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A new approach for realizing the "antioncogram".

On the basis of an organoid culture method which allows organoid reorganization and histotypical growth of human carcinomas under in vitro conditions, we propose in the present study an organoid culture assay (OCA) as "antioncogram", i.e., as in vitro model for testing the drug sensitivity and resistance of individual patients' carcinomas previous to clinical chemotherapy. At the beginning of the assay, specimens of human carcinomas are disaggregated to dense single cell suspensions and dropped on a filter sheet at the air-medium interface. Organoid culture nodules develop within several days to weeks. They are exposed to cytostatics by adding the drugs for 2-3 days to the growth medium below the filter sheet. At the end of the exposure period, the cytotoxic effects are estimated by determining the fraction of viable cells, measured by the uptake of neutral red in relation to the total cell mass. In the present study we could show that this assay actually reflects the different levels of experimentally induced resistance of three human carcinoma strains of an epidermoid hypopharynx carcinoma to the cytostatic drug cisplatin and is obviously suited to predict the response of individual human carcinomas to chemotherapy in a rapid and feasible manner.

Carcinoma, Squamous Cell↗

Odontogenic ghost cell carcinoma.

An unusual malignant odontogenic tumor containing large numbers of ghost cells is described. A 46-year-old white man had an aggressive lesion of the right maxilla, multiple pulmonary nodules developed, and he died 1 year after initial diagnosis. Histologic features included columnar odontogenic epithelium, malignant epithelium, microcysts, masses of ghost cells with focal calcification, and small areas of "dentinoid." The relationship is explored between this tumor and calcifying odontogenic cysts, particularly the "dentinogenic ghost cell tumor" variant.

Cytoplasm↗

Periocular granuloma annulare.

A 2-year-old boy presented with a 3-month history of nontender masses involving the right superotemporal orbit and scalp. Over the three-week period before presentation he also developed nodules on his wrist, abdomen, and buttocks. The remainder of the ocular and general physical exam was unremarkable. A biopsy of the right orbital mass demonstrated stellate areas of collagen necrosis surrounded by pallisading epithelioid histiocytes and scattered multinucleated giant cells. Special stains for connective tissue mucin were positive in the areas of necrosis. The diagnosis reached pathologically and clinically were that of pseudorheumatoid nodules and granuloma annulare syndrome respectively. These two diagnostic terms have been used independently in the ophthalmologic and dermatologic literature, despite the identical histologic and clinical behaviors seen by both medical groups. A unified nomenclature system of pseudorheumatoid nodule for the histopathology of an individual lesion and granuloma annulare for the syndrome is suggested.

Biopsy↗

Rhizobium meliloti mutants that fail to succinylate their calcofluor-binding exopolysaccharide are defective in nodule invasion.

We have identified a set of Tn5-generated mutants of Rhizobium meliloti on the basis of their failure to form a fluorescent halo under UV light when grown on agar medium containing Calcofluor. These mutations define a new genetic locus we have termed exoH. Alfalfa seedlings inoculated with exoH mutants form ineffective nodules that do not contain intracellular bacteria or bacteroids. Root hair curling is significantly delayed and infection threads abort in the nodule cortex. Analyses of exopolysaccharide secreted by exoH mutants have shown that it is identical to the Calcofluor-binding exopolysaccharide secreted by the exoH+ parental strain except for the fact that it completely lacks the succinyl modification. In vitro translation of total RNA isolated from nodules induced by an exoH mutant has shown that only one of the plant-encoded nodulins is induced, as compared with the 17 nodulins induced by wild-type strains. These observations suggest that succinylation of the bacterial polysaccharide is important for its role(s) in nodule invasion and possibly nodule development.

DNA Transposable Elements↗

Giant recurrence of a multiple agminated Spitz nevus.

An 11-year-old boy had multiple agminated pigmented lesions distributed over the left scapula since the age of 2 years. Shave excision of four grouped lesions showed Spitz nevi (benign juvenile melanoma, spindle or epithelioid cell nevi) that were not totally excised basally. Three years later, a tumorous, keloidlike nodule developed on that site. To the best of our knowledge, giant recurrence within an agminated Spitz nevus has not previously been reported.

Child↗

Atypical varicella-zoster virus infection in an immunocompromised patient: result of a virus-induced vasculitis.

We describe a patient with cutaneous T-cell lymphoma in whom persistent, painless, ecthymatous nodules developed as a result of a varicella-zoster virus infection. The localized infection occurred without a vesicular stage. Ultrastructural studies revealed a lack of epidermal involvement and massive varicella-zoster virus replication within endothelial cells, leading to an obliterative vasculitis. This suggests direct infection of dermal vessels from adjacent nerves, bypassing the epidermis, which is usually infected first in the classic infectious pathway during varicella-zoster virus reactivation from sensory nerves.

Blood Vessels↗

Density dependent diffusional model of an infective population.

In this work, we present a density-dependent diffusional model which, coupled to three different types of growth, permitted us to study the infective potential of a bacteria species. The results show that those species with strong internal competency have the higher colonizing capacity in terms of invasion speed. Here, we also advanced a model for the static spatial inhomogeneous distribution that some species establish after migration. It is proposed that the origin of these patterns is the result of a balance between the dispersal tendency and the attractive behavior. The results obtained were compared with the observed behavior of Rhizobium spp. during infection of leguminous roots. A possible explanation of the observed morphologies of nodule development in different legumes is suggested.

Bacterial Infections↗

Sequential histopathological analysis of hepatocarcinogenesis in rats during promotion with orotic acid.

In the present study, sequential histopathological changes during hepatocarcinogenesis promoted by orotic acid were examined. Male Fischer 344 rats were given 1,2-dimethylhydrazine.2HCl (100 mg/kg, i.p.) 18 h after 2/3 partial hepatectomy. After 1 week of recovery, they were divided into 2 groups; group 1 was continued on a semisynthetic basal diet while the group 2 received the basal diet containing 1% orotic acid. Rats were sacrificed after 5, 10, 20, 29, 40 and 53 weeks of promotion. Histopathological analysis indicated that emergence of hepatocellular carcinomas was preceded first by foci of morphologically and histochemically altered hepatocytes and then by the appearance of hepatocyte nodules. Clear cell foci, eosinophilic ground glass foci and gamma-glutamyltransferase positive foci were detectable after 5 weeks in initiated rats fed orotic acid. Hepatocyte nodules developed in 56% of the rats after 20 weeks of promotion, while the first hepatocellular carcinoma was observed in one rat sacrificed after 29 weeks of orotic acid promotion. Cancer incidence steadily increased with the duration of the orotic acid treatment and 59% developed hepatocellular carcinomas with 30% metastasis to lungs by 53 weeks of promotion. A relevant feature of this model is that during exposure to orotic acid no liver hyperplasia, nor bile duct or oval cell proliferation were seen and the liver architecture in the tissue surrounding focal lesions was well preserved throughout the sequence.

1,2-Dimethylhydrazine↗

Spectra of antinuclear antibodies in patients with squamous cell carcinoma of the lung and of the head and neck.

Squamous cell carcinoma of the head and neck (HNSCC) and of the lung (LSCC) share some important risk factors, but differ substantially in terms of prognosis and treatment. A pulmonary nodule developing in patients with surgically cured HNSCC may pose a diagnostic dilemma. Markers able to distinguish these two common malignancies would be of major clinical importance. In this work we compared the spectrum of antinuclear antibodies (ANA) from 22 patients with SCCL to that of 40 patients with HNSCC. Patient sera were used to probe immunoblots of nuclear extracts from all four major lung cancer cell types, normal lung fibroblasts, cells cultured from a HNSCC, and keratinocytes cultured from the field cancerization. The ability to classify retrospectively LSCC from HNSCC based on serum ANA reactivities was determined by recursive partitioning analyses. We found that while both malignancies share reactivities to a small group of nuclear antigens, other reactivities are directed against proteins uniquely or preferentially expressed in either SCCL or in SCCHN cells. Our work shows that autoimmunity is a prominent feature of squamous cell carcinoma and suggests that molecular characterization of nuclear antigens recognized by ANAs may lead to the discovery of markers valuable to distinguish LSCC from HNSCC.

Antibodies, Antinuclear↗

Granulomatous reaction to titanium alloy: an unusual reaction to ear piercing.

A 68-year-old man presented with 4 firm, flesh-colored, and slightly erythematous nodules located on the superior pole and lobule of each ear. Although reluctant to provide details, it was discovered he had pierced his ears approximately 10 years earlier, and the nodules developed at the sites of the piercings. Keloids were suggested clinically and the lesions were excised. Microscopic examination demonstrated epithelialized tracts surrounded by a granulomatous infiltrate of macrophages, lymphocytes, and plasma cells. Closer examination revealed minute brown-black particles within macrophages. Dark-field microscopy confirmed the metallic nature of the particles. Environmental scanning electron microscopy with energy dispersive spectroscopy revealed the particles to be composed of titanium, aluminum, and vanadium. It would appear that in rare circumstances titanium alloy used in body piercing may engender a granulomatous dermatitis. The rarity of such a response to titanium alloy is discussed and the literature appraised.

Aged↗

Application of Aspergillus niger-treated agrowaste residue and Glomus mosseae for improving growth and nutrition of Trifolium repens in a Cd-contaminated soil.

The microbial transformation of sugar beet (SB) agrowaste with or without rock-phosphate (RP) has utility for the improvement of plant growth in a Cd (5 microg g-1) artificially contaminated soil, particularly when the soil is co-inoculated with arbuscular mycorrhizal (AM) fungus Glomus mosseae isolated from a Cd-polluted area. Under such Cd-polluted conditions, the limited growth, mineral nutrition, symbiotic developments (nodulation and AM-colonization) and soil enzymatic activities were stimulated using SB or SB+RP as soil amendments and G. mosseae as inoculant. G. mosseae enhanced plant establishment in a higher extent in amended soil; it is probably due to the interactive effect increasing the potential fertility of such compounds and its ability for decreasing Cd transfer from soil to plant. The amount of Cd transferred from soil solution to biomass of AM-colonized plants ranged from 0.09 microg Cd g-1 (in SB+RP-amended soil) to 0.6 microg Cd g-1 (in non-amended soil). Nodule formation was more sensitive to Cd than AM-colonization, and both symbioses were stimulated in amended soils. Not only AM-colonization but also amendments were critical for plant growth and nutrition in Cd-polluted soil. The high effectiveness of AM inoculum increasing nutrients and decreasing Cd in amended soil indicated the positive interaction of these treatments in increasing plant tolerance to Cd contamination.

Agriculture↗

Public health aspects of dirofilariasis in the United States.

Coin lesions in the human lung present significant differential diagnostic problems to the physician. There are at least 20 known causes of such lesions, including neoplastic lesions, infectious diseases, and granulomas. The human medical literature contains many misconceptions about the life cycle of Dirofilaria immitis, including the method of entry of the infective-stage larvae and the development of the young adult worm. These misconceptions have obscured the recognition of the clinical presentation of pulmonary dirofilariasis and the potential for D. immitis to lodge in many other areas of the human body besides the lung. Exposure to infective larvae of D. immitis is more common in humans than is currently recognized. Reported cases in humans reflect the prevalence in the canine population in areas of the United States. The veterinary literature provides compelling evidence that D. immitis is a vascular parasite, not an intracardiac one. Its presence in the right ventricle is a post-mortem artifact, because it has never been shown to be there by echocardiography or angiography in a living dog, even though these techniques have demonstrated adult D. immitis in the pulmonary, femoral, and hepatic arteries; posterior vena cava; and right atrium of live dogs. Physicians have taken the name "heartworm" literally, believing that the worm lives in the heart and only after it dies does it embolize to the pulmonary artery. However, the coin lesion is spherical in shape, not pyramidal, as embolic infarcts to the lung in humans are known to be. The coin lesion is an end-stage result of the parasite's death in the vascular bed of the lungs and the stimulation of a pneumonitis followed by granuloma formation. This pneumonitis phase of human pulmonary dirofilariasis is often not recognized by the radiologist because of the way pneumonitis is diagnosed and treated and because the developing nodule is obscured by the lung inflammation. Serologic methods for use in humans are needed for clinical evaluations of patients with pneumonitis living in highly enzootic D. immitis regions. As well, epidemiological surveys are needed to determine the real extent of this zoonotic infection.

Animals↗

Mycetoma: a thorn in the flesh.

Mycetoma is a chronic, granulomatous, subcutaneous, inflammatory disease caused by true fungi (eumycetoma) or filamentous bacteria (actinomycetoma). It occurs in the mycetoma belt stretching between the latitudes of 15 degrees South and 30 degrees North and is endemic in relatively arid areas. The organisms are present in the soil and may enter the subcutaneous tissue by traumatic inoculation. Mycetoma commonly affects adults aged 20 to 40 years, predominantly males. The foot is most commonly affected. Both forms of mycetoma present as a progressive, subcutaneous swelling, although actinomycetoma has a more rapid course. Multiple nodules develop which may suppurate and drain through sinuses, discharging grains during the active phase of the disease. Diagnosis may involve radiology, ultrasonic imaging, cytology, culture, histology or immunodiagnosis. Actinomycetoma is amenable to treatment by antibiotics, preferably by combined drug therapy for long periods. Eumycetoma is usually treated by aggressive surgical excision combined with medical treatment.

Antifungal Agents↗

The ophthalmic trials of G. H. A. Hansen.

G. H. A. Hansen (1841-1912) is widely known as the discoverer of the infectious cause of leprosy. It is less well known that his career was threatened by an episode involving experimentation on the eye. As a staff physician at the leprosy hospitals of Bergen, Norway, early in his career, Hansen learned about ocular involvement in leprosy and co-authored Leprous Diseases and the Eye. In 1873 he observed bacilli in leprous nodules, but proof of an infectious origin was difficult to obtain because the agent could not be cultured and no one had demonstrated direct transmission. Hansen tried several unsuccessful experiments, and in 1879 he passed a cataract knife that had incised an active leprous nodule into a woman's conjunctiva. No nodule developed, but the woman complained of pain and said she was never asked for permission. Hansen was brought to trial where eminent physicians testified on his behalf-but Hansen himself readily admitted that no permission had been sought for fear the woman would say no. He was convicted, and relieved of his post as staff physician, but he was allowed to retain an appointment as Chief Medical Officer of Health for Leprosy, in which capacity he worked for the rest of his life.

Disease Transmission, Infectious↗

Leucine-rich repeat receptor kinases in plants: structure, function, and signal transduction pathways.

Leucine-rich repeat receptor kinases (LRR-RKs) comprise the largest subfamily of transmembrane receptor-like kinases in plants, with over 200 members in Arabidopsis. LRR-RKs regulate a wide variety of developmental and defense-related processes including cell proliferation, stem cell maintenance, hormone perception, host-specific as well as non-host-specific defense response, wounding response, and symbiosis. Several studies indicate that LRR-RKs act as dimers, and some may form a receptor complex with leucine-rich repeat receptor-like proteins (LRR-RPs) that lack a cytoplasmic kinase domain. Despite the fact that structural features of LRR-RKs are fairy similar, five available ligand molecules for LRR-RKs are structurally diverse, from steroids (brassinolides) to peptides (phytosulfokine and systemin) and secreted proteins (CLV3). Precise ligand-binding sites of LRR-RKs are not understood. However, the extracellular "island" domain that intercepts the LRR domain in some LRR-RKs may play an important role in ligand binding. Advances in unveiling components of three LRR-RK signaling pathways, namely BRI1 in steroid signaling, CLV1 in meristem maintenance, and FLS2 in bacterial elicitor perception, revealed an intriguing link between plant LRR-RK and animal receptor signaling pathways. Finally, rapid progress made in LRR-RK research beyond the model system Arabidopsis has provided exciting, novel insights into the evolution of the LRR-RK signaling system in plants, such as BRI1 utilized in the wound-responsive signaling pathway in Solanaceae plants and recruitment of CLV1 in nodule development in leguminous plants.

Binding Sites↗

A Phaseolus vulgaris lipoxygenase gene expressed in nodules and in Rhizobium tropici inoculated roots.

A genomic clone encoding a common bean lipoxygenase (PvLOX5) was isolated from a Phaseolus vulgaris library. Reverse transcription-polymerase chain reaction analysis revealed that PvLOX5 is expressed during nodule development and in Rhizobium tropici inoculated roots. There was no detectable expression of PvLOX5 in non-inoculated roots, healthy leaves, leaves after Pseudomonas syringae pv. tabaci infection, floral buds or dry seeds.

Amino Acid Sequence↗

Human dirofilariasis in the European Union.

The dog parasites Dirofilaria immitis and D. (Nochtiella) repens, well known as zoonotic agents, are widely distributed in southern Europe. Although both species are canine parasites, infection with immature worms has been found in humans, who develop nodules, mainly in subcutaneous tissue or in lung parenchyma arising from branches of the pulmonary artery. In humans, the parasites do not usually reach the adult stage and microfilaremia is absent, as has been shown by diagnosis using invasive methods for removing the nodules. In this article, Antonio Muro, Claudio Genchi, Miguel Cordero and Fernando Simón review the current situation concerning the clinical and epidemiological aspects, immune response and diagnosis of human dirofilariases.

Adult↗