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Epithelioid sarcoma. An immunohistochemical study.

The immunohistochemical findings in 14 epithelioid sarcomas, neoplasms of uncertain histogenesis, indicate that they react with antibodies against cytokeratin, epithelial membrane antigen, and vimentin. All cases were nonreactive for leukocyte common antigen, myoglobin, and Factor VIII-related antigen. These results point to the fact that epithelioid sarcoma expresses phenotypic characteristics more often associated with epithelioid neoplasms, rather than the mesenchymal profile of most soft tissue sarcomas. One explanation for this observation is that epithelioid sarcoma is in fact a carcinoma originating in the deep soft tissues. On the other hand, the pluripotential mesoderm has a known embryonic capacity to differentiate into epithelium and, therefore, it is plausible that epithelioid sarcoma is a mesenchymally derived neoplasm. Aside from histogenetic considerations, epithelioid sarcoma may be confused with a number of other neoplastic and granulomatous processes. Differential immunohistochemical stains are useful in selected instances wherein light and electron microscopic findings are diagnostically equivocal.

Adolescent↗

Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review.

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

Humans↗

Evolutionary relationships of cultivated psychrophilic and barophilic deep-sea bacteria.

Evolutionary relationships of cultivated barophilic bacteria were determined. All psychrophilic and barophilic isolates were affiliated with one of five genera of the gamma subdivision of the class Proteobacteria ((gamma)-Proteobacteria): Shewanella, Photobacterium, Colwellia, Moritella, and a new group containing strain CNPT3. The data indicate that the barophilic phenotype has evolved independently in different (gamma)-Proteobacteria genera.

Journal Article↗

New Salmonella typhimurium mutants with altered outer membrane permeability.

We describe three new classes of Salmonella typhimurium mutants with increased sensitivity to hydrophobic agents. In contrast to many previously described mutants, the phage sensitivity pattern of these mutants did not give any indication of defective lipopolysaccharide. Furthermore, they had no detectable changes in their phospholipid or outer membrane protein composition, and their growth rate and cell morphology were normal. Class B mutants were nearly as sensitive to novobiocin, fusidic acid, erythromycin, rifampin, and clindamycin as are deep rough (heptoseless) mutants; in addition they were sensitive to methicillin, penicillin (to which heptoseless mutants are resistant), gentian violet, and anionic and cationic detergents. Class A and C mutants had less sensitive, but characteristic phenotypes. None of the three classes were sensitive to serum bactericidal action. The class B mutation mapped between map positions 7 and 11 on the S. typhimurium chromosome, and the class C mutation mapped between positions 5 and 7. The map position for the class A mutation remained undefined, but it was separate from the class B and C mutations and, like those, did not correspond to any gene loci known to participate in the synthesis of major outer membrane constituents.

Bacterial Outer Membrane Proteins↗

[Functional activity of lymphoblastoid cells infected by human adenovirus type 2 and Epstein-Barr virus].

The paper deals with the influence of the adenovirus (Ad) and Epstein-Barr virus (EBV) on functional activity of lymphocytes, in particular, the production of alpha- and gamma-interferons, tumor necrosis factor (TNF) in conditions of mono- or double infection of B- and T-phenotype (CEM) lymphoblastoid cells. It is shown, that Ad, EBV or both viruses induce high enough levels of interferon on both lines of cells and in control epithelial cells. The lymphoblastoid cells infected by viruses deep ability to synthesize alpha- and gamma-interferons under the influence of the corresponding inducers (Newcastle disease virus and hemagglutinine). Nevertheless, the levels of their formation are not high. Rather high parameters of activity of the tumor necrosis factor (TNF) were revealed during a day in the initial B95-8 cells and superinfected Ad after the effect of LPS of E. coli. Their activity in CEM cells also did not depend on the infection type.

Adenovirus Infections, Human↗

Motor performance and regional brain metabolism of spontaneous murine mutations with cerebellar atrophy.

Three spontaneous mutations with cerebellar atrophy were evaluated for motor coordination and regional brain metabolism, as assessed by cytochrome oxidase (CO) activity. Despite similar neuropathological characteristics, the behavioral phenotype of Lurcher is less severe than that of staggerer, possibly caused by the slower onset of their neuronal degeneration. Although fewer cerebellar cells degenerate in hot-foot than in Lurcher, their motor deficits are more severe, indicating the presence of dysfunctional cells. CO activity in the deep cerebellar nuclei was increased in Lurcher and staggerer but unchanged in hot-foot, probably due to the severe loss of GABAergic input from Purkinje cells in the first two mutants but not the third. Altered CO activity in cerebellar-related pathways was linearly correlated with motor performance, indicating that the activity of this enzyme is associated not only with neuronal activity but also with motor performance.

Animals↗

Effects of 20-week intermittent cold-water-immersion on phenotype and myonuclei in single fibers of rat hindlimb muscles.

The effects of 20 weeks of intermittent cold-water-immersion on myosin heavy chain (MHC) expression,cross-sectional area (CSA), myonuclear number, and myonuclear domain size in isolated single fiber of soleus and extensor digitorum longus (EDL) muscles were studied in male Wistar rats. Cold exposure was accomplished by submerging the rats in shoulder-deep water, maintained at approximately 18 degrees C, for 1 hour/day, 5 days/week and for 20 weeks. Cold exposure resulted in a significant inhibition of body and soleus muscle weight gain. The percent type IIa MHC fibers of EDL muscle was increased, whereas that of type IIa + b MHC fibers was less in cold-exposed group than controls (p < 0.05). The mean CSA and myonuclear number in type I MHC fibers of soleus muscle in cold-exposed group were significantly less than controls. Myonuclear domain in type IIa fibers of EDL in the cold-exposed group was greater than controls (p < 0.05). It is suggested that prolonged cold exposure causes the fiber-type-specific adaptation in rat hindlimb muscles. It is further indicated that cold-exposure-related modulation of myonuclear number was closely related to reduction of fiber CSA, not the shift of fiber phenotype.

Animals↗

Molecular and phenotypic characterization of nonmotile Gram-negative bacteria associated with spoilage of freshwater fish.

AIMS: Characterization of nonmotile bacteria associated with freshwater fish spoilage and that phenotypically resembled Psychrobacter spp. METHODS AND RESULTS: A population of 44 nonmotile Gram-negative rods could not be assigned to the genus Psychrobacter on the basis of a definitive test (transformation assay). Conventional and commercial phenotypic systems did not help in identification. A second extensive phenotypic analysis using different temperatures and media confirmed these isolates as nonmotile although electron microscopic examination showed that all but two had one to four polar flagella and other appendages. On the basis of numerical taxonomy, this population was divided into six clusters, one of them consisting of five fluorescent strains. Sequencing of fluorescent and non fluorescent representative strains from each cluster demonstrated that strains from five clusters had between 97.8 and 98.8% sequence homology with Pseudomonas fragi IFO 3458. This and an unknown strain from deep sea were the closest organisms (80.9% sequence homology) to one aflagellated representative strain of the remaining cluster. CONCLUSIONS: Oxidase-positive, nonmotile, nonfermenter Gram-negative rods isolated from freshwater fish can be wrongly ascribed to the genus Psychrobacter. SIGNIFICANCE AND IMPACT OF THE STUDY: Molecular methods are necessary for the identification of environmental isolates and species with an incomplete phenotypic description. This work emphasizes the need for a sound description of Ps. fragi based on molecular and phenotypic characterization.

Animals↗

Trisomy 8 mosaicism syndrome. Two cases demonstrating variability in phenotype.

The paper presents clinical manifestations and results of cytogenetic examination of two patients with trisomy 8 mosaicism syndrome. The findings confirm the extreme phenotype variability of this syndrome. Both the first patient, a mentally retarded child with multiple dysmorphic changes, and the second, a 31-year-old woman with normal IQ and hypogammaglobulinemia as a predominant sign, revealed osteoarticular anomalies. Dermatoglyphic studies in both patients were typical for trisomy 8, and correlated with deep skin furrows. The chromosomal analysis was based on two types of lymphocyte cultures: 3-day and 2-day. A decreased percentage of trisomic cells in 3-day cultures in comparison to 2-day cultures may suggest the influence of environmental factors on spontaneous elimination of trisomic cells in vitro.

Abnormalities, Multiple↗

Melanocytic proliferations associated with lichen sclerosus.

OBJECTIVES: To describe the clinicopathologic features of melanocytic proliferations associated with lichen sclerosus (LS) and to compare these findings with those in controls. DESIGN: Cohort study. SETTING: Academic and private practice dermatology and dermatopathology services. PATIENTS: Cases of melanocytic proliferations associated with LS and consecutive controls with persistent (recurrent) melanocytic nevi, persistent malignant melanomas, and compound melanocytic nevi. MAIN OUTCOME MEASURES: Diagnostic criteria and disease recurrence. RESULTS: Eleven patients, all female, with a mean age of 40 years (range, 8-83 years), presented with pigmented lesions clinically suspected to be malignant melanoma or atypical melanocytic nevi affecting the vulva (7 patients), perineum (3 patients), or chest (1 patient). Lichen sclerosus was first identified in the biopsy specimen and subsequently confirmed clinically. In 10 cases, a melanocytic nevus was superimposed on LS (overlying or entrapped by sclerosis), whereas LS was found at the periphery of vulvar malignant melanoma. After complete excision, no recurrences have been reported for the melanocytic nevi in LS (mean follow-up, 29 months; range, 4-60 months). Compared with control lesions, the LS melanocytic nevi most closely resembled persistent melanocytic nevi and could be distinguished from persistent malignant melanoma histologically. Melanocytes, nevoid or malignant, proliferating contiguously with fibrotic or sclerotic collagen, contained abundant melanin, diffusely expressed HMB-45, and had a higher Ki-67 labeling index than ordinary melanocytic nevi. However, persistent malignant melanoma exhibited mitotic figures, significantly higher Ki-67 labeling index, and deep dermal HMB-45 expression compared with LS melanocytic nevi and persistent melanocytic nevi. CONCLUSIONS: Melanocytic nevi occurring in LS have features in common with persistent melanocytic nevi and can mimic malignant melanoma. An "activated" melanocytic phenotype is seen in LS melanocytic nevi, implicating a stromal-induced change.

Adolescent↗

Tolerance of staphylococci to bactericidal antibiotics.

Antibiotic therapy for deep-seated staphylococcal infections, especially when they are associated with artificial devices used for orthopedic surgery is often associated with failure. Standard anti-staphylococcal bactericidal antibiotics, such as semi-synthetic penicillins, cephalosporins, or glycopeptides, are effective when given prophylactically in clinical conditions or experimental trials of implant-related infections. However, the efficacy of all anti-staphylococcal agents is seriously diminished on already established implant-related deep-seated infections, which then frequently require surgical implant removal to obtain a cure. The failure of antibiotic therapy to cure established staphylococcal foreign-body infections may arise in part from a broad-spectrum phenotypic tolerance expressed in vivo to different classes of antimicrobial agents. The molecular and physiological mechanisms of this in vivo tolerance remain poorly understood.

Animals↗

Mechanisms of the adaptive immune response inside the central nervous system during inflammatory and autoimmune diseases.

In this review we will discuss the unique features that make the central nervous system (CNS) a specialized microenvironment where immune responses are tightly regulated in order to properly face pathogens without damaging the neural cells. We will show how every paradigm of this theoretical model has been addressed by the scientific literature over the past decades providing new insights on the immune response within the CNS. In particular, new light has been shed on the trafficking of the immune cells inside and outside the CNS. Dendritic cells (DCs) have been described in the context of structures in direct contact with the cerebrospinal fluid (CSF) and their migration, upon antigen encounter, outside the CNS into deep cervical lymph nodes (DCLNs) has been further clarified. T-cells, B-cells, and antibody-secreting cells (ASCs) have been found in the CSF and CNS parenchymal lesions of inflammatory disorders and their phenotype depicted. Moreover, in chronically inflamed CNS, ectopic lymphoid structures have been observed and a germinal center reaction similar to the one found in peripheral lymph nodes has been described. These structures may play a role in the maintenance and expansion of the local autoimmune response. Although the complex interactions between immune and neural cells still remain far to be elucidated, the data discussed here suggest that the physiopathology of the adaptive immune response inside the CNS mimics, although in a mitigated fashion, what occurs in other organs and tissues.

Animals↗

Microcella putealis gen. nov., sp. nov., a gram-positive alkaliphilic bacterium isolated from a nonsaline alkaline groundwater.

Three Gram-positive bacteria designated CV-2T, CV-40 and AC-30 were isolated from a highly alkaline groundwater environment (pH 11.4). These organisms formed very small rod-shaped cells, are aerobic, non-spore-forming, catalase-positive, oxidase-negative, with an optimum growth temperature of 35 degrees C and optimum pH value of growth between 8.5 and 9.0. The strains possessed a novel B-type cell-wall peptidoglycan structure with lysine as the diamino acid; the major respiratory quinones were menaquinone 12 (MK12) and MK13. The G + C content of DNA was between 67.1 and 70.7 mol%. The phylogenetic analyses of the sequences of the 16S rRNA genes reveled that they formed a deep branch within the family Microbacteriaceae, with the highest similarity of approximately 95.6% with members of the genera Agreia, Agrococcus, Cryobacterium, Clavibacter, Frigoribacterium, Leifsonia, Mycetocola, Rhodoglobus, Salinibacterium and Subtercola. Based on the phylogenetic analyses and distinct phenotypic characteristics, we are of the opinion that strains CV-2T, CV-40 and AC-30, represent a new species of a novel genus within the family Microbacteriaceae for which we propose the name Microcella putealis gen. nov., sp. nov.

Actinomycetales↗

The ratio of leaf to total photosynthetic area influences shade survival and plastic response to light of green-stemmed leguminous shrub seedlings.

Different plant species and organs within a plant differ in their plastic response to light. These responses influence their performance and survival in relation to the light environment, which may range from full sunlight to deep shade. Plasticity, especially with regard to physiological features, is linked to a greater capacity to exploit high light and is usually low in shade-tolerant species. Among photosynthetic organs, green stems, which represent a large fraction of the total photosynthetic area of certain species, are hypothesized to be less capable of adjustment to light than leaves, because of biomechanical and hydraulic constraints. The response to light by leaves and stems of six species of leguminous, green-stemmed shrubs from dry and high-light environments was studied by growing seedlings in three light environments: deep shade, moderate shade and sun (3, 30 and 100 % of full sunlight, respectively). Survival in deep shade ranged from 2 % in Retama sphaerocarpa to 74 % in Ulex europaeus. Survival was maximal at moderate shade in all species, ranging from 80 to 98 %. The six species differed significantly in their ratio of leaf to total photosynthetic area, which influenced their light response. Survival in deep shade increased significantly with increasing ratio of leaf to total photosynthetic area, and decreased with increasing plasticity in net photosynthesis and dark respiration. Responses to light differed between stems and leaves within each species. Mean phenotypic plasticity for the variables leaf or stem specific mass, chlorophyll content, chlorophyll a/b ratio, and carotenoid to chlorophyll ratio of leaves, was inversely related to that of stems. Although mean plasticity of stems increased with the ratio of leaf to total photosynthetic area, the mean plasticity of leaves decreased. Shrubs with green stems and a low ratio of leaf to total photosynthetic area are expected to be restricted to well-lit habitats, at least during the seedling stage, owing to their inefficient light capture and the low plasticity of their stems.

Cell Respiration↗

Gingival keratinocytes express HLA-DR antigens in chronic gingivitis.

The expression of the histocompatibility antigens HLA-DR and HLA-A, B, C within periodontally diseased tissue was investigated using immunohistological and histochemical techniques. Tissue was obtained from 18 patients with periodontal disease and from 2 healthy volunteers. HLA-DR antigen was expressed by the keratinocytes of the oral epithelium in all inflamed samples but was not a feature of normal tissue where HLA-DR reactivity was confined to Langerhans cells. These results are consistent with an underlying cellular immune process. Using a variety of phenotypic markers it was possible to characterize the macrophage population within the connective tissue into 2 distinct types: an antigen-presenting cell type located subjacent to the oral epithelium and a phagocytic cell type situated deep within the connective tissue.

Chronic Disease↗

Chondrocyte differentiation in human osteoarthritis: expression of osteocalcin in normal and osteoarthritic cartilage and bone.

Osteocalcin (OC), which is a marker of the mature osteoblasts, can also be found in posthypertrophic chondrocytes of the epiphyseal growth plate, but not in chondrocytes of the resting zone or in adult cartilage. In human osteoarthritis (OA), chondrocytes can differentiate to a hypertrophic phenotype characterized by type X collagen. The protein- and mRNA-expression pattern of OC was systematically analyzed in decalcified cartilage and bone sections and nondecalcified cartilage sections of human osteoarthritic knee joints with different stages of OA to investigate the differentiation of chondrocytes in OA. In severe OA, we found an enhanced expression of the OC mRNA in the subchondral bone plate, demonstrating an increased osteoblast activity. Interestingly, the OC protein and OC mRNA were also detected in osteoarthritic chondrocytes, whereas in chondrocytes of normal adult cartilage, both the protein staining and the specific mRNA signal were negative. The OC mRNA signal increased with the severity of OA and chondrocytes from the deep cartilage layer, and proliferating chondrocytes from clusters showed the strongest signal for OC mRNA. In this late stage of OA, chondrocytes also stained for alkaline phosphatase and type X collagen. Our results clearly show that the expression of OC in chondrocytes correlates with chondrocyte hypertrophy in OA. Although the factors including this phenotypic shift in OA are still unknown, it can be assumed that the altered microenvironment around osteoarthritic chondrocytes and systemic mediators could be potential inducers of this differentiation.

Aged↗

Phenotypical response in different cell types of rat uterus to centchroman. A qualitative analysis.

To assess the alleged estrogenic and antiestrogenic profile of centchroman, a phenotypical response was studied in native uterine cells or migrant blood cells in adult ovariectomized rats under the influence of estradiol-dipropionate (EDP) and centchroman (CC) given per se and together. Histologic observations were divided arbitrarily into the following regions: luminal epithelium, superficial and deep stroma, and the two layers of muscularis. Glandular cell proliferation, mitoses, and vascularity were examined additionally. It was found that CC per se stimulated luminal epithelial cell height and glandular cell proliferation better than EDP. Leukocytic infiltration and vascularity were also more pronounced in the uteri of CC-treated rats. Furthermore, except for a slight reduction in glandular cell size and edematous condition of circular muscle layer, the changes remained unaffected after conjoint treatment of CC and EDP. The observations revealed that some of the nongenomic responses, elicited by the rat uterus after CC treatment, seem to be unrelated to the hormonal attributes of the molecule.

Animals↗

Immunochemical and immunohistological expression of Lewis histo-blood group antigens in small intestine including individuals of the Le(a+b+) and Le(a-b-) nonsecretor phenotypes.

Histological samples and total non-acid glycosphingolipids were prepared from small intestine of human cadavers with the Le(a+b+) and Le(a-b-) nonsecretor phenotypes and contrasted with the more common Lewis phenotypes. Glycolipid fractions were analysed by thin-layer chromatography and tested for Lewis activity with monoclonal antibodies reactive to Lewis epitopes. Paraffin-embedded small intestine sections were also fluorescently immunostained with anti-Lewis antibodies. Unlike the common Lewis positive phenotypes, we were immunochemically able to demonstrate the copresence of large amounts of Lea and Leb glycolipids in the Le(a+b+) sample. In addition we demonstrated increased formation of extended Lewis structures in this phenotype. By immunohistochemistry Lea, Leb and type 1 precursor chain epitopes could be demonstrated in the brush border. These results show that the expression of the Le(a+b+) phenotype at the erythrocyte phenotyping level parallels the small intestinal expression of this phenotype, and the patterns of Lewis antigen expressions are unique to this phenotype. By immunohistochemistry and immunochemistry we also demonstrated the presence of trace amounts of Lewis active glycoconjugates in the small intestine of the Le(a-b-) nonsecretor and Le(a+b-) samples. In the Le(a-b-) nonsecretor Lea and Leb activity was absent and type 1 precursor was present in brush border, while Leb activity was immunohistologically demonstrated in the Golgi apparatus of the deep glands. Trace amounts of both Lea and Leb glycolipids were identified in this sample. In parallel trace Leb activity could also be detected in the glycolipids of the Le(a+b-) sample and could be immunohistologically demonstrated to be fully expressed in occasional cells in the deep glands of the small intestine, a pattern quite dissimilar to that of the Le(a-b-) nonsecretor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗