Regulation and targeting of antiapoptotic XIAP in acute myeloid leukemia.

XIAP is a member of the inhibitors-of-apoptosis family of proteins, which inhibit caspases and block cell death, with prognostic importance in AML. Here we demonstrate that cytokines regulate the expression of XIAP in leukemic cell lines and primary AML blasts. Inhibition of phosphatidylinositol-3 kinase (PI3K) with LY294002 and of the mitogen-activated protein kinase (MAPK) cascade by PD98059 resulted in decreased XIAP levels (34+/-8.7 and 23+/-5.7%, respectively). We then generated OCI-AML3 cells with constitutively phosphorylated Akt (p473-Akt) by retroviral gene transfer. Neither these nor Akt inhibitor-treated OCI-AML3 cells showed changes in XIAP levels, suggesting that XIAP expression is regulated by PI3K downstream effectors other than Akt. The induction of XIAP expression by cytokines through PI3K/MAPK pathways is consistent with its role in cell survival. Exposure of leukemic cells to chemotherapeutic agents decreased XIAP protein levels by caspase-dependent XIAP cleavage. Targeting XIAP by XIAP antisense oligonucleotide resulted in downregulation of XIAP, activation of caspases and cell death, and sensitized HL-60 cells to Ara-C. Our results suggest that XIAP is regulated by cytokines through PI3K, and to a lesser degree through MAPK pathways. Selective downregulation of XIAP expression might be of therapeutic benefit to leukemic patients.     

Human papillomavirus, cytomegalovirus and herpes simplex virus infections for cervical cancer in Taiwan

Previously, we had reviewed 43 cases of invasive cancers, adenosquamous cell carcinoma and adenocarcinoma for HPV type infections. With the same cases we extended the investigation to cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. Results show that the prevalence of CMV and HSV infections from these cases of cervical carcinoma was 67 and 76%, respectively, by polymerase chain reaction. The results of the analysis of the association of HPV, CMV and HSV with various clinical characteristics of cervical cancer patients indicated that the correlation between HSV infections and clinical stages of squamous carcinoma was marginally significant (P=0.068). HSV infections seemed to have a higher association with cell keratinization pattern as compared with the other two viral infections.     

Paracrine effects of hepatocyte growth factor/scatter factor on non-small-cell lung carcinoma cell lines.

We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF stimulated proliferation in only three cell lines and exerted no mitogenic activity on six lines. The growth of the remaining six lines was inhibited. The mitogenic effects were not related to the ras genotype of these cell lines, but the inhibitory effect was more commonly observed in cell lines with relatively high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced both scatter activity on monolayer culture and single-cell invasion in collagen gels in approximately half of these cell lines. Although the ras genotype of tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines with the mutant ras genotype more commonly demonstrated a spontaneous motogenic activity than those with the wild-type ras genotype. When tumour cells were grown in collagen gels, HGF/SF induced irregular branching extensions of cell aggregates formed by five out of eight adenocarcinoma cell lines, but significant lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop in these tumour cell lines did not influence their spontaneous or HGF/SF-induced mitogenic, motogenic or morphogenic activities. Overall, our data suggest that stimulation of cell motility, rather than proliferation or differentiation, is the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.     

Interspeaker variation in habitual speaking rate: additional evidence.

PURPOSE: The purpose of the present study was to test the hypothesis that talkers previously classified by Y.-C. Tsao and G. Weismer (1997) as habitually fast versus habitually slow would show differences in the way they manipulated articulation rate across the rate continuum. METHOD: Thirty talkers previously classified by Tsao and Weismer (1997) as having habitually slow (n = 15; 7 males, 8 females) and habitually fast (n = 15; 8 males, 7 females) articulation rates produced a single sentence at 7 different rates, using a magnitude production paradigm. Hence, the participants were not randomly assigned to conditions. RESULTS: Quadratic regression functions relating measured to intended articulation rates were all statistically significant, and most important, there were significant differences between the slow and fast groups in the y intercepts of the functions, for both males and females. CONCLUSIONS: This study provides a constructive replication of Tsao and Weismer (1997), showing a difference between slow and fast talkers with a new set of speech materials and in a new task. The findings appear to be consistent with a biological basis for intertalker rate differences.     

Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO₄) and an iron-deficient group (ID group, <5 ppm FeSO₄). After three weeks, the iron-deficient group was divided into an original iron-deficient group and five iron-supplemented groups, the latter fed diets containing different doses of FeSO₄ (6, 12, 18, 24, and 35 ppm). After five weeks, blood and testis tissue were analyzed. We presented as median (interquartile range, IQR) for continuous measurements and compared their differences using the Kruskal–Wallis test followed by the Mann–Whitney U test among groups. The results showed that as compared with the AI group, the ID group had significantly lower serum testosterone and poorer spermatogenesis (The medians (QR) were 187.4 (185.6–190.8) of AI group vs. 87.5 (85.7–90.4) of ID group in serum testosterone, p < 0.05; 9.3 (8.8–10.6) of AI group vs. 4.9 (3.4–5.4) of ID group in mean testicular biopsy score (MTBS], p < 0.05); iron supplementation reversed the impairment of testis tissue. In the testosterone biosynthesis pathway, iron supplementation improved the lowered protein expressions of hydroxysteroid dehydrogenases caused by iron deficiency. Additionally, decreased activities of glutathione peroxidase and catalase, and increased cleaved-caspase 8 and caspase 3 expression, were found in the iron-deficient rats. The iron-supplemented rats that received > 12 ppm FeSO₄ exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.     

Biosynthesis of the ansamycin antibiotic ansatrienin (mycotrienin) by Streptomyces collinus

The biosynthesis of ansatrienin (mycotrienin) has been studied in radioactive and stable isotope feeding experiments with Streptomyces collinus Tü 1892. The m-C7N unit of the ansa ring is efficiently and specifically derived from 3-amino-5-hydroxybenzoic acid; shikimic acid is not incorporated into this part of the molecule but does label the cyclohexanecarboyxlic acid moiety, providing all seven of its carbon atoms. Incorporation of methionine confirms origin of the methoxy group by transmethylation. The D-alanine moiety is derived directly from D-alanine rather than L-alanine. The terminal steps in the conversion of shikimic acid into cyclohexanecarboyxlic acid seem to be sequential reduction of 2,5-dihydrobenzoic acid and cyclohexene-1-carboxylic acid as evidenced by feeding experiments and the detection of a new ansatrienin containing a 1-cyclohexene instead of the cyclohexane moiety.     

Right- and Left-Subclavian Vein Port-A-Cath Systems: Comparison of Complications

Background: Central venous access systems are frequently used for delivery of medications; however, few studies have compared surgical and postoperative complications of right versus left access via the subclavian vein (SCV). The aim of this study was to compare the surgical and postoperative complications associated with Port-A-Cath system insertion via the right and left SCV. Methods: The medical records of patients who received Port-A-Cath insertion via the SCV for parenteral chemotherapy between August 2004 and July 2008 were reviewed. The incidence of surgical and postoperative complications was compared between patients who received right- versus left-SCV Port-A-Cath insertion. Results: A total of 1,848 patients were included in the study. Right-SCV catheterization was attempted in 1,029 (55.7%) patients and was successful in 866 (84.2%). Left-SCV catheterization was attempted in 819 (44.3%) patients and was successful in 651 (79.5%). The mean length of postoperative follow-up was 417.3 ± 401.3 and 396.7 ± 379.9 days for the right- and left-SCV groups, respectively. The incidence of SCV puncture failure was significantly lower in the right-SCV group (12.3%) compared with the left-SCV group (16.8%, p = 0.006). The incidence of catheter knotting at the ipsilateral brachiocephalic vein was also significantly lower in the right-SCV group (0.0%) compared with the left-SCV group (0.5%, p = 0.038), as was the incidence of catheter occlusion (1.0% for right SCV vs. 3.5% for left SCV, p = 0.001). Conclusion: These findings suggest that the right-SCV approach is superior to the left-SCV approach for Port-A-Cath insertion.     

Correction to: Non-alcoholic Wernicke’s encephalopathy with cortical involvement and polyneuropathy following gastrectomy

In the original publication of the article, author name Hong-Shiu Chang was incorrectly written as Hong-Chiu Chang.

     

BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumors

Although discussed using variable terminology, cutaneous BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumor (BIMT) has been considered a discrete diagnostic entity since 2011. Here, we review the initial genomic studies that identified these distinct melanocytic tumors and the clinical and histopathological features that define these tumors. These epithelioid, predominantly dermal, and melanocytic tumors present as erythematous nodules and histopathologically have features that may overlap with Spitz nevi and nevoid melanoma. There is no sex predilection, and cutaneous BIMTs can appear at any age; however, in most familial (germline mutant) cases patients have multiple cutaneous tumors with a first diagnosis in the second or third decade of life; ocular melanoma and other tumors are increasingly identified in these kindreds with germline BAP1 mutation. These tumors have been described with a myriad of terms including: Wiesner nevus, nevoid melanoma‐like melanocytic proliferation (NEMMP), BAP1 mutant Spitz nevus, BAP1 mutant nevoid melanoma, cutaneous BAPoma, and most recently cutaneous BIMT.