Takashi Morimoto

CYP1A1 CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to squamous-cell carcinoma of the esophagus

We investigated the genetic polymorphisms of CYPIAI, CYP2EI and GSTMI in Japanese esophageal cancer patients (n = 53) with a histological diagnosis of squamous‐cell carcinoma, to determine whether susceptibility to esophageal cancer is associated with these polymorphisms. There were no significant differences in the frequency distribution of any one of the 3 polymorphisms between esophageal cancer patients and 132 healthy Japanese controls. The genotype distributions in tobacco smokers or alcohol drinkers were also quite similar for male patients and male controls. The age at onset of esophageal cancer was also similar for patients with any genotype of the 3 polymorphisms. We conclude that the 3 polymorphisms are unlikely to be associated with esophageal cancer susceptibility. Int. J. Cancer 71:192–195, 1997.

does Serum Ca19-9 Play a Practical Role in the Management of Patients With Colorectal Cancer?

PURPOSE: CA19-9 is often used in combination with carcinoembryonic antigen to manage patients with colorectal cancer, even though there is insufficient evidence to support this use of CA19-9. Carcinoembryonic antigen, by contrast, has been regarded as a better indicator of poor prognosis and recurrence. The purpose of this study is to clarify whether CA19-9 is, in fact, a useful marker in the management of colorectal cancer patients by comparing it with carcinoembryonic antigen. METHODS: A retrospective investigation was done for a consecutive series of 155 patients with colorectal adenocarcinoma who underwent potentially curative surgery between 1995 and 1999. Excluded were patients with postoperative assays performed less than three times for either carcinoembryonic antigen or CA19-9 and those who had developed secondary cancers. Data from 118 patients were analyzed in terms of prediction of prognosis and detection of recurrences. RESULTS: The sensitivities of preoperative CA19-9 and carcinoembryonic antigen were 29.8 percent and 45.3 percent, respectively. In the univariate analysis of preoperative carcinoembryonic antigen and CA19-9 assays in 114 patients, high carcinoembryonic antigen level was significantly associated with poor prognosis (P = 0.0090 by log-rank test). We could not find a significant association between preoperative CA19-9 abnormality and survival (P = 0.12). Multivariate analysis of preoperative factors indicated significance in TNM stage (P = 0.0094) and tumor location (P = 0.036) but in neither carcinoembryonic antigen (P = 0.061) nor CA19-9 (P = 0.22). Among 40 patients with recurrences, postoperative elevations of tumor markers were seen in 19 cases for CA19-9 and in 37 for carcinoembryonic antigen throughout the follow-up periods. Sensitivity, specificity, positive predictive value, and negative predictive value were 0.48, 0.88, 0.68, and 0.77, respectively, for CA19-9, and 0.93, 0.88, 0.80, and 0.96, respectively, for carcinoembryonic antigen. In patients with recurrences, the initial postoperative elevation of tumor markers was seen earlier than the detection of recurrence in 68.4 percent of those with CA19-9 elevation and in 67.6 percent of those with carcinoembryonic antigen elevation. There was only one patient with recurrence who had CA19-9 elevation without carcinoembryonic antigen elevation, while 19 recurrent patients had carcinoembryonic antigen elevation without CA19-9 elevation. Multivariate analysis showed a significant risk of carcinoembryonic antigen elevation against recurrence with an odds ratio of 32.0 (P < 0.0001), in contrast to an insignificant association of CA19-9 elevation (P = 0.23). CONCLUSION: We could not find clinical significance to support the use of CA19-9 to predict the prognosis and detect recurrence of colorectal cancer. Because of this, we do not recommend routine use of CA19-9 in staging and surveillance of colorectal cancer patients.

The Significance of the Intraoperative Repeated Dosing of Antimicrobials for Preventing Surgical Wound Infection in Colorectal Surgery

PurposeIt is widely accepted that antimicrobial prophylaxis is useful for the prevention of surgical wound infection, especially in colorectal surgery. While many reports support the finding that the first dose should be administered immediately before surgery, there is less evidence concerning the ideal timing for the second dose. The purpose of this study is to examine the significance of intraoperative repeated dosing.MethodsA surgical series of 131 patients with primary colorectal cancer was retrospectively analyzed for 14 parameters, including the protocols of antimicrobial administration to determine the clinical risk factors for surgical wound infection.ResultsThe overall surgical wound infection rate of the 131 patients was 16.0% (21/131). When the operation finished within 4 h after the first dose (n = 29), wound infection was observed in only one patient (3.4%). In a prolonged operation exceeding 4 h after the first dose, the surgical wound infection rates were 8.5% and 26.5%, respectively, for those with (n = 47) and without (n = 49) intraoperative repeated dosing, which were significantly different based on both a univariate analysis (P = 0.031) and a multivariate analysis (P = 0.0079).ConclusionIntraoperative repeated antimicrobial dosing is therefore recommended to prevent the surgical wound infection for prolonged colorectal surgery.

Effects of Nucleosides and a Nucleotide Mixture on Gut Mucosal Barrier Function on Parenteral Nutrition in Rats

BACKGROUND We have previously reported that the addition of nucleosides and a nucleotide mixture (OG-VI) to total parenteral nutrition (TPN) prevents TPN-induced intestinal mucosal atrophy and results in increased intestinal cathepsin activities under TPN. The aims of the present study are to examine the effects of OG-VI on mucosal barrier functions and to clarify whether the intestinal cathepsins can be used as a new marker of mucosal barrier function. METHODS Male Wistar rats were divided into three groups: FED (food ad libitum), TPN (a standard TPN solution), and OG (OG-VI in addition to the TPN solution). Mucosal barrier functions were analyzed by the lactulose/mannitol (L/M) test, mucosal ZO-1 messenger RNA level, and electron micrographs in the gut. Intestinal cathepsin B, H, and L activities were also measured. RESULTS The L/M ratio for TPN was much higher than that for FED. Only lactulose excretion was significantly reduced by OG-VI. The intercellular spaces of the mucosal cells for TPN were significantly wider than those for FED, but were reduced in size by the addition of OG-VI. All cathepsin activities of the ileum were higher for TPN than for FED, whereas OG showed no increase. CONCLUSION OG-VI contributes to the improvement of gut mucosal barrier function. Intestinal cathepsin activities can be used as a new marker of mucosal barrier function.

Modulation of thermogenic response to parenteral amino acid infusion in surgical stress.

Thermogenic response to parenteral infusion of amino acid mixtures in rats undergoing surgical stress was investigated with the aid of a small animal indirect calorimeter. Male Wistar rats (n = 12) were laparotomized and received intestinal abrasion along with construction of a parenteral route. After 48 h, nutrient-induced thermogenesis (NIT) produced by amino acid mixtures was examined and compared with that of control rats (n = 12) without surgical stress. The NIT values of the leucine-enriched solution were greater than those of the control solution in both rats with and without surgical stress. The NIT generated by the leucine-enriched solution in rats with surgical stress was significantly higher than that in rats without. NIT values for 10 different kinds of single amino acid solutions with identical concentrations was then examined in 60 rats. The NIT values of the leucine and the glycine solutions were relatively higher than those of other solutions. However, when puromycin was injected intraperitoneally into 12 rats just before measurement of the NIT in response to amino acid mixtures, no significant differences were found in NIT values between the mixtures. In summary, surgical stress increased the thermogenic response to the leucine-enriched solution, indicating that utilization of leucine may be augmented under surgical stress. In fact, leucine itself may be a thermogenic amino acid. Inhibition of protein synthesis prevented the increase in thermogenic response induced by the leucine-enriched solution. We conclude that thermogenic responses to parenteral amino acid mixtures may differ depending not only upon the compositions of amino acids but also upon the host conditions.

Modulation of circadian expression of D‐site binding protein by the schedule of parenteral nutrition in rat liver

The aim of this study was to investigate the changes in the circadian rhythm of the expression of liver‐specific genes caused by different schedules of parenteral nutrition (PN). Rats received PN continuously throughout the day or intermittently during the night or day for 7 days. They were examined for gene expression of D‐site binding protein (DBP), albumin, and cytochrome P450 cholesterol 7α‐hydroxylase (CYP7) in the liver. The nocturnal PN group showed circadian expression of DBP messenger RNA (mRNA) and protein with a peak at 10 PM, in the same manner as the control rats receiving normal chow feeding. However, the diurnal PN group showed inverted expression of DBP mRNA and protein with a peak at 10 AM. CYP7 mRNA levels exhibited good synchronization with the levels of DBP mRNA in all groups, whereas albumin mRNA levels did not show such synchronization. Gel mobility‐shift assay disclosed that the binding activity of the nuclear extracts to the CYP7 gene promoter was changed by the PN schedule in accordance with the expression of CYP7 mRNA. The PN schedule modulates the circadian rhythm of DBP expression and may have an effect on hepatic bile acid formation through transcriptional regulation of the CYP7 gene.

Increased Urinary Excretion of Bilirubin Metabolites in Association with Hyperbilirubinemia After Esophagectomy

This study was conducted to investigate the rationale for postoperative hyperbilirubinemia after major surgery. The serum bilirubin values and urinary excretion of bilirubin metabolites (BM) were monitored in 11 patients who underwent esophagectomy via right thoracotomy for esophageal cancer. Both the serum bilirubin values and the urinary excretion of BM increased postoperatively in all patients. The maximum serum bilirubin level in four patients with septic complications, two of whom developed pneumonia and two, anastomotic leakage (group A), was significantly higher at 5.25+/-4.16 mg/dl than in the remaining patients without septic complications (group B), at 2.11+/-0.07 mg/dl. The peak value of urinary BM was 99.5+/-88.2 micromol/day in group A and 23.5 +/-26.7 micromol/day in group B. The correlation between the level of serum bilirubin and urinary BM excretion was found to be significant. Thus, the metabolism of bilirubin was increased by extensive surgical stress and septic insult.

Optical second-harmonic generation by quasi-phase matching in channel waveguide structure using organic molecular crystal

Waveguide quasi-phase matching second-harmonic generation (QPM-SHG) using an organic molecular crystal as a nonlinear material was demonstrated for the first time. The device is constructed with an array of SiN channel guides with grooves of a fan-out grating pattern and mNA single crystal grown over the waveguides. A normalized efficiency of 0.04%/W was obtained in an experiment involving frequency doubling of CW Nd:YAG laser light.<<ETX>>

Effect of parenteral and enteral nutrition on hepatic albumin synthesis in rats

The route of nutrient delivery may alter the production of albumin and induce changes at the molecular level. Donryu rats (n = 75) were divided into the following three groups. The oral feeding (OR) group received a non-purified solid diet ad libitum, the parenteral nutrition (PN) group received a total parenteral nutrition (TPN) solution intravenously, and the enteral nutrition (EN) group received intragastric infusions of the TPN solution for 7 d. Serum albumin and glucocorticoid levels were measured and messenger RNA (mRNA) levels of albumin and hepatic specific transcription factors in the liver were analyzed. Serum albumin and albumin mRNA levels in the PN group became significantly decreased compared to those in the OR group, whereas the EN group did not show a significant difference compared to the OR group. mRNA levels of DBP, D-site binding transcription factor for the albumin gene, showed a circadian rhythm in the OR and EN groups, but not in the PN group, as indicated by a DBP mRNA level at 2200 h in the PN group that was significantly lower than that in the OR group. mRNA levels of C/EBP alpha, CCAAT-enhancer binding protein alpha, were highest in the OR group and lowest in the PN group. In contrast, mRNA levels of C/EBP beta were highest in the PN group and lowest in the OR group. Serum glucocorticoid level showed a circadian rhythm in the OR group, highest at 2200 h and lowest at 1000 h, whereas such a rhythm was not found in either the PN or the EN group. Albumin synthesis was down-regulated in PN in association with changes in transcription factors. A loss of circadian rhythm reflected in changes of DBP mRNA and serum glucocorticoid level may play a role. Down-regulation of albumin was improved by enteral feeding, indicating that EN is more advantageous for albumin synthesis than PN.

General coupled-mode analysis of Cerenkov-radiation-type second-harmonic generation in channel and fiber waveguides

Coupled-mode analysis of Cerenkov-radiation-type second-harmonic generation, using channel and fiber waveguides, is presented from the viewpoint of device design. Nonlinear coupled-mode equations generally applicable for various waveguide configurations are derived and solved by considering the effects of pump-power depletion, waveguide loss, and effects of nonlinear gratings. Analytical expressions for the conversion efficiency as well as the near- and far-field radiation patterns are given, and the physical implications are discussed. The approximate results calculated for typical device configurations are summarized in graphic form, with normalized parameters. Guidelines for optimum design are given. >