Comparative Study of 6-Mercaptopurine Metabolism in Human Leukemic Leukocytes and L1210 Cells

Leukocytes from patients with leukemia and L1210 cells from mice were examined for the rate of formation and cellular concentration of phosphoribosylpyrophosphate, the rate of thioinosinic acid formation, and a number of selected enzymes involved in purine nucleotide synthesis. The amount of thioinosinic acid formed in L1210 cells was much higher than that in human leukemic leukocytes. In cell extracts, the synthesis of thioinosinic acid was similar in both cell types, and the amount of purine phosphoribosyltransferase was not rate limiting in either case. Much higher concentrations and rates of formation of phosphoribosylpyrophosphate were found in L1210 cells than in human leukemic leukocytes. The difference in response to 6-mercaptopurine between L1210 cells and human leukemic leukocytes might be attributed to their difference in supply of phosphoribosylpyrophosphate. Phosphoribosylpyrophosphate-amidotransferase was found to be high in L1210 cells, but was not detected in human leukemic leukocytes.     

Peritoneal recurrence of colon cancer detected by positron emission tomography: Report of a case

Increased glucose metabolism has been reported to occur in association with colorectal cancer. As positron emission tomography (PET) using [¹⁸F]fluorodeoxyglucose is able to depict hypermetabolic sites, it can therefore be used to detect colorectal cancer. A 69-year-old male patient with a recurrent solitary liver metastasis from colon cancer underwent whole-body PET which revealed high [¹⁸F]fluorodeoxyglucose uptake in the lesion. Furthermore, PET revealed peritoneal metastases that had not been detected by conventional imaging methods. Consequently, PET proved useful in helping us to avoid performing unnecessary treatment for the liver metastasis. Although it is uncertain whether early identification of recurrence can prolong survival, it may help to prevent unnecessary treatments being carried out. Thus, the application of PET in carefully selected patients could be beneficial to the management of recurrent colorectal cancer.     

Antiviral effect of octyl gallate against DNA and RNA viruses

The effects of gallic acid (3,4,5-trihydroxybenzoic acid) and its alkyl esters on virus growth and virion infectivity were examined. All the compounds tested showed an inhibitory effect on the growth of herpes simplex virus type 1 (HSV-1) in HEp-2 or Vero cells. The antiviral activity of gallic acid alkyl esters was enhanced by increasing the number of carbon in the alkyl moieties of the compounds, reaching maximum at a carbon number of 12 (lauryl gallate), but both cytocidal activity and cytopathic effect of the compounds were also significantly increased simultaneously. Among these compounds, octyl gallate showed a marked antiviral effect with a relatively moderate cytotoxity. In addition, octyl gallate suppressed the multiplication of RNA viruses, such as vesicular stomatitis virus and poliovirus. Quantitative characterization of the HSV-1 infection in the presence of octyl gallate revealed that: (1) this reagent can directly inactivate HSV-1 (virucidal activity), (2) it suppresses both the intracellar multiplication and the release of the virus, (3) it selectively accelerates death of the virus-infected cells and (4) the addition of the reagent even at 6-h post infection completely abolishes the formation of progeny virus in the infected cells.     

Comparative study of the effects of percutaneous ethanol injection and radiofrequency ablation in cases treated with a straight or expandable electrode

Radiofrequency ablation (RFA) has become mainstream among non-surgical treatment modalities in clinical settings for the treatment of hepatocellular carcinoma. We have previously described the novel combination therapy of percutaneous ethanol injection and RFA (PEI-RFA) and reported that this combination therapy was more effective than RFA alone in terms of the induced volume of coagulated necrosis and the energy requirement for the treatment. RFA instruments are mainly divided into two types according to the electrode used, either the straight or expandable type electrode. Although PEI-RFA can be performed by either of the electrodes, there may be some important differences in PEI-RFA according to the type of electrode used. In the present study, the effect of using the straight or expandable electrode in PEI-RFA was evaluated by analyzing the ablation time, volume of coagulated necrosis, the energy requirement for ablation and the amount of injected ethanol into HCC. The comparative study showed that ablation time, total energy requirement and per unit volume of energy requirement for whole and marginal coagulated necrosis were significantly smaller in the group treated with the expandable electrode (E group) than those in the group treated with the straight electrode (S group). The volume of coagulated necrosis was similar between these groups. In group E, the amount of injected ethanol showed a positive correlation with the volume of coagulated necrosis and the size of the tumors. These results suggest that prior injection of ethanol works mainly by shortening the time and energy requirement for ablation in the time-lag PEI-RFA using the expandable electrode. Thus, prior injection of ethanol before RFA may make RFA treatment less invasive in the time-lag PEI-RFA using the expandable electrode as previously shown HCC cases treated with straight electrode.     

Development and validation of a new formula for sex estimation based on multislice computed tomographic measurements of maxillary and frontal sinuses among Brazilian adults

Objectives:To evaluate the accuracy of the measurements of the maxillary sinus (MS) and frontal sinus (FS) in sex estimation among Brazilian adults using multislice computed tomography (MCT) and to develop and cross-validate a new formula for sex estimation.Methods:The present cross-sectional research was conducted in two phases: (1) development of a formula on the basis of the measurements of both the sinuses (50 males and 50 females); and (2) validation study (20 males and 20 females). The linear measurements (height, width and diameter) were assessed using the RadiAnt DICOM software. A new formula for sex estimation was developed (multivariate statistical approach) and validated. Receiver operating characteristic curves, area under the curve, sensitivity, specificity, positive and negative predictive values, accuracy and likelihood ratio were estimated.Results:Males displayed higher mean values (width, height and diameter) of the FS and MS (p < 0.05). The MS was a better predictor in sex estimation (males vs females), compared to the FS (accuracy between 61–74% and 58–69%, respectively). The distance between the right and left MS displayed the highest accuracy (74%). The sensitivity, specificity and accuracy of the new formula were 80%, 95.5% and 87.5%, respectively. 63.1% reduction was observed in the number of predictive values for sex estimation (individuals older than 30 years).Conclusions:The present MCT measurements showed a higher accuracy in the estimation of sex in males. The highest accuracy was associated with the distance between the right and left MS. The new formula displayed high precision for sex estimation.     

Septic shock induced by Serratia marcescens complicating adult T-cell leukemia (ATL)

A 75-year-old woman was admitted with fever of unknown origin and liver damage, and treated with prednisolone. Hypercalcemia appeared when of the dose of prednisolone was reduced, and human T-cell lymphotropic virus type-I (HTLV-I) proviral DNA was detected in the leukemic cells by Southern blot analysis, and a diagnosis of acute adult T-cell lymphoma (ATL) was made. After chemotherapy with sobuzoxane was started, she went into septic shock caused by multiple resistant Serratia marcesense, and was treated with PMX-DHP and antibiotics. Although ner general condition and her serum cytokine leyels improved, the septic shock became more severe, and the patient died. Serratia marcesense expreses lipopolysaccharide (LPS), a biologically active substance that is present in gram-negative bacteria. Exposure to LPS leads to activation of cytokines, including TNF-alpha, IL-1beta, IL-6, and IFN-gamma. After treatment with PMX-DHP, the patient's general condition improved, but she died of septic shock. Bacterial infection may be a life-threatening complication in the immunocompromised hosts and elderly patients, particularly when granulocytopenia has been induced by chemotherapy, and thus such these patients require careful management.     

Identification of the up- and down-regulated genes in the heart of juvenile visceral steatosis mice

Juvenile visceral steatosis (JVS) mice, novel animal models of systemic carnitine deficiency, exhibit a remarkably increased number of mitochondria in their cardiac myocytes. To date, however, there has been no reported investigation of the molecular mechanism of this increased number of mitochondria. Here, we analyzed the gene expression profile from the hearts of JVS and control mice by Affymetrix GeneChip analysis representing 34323 genes. We found that 176 genes, containing 93 known genes and 83 novel genes, were up-regulated in JVS mice compared with control mice, and 167 genes, containing 67 known genes and 100 novel genes, were down-regulated in JVS mice compared with control mice. We found several interesting molecular aspects that have not yet been identified in the hearts of JVS mice, including down-regulation of a number of ion channels and up-regulation of regulators involved in cell cycle progression. This genome-wide analysis should contribute to a greater understanding of the molecular mechanism of mitochondrial biogenesis in the heart of JVS mouse and provide a strategy for identifying novel genes involved not only in mitochondrial biogenesis but also in cardiac hypertrophy.     

A case of peritonitis carcinomatosa of pulmonary adenocarcinoma in which gefitinib was effective

We report a case in which gefitinib was effective in reducing the amount of ascites. A 61-year-old man with peritonitis carcinomatosa due to metastasis from pulmonary adenocarcinoma was admitted to our hospital. Various chemotherapies were not effective for controlling his ascites. Therefore, we orally delivered gefitinib at a dose of 250 mg/day. Three days after administration, a reduction in the amount of ascites was noticed. Subjective symptoms including general fatigue and difficulty breathing were dramatically improved as was QOL. We conclude that this case was a good candidate for treatment using gefitinib.     

Benzoylphloroglucinol derivatives from Hypericum scabrum

Nine new polyprenylated benzoylphloroglucinol derivatives, hyperibones A-I (1-9), were isolated from the aerial parts of the Uzbekistan medicinal plant Hypericum scabrum. Their structures were determined mainly on the basis of spectroscopic evidence (2D NMR and HRMS). Compounds 1, 2, and 4 showed mild in vitro antibacterial activity against methicillin-resistance Staphylococus aureus (MRSA) and methicillin-sensitive Staphylococus aureus (MSSA).     

Flavone markedly affects phenotypic expression of beta-lactam resistance in methicillin-resistant Staphylococcus aureus strains isolated clinically

Flavone and its derivatives had very weak antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus, but dramatically intensified MRSA's susceptibility to beta-lactams. We named these compounds "ILSMR (intensifier of beta-lactam-susceptibility in MRSA)." We also found discrepancies among MRSA strains in their responses to flavone; some strains showed phenotypic susceptibility to methicillin while others showed phenotypic resistance to it. To understand the mechanism underlying this discrepancy, we characterized 20 MRSA strains in detail, analyzed their conventional and molecular typings, and examined each strain's resistance to beta-lactams, with COL serving as a reference. Neither SCCmec typing nor coagulase typing explained the diverse effects of flavone on the beta-lactam MICs of these strains. Likewise, changes in pulsed-field gel electrophoresis (PFGE) type were not associated with the profiles of ILSMR effects. However, the present observations suggest that the ILSMR effects on MRSA is strain-specific, and that this effect depends on an as-yet unknown mechanism that is essential for the expression of the phenotype conferring beta-lactam resistance to MRSA strains, independently of an interaction with the mecA-encoded penicillin-binding protein 2a or with the beta-lactamase.