CONCLUSION:Pancreatitis-associated protein (PAP) mRNA is expressed in some cases of gastric and colorectal cancers resulting from an ectopic expression in dedifferentiated cancer cells.BACKGROUND:The PAP gene is identical to the hepatoma-intestine-pancreas (HIP) gene, which is expressed in hepatoma. Expression in cancer might be another characteristic of PAP.METHODS:Fresh surgical specimens of 100 gastrointestinal cancers, 14 benign digestive diseases, and six normal organs were studied with nonisotopic in situ hybridization (ISH) using biotin-labeled cDNA probe.RESULTS:PAP mRNA was detected in 10% (6/60) of gastric cancers, 21.4% (6/28) of colorectal cancers, 20.0% (1/5) of pancreatic cancers and 0% of biliary tract (three), esophageal (one), and hepatocellular cancers (three). Reverse transcription-polymerase chain reaction (RT-PCR) detected PAP mRNA in these ISH-positive cases. PAP mRNA was not detected in noncancerous portions, benign disease tissues, or normal organs except for the small intestine. There was no relationship between PAP mRNA expression and any clinicopathological factors.

The nucleotide sequences of cDNAs encoding human and mouse homologues for rat pancreatitis-associated protein (PAP) (J. Iovanna et al. (1991) J. Biol. Chem. 266, 24664–24669) were determined. The expression level of PAP mRNA was very low in healthy pancreas, but an unexpectedly high level was found in normal small intestine.

rig , a gene originally isolated from a rat insulinoma cDNA library, codes for a basic 145 amino acid protein [(1986) Diabetes 35, 1178–1180]. Here we show that the immunoreactivity to a monocional antibody against the deduced rig protein and the translation product of rig mRNA comigrated with ribosomal protein S15. The amino acid sequence of ribosomal protein S15 purified from rat liver coincided with that deduced from the nucleotide sequence of rig mRNA, but there were indications that the initiator methionine was removed and the succeeding alanyl residue was monoacetylated. From these results, we conclude that the product of rig is ribosomal protein S15.

AbstractS‐8666, a newly developed antihypertensive uricosuric diuretic, possesses an asymmetric carbon and exists as a racemic mixture. The enantioselectivity of S‐8666 in natriuresis and the renal excretory mechanisms of the S‐8666 enantiomers were examined. Dose‐dependent natriuresis of the S‐(−)‐enantiomer was observed in male Sprague‐Dawley rats (3–100 mg/kg, p.o.), female Slc:ddy mice (3–300 mg/kg, p.o.) and male NIBS Japan white rabbits (1–10 mg/kg, i.v.). The R‐(+)‐enantiomer produced no significant change in sodium excretion within dose ranges of 100–200 mg/kg p.o. for rats, 3–300 mg/kg p.o. for mice, and 10 mg/kg i.v. for rabits. The (−)‐enantiomer and racemic S‐8666 showed a high‐ceiling property like that of furosemide and unlike that of trichlormethiazide. Plasma protein binding of S‐8666 was over 95% in rabbits and 73% in beagle dogs. In rabbits, both enantiomers of S‐8666 were secreted equally from the proximal tubule; however, only the (−)‐enantiomer of S‐8666 showed diuresis in a stop‐flow pattern. In beagle dogs, secretion of racemic S‐8666 occurred from the proximal tubule and could be inhibited by probenecid. The renal excretion of S‐8666 was largely the result of tubular excretion in rabbits whereas in beagle dogs, some glomerular filtration was also involved in urinary excretion. In conclusion, S‐8666 shows enantioselectivity in natriuresis. Both enantiomers of S‐8666 are excreted mostly by the organic acid transport system in the proximal tubule, but only the (−)‐enantiomer of S‐8666 induces natriuresis from the luminal side of the tubule.

reg was originally identified as a gene expressed during the regeneration of insulin-producing pancreatic beta-cells of the rat. We built an expression vector containing human reg cDNA to drive Saccharomyces cerevisiae to synthesize the reg protein, and purified it from the culture medium. The 144-amino acid sequence of the recombinant protein was consistent with that deduced from the cDNA and genomic DNA sequence except that the signal sequence of 22 amino acids was eliminated, and the amino-terminal residue of the protein was pyroglutamic acid. The secondary structure of the reg protein was predicted by determination of the intramolecular cystine linkage and of alpha-helix and beta-sheet contents.

Several steroid derivatives having the delta 11-pregnane skeleton with a 17-gamma-spirolactone function were synthesized to evaluate their antialdosterone activity and to elucidate the relation between their binding affinity to mineralocorticoid receptor (MR) and their mineralo- and/or antimineralocorticoid activity. Although many of the synthesized compounds showed strong binding affinity for the MR and aldosterone agonist activity, 3-(17 beta-hydroxy-3-oxoandrosta-1,4,6,11-tetraen-17 alpha-yl)propionic acid gamma-lactone exhibited good aldosterone antagonist activity in an in vivo assay. Its in vivo antiandrogenic activity was also found to be relatively weak.

Age and sex dependent differences of N-acetyl-β-D-glucosaminidase (NAG) and L-alanine aminopeptidase (AAP) activities in kidney, urine and plasma of male and female mice were studied. The sex difference in NAG activity appeared between 27 and 38 days of age with the manifestation of significant differences in body weight and kidney growth. NAG activity in male kidneys was 3-fold that in females and its urinary level in mature males was over 10-fold higher. Androgenic regulation was found not only in the NAG contents in the kidneys and in the urinary excretion but also in the plasma NAG level, which showed higher in females. On the other hand, AAP activity in kidney, urine and plasma did not show much sex differences. Age related changes in AAP activity were not found except in the kidney and marked androgenic regulation was also not found in AAP. These results indicate that NAG and AAP, which are both urinary enzymes used as indicators of renal lesions, may be regulated differently.

Statistical studies on the prognosis of anorexia nervosa were carried out by our research group. Subjects were 224 cases from 36 university hospitals throughout Japan. A questionnaire was mailed to each of the 224 patients in cooperation with their doctors. The outcome of 143 of the 224 cases was judged by their doctors as 'good' in 47 cases, 'intermediate' in 69 cases and 'poor' in 19 cases. 8 of the patients had died. The prognosis of typical cases was much poorer than that of atypical cases.

N-Acetyl-beta-D-glucosaminidase (NAG) activities in urine, kidney, and plasma were compared in an age-matched group of male and female ds mice. In males, the NAG activity in the kidney was significantly higher (p less than 0.001), and the urinary NAG activity (unit/g creatinine) was 8-fold higher than those for females, while plasma NAG levels were significantly lower (p less than 0.001). These findings indicate that when using urinary NAG activity to detect drug nephrotoxicity in mice, the different basal levels between males and females should be considered before drug administration.

L-Alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) activities in urine are sensitive indicators of renal damage. However, urinary AAP loses its activity during storage in the frozen state. This study proposes a method for preventing the inactivation of AAP by adding glycerol to a final concentration of 10% to a urine sample before freezing and thawing. This study also showed that NAG is stable to freezing and thawing and is not affected by addition of glycerol.

Urinary N-acetyl-beta-D-glucosaminidase (NAG), a sensitive marker for renal damage, was much higher in male beagles than in females. The daily output of NAG into urine in male beagles was almost three times that in females. Following bilateral vasectomy or castration, marked decreases occurred in urinary NAG output. These results led to the conclusion that the high urinary NAG output in male beagles is largely due to an admixture of secreted fluid from the gonadal system in the bladder. Thus, when using beagles for nephrotoxicity studies with NAG as a parameter, females are preferable.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity differed greatly between male and female beagle dogs in an age-matched group. The NAG activity in males per animal, per body weight, or per 16-hour urine sample was approximately double that in females and was 2.4-fold higher when the activity was considered relative to urinary creatinine. On the other hand, alanine aminopeptidase activity relative to urinary creatinine was not significantly different between males and females. These findings indicate that when using urinary NAG activity to detect drug nephrotoxicity in dogs, some consideration must be given to different control levels between males and females before starting drug administration.