Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix

Epithelial neoplasms of appendix are infrequent, and their pathological features are not fully characterized. We collected 33 cases of appendiceal tumors and examined immunohistochemically the expression of cytokeratins (CK, CK7, and CK20), mucin core protein (MUC1, MUC2, MUC5AC, and MUC6), E-cadherin, chromogranin A, and p53 protein. Gene analysis of TP53 was also conducted on exons 5 to 8. Clinically, mucinous tumors were predominant in females. Immunohistochemically, all the tumors expressed CK20, whereas CK7 was positive in one third of the cases. Similarly, MUC2 was expressed in all the tumors, whereas MUC1 and MUC5AC were detected in about a half of the cases. Although chromogranin A-positive cells are generally sparse in normal appendix, they were more common in mucinous tumors than in nonmucinous tumors. Contrary to the previous data reported (Mod Pathol 2002;15:599-605), mucinous carcinoma exhibited a higher frequency of p53-positive cells (mean 29%) compared with mucinous adenoma (2.8%) (P < .001), whereas nonmucinous tumors showed high levels of p53-positive cells to similar extent (51%-67%) in both adenoma and carcinoma. The high expression of p53 protein coincided with the presence of mutations in multiple sites of TP53 gene in mucinous tumors. This is the first report that characterized the immunophenotypic profile of appendiceal epithelial neoplasms with an emphasis of a higher frequency of p53 positivity in mucinous carcinoma cases compared with mucinous adenoma in the appendix.     

Effects of various compounds on histidine decarboxylase activity: Active site mapping

The effect of about one hundred compounds on the activity of histidine decarboxylase partially purified from whole bodies of fetal rats was determined. Most of them at their 10 mM concentration had little effect on the enzyme activity; but 12 compounds inhibited the enzyme to a greater extent than 30%. Among these, except for -methylhistidine that has been known to be a strong and specific inhibitor, DOPA, homocysteine, cysteine, methionine and urocanic acid were the best inhibitors; -phenyllactic acid, phenylpyruvic acid and carnosine were less strong inhibitors; valine, oxaloacetic acid andN -methylimidazole acetic acid were weak inhibitors. Histamine had no inhibitory action. Thus, the substrate binding site of histidine decarboxylase is very rigid and specific forl-histidine.     

SYNDROME OF THE SEA-BLUE HISTIOCYTE —The First Case Report in Japan and Review of the Literature—

A case of the syndrome of sea-blue histiocyte is presented in a 53-year-old Japanese woman, which is the first recorded case in Japan. The patient had hepatosplenomegaly, bleeding manifestations, mild thrombocytopenia, fatty metamorphosis and cirrhosis of the liver, as well as abnormal serum lipid profiles. Her parents were consanguineous and her maternal grandmother with hepatomegaly died of hepatic failure. Histologically, peculiar histiocytes containing numerous, intracytoplasmic sea-blue stained granules on May-Giemsa stain were demonstrated in biopsy materials of the bone marrow, lymph node and liver. The sea-blue granules in these histiocytes proved to have histochemical staining characteristics of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic inclusions of heterogeneous nature, including electron-dense amorphous or variegatedly osmiophilic, frequently laminated materials. Enzyme cyto-chemically, localization of acid phosphatase activity was demonstrated in and around the intracytoplasmic inclusions. With regard to the pathogenesis of the sea-blue histiocytes in this case, it may be suggested that the existence of the abnormality in lipid metabolism plays an imporant role in intralysosomal ceroidogenesis in these histiocytes.     

Intracytoplasmic immunoglobulin crystals in follicular lymphoma

We report a case of follicular lymphoma with crystal inclusions. Swollen lymph nodes taken from the left neck of a 53- year-old Japanese woman were replaced by follicular proliferation of atypical centroblastic and centrocytic cells with intracytoplasmic crystal inclusions. The crystals were confined to lymphoma cells and were not found in histiocytes. Lymphoma cells were positively immunostained with lambda light chain and mu heavy chain, but the crystals were only weakly so. In situ hybridization of light chains disclosed a monoclonal expression of lambda light chain mRNA in lymphoma cells. The crystals had a periodic linear substructure with about 5-nm intervals. The worldwide literature reports 8 cases, including the current case of non-Hodgkin's lymphoma with crystals confined to the neoplastic cells. The cases did not accompany paraproteinemia and crystal-storing histiocytosis and appear to follow a favorable clinical outcome.     

Detection of ornithine transcarbamylase deficiency heterozygotes by measuring of urinary uracil

The importance of detecting heterozygosity for X-linked ornithine transcarbamylase deficiency is well known. Although the DNA analysis and the allopurinol loading tests are commonly used for this purpose, both methods require complicated procedures. In order to establish a simple test for detecting female heterozygotes, we examined the uracil and orotic acid in single-voided urine samples from 70 healthy women, and from 12 asymptomatic females with ornithine transcarbamylase deficiency. Based on the results of healthy women, we were able to determine a screening cut-off line of 11.9 micromol/mmol creatinine (mean +/- 1SD in logarithmic form) for uracil. Using this cut-off line, the sensitivity of OCT heterozygotes was 100%. We were also able to establish a second cut-off line of 28.9 micromol/mmol creatinine (mean +/- 3SD in logarithmic form) for diagnosis. Using this second cut-off line, the specificity of OCT heterozygotes was 100%. Our study has shown that the measurement of urinary uracil is a relatively simple and effective method for detecting female heterozygotes.     

High-performance liquid chromatography with peroxyoxalate chemiluminescence detection of bisphenol A migrated from polycarbonate baby bottles using 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride as a label

A highly sensitive and selective high-performance liquid chromatographic method with peroxyoxalate chemiluminescence detection for the determination of bisphenol A at sub-ppb levels is described. Bisphenol A was derivatized with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride and the excess unreacted reagent was removed by a simple solid-phase extraction procedure with recoveries of approximately 60%. The separation was carried out isocratically on an ODS column and the derivatized bisphenol A was detected by peroxyoxalate chemiluminescence. A mixture of bis[2-(3,6,9-trioxadecanyloxycarbonyl)-4-nitrophenyl]oxalate (0.6 mM) and hydrogen peroxide (25.0 mM) dissolved in acetonitrile was used as a chemiluminescence reagent solution with a mixture of imidazole-HNO3 buffer (40.0 mM, pH 7.0): acetonitrile (17:83, v/v) as a mobile phase. The linear standard curve was obtained over the range from 0.57 (2.5) to 22.8 (100) ppb (nM) (r=0.996) with a detection limit of 0.38 ppb (2.8 fmol on column) at a signal-to-noise ratio of 3. The method was successfully applied to the determination of bisphenol A in hot water in contact with commercially available baby bottle samples.     

Fate of odontoblasts and blood capillaries in the incisal region of the rat incisor pulp

Transmission electron microscopy of thin sections of the rat incisor pulp revealed that in the middle region of the incisor there were fenestrated capillaries in the “predentinal plexus” and that this region contained the tallest odontoblasts. The odontoblasts gradually became shortened in the incisal part of this region: the fenestrated capillaries in the predentinal plexus changed to continuous type capillaries. Almost all the odontoblasts had degenerated near the incisal end of the tooth. The predentinal plexus disappeared in this region, but the “subodontoblastic capillary plexus” persisted. In a specific region just beneath the worn incisal end, numerous macrophages and polymorphonuclear neutrophils appeared and scavenged the degenerating cells, possibly including the odontoblasts. © 1993 Wiley-Liss, Inc.     

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.