Cutaneous metastases of visceral tumours: a review

Background  Up to 10% of all visceral malignancies develop cutaneous metastases. As cutaneous metastases are underestimated and underdiagnosed they can be a clinical challenge. The clinical appearance and patterns of distribution of cutaneous metastases, the characterisation of clinical outcomes and available therapeutic options are compiled. Patients and methods  Literature (over the last 6 years) MESH in terms of cutaneous metastases was comprehensively evaluated. Characteristics from 92 available cases are elaborated and adjusted with terms (time unlimited) of published epidemiological reviews to single organs. Results  The broad clinical spectrum with differential diagnoses is displayed. An allocation of cutaneous metastases and a particular organ is not reliable. In 22% of all cases cutaneous metastases can lead to the diagnosis of an internal malignoma. The majority of cases reveal cutaneous metastases to emerge in a tumour-free interval in about 36 months, after a successful treatment of the primary tumour, most commonly along with other organ metastases. Probable survival turned out to be less than 12 months. Consistently with this end-stage condition, treatment aligns with rules of palliation. Local treatment of choice is excision. Only a minority of investigators attempted to come up with tumour-specific treatment strategies, and almost no randomised therapy studies can be presented. Conclusion  A reference guide of cutaneous metastases is given; the clinical spectrum is adjusted to an actual status; state of the art of the treatment is accomplished. An epidemiological, improved registration and diagnostic work-up for targeted therapies in conjunction with dermatologists are favoured.     

Cutaneous metastases from internal malignancies

Cutaneous metastases of internal malignancies still seem to occur infrequently, although medical publications report an incidence rate of up to 10.4%. Common sense, however, fosters suspicion that we might underdiagnose the problem distracted by harder striking facets of an advanced disease. With contemporary knowledge, morphology and behavior of cutaneous metastases resemble each other regardless of the site of origin. This article itemizes clinical presentations according to organ systems, specific features, and differential diagnoses. In general, the survival turned out to be less than 12 months. But incremental awareness of cutaneous metastases proclaims this paradigm insufficient. Although excision is the local treatment of choice, investigations attempt to propose tumor-specific chemotherapeutic/immunological approaches. This paper endeavors to critically review the state of the art concerning the clinic, prognosis, and therapeutic concepts.     

The serial reaction time task in the rat: effects of D1 and D2 dopamine-receptor antagonists

Sequential behaviour, probably reflecting procedural learning, has intensively been investigated in humans and monkeys using so-called serial reaction time tasks (SRTT), where serial stimuli are either presented in a random or sequential fashion. Learning of sequences is typically inferred from faster reaction times to such sequences as compared to random blocks of stimuli. Work with such tasks has shown that sequential behaviour seems to be mediated by specific brain systems, including the basal ganglia and the neurotransmitter dopamine. We have recently developed a rat version of the human serial reaction time task, in which rats have to respond to visual stimuli in one of four spatial locations by nose-poking in order to obtain food reward under a fixed ratio schedule (FR13). Here, we used a test version where random and sequential condition phases (10 min each) were alternated within-sessions. In support of our previous work, we found that well-trained (i.e. skilled) rats display superior performance under sequential than random conditions, namely, faster reaction times and higher response accuracies. Furthermore, we investigated the effects of selective dopamine-receptor blockade, by systemically administering SKF 83566, a D1 antagonist (.05-.15 mg/kg), or raclopride, a D2 antagonist (.05-.20 mg/kg), in two separate experiments. Both antagonists impaired responding to the conditioned visual stimuli in a dose-related way, i.e. they decreased, or even blocked, nose-poke rates. In those rats, which kept responding, the speeding of reaction times during sequential conditions was no longer observed with the D1 antagonist, whereas the enhancements in accuracy were preserved, or even enhanced as compared to vehicle. The D2 antagonist also impaired instrumental behaviour, but did not alter sequence effects on accuracy or reaction times. In contrast to responses to the conditioned stimuli, reaction times to the unconditioned stimuli (food pellets) were not substantially affected by either drug. These results are discussed with respect to methodological factors, and the possible role of dopamine for instrumental behaviour, in general, and sequential behaviour, in specific.     

A B-cell lymphoma-associated chromosomal translocation in a progressive transformation of germinal center

Progressive transformation of germinal center (PTGC) is a pattern of lymph node reactive hyperplasia. It can also be the predominant pattern in a hyperplastic lymph node known as florid PTGC. It is characterized histologically by the expansion of the mantle zone lymphocytes into both the adjacent sinusoids and germinal centers. The lymphocytes destroying the germinal centers are predominantly B cells, with a minor population of T cells. Morphologically, it can be confused with nodular lymphocyte-predominant Hodgkin disease (NLPHD) because of its nodular pattern and because of the presence of large cells that can be incorrectly identified as lymphocytic and histiocytic cells. A relationship between PTGC and NLPHD remains unclear, and many authors have suggested that PTGC can represent a precursor lesion of NLPHD. Here we report the first karyotype obtained in PTGC, in a 12-year-old boy. It shows a t(3;22)(q27;q11) translocation, probably involving the BCL6 gene. This translocation has previously been described in diffuse large B-cell lymphomas and in NLPHD with BCL6 rearrangement. This finding offers an insight into a possible tumorigenic pathway from PTGC to NLPHD. Further studies will be required to confirm this hypothesis.     

Deletion of the Escherichia coli uup gene encoding a protein of the ATP binding cassette superfamily affects bacterial competitiveness

Bacteria use a variety of mechanisms for intercellular communication. Here we show that deletion of the uup gene, which encodes a soluble ATP binding cassette (ABC) ATPase, renders the mutant strain sensitive to its parent when they are grown together in the same medium. Our data suggest that the decrease in viability of the mutant is dependent on direct cell-to-cell contact with the parent strain. Furthermore, we show that the presence of intact Walker B motifs in Uup is required for immunity or resistance to the parental strain, suggesting that ATP hydrolysis is an important determinant of this phenotype.     

Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma: role of NKG2D-dependent pathway

Natural cytotoxicity receptors and NKG2D correspond to major activating receptors involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression of NKG2D ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB and UL16-binding proteins 1, 2 and 3, on a panel of human non-small-cell lung carcinoma cell lines, and we analyzed their role in tumor cell susceptibility to NK cell lysis. Although adenocarcinoma (ADC) cells expressed heterogeneous levels of NKG2DLs, they were often resistant to NK cell-mediated killing. Resistance of a selected cell line, ADC-Coco, to allogeneic polyclonal NK cells and autologous NK cell clones correlated with shedding of NKG2DLs resulting from a matrix metalloproteinase (MMP) production. Treatment of ADC-Coco cells with a MMP inhibitor (MMPI) combined with IL-15 stimulation of autologous NK cell clones lead to a potentiation of NK cell-mediated cytotoxicity. This lysis is mainly NKG2D mediated, since it is abrogated by anti-NKG2D-neutralizing mAb. These results suggest that MMPIs, in combination with IL-15, may be useful for overcoming tumor cell escape from the innate immune response.     

Multilocus sequence typing reveals that the population structure of Candida dubliniensis is significantly less divergent than that of Candida albicans

The pathogenic yeast Candida dubliniensis is phylogenetically very closely related to Candida albicans, and both species share many phenotypic and genetic characteristics. DNA fingerprinting using the species-specific probe Cd25 and sequence analysis of the internal transcribed spacer (ITS) region of the ribosomal gene cluster previously showed that C. dubliniensis is comprised of three major clades comprising four distinct ITS genotypes. Multilocus sequence typing (MLST) has been shown to be very useful for investigating the epidemiology and population biology of C. albicans and has identified many distinct major and minor clades. In the present study, we used MLST to investigate the population structure of C. dubliniensis for the first time. Combinations of 10 loci previously tested for MLST analysis of C. albicans were assessed for their discriminatory ability with 50 epidemiologically unrelated C. dubliniensis isolates from diverse geographic locations, including representative isolates from the previously identified three Cd25-defined major clades and the four ITS genotypes. Dendrograms created by using the unweighted pair group method with arithmetic averages that were generated using the data from all 10 loci revealed a population structure which supports that previously suggested by DNA fingerprinting and ITS genotyping. The MLST data revealed significantly less divergence within the C. dubliniensis population examined than within the C. albicans population. These findings show that MLST can be used as an informative alternative strategy for investigating the population structure of C. dubliniensis. On the basis of the highest number of genotypes per variable base, we recommend the following eight loci for MLST analysis of C. dubliniensis: CdAAT1b, CdACC1, CdADP1, CdMPIb, CdRPN2, CdSYA1, exCdVPS13, and exCdZWF1b, where “Cd” indicates C. dubliniensis and “ex” indicates extended sequence.     

Effect of fluid loading during hypovolaemic shock on caspofungin pharmacokinetic parameters in pig

Introduction  

Caspofungin treatment is frequently initiated in shock patients. In the present study, we investigated the influence of hypovolaemic shock requiring fluid loading on the plasma and pulmonary pharmacokinetic parameters of caspofungin in the pig.     

Distinct Patterns of Antiamyloid-β Antibodies in Typical and Atypical Alzheimer Disease

OBJECTIVE To compare serum antiamyloid-β (Aβ) antibodies in typical and atypical Alzheimer disease (AD). DESIGN Preliminary observations. SUBJECTS Thirteen patients with AD, 8 patients with posterior cortical atrophy with evidence of AD (PCA-AD) pathophysiological process by both cerebrospinal fluid (CSF) biomarkers and amyloid imaging, and 12 age-matched control individuals. INTERVENTIONS The class and subclass levels of serum anti-Aβ antibodies were measured using an oligomer-based enzyme-linked immunosorbent assay. This method allowed measuring both free antibodies and, after acidic treatment, the total fraction that includes all antibodies complexed with circulating Aβ40/42 and any cross-reacting antigen. RESULTS Anti-Aβ IgG were restricted to the IgG1 and IgG3 subclasses. Their total levels were strikingly lower and more homogeneous in patients with PCA compared with both typical AD and controls, while biomarkers of amyloid deposition (CSF Aβ42 and positron emission tomography amyloid imaging) were similar in patients with AD and patients with PCA. CONCLUSIONS Serum anti-Aβ IgG1 and IgG3 antibodies differ between distinct forms of AD. Its significance is discussed for possible implications as immune effectors in the specific pathophysiology of AD variants.