Deletion mapping of chromosomes 8, 10, and 16 in human prostatic carcinoma

In an allelotyping study prostatic carcinoma, we found the highest frequency of allelic deletions on chromosomes 8, 10, 16, and 18. In all cases with allelic deletions, at least one of the chromosomes 8, 10, and 16 were involved. A detailed deletion mapping of these chromosomes in 18 cases was carried out with probes that detect restriction fragment length polymorphisms (RFLP) on chromosomes 8 (6 probes), 10 (11 probes), and 16 (9 probes). The highest frequency of allelic deletions were found on 8p (65%), where the minimally deleted region was between the PLAT locus and pter. The long arm of chromosome 16 had allelic deletions in 56% of informative cases, with three different break points, the most distal being located between D16S4 and D16S7. Chromosome 10 exhibited a complex deletion pattern with terminal deletions of the p or the q arm (2 cases each), a deletion pattern that could be interpreted as nonreciprocal translocations of the q arm (2 cases), or allelic losses on all informative loci, suggesting monosomy (2 cases). Our data suggest that tumor suppressor genes involved in the oncogenesis of prostatic carcinoma may be localized between 8 pter and the PLAT locus and that additional/alternative tumor suppressor genes may be localized on chromosome 10 and on the long arm of chromosome 16 distal to the D16S4 locus.     

Lack of mutation at codon 12 of the C-h-ras oncogene in 51 human sarcomas assessed by PCR-rflp

Mutations of the ras genes in codons 12, 13 or 61 make them oncogenic. There are several methods to determine the point mutations in the ras family. In an attempt to do so in a sensitive and time saving manner we have checked a total of 51 sarcomas (14 bone tumors and 37 soft tissue tumors) for mutations in codon 12 of the c-H-ras oncogene. First we amplified a 100 bp fragment covering this codon and then performed RFLP analysis after digestion with restriction endonuclease Msp I. We did not find mutations in any of the tumors. Our results, may reinforce previous data on the fact that ras genes do not play an important role in tumorigenesis of sarcomas.     

Genome sequence and organization of a nucleopolyhedrovirus isolated from the smaller tea tortrix, Adoxophyes honmai

Adoxophyes honmai nucleopolyhedrovirus (AdhoNPV) has a distinctive pathology in A. honmai larvae, killing the host more slowly than other NPVs. To further understand the pathology of AdhoNPV, its genome was completely sequenced and compared with those of other baculoviruses. The AdhoNPV genome is 113,220 bp, with a G + C content of 35.6%. It contains 125 putative open reading frames (ORFs), of which 8 are unique to AdhoNPV, and 4 homologous regions. The other 117 ORFs display similarity to previously characterized baculovirus genes involved in early and late gene expression, DNA replication, and structural and auxiliary functions. The phylogenetic position of AdhoNPV, in relation to 15 other baculoviruses whose genomes have been completely sequenced, was assessed by three different analyses: gene sequence, gene order, and gene content. Although gene content analysis failed to support the group II NPVs, phylogenetic trees based on gene sequence and gene order showed AdhoNPV to be closely related to the group II NPVs.     

Assignment of the gene encoding type 1γ protein phosphatase catalytic subunit (PPP1CC) on human,rat, and mouse chromosomes

Summary Using fluorescentin situ hybridization (FISH) method, a gene encoding the catalytic subunit of protein phosphatase type 1 (PPP1CC) was mapped to human 12q24.1-q24.2, rat 7q22, and mouse 10C. These results indicate that thePPP1CC is a member of conserved synteny group between rat chromosome 7, mouse chromosome 10 and human chromosome 12. These data and mapping data about other members of PP1 family show that in spite of the high identity of PP1 isoforms, each isoform is encoded by different genes which located on different chromosomes in human, rat, and mouse.     

Effects of FPL-52694, a new mast cell stabilizer,on gastric secretion and various acute gastric lesions in rats

Oral FPL-52694 [5-(2-hydroxypropoxy)-8-propyl-4-oxo-4H-1-benzopyran-2-carboxylic acid Na], a new mast cell stabilizer, dose-dependently inhibited gastric acid secretion but increased the volume and pepsin output in pylorus-ligated rats. Intraduodenal FPL-52694 significantly inhibited all of the volume, acidity, acid output and pepsin output. Concerning the acidity, oral administration of the agent showed much more potent inhibition than intraduodenal administration. Oral FPL-52694 markedly inhibited the development of pylorus-ligated ulcers, water-immersion stress- and aspirin-induced gastric erosions and moderately inhibited the formation of reserpine-induced gastric erosions in rats. Intraduodenal FPL-52694 also inhibited pylorus-ligated ulcers whereas it had no effect on aspirin-induced gastric erosions. Histamine-induced gastric erosions were not affected by oral FPL-52694. These effects of FPL-52694 were almost the same as those of cimetidine, except that cimetidine tended to inhibit histamine-induced gastric erosions. Although the precise mechanism of action of FPL-52694 remains unknown, oral FPL-52694 appears to be a promising agent for the treatment of peptide ulcers.     

High-fat diet inhibits PGC-1α suppressive effect on NFκB signaling in hepatocytes

Purpose

The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1α exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1α expression in mice. In this study, we investigated the role of PGC-1α in the inflammatory changes observed in steatohepatitis induced by high-fat diet.

Methods

C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-α, and IL-1β quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NFκB nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1α on inflammatory mediators’ production by hepatocytes.

Results

The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines’ levels, decreased PGC-1α expression, and marked increase in p65 NFκB nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1α expression. The knockdown of PGC-1α content caused an increase in IL-6 expression and release via enhanced IκBα phosphorylation and subsequent increase of p65 NFκB nuclear translocation.

Conclusion

High-fat diet induces liver inflammation by inhibiting PGC-1α expression and its suppressive effect in NFκB pathway.

     

Direct comparison between pharmacological stress with adenosine triphosphate disodium and exercise stress myocardial perfusion imagings

To clarify the significance of adenosine triphosphate disodium stress myocardial perfusion imaging (ATP-MPI), we directly compared the findings of ATP-MPI with those of exercise stress myocardial perfusion imaging (Ex-MPI). ATP-MPI, Ex-MPI, and coronary angiography (CAG) were performed within 60 days in 17 coronary artery disease patients with mean age of 62.1+/-7.9 years. CAG revealed single-vessel disease (SVD) in 10 patients and multivessel disease (MVD) in seven patients. The summed stress score (SSS) of ATP-MPI was significantly higher than that of Ex-MPI (10.0 [7.8-14.3] vs. 8.0 [4-18], P<0.05). No difference in the SSS was observed between ATP-MPI and Ex-MPI in patients with SVD (8.0 [6.0-9.0] vs. 8.0 [6.0-10.0], NS), whereas this difference was significant in patients with MVD (15.0 [14.0-22.8] vs.9 [7.3-16.3], P<0.05). There was no difference in the summed rest score between ATP-MPI and Ex-MPI. The univariate logistic analysis showed that "MVD" was the significant factor influencing to the overt discrepancy between ATP-MPI and Ex-MPI (odds ratio: 9.0, 95% confidence interval: 1.07-75.84, P=0.043). The accuracy of ATP-MPI and Ex-MPI in detecting the territory of stenotic coronary vessel or previous myocardial infarction was 98.0% and 92.1% (NS), respectively. In conclusion, ATP-MPI is useful for detecting potential ischemic areas that cannot be detected by Ex-MPI, particularly in patients with MVD.     

Radiofrequency capacitive hyperthermia combined with irradiation of chemotherapy for patients with invasive bladder cancers

To assess the immediate therapeutic clinical efficacy and long-term outcome, hyperthermia in combination with irradiation or chemotherapeutic agent was used in 46 patients with invasive bladder cancer. Radiohyperthermia (RH) was employed in 19 cases and chemohyperthermia (CH) in 27 cases. Complete response (CR) was obtained in 5 and partial response (PR) in 15 of the 46 cases. One-year survival rates by the Kaplan-Meier method were 65.0% in the CR/PR group and 46.2% in the no change (NC)/progressive disease (PD) group. Five-year survival rates were 43.8% and 18.3%, showing no difference in survival rate between the CR/PR group and the CN/PD group. The overal median survival period for the CR/PR group without metastasis was 61.6 months compared to 32.3 months for the NC/PD group without metastasis (P<0.05).     

To avoid post-operative refractive error in cataract surgery

One of the greatest issues facing the cataract surgeon today is accurate prediction of post-operative refractive error. With use of intraoperative autorefractometry (IOAR), such errors can be detected and post-operative refractive errors avoided. An 83-year-old woman was admitted for right eye phacoemulsification, with aimed at −1.78D with Sanders/Retzlaff/Kraff/T (SRK/T) formula implantation under local anesthesia. IOAR was performed after IOL insertion. The first estimate was +1.1D, indicating hyperopia, and far from the desired refraction above 2D. IOL exchange to +11.5D was, therefore, performed. The second estimate was −0.13D and the operation was completed. The final refraction (3 years after operation) was −0.25D.With IOAR, we were able to avoid the unpleasant surprise of a mistaken intraocular lens power. Intraoperative autorefractometry is useful for avoiding errors in IOL power.