces and sub-chondral cysts were present. There was fibro-cartilage and new bone formation. This model of human HS should be useful to fully evaluate the biochemical and molecular changes that occur following joint bleeding and to test novel therapeutics to prevent HS.

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Antithyroid Autoantibody‐Associated Dermatitis in Individuals with Undifferentiated Connective Tissue Disease – An Unrecognized Subset of Autoimmune Disease?

Skin conditions in individuals with undifferentiated connective tissue disease (UCTD) are poorly classified and characterised. We reviewed 892 consecutive cases of individuals who had a workup for UCTD. ATAbs were positive in 526(59%). The ATAb(+) and ATAb(−) groups had similar antinuclear antibody (ANA) positivity (32% versus 28% respectively), average age (59 versus 58), and female‐male ratio (8:1 versus 6:1). ATAb positivity was significantly associated with a dermatitis, manifested as erythematous macules/patches or papules on legs, shoulders or upper backs, in 9%(47/526) individuals versus 2%(7/366) in ATAb(−) individuals (Pearson’s chi‐square = 18.7, p < 0.0001). Sixteen individuals with dermatitis had biopsies, 14 ATAb(+) and 2 ATAb(−). Routine hematoxylin‐eosin and colloidal iron‐stained sections were examined. Eleven biopsies (79%) from ATAb(+) individuals (5 ANA‐negative, 5 with thyroid disease) and one from ATAb(−) ANA(−) individuals showed interface/lichenoid dermatitis with mild basal keratinocyte vaculopathy, variable dermal mucin deposition, and perivascular mononuclear inflammatory cell infiltrates in the upper dermis. The interface dermatitis was not significantly associated with ANA positivity or thyroid disease. In summary, we report an ATAb‐associated interface dermatitis in UCTD patients which may represent a new subset of autoimmune disease, and suggest that ATAb tests may be a useful marker for UCTD.

Experimental Autoimmune Gastritis: Mouse Models Of Human Organ-specific Autoimmune Disease

Experimental autoimmune gastritis (EAG) is an excellent model of human autoimmune gastritis, the underlying cause of pernicious anaemia. Murine autoimmune gastritis replicates human gastritis in being characterized by a chronic inflammatory mononuclear cell infiltrate in the gastric mucosa, destruction of parietal and zymogenic cells, and autoantibodies to the α-and β-subunits of the gastric H+/K+ ATPase. Disease is induced strain specifically in gastritis-susceptible BALB/c mice by methods with a greater variety than those for most other experimental autoimmune diseases. The disease is induced in the regional gastric lymph node in which pathogenic CD4+ T cells are recruited. The model provides an excellent illustration of regulation by CD4+CD25+T cells, and, indeed, the removal of such regulatory cells, e.g., by neonatal thymectomy, is thought to be a major mechanism by which disease can develop. The culprit T helper type 1 (Th1) CD4+ T cells recognize either the α- or β-subunits of the gastric H+/K+ ATPase, but the β-subunit appears to be the initiating autoantigen, while the α-subunit may have a role in perpetuating disease. Since no specific environmental modifiers are identifiable, the origins of the disease are intrinsic; this is illustrated by the capacity of a cytokine (GM-CSF)-dependent inflammatory stimulus in the stomach to initiate EAG, according to a transgenic model in which thymectomy is dispensible. Thus, EAG is an exquisite model for a reductionist analysis of the multiple elements that in combination induce autoimmunity in humans.

A light microscopical study on the structure of traumatic neuromas of the human lingual nerve

To determine the morphologic characteristics of traumatic neuromas resulting from damage to the lingual nerve during the surgical removal of lower third molar teeth. Using light microscopy, we examined hematoxylin and eosin-stained sections of neuromas removed at the time of microsurgical nerve repair in 31 patients. Changes in fascicular pattern were quantified and evidence of inflammation was recorded. Statistical comparisons were made between the sections from patients with and without symptoms of dysesthesia, and with sections of normal lingual nerve obtained from organ donor retrieval patients. The neuromas were found to contain large numbers of small and haphazardly arranged regenerating nerve fascicles within a densely collagenous and fibroblastic stroma. The mean number of fascicles was 31 (+/- SD 28) in normal lingual nerve, but 462 (+/- 366) within traumatic neuromas. Mean fascicle diameter was 44 (+/- 10) microm in neuromas, but 273 (+/- 101) microm in normal nerve. A chronic mononuclear cell inflammatory infiltrate was observed in 42% of neuroma specimens, and histologic signs of inflammation were frequently seen in patients with symptoms of dysesthesia. Damage to the lingual nerve during third molar removal results in marked changes to the fascicular pattern and sometimes the presence of chronic inflammation in the injured nerve. These changes could contribute to the altered electrophysiological properties of axons trapped within traumatic neuromas, but we found no significant differences between the specimens studied from patients with or without symptoms of dysesthesia.

119th ENMC international workshop: Trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands

Department of Neurology, University Medical Center, Heidelberg laan 100, Utrecht, CX 3584, The Netherlands Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA The Walton Centre for Neurology and Neurosurgery, Liverpool, UK Department of Rheumatology, King’s College Hospital, London, UK Rheumatology Unit, Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden King’s Neurosciences Centre, King’s College Hospital, London, UK Institute of Rheumatology, Prague, Czech Republic Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands Department of Clinical Neurosciences, Guy’s, King’s and Thomas’ School of Medicine, London, UK

Pollution correlated modifications of liver antioxidant systems and histopathology of fish (Cyprinidae) living in Seyhan Dam Lake, Turkey

Specimen of freshwater fish (Cyprinidae) was collected from polluted and clean areas in dam Lake of Seyhan. Ten (n=10) fish were taken from each site. Liver preparations of fish from the two sources were comparatively assayed for glutathione-S-transferase (GST), lactic dehydrogenase (LDH), catalase (CAT), glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and malondialdehyde (MDA). All systems were significantly (p<0.1) affected at the polluted site.The microscopic examination of the liver tissues of the fish living in the polluted area showed mononuclear inflammatory cell infiltration, cloudy degenerations, congestions and also micro- and macrovesicular fatty degenerations. These results provide evidence that both biochemical parameters and histopathological observations can be assumed as sensitive indicators of fish liver metabolism for polluted areas.

Pesquisa de anticorpos contra Leptospira spp. em animais silvestres e em estado feral da região de Nhecolândia, Mato Grosso do Sul, Brasil: utilização da técnica de imuno-histoquímica para detecção do agente

Foram examinadas 315 amostras de soros sangüíneos de diversas espécies de animais que vivem em estado feral ou silvestre na região de Nhecolândia, Corumbá, MS, por meio da prova de soroaglutinação microscópica para leptospirose. Dessas amostras, 67 foram de bois baguás (Bos taurus indicus), 39 de porcos-monteiros (Sus scrofa), 39 de búfalos (Bubalus bubalis), nove de quatis (Nasua nasua), 41 de veados-campeiros (Ozotoceros bezoarticus), 10 de veados-mateiros (Mazama americana) e 110 amostras de ovinos (Ovis aries). Em 12 animais que vieram a óbito, seis porcos-monteiros, quatro veados-campeiros e dois ovinos, foram realizadas tentativas de isolamento de Leptospira do fígado e dos rins por cultura em meio semi-sólido. Fragmentos desses órgãos foram submetidos a exame histopatológico e também a exame para detecção das Leptospiras pela técnica de imuno-histoquímica. Os resultados dos exames sorológicos mostraram que 64 (20,3%) das amostras foram reagentes para, pelo menos, um sorovar de Leptospira patogênica; foram reagentes 41,0% das amostras de búfalos, 40,3% das de bois baguás, 17,9% das de porcos-monteiros, 9% das de ovinos e 9,7% das amostras de veados-campeiros; nenhuma das amostras de veados-mateiros e de quatis foi reagente. Os sorovares mais freqüentes foram: pomona, para búfalos e ovinos; icterohaemorrhagiae, para ovinos, veados-campeiros e suínos; e copenhageni, para veados-campeiros e suínos. As tentativas de isolamento dos rins e fígados foram todas negativas, e pela técnica da imuno-histoquímica foi detectada Leptospira no fígado de um porco-monteiro. As principais alterações estruturais, encontradas nos rins de dois veados-campeiros e de um porco-monteiro, foram infiltrado inflamatório intersticial com congestão associada a hemorragias.

Lymphangiogenesis in human dental pulp

To investigate the impact of inflammation on lymphangiogenesis in human dental pulp. Eleven samples of dental pulp without inflammation and 11 dental pulps with moderate to intense mononuclear cell inflammatory infiltrate associated with dentine caries were selected. The streptavidin-biotin complex stain was used to detect CD31, vascular endothelial growth factor receptor-3 (VEGFR-3) and alpha-smooth muscle actin. The number of lymphatic vessels was obtained by counting the number of vessels positive for CD31 and VEGFR-3 and negative for alpha-smooth muscle actin. The results demonstrated that the mean number (+/-SD) of vessels positive for CD31 and VEGFR-3 (lymphatic vessels) in the group with inflammation (6.09 +/- 1.81) was statistically higher (P = 0.0123) than the mean number in the group without inflammation (3.73 +/- 2.20). Increased co-immunostaining of CD31 and VEGF-3 in vessels associated with human dental pulp inflammation occurred, which suggests lymphangiogenesis.

Hemofagositik Sendrom Bir Otopsi Olgusu

Hemofagositik sendrom (HPS), ateş, sitopeni, hepatosplenomegali, anormal karaciğer fonksiyon testleri, hipertrigliseridemi ve hipofibrinojenemi gibi klinik bulgularla karşımıza çıkabilen ve sıklıkla ölümcül olan bir tablodur. Çalışmada amacımız, çocuk otopsilerinde sık karşılaşmadığımız bu sendromu sunmak, benzer klinik bulgulara sahip otopsilerde ayırıcı tam içine bu sendromu da alarak, kemik iliği, dalak, lenf düğümü gibi organ örneklemelerinin yapılması gerekliliğini vurgulamaktır. Olgu, Adli Tıp Kurumu Morg İhtisas Dairesinde otopsisi yapılan 4 aylık erkek bebekti. Harici travmatik bulgu saptanmayan olgunun otopsisinde, makroskopik olarak beyinde küçük çaplı subaraknoidal kanamalar, kalpte 0,5 cm çapmda atrial septal defekt, her iki akciğerde alacak, atelektatik görünüm saptandı. Karaciğer 380 gr ağırlığında, sarı renk değişimi göstermekte, dalak ise 320 gr ağırlığında olup, yoğun konjesyon dışında makroskopik özellik göstermemekteydi. Diğer organlarda makroskopik patolojik özellik görülmedi. Organlara ait histopatolojik incelemede, myokard, akciğer, beyin, beyincik, lenf düğümü ve kemik iliğinde histiyosit üstünlüğü gösteren mononükleer iltihabi hücre infiltrasyonu izlenmekteydi. Özellikle kemik iliğinde bazı histiyosit sitoplazmalarında eritrosit, seyrek polimorf nüveli lökosit ve lenfosit fagositozu (emperipolezis) saptanmıştı. Beyin ve beyincikte bu infiltrasyon granülom benzeri yapılar oluşturmuştu. Akciğerde ise, bu infiltrasyona alveolit, alveol epitel zararı ve hyalen membran oluşumları eşlik etmekteydi. Ancak primer viral inklüzyona rastlanamadı. Karaciğer, böbrek ve dalak otoliz nedeniyle ayrıntılı olarak değerlendirilemedi. Klinik ve mikroskopik bulgular eşliğinde tanı 'Hemofagositik sendrom' olarak düşünüldü. Toksikolojik incelemede herhangi bir özellik göstermeyen olgunun ölüm nedeni viral bir enfeksiyon sonrasında gelişmiş olabileceği düşünülen hemofagositik sendrom olarak değerlendirildi. Sonuç olarak, farklı merkezlerde tedavi edilen ancak kesin tanısı konulamadan kaybedilen ve ender rastlanan bu tür olgularda sistemik otopsinin bilim ve adalet açısmdan değerinin birkez daha vurgulanması gerektiği inancındayız.Anahtar kelimeler: Kemik iliği, hemofagositik sendrom, otopsi

The varieties of “eczema”: clinicopathologic correlation

Eczema is defined in the third Webster’s unabridged dictionary as an “acute or chronic noncontagious inflammatory condition of the skin characterized by redness, itching, oozing...associated with exposure to chemicals or irritants.” The word derives from Greek, meaning literally to erupt, ferment, or boil. The broadness of this term and its association with just about any inflammatory condition of the skin has prompted some authors to opine that “ it is devoid of meaning” and that it should be “expunged” from the dermatologic lexicon. The consensus among many dermatopathologists and a few dermatologists is that the expression eczema should be replaced with the term “spongiotic dermatitis.” Spongiosis refers to the histopathologic changes that underlie most of the so-called eczemas, ie, edema between the keratinocytes of the stratum malpighii, which gives a spongy appearance to the epidermis. Although most authors have accepted this concept, it is actually a gross oversimplification. Spongiosis occurs in numerous other dermatoses that are not, by conventional wisdom, classified as “eczema.” Examples include, but are not limited to pityriasis rosea, Gianotti Crosti syndrome, the annular erythemas, miliaria, Grover’s disease, polymorphous light eruptions, papular urticaria, lichen striatus, and some pigmented purpuras. Because a full discussion of this issue is beyond the scope of this article, for purposes of discussion, eczema is defined here as “an inflammatory skin disorder that histologically shows spongiosis and is related etiologically to some type of immunologic perturbation.” This review will cover two major points concerning spongiotic dermatitis. First, spongiotic dermatitis will be examined as a histologic continuum. If the antigenic insult is severe and reaction time is short, the resulting dermatitis is designated as acute. If the antigenic stimulus is weaker and takes place over an extended period of time, then it is referred to as chronic. Severe chronic reactions typified by maximal physical changes are termed lichen simplex chronicus and prurigo nodularis. Although this histopathologic schema is a convention in common use by dermatopathologists, it should be understood that pathologic changes don’t always correlate exactly with a defined time course in a clinical dermatitis. The second major consideration of this paper will be the varieties of spongiotic dermatitis that occur at different anatomic sites and that may have varying etiologies. An attempt will be made to differentiate the characteristic histopathologic changes occurring at different anatomic locations and those occurring within different subtypes of spongiotic dermatitis; we will also discuss whether such changes can be readily identified by the dermatopathologist. For some of the dermatitides, a short summary of pathogenesis is included if it is relevant to understanding the pathology. There are five general categories of spongiotic dermatitis: 1) acute spongiotic dermatitis; 2) subacutespongiotic dermatitis; 3) chronic spongiotic dermatitis; 4) lichen simplex chronicus; and 5) prurigo nodularis. The first three categories actually represent a pathologic continuum, whereas the last two are a pathologic response to trauma superimposed by the patient on the underlying dermatitis. In acute spongiotic dermatitis, the spongiosis is typified by massive intercellular edema of the epidermis with widening of the intercellular spaces. The edema produces disruption of desmosomal attachments, and as a consequence, numerous microvesicles form. Although these vesicles are usually intraepidermal, with sufficient vesiculation they can become subepidermal. In general, the degree of epidermal acanthosis is slight. Dermal edema is common, and it is often accompanied by a pronounced inflammatory infiltrate of mononuclear cells and eosinophils. Although there may be some parakeratosis, in general, the changes in the horn are slight given the rapidity at which the process usually develops. A frequent accompaniment is a scale crust composed of neutrophils, plasma, and bacterial colonies ie, so-called impetiginization (Fig. 1). In subacute spongiotic dermatitis, the vesicles are smaller and there is greater acanthosis of the epidermis. From the Departments of Dermatology and Pathology, Mount Sinai School of Medicine, New York, New York. Address correspondence to Dr. Robert G. Phelps, Dermatopathology Division, Box 1194, 1 Gustave L. Levy Place, New York, NY 10029. E-mail address: bobpderm@aol.com.

Cerebrospinal setariosis with Setaria marshalli and Setaria digitata infection in cattle.

Setaria digitata and S. marshalli larvae were observed in the cerebrospinal cavity of 2 paralyzed cattle in Taiwan. The 2 affected cattle showed quadriplegia and lumbar paralysis, respectively. At necropsy, which was performed 7 days after the 7-month-old cattle became quadriplegic, three and nineteen S. marshalli larvae as well as two female adult worms were found in the cranial cavity, spinal cavity and peritoneal cavity of the cattle, respectively. Necropsy on the other 8-month-old cattle was also performed 3 days after it showed lumbar paralysis, and ten S. digitata larvae were found in the spinal cavity. In both cattle, many mononuclear inflammatory cells mixed with a few eosinophils were seen accumulated in the connective tissue around the root of the spinal nerves. Infiltration of eosinophils and mononuclear inflammatory cells into the epidura and arachnoidea of the brain were also observed. The major inflammatory cell was lymphocytes, but neutrophils and eosinophils were also present. The number of cells in the cerebrospinal fluid collected initially from the two affected cattle were 105/0.01 ml and 143/ 0.01 ml, respectively. This is the first report of cerebrospinal setariosis in cattle associated with S. marshalli.

The presence of chemokine (MCP-1, MIP-1alpha, MIP-1beta, IP-10, RANTES)-positive cells and chemokine receptor (CCR5, CXCR3)-positive cells in inflamed human gingival tissues.

Chemokines are said to be small peptides that are chemoattractants for leukocyte subpopulations within local inflammation sites. Gingival inflammation is characterized by infiltration of inflammatory mononuclear cells. The point of this study was to examine the presence or absence of chemokine-positive cells and chemokine receptor-positive cells by means of immunohistochemical methods in samples of gingival tissues obtained from patients with marginal periodontitis. Macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, (IFN-gamma)-inducible protein-10 (IP-10) and RANTES-producing cells were found to be present in inflamed human gingival tissues. In addition, CCR5- and CXCR3-positive cells were present. In contrast, no factor expression was observed in periodontally healthy gingival tissue. Our findings suggest that these chemokines may be responsible for modulating the process of infectious disease such as marginal periodontitis.