Intrinsic chemoresistance to gemcitabine is associated with decreased expression of BNIP3 in pancreatic cancer.

PURPOSE: Although chemotherapy with gemcitabine is a common mode of treatment of pancreatic cancer, 75% of patients do not benefit from this therapy. It is likely that the sensitivity of cancer cells to gemcitabine is determined by a number of different factors. EXPERIMENTAL DESIGN: To identify genes that might contribute to resistance to gemcitabine, 15 pancreatic cancer cell lines were subjected to gemcitabine treatment. Simultaneously, gene expression profiling using a cDNA microarray to identify genes responsible for gemcitabine sensitivity was performed. RESULTS: The pancreatic cancer cell lines could be classified into three groups: a gemcitabine "sensitive," an "intermediate sensitive," and a "resistant" group. Microarray analysis identified 71 genes that show differential expression between gemcitabine-sensitive and -resistant cell lines including 27 genes relatively overexpressed in sensitive cell lines whereas 44 genes are relatively overexpressed in resistant cell lines. Among these genes, 7 genes are potentially involved in the phosphatidylinositol 3-kinase/Akt pathway. In addition to this major signaling pathway, Bcl2/adenovirus E1B 19 kDa protein interacting protein (BNIP3), a Bcl-2 family proapoptotic protein, was identified as being expressed at lower levels in drug-resistant pancreatic cancer cell lines. In an analysis of 21 pancreatic cancer tissue specimens, more than 90% showed down-regulated expression of BNIP3. When expression of BNIP3 was suppressed using small interfering RNA, gemcitabine-induced cytotoxicity in vitro was much reduced. CONCLUSIONS: These results suggest that BNIP3 and the phosphatidylinositol 3-kinase/Akt pathway may play an important role in the poor response to gemcitabine treatment in pancreatic cancer patients.     

Psychometric qualities of the Fatigue Assessment Scale in Croatian sarcoidosis patients

BACKGROUND AND AIM: Fatigue is an unspecific symptom, but a major problem in sarcoidosis patients. There is a need for a reliable and valid way to measure fatigue. The Fatigue Assessment Scale (FAS) has good psychometric properties in healthy and sarcoidosis samples in the Netherlands, but nothing is known about the psychometric qualities of the FAS in sarcoidosis samples from other countries. Therefore, we examined the reliability, construct, and content validity in Croatian sarcoidosis patients. METHODS: Croatian sarcoidosis patients from a pulmonary outpatient clinic completed the FAS and a symptom inventory questionnaire. RESULTS: The internal consistency of the FAS was 0.91. Using exploratory factor analysis and Mokken scale analysis, the scale was unidimensional. A dichotomous fatigue item distinguished between individuals who scored high or low on the FAS. Concerning discriminant validity, individuals reporting health complaints were more tired. The FAS correlated moderately with a number of neurological and psychological problems. Females and lower educated individuals reported more fatigue. CONCLUSIONS: The Croatian translation of the FAS has good reliability and validity in a sarcoidosis sample. Future research is needed to explore the psychometric qualities (i) of the Croatian FAS in healthy individuals and (ii) of the FAS in other languages.     

Multiple primary intrathoracic neoplasms: case report and a review of the literature

This is a case report of a patient diagnosed with three distinct primary intrathoracic tumors (mesothelioma, carcinoid and B-cell lymphoma). The patient had previously had mycosis fungoides. The occurrence of multiple neoplasms in a single patient, synchronous or metasynchronous, is not a rare phenomenon; the incidence varies from 1-11% of all neoplasms. They can be hereditary, or connected with some environmental agents or previous therapies. The incidence of multiple neoplasms increases with age. We report an extremely rare case of multiple intrathoracic neoplasms in a 71-year-old man. A left upper lobectomy was performed, followed by 6 courses of chemotherapy and irradiation of the sternum. The patient was stable two years later.     

Cervids as Babesiae hosts, Slovenia

We describe cervids as potential reservoir hosts of Babesia EU1 and B. divergens. Both babesial parasites were found in roe deer. Sequence analysis of 18S rRNA showed 99.7% identity of roe deer Babesia EU1 with the human EU1 strain. B. divergens detected in cervids was 99.6% identical to bovine B. divergens.     

Gene structure of the goldfish agouti-signaling protein: a putative role in the dorsal-ventral pigment pattern of fish

One of the most successful chromatic adaptations in vertebrates is the dorsal-ventral pigment pattern in which the dorsal skin is darkly colored, whereas the ventrum is light. In fish, the latter pattern is achieved because a melanization inhibition factor inhibits melanoblast differentiation and supports iridophore proliferation in the ventrum. In rodents, the patterned pigmentation results from regional production of the agouti-signaling protein (ASP). This peptide controls the switch between production of eumelanin and pheomelanin by antagonizing alphaMSH effects on melanocortin receptor (MCR) 1 in the melanocytes. In addition, ASP inhibits the differentiation and proliferation of melanoblast. Thus, the mammalian ASP may be homologous to the poikilotherm melanization inhibition factor. By screening of a genomic library, we deduced the amino acid sequence of goldfish ASP. The ASP gene is a four-exon gene spanning 3097 bp that encodes a 125-amino acid precursor. Northern blot analysis identified two different ASP mRNAs in ventral skin of red- and black-pigmented and albino fish, but no expression levels were observed in the dorsal skin of the same fish. The dorsal-ventral expression polarity was also detected in both black dorsally pigmented fish and albino fish. Pharmacological studies demonstrate that goldfish ASP acts as a melanocortin antagonist at Fugu MC1R and goldfish MC4R. In addition, goldfish ASP inhibited Nle4, D-Phe7-MSH-stimulated pigment dispersion in medaka melanophores. Our studies support agouti signaling protein as the melanization inhibition factor, a key factor in the development of the dorsal-ventral pigment pattern in fish.     

Interexaminer repeatability of antidromic ulnar sensory nerve conduction velocity measurements

OBJECTIVE: To determine the interexaminer repeatability of the ulnar antidromic sensory nerve conduction velocity (NCV). DESIGN: Test-retest design. Based on a randomization list of various combinations and sequences from 2 of a total of 3 examiners, the measurement was repeated within half an hour by a second examiner blinded to the results of the first examiner. SETTING: Outpatient department. PARTICIPANTS: Twenty-four consecutive healthy subjects (mean age, 38 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The intraclass correlation coefficient (ICC) and the coefficient of repeatability (CR) were determined for the below elbow to wrist (BE-to-W), above elbow to below elbow (AE-to-BE), and axilla to above elbow (AX-to-AE) segments. RESULTS: The ICC was .42 for the BE-to-W, .15 for the AE-to-BE, and -.05 for the AX-to-AE segment. The CR was 12.2m/s for the BE-to-W, 16.2m/s for the AE-to-BE, and 21.4m/s for the AX-to-AE segment. CONCLUSIONS: During the assessment of the antidromic sensory NCV of the ulnar nerve, a moderate amount of interexaminer variability must be taken into account for the BE-to-W segment. More proximally, an extremely large amount of interexaminer variability must be taken into account. This calls into question the usefulness of the antidromic ulnar sensory NCV for the AX-to-AE and AE-to-BE segments.     

After major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation, erythroid engraftment occurs later in patients with donor blood group A than donor blood group B

BACKGROUND: Isohemagglutinins directed against the donor blood group frequently delay erythroid engraftment after major ABO-mismatched allogeneic hematopoietic progenitor cell transplantation (HPCT). Graft-versus-host reactions are capable of accelerating the clearance of isohemagglutinins. Whether immunogenicity of the A- and B-antigen is important in this process is unknown. PATIENTS AND METHODS: Data of 807 patients from three centers were screened for patients with major or bidirectionally ABO-mismatched donors. Clinical data and red blood cell (RBC) transfusion support were analyzed retrospectively. RESULTS: A total of 158 patients with major or bidirectionally mismatched donors were identified. After major mismatched HPCT, patients with anti-A directed against the donor blood group required RBC transfusion support for a median of 109 days (range, 0-324 days) compared to 21 days (range, 2-98 days) for patients with anti-B directed against donor blood group (log-rank test, p = 0.0001). Other risk factors associated with prolonged RBC transfusion support in univariate analysis were age (p = 0.024), cytomegalovirus infection (p = 0.016), hemolytic anemia (p = 0.027), and chronic bleeding disorders (p = 0.038). The independent influence of donor blood group and recipient age were confirmed in a multivariate analysis. CONCLUSION: These results indicate that the immunogenicity of the ABO antigen plays an important role for the kinetics of erythroid engraftment after ABO-mismatched HPCT.