Non-Hodgkin lymphoma presenting with spinal cord compression: A population-based analysis of the NHL-BFM study group.

BACKGROUND: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time. METHODS: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files. RESULTS: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up. CONCLUSION: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.

Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions.

Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a ß subunit that together form a composite cytokine. Within the IL-12 family, IL-35 remains particularly ill-characterized on a molecular level despite its key role in autoimmune diseases and cancer. Here we show that both IL-35 subunits, IL-12α and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12α and EBI3 are stable proteins in isolation that act as anti-inflammatory molecules. Both reduce secretion of proinflammatory cytokines and induce the development of regulatory T cells. Together, our study reveals IL-12α and EBI3, the subunits of IL-35, to be functionally active anti-inflammatory immune molecules on their own. This extends our understanding of the human cytokine repertoire as a basis for immunotherapeutic approaches.

Isolation of Bacterial and Fungal Microbiota Associated with Hermetia illucens Larvae Reveals Novel Insights into Entomopathogenicity.

Larvae of the black soldier fly (BSF) Hermetia illucens are polyphagous feeders and show tremendous bioconversion capabilities of organic matter into high-quality insect biomass. However, the digestion of lignocellulose-rich palm oil side streams such as palm kernel meal (PKM) is a particular challenge, as these compounds are exceptionally stable and are mainly degraded by microbes. This study aimed to investigate the suitability of BSF larvae as bioconversion agents of PKM. Since the intestinal microbiota is considered to play a key role in dietary breakdown and in increasing digestibility, the bacterial and fungal communities of BSF larvae were characterized in a culture-dependent approach and screened for their putative entomopathogenicity. The lethality of six putative candidates was investigated using intracoelomal injection. In total, 93 isolates were obtained with a bacterial share of 74% that were assigned to the four phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Members of the genera Klebsiella, Enterococcus, and Sphingobacterium are part of the core microbiome, as they were frequently described in the gut of Hermetia larvae regardless of diet, nutritional composition, or rearing conditions. With 75%, a majority of the fungal isolates belonged to the phylum Ascomycota. We identified several taxa already published to be able to degrade lignocelluloses, including Enterococcus, Cellulomonas, Pichia yeasts, or filamentous Fusarium species. The injection assays revealed pronounced differences in pathogenicity against the larvae. While Alcaligenes faecalis caused no, Diutina rugosa weak (23.3%), Microbacterium thalassium moderate (53.3%), and Pseudomonas aeruginosa and Klebsiella pneumoniae high (≥80%) lethality, Fusarium solani injection resulted in 100% lethality.

Pulmonary sclerosing pneumocytoma: Cytomorphology and immunoprofile.

BACKGROUND: Sclerosing pneumocytoma (SP) is a rare, benign pulmonary neoplasm. To the authors' knowledge, the current study is the first to evaluate the cytomorphology and immunoprofile of SP in a series. METHODS: A total of 9 fine-needle aspiration cases of SP (7 of which were computed tomography guided and 2 of which were endobronchial ultrasound guided) including histopathology and immunohistochemistry were collected from 5 institutions. RESULTS: The female-to-male ratio was 3.5:1, and the mean age of the patients was 54 years (range, 27-73 years). All cases presented as lung nodules, with a mean size of 2.2 cm (range, 1.1-5 cm), and were interpreted as atypical on rapid on-site evaluation. The final diagnoses were favor adenocarcinoma (1 case), well-differentiated lung adenocarcinoma (2 cases), low-grade epithelial neoplasm (2 cases), and sclerosing pneumocytoma (4 cases). Samples were moderately cellular, and consisted of round epithelioid cells with clear cell features, columnar cells, and spindle cells. A papillary arrangement with prominent hyalinized fibrovascular cores was the most common architectural pattern, followed by flat sheets and acinar formations. Tumor cells demonstrated mild, focally moderate nuclear pleomorphism with prominent nucleoli, hyperchromasia, nuclear elongation, nuclear overlap, and occasional nuclear inclusions and grooves. The background consisted of foamy macrophages (9 cases), hemosiderin pigment (6 cases), and lymphoid aggregates (3 cases) with no mitoses and/or necrosis. The surface cells and underlying round cells were positive for both thyroid transcription factor 1 and epithelial membrane antigen in all cases, which was the most notable immunohistochemical finding. CONCLUSIONS: Cytomorphological findings of SP overlap with those of well-differentiated lung adenocarcinoma. Awareness of these cytomorphologic findings and the distinct immunoprofile of the 2 cell types found in SP should prevent a misdiagnosis and aggressive treatment.

Progressive or relapsed Burkitt lymphoma or leukemia in children and adolescents after BFM-type first-line therapy.

Children with refractory or relapsed Burkitt lymphoma (BL) or Burkitt leukemia (B-AL) have a poor chance to survive. We describe characteristics, outcome, reinduction, and transplantation approaches and evaluate risk factors among children with progression of a BL/B-AL included in Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Münster studies between 1986 and 2016. Treatment recommendation was reinduction including rituximab from the early 2000s followed by blood stem cell transplantation. The 3-year survival of the 157 children was 18.5 ± 3%. Survival significantly improved from 11 ± 3% before to 27 ± 5% after 2000 (P < .001), allowing for risk factor analyses among the latter 75 patients. Survival of 14 patients with relapse after initial therapy for low-risk disease (R1/R2) was 50 ± 13% compared with 21 ± 5% for 61 patients progressing after R3/R4 therapy (P < .02). A total of 25 of 28 patients with progression during first-line therapy, 31 of 32 with progression during reinduction, 15 of 16 not reaching a complete remission (CR) before transplantation, 9 of 10 treated with rituximab front-line, and all 13 patients not receiving rituximab during reinduction died. Forty-six patients received stem cell transplantation (20 autologous, 26 allogeneic). Survival after a regimen combining rituximab with continuous-infusion chemotherapy followed by allogeneic transplantation was 67 ± 12% compared with 18 ± 5% for all other regimen and transplantations (P = .003). Patients with relapsed BL/B-AL have a poor chance to survive after current effective front-line therapies. Progression during initial or reinduction chemotherapy and initial high-risk disease are risk factors in relapse. Time-condensed continuous-infusion reinduction followed by stem cell transplantation forms the basis for testing new drugs.

V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma.

V-domain Ig-containing suppressor of T-cell activation (VISTA) is an immune checkpoint gene that inhibits anti-tumor immune responses. Since most malignant pleural mesotheliomas do not respond to anti-programmed cell death(-ligand)1 (PD-(L)1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy and given the recent finding of The Cancer Genome Atlas Study that pleural mesothelioma displays the highest expression of VISTA among all cancers studied, we examined VISTA expression in a large pleural mesothelioma cohort. VISTA and PD-L1 immunohistochemistry were performed on tissue microarray of immunotherapy-naive pleural mesotheliomas (254 epithelioid, 24 biphasic and 41 sarcomatoid) and ten whole-tissue sections of benign pleura (VISTA only). Percentages of tumor and inflammatory cells with positive staining were assessed. Optimal prognostic cutoff percentages were determined using maximally selected rank statistics. Overall survival was evaluated using Kaplan-Meier methods and Cox proportional hazard analysis. All benign mesothelium expressed VISTA. Eighty-five percent of 319 and 38% of 304 mesotheliomas expressed VISTA and PD-L1 (88% and 33% of epithelioid, 90% and 43% of biphasic, and 42% and 75% of sarcomatoid), respectively. Median VISTA score was significantly higher in epithelioid (50%) (vs. biphasic [20%] and sarcomatoid [0]) (p < 0.001), while median PD-L1 score was significantly higher in sarcomatoid tumors (20%) (vs. biphasic and epithelioid [both 0%]) (p < 0.001). VISTA and PD-L1 were expressed in inflammatory cells in 94% (n = 317) and 24% (n = 303) of mesothelioma, respectively. Optimal prognostic cutoffs for VISTA and PD-L1 were 40% and 30%, respectively. On multivariable analysis, VISTA and PD-L1 expression in mesothelioma were associated with better and worse overall survival (p = 0.001 and p = 0.002), respectively, independent of histology. In a large cohort of mesothelioma, we report frequent expression of VISTA and infrequent expression of PD-L1 with favorable and unfavorable survival correlations, respectively. These findings may explain poor responses to anti-PD-(L)1 immunotherapy and suggest VISTA as a potential novel target in pleural mesothelioma.

Cytologic features of upper gynecologic tract adenocarcinomas exhibiting mesonephric-like differentiation.

BACKGROUND: Mesonephric adenocarcinomas are rare neoplasms which most commonly arise in the lateral cervix and vagina. Tumors with similar morphologic, immunophenotypic, and molecular characteristics recently have been described in the uterine corpus and ovary. Herein, the authors sought to characterize the cytomorphologic features of adenocarcinomas exhibiting mesonephric-like differentiation arising in the upper gynecologic tract. METHODS: Institutional databases were queried retrospectively for tumors of the upper gynecologic tract described as a "tumor of Wolffian origin" or "with mesonephric features" between 2007 and 2017. All available cytologic material was reviewed. Cytomorphologic characteristics were evaluated by 3 pathologists. RESULTS: The current study cohort consisted of 8 cases taken from 7 patients. Primary sites included the ovary (3 cases); endometrium (4 cases); and pelvis, not otherwise specified (1 case). All cases demonstrated tight 3-dimensional clusters of overlapping cells. Additional architectural features included tubular (5 of 8 cases; 63%) and papillary (3 of 8 cases; 38%) formations. Cells were small with scant (7 of 8 cases; 88%) to moderate (1 of 8 cases; 12%) cytoplasm. Three of the 8 cases (38%) demonstrated extracellular hyaline globules. Nuclei were uniform in size (6 of 8 cases; 75%) or showed mild anisonucleosis (2 of 8 cases; 25%). Nuclear grooves and indentations were observed in all cases. Mitoses (5 of 8 cases; 63%) and apoptotic bodies (4 of 8 cases; 50%), when present, were rare. No necrosis was noted. CONCLUSIONS: Adenocarcinomas exhibiting mesonephric-like differentiation show a monotonous population of small cells with scant to moderate cytoplasm and abundant nuclear grooves arranged in tight, overlapping, 3-dimensional clusters. Occasionally, papillary or tubular architecture, as well as extracellular hyaline globules, may be seen. These features should prompt further testing (eg, immunohistochemistry) to confirm the diagnosis and to exclude potential mimics.

Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors.

Smooth muscle tumors of the uterus are a diagnostically challenging group of tumors. Molecular surrogate markers reliably distinguishing between benign and malignant tumors are not available. Therefore, the diagnosis is based on morphologic criteria. The aim was to investigate a well-characterized group of challenging uterine smooth muscle tumors consisting of 20 leiomyomas, 13 leiomyomas with bizarre nuclei, and 14 leiomyosarcomas for copy number alterations, MED12 mutations and FH deletions to search for potential diagnostically useful surrogate markers. MED12 mutations were detected in 47, 15, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. MED12 mutations in leiomyomas with bizarre nuclei were detected outside the hotspot region. FH-deletions were seen in 27, 30.8, and 25% of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas, respectively. By using copy number alteration profiling a clear separation of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas could not be observed. Copy number alterations revealed clear genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas. Leiomyosarcomas showed a similar pattern of gains and losses as leiomyomas with bizarre nuclei, with additional copy number alterations and more homozygous losses and high-level amplifications compared to leiomyomas with bizarre nuclei. In conclusion, this study demonstrates that known FH-deletions, a recurrent molecular change in leiomyomas, occur in morphologically challenging variants of leiomyomas, leiomyomas with bizarre nuclei and leiomyosarcomas. Although MED12 mutations are common in leiomyomas, they infrequently occur in leiomyomas with bizarre nuclei and leiomyosarcomas. The genetic similarities between leiomyomas with bizarre nuclei and leiomyosarcomas raise the intriguing possibility that uterine leiomyomas with bizarre nuclei and leiomyosarcomas are closely related and challenge the traditional concept that leiomyoma with bizarre nuclei is a tumor with just marked 'degenerative' cellular changes. These findings support the hypothesis that tumor progression within uterine smooth muscle tumors might occur.

Rare presentation of primary (AL) amyloidosis as gastrointestinal hemorrhage without systemic involvement.

We are reporting a rare case of a patient with primary (AL) amyloidosis presenting with an acute non-variceal upper gastrointestinal hemorrhage in the absence of other systemic involvement. The case report involves a 58-year-old woman with significant cardiac history and hereditary blood disorder who came in complaining of abdominal pain and coffee-ground emesis for two days. Computed tomography (CT) scan of the abdomen and pelvis with contrast revealed segmental wall thickening of the proximal jejunum with hyperdense, heterogenous luminal content. Similar findings were evident in the left lower small bowel region, suspicious for small bowel hematoma and the possibility of intraluminal clots. Esophagogastroduodenoscopy performed post resuscitation showed punctate, erythematous lesions throughout the stomach as well as regions of small bowel mucosa that appeared scalloped, ulcerated, and hemorrhaged on contact. Despite initial treatment for immunostain-positive focal cytomegalovirus gastritis, follow-up esophagogastroduodenoscopy after two months continued to demonstrate friable and irregular duodenal mucosa hinting at a different underlying etiology. Pathology reports from analyses of biopsy samples highlighted infiltration and expansion of the lamina propria and submucosa. Subsequent staining with congo red/crystal violet and appropriate subtyping established the diagnosis of AL (kappa)-type amyloidosis. The significance of this case lies in the fact that our patient did not have the typically seen diagnostic systemic involvements-namely of heart and kidneys-usually seen in primary (AL) amyloidosis patients. It was the persistent endoscopic findings and biopsy results which gave clues to the physicians regarding the possibility of an abnormal protein-deposition entity.

Multiplex genetic cancer testing identifies pathogenic mutations in TP53 and CDH1 in a patient with bilateral breast and endometrial adenocarcinoma.

BACKGROUND: Germline genetic testing for familial cancer syndromes is usually performed serially for the most likely genetic causes. In recent years the way genetic testing carried out has changed, as next generation sequencing now allows the simultaneous testing of multiple susceptibility genes at low costs. CASE PRESENTATION: Here, we present a female with bilateral breast cancer and endometrial adenocarcinoma. After simultaneous sequencing of 150 genes (890 kb) associated with hereditary cancer we identified pathogenic mutations in two high-penetrance genes, i.e. TP53 and CDH1 that would most likely not have been elucidated by serial screening of candidate genes. CONCLUSION: As the two mutated genes are located on different chromosomes and cause different cancer syndromes these findings had a tremendous impact not only on genetic counseling of the index patient and her family but also on subsequent surveillance strategies.

Fumonisin B1 and the kidney: modes of action for renal tumor formation by fumonisin B1 in rodents.

The mycotoxin fumonisin B1 (FB1) is an important contaminant of maize and maize-based products. In rodent toxicity studies, FB1 was shown to be hepato- and nephrotoxic, and to induce renal tumors in rats when administered via the diet. Of particular note are the aggressive growth characteristics of FB1-induced tumors with a high potential to metastasize. While genotoxicity does not appear to contribute to FB1 carcinogenicity, it is well established that FB1-mediated disruption of sphingolipid metabolism plays a key role in FB1 toxicity. This review provides an overview on human dietary exposure to FB1, FB1 toxicity and carcinogenicity, and potential mechanisms involved in FB1-mediated tumor formation, with a particular focus on cellular functions of sphingolipids and biological consequences of FB1-mediated perturbation of sphingolipid metabolism.

Do the media provide transparent health information? A cross-cultural comparison of public information about the HPV vaccine.

The media is a powerful tool for informing the public about health treatments. In particular, the Internet has gained importance as a widely valued source for health information for parents and adolescents. Nonetheless, traditional sources, such as newspapers, continue to report on health innovations. But do websites and newspaper reports provide balanced information? We performed a systematic media analysis to evaluate and compare media coverage of the human papillomavirus (HPV) vaccine on websites and in newspapers in Germany and Spain. We assessed to what extent the media provide complete (pros and cons), transparent (absolute instead of relative numbers), and correct information about the epidemiology and etiology of cervical cancer as well as the effectiveness and costs of the HPV vaccine. As a basis for comparison, a facts box containing current scientific evidence about cervical cancer and the HPV vaccine was developed. The media analysis included 61 websites and 141 newspaper articles in Germany, and 41 websites and 293 newspaper articles in Spain. Results show that 57% of German websites and 43% of German newspaper reports communicated correct estimates of epidemiological data, whereas in Spain 39% of the websites and 20% of the newspaper did so. While two thirds of Spanish websites explicitly mentioned causes of cervical cancer as well as spontaneous recovery, German websites communicated etiological information less frequently. Findings reveal that correct estimates about the vaccine's effectiveness were mentioned in 10% of German websites and 6% of German newspaper reports; none of the Spanish newspaper reports and 2% of Spanish websites reported effectiveness correctly. Only German websites (13%) explicitly referred to scientific uncertainty regarding the vaccine's evaluation. We conclude that the media lack balanced reporting on the dimensions completeness, transparency, and correctness. We propose standards for more balanced reporting on websites and in newspapers.

Targeted expression of tumor necrosis factor-related apoptosis-inducing ligand TRAIL in skin protects mice against chemical carcinogenesis.

BACKGROUND: Gene ablation studies have revealed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L, TNFSF10) plays a crucial role in tumor surveillance, as TRAIL-deficient mice exhibit an increased sensitivity to different types of tumorigenesis. In contrast, possible tumor-protective effect of increased levels of endogenous TRAIL expression in vivo has not been assessed yet. Such models will provide important information about the efficacy of TRAIL-based therapies and potential toxicity in specific tissues. METHODS: To this aim, we engineered transgenic mice selectively expressing TRAIL in the skin and subjected these mice to a two-step chemical carcinogenesis protocol that generated benign and preneoplastic lesions. We were therefore able to study the effect of increased TRAIL expression at the early steps of skin tumorigenesis. RESULTS: Our results showed a delay of tumor appearance in TRAIL expressing mice compared to their wild-type littermates. More importantly, the number of tumors observed in transgenic animals was significantly lower than in the control animals, and the lesions observed were mostly benign. Interestingly, Wnt/ß-catenin signaling differed between tumors of wild-type and TRAIL transgenics. CONCLUSION: Altogether, these data reveal that, at least in this model, TRAIL is able on its own to act on pre-transformed cells, and reduce their tumorigenic potential.

Markers of enhanced cholesterol absorption are a strong predictor for cardiovascular diseases in patients without diabetes mellitus.

OBJECTIVE: Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD), and diabetes mellitus and statin treatment affect cholesterol metabolism. The aim of the present study was to evaluate markers of cholesterol metabolism and determine their relationship with CVD in patients without diabetes mellitus who were not receiving statin treatment. METHODS: In addition to conventional CVD risk factors, plasma levels of campesterol and sitosterol (indicators of cholesterol absorption) and lathosterol (an indicator of cholesterol synthesis) were determined in 835 consecutive patients referred for coronary angiography. Coronary artery disease was evaluated by coronary angiograms, carotid atherosclerosis and peripheral vascular disease were assessed by Doppler ultrasound, and cerebrovascular accidents and transient ischemic attacks were identified by medical history. RESULTS: After excluding patients with known diabetes mellitus and those receiving statin treatment, 177 patients were included in the analysis. Compared to patients without CVDs (n=111), patients with concomitant CVDs (n=66) had a reduced lathosterol-to-cholesterol ratio (1.25±0.61 vs. 1.38±0.63, P<0.05) and an increased campesterol-to-cholesterol ratio (1.81±1.04 vs. 1.50±0.69, P<0.05), indicating that enhanced absorption and reduced synthesis of cholesterol is associated with CVD development. Logistic regression analysis including all established cardiovascular risk factors (age, sex, total cholesterol, arterial hypertension, body mass index and smoking) revealed that campesterol and the campesterol-to-cholesterol ratio were significant predictors of concomitant CVD in this patient population. CONCLUSION: In patients without diabetes mellitus, markers of enhanced cholesterol absorption were a strong predictor for concomitant CVD.

A functionally relevant IRF5 haplotype is associated with reduced risk to Wegener's granulomatosis.

Wegener's granulomatosis (WG), characterized by systemic vasculitis and granulomatous inflammation, is a rare chronic rheumatic condition potentially sharing some etiopathological principles with other autoimmune disorders, e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Several large association studies have identified genetic risk factors for RA and SLE. Thereof, we have evaluated the relevance of the most promising ones in WG. 22 single nucleotide polymorphisms (SNPs) within or in the vicinity of CCL21, CD40, CDK6, IL21, IL2RB, IRF5, KIF5A, KLF12, MMEL1, PRKCQ, STAT4, TNFAIP3, and TRAF1/C5 have been genotyped in >600 German WG cases and >800 matched controls. While most polymorphisms did not show suspicious effects on WG susceptibility, SNPs representing TNFAIP3 (rs6922466, p = 0.032, odds ratio (OR) 0.83, 95% confidence interval (CI) 0.7--0.98) and CDK6 (rs42041, p = 0.0201, OR 1.21, 95% CI 1.03-1.43) revealed nominally significant differences in allele distribution. The strongest association was detected for a functionally relevant four SNP haplotype of IRF5, which comprised a protective effect (p = 0.0000897, p (corrected) = 0.0012, OR 0.73, 95% CI 0.62-0.85) similar to those previously seen in RA and SLE. Thus, we suggest that WG, SLE, and RA share some, but not many, genetic risk factors, which supports models of partly overlapping etiopathological mechanisms in these disorders.

A nodular granulomatous posthitis caused by Halicephalobus sp. in a horse.

This report describes a case of nodular posthitis caused by Halicephalobus gingivalis in a 24-year-old warmblood horse. Macroscopic examination revealed a multinodular, partially ulcerated mass on the external lamina of the prepuce. Nematode migration from unfixed biopsy material in phosphate-buffered saline revealed adult nematodes with the typical morphological features of H. gingivalis: distinctive rhabditiform oesophagus with corpus, isthmus and bulb and the dorsoflexed ovary. The main histopathological features consisted of submucosal confluent granulomatous foci containing cross- and tangential sections of larval and adult nematodes surrounded by cellular debris, epitheloid macrophages, multinucleated giant cells, lymphocytes and plasma cells. Therapy including oral administration of moxidectin and local application of an ointment containing prednisolone and moxidectin was initiated but clinical response was poor. Five months later, the nodular mass was still present and histologically, the same lesions with numerous intact nematodes were identified. In the present case, a localized infection with granuloma formation in the area of the prepuce was observed. Clinically, it cannot be distinguished from other nematode infections or even from a squamous cell carcinoma. An accurate clinical examination followed by histopathological and parasitological examinations was necessary to establish the final diagnosis. This case is unusual in that the lesions were locally very extensive (10 cm), but they remained confined to the preputium and the nematodes did not spread haematogenously to other internal organs.

2-D differential membrane proteome analysis of scarce protein samples.

Proteome studies with small sample amounts are difficult to perform, especially when membrane proteins are the focus of interest. In our study a new method for the analysis of scarce membrane protein samples combining large gel 2-D-CTAB/SDS-PAGE with fluorescence dye saturation labelling (satDIGE) was developed, allowing a highly sensitive differential analysis of different cell states. After Triton X-114 phase partitioning, enriched membrane protein samples of T cells were labelled at cysteine residues using fluorescence dyes and separated by large gel 2D-CTAB/SDS-PAGE. For a differential analysis 3 mug protein was found to be sufficient to detect proteins in a widespread well-separated diagonal spot pattern.