Late-onset type ornitine transcarbamirase deficiency (OTCD) with fulminant onset following a fatal prognosis]

A 16-year-old man was admitted to our hospital with nausea, general fatigue, and consciousness disturbance along with extreme hyperammoniemia eight days after the onset of symptoms. Familial history and the high concentration of orotic acid in urine lead us to a diagnosis of OTCD. We immediately initiated intensive treatment such as continuous hemodiafiltration and sodium benzoate administration; however, the patient died twelve days after admission. Since OTCD is not so rare and can be found in all ages, it should be considered fundamental for evaluation of hyperammoniemia. This case suggested that for a better prognosis of OTCD patients it is very important to prevent such an onset, and to make an as early as possible diagnosis and start to treatment.     

Histologic and immunohistochemical studies of alpha-fetoprotein (AFP)-producing gastric carcinoma

Five gastric adenocarcinomas and their metastatic nodules in the liver with high serum AFP levels were examined by histologic and immunohistochemical methods. The examination revealed that AFP-producing stomach cancers were poorly differentiated carcinoma cells, especially with medullary arrangements, or pleomorphic or multinucleated giant cells. Well-differentiated papillotubular adenocarcinoma tissues on the glandular epithelium were not stained with anti-AFP. One out of the five AFP-producing adenocarcinomas with medullary patterns resembled liver cell carcinoma on light microscopy. However, an ultrastructural study showed tumor cells of the intestinal type, since the cells possessed a ductal lumina with abundant microvilli and a secretory granules. The findings suggest that the tumor cells differentiated in an intestinal direction rather than hepatic direction. In addition, we noted three simultaneously CEA-positive cases out of five AFP-producing gastric carcinomas. CEA was strongly stained in well differentiated adenocarcinoma tissues in the glandular epithelium or in areas of medullary type carcinoma invasion. However, CEA was not detected in undifferentiated carcinoma cells.     

Hamartoma of the parotid gland: A case report with immunohistochemical and electron microscopic study

Summary A case of a solid parotid tumour in a 16-year-old boy is presented. Histologically, the tumour demonstrated some peculiar findings. An acinar pattern was predominant although every component seen in the normal salivary gland was present, namely, serous and mucous gland acini, ducts, myoepithelial cells, adipose and lymphoid tissue. Large eosinophilic granules were abundant in the large acinar cell cytoplasm. Immunohistochemically, the tumour demonstrated the proteins which are present in the normal parotid gland, for example, amylase, lactoferrin and lysozyme. Electron microscopic features were quite similar to those of normal parotid tissue except for accumulation of a large number of cytoplasmic granules in the acinar cells. There has been no previous report of a tumour with the same features as seen in this case. Our pathological diagnosis is hamartoma, although the possibility of hyperplasia or neoplasia can not be excluded.     

Application of in vivo microdialysis to pineal research in birds: Measurement of circadian rhythms of melatonin

Circadian rhythms of pineal melatonin release were measured in free-moving pigeons, Japanese quails, and chickens under light-dark cycles followed by constant dim light. Although melatonin levels differed among individual birds, circadian rhythms of melatonin were observed in all of them. Using this technique, we could examine phase shifts of melatonin rhythms and suppression of melatonin release by photic stimulation in pigeons. We could also examine effects of norepinephrine infusion on melatonin release. These results indicate that microdialysis is useful for the study of pineal melatonin rhythms in birds.     

Role of the N-terminus in permeability of chicken connexin45.6 gap junctional channels

Previous studies have shown that gap junctional channels formed from the lens connexins Cx50 (or its chicken orthologue, Cx45.6) and Cx43 exhibit marked differences in transjunctional voltage gating and unitary conductance. In the present study, we used the negatively charged dye, Lucifer Yellow (LY), to examine and compare quantitative differences in dye transfer between pairs of HeLa cells stably transfected with Cx45.6 or Cx43. Our results show that Cx45.6 gap junctional channels are three times less permeable to LY than Cx43 channels. Replacement of the N-terminus of Cx45.6 with the corresponding domain of Cx43 increased LY permeability, reduced the transjunctional voltage ( V _j) gating sensitivity, and reduced the unitary conductance of Cx45.6–43N gap junctional channels. Further experiments, using a series of Alexa probes that had similar net charge but varied in size showed that the Cx45.6–43N had a significantly higher permeability for the two largest Alexa dyes than Cx45.6. These data suggest that the N-terminus plays a critical role in determining many of biophysical properties of Cx45.6 gap junctional channels, including molecular permeability and voltage gating.     

Clonal expansion of multiphenotypic Epstein-Barr virus-infected lymphocytes in chronic active Epstein-Barr virus infection

Chronic active Epstein-Barr virus (EBV) infection has been recognized as clonal non-neoplastic lymphoproliferative diseases. However, some reports of cases with a multiphenotypic expansion of EBV-infected lymphocytes give rise to questions of how EBV infects multiphenotypic lymphocytes and whether chronic active EBV infection is a truly monoclonal lymphoproliferative disease. We report two patients with chronic active EBV infection who showed expansion of multiphenotypic EBV-infected lymphocytes. EBV DNA was detected in CD4+ and CD8+ T cells and in B cells from pleural fluid of one patient and in T and B cells from a cervical lymph node of the other patient by polymerase chain reaction (PCR). Although real-time PCR showed that there were equally high loads of EBV genomes in CD4+ and CD8+ T cells from the pleural fluid, Southern blot hybridization with terminal repeats of the EBV genome showed a single band of the same molecular weight in three tissue samples from the patient. The results indicated biphenotypic expansions of CD4+ and CD8+ T cells infected with the same clone of EBV. Furthermore, bisulfite PCR analysis showed hypermethylated status in the Cp region in the two patients regardless of their cell populations. There has been a discrepancy between clonality and expansion of multiphenotypic EBV-infected lymphocytes. We speculate that lymphoid progenitor cells that have not differentiated into T and B cell progenitors are infected with EBV, resulting in clonal expansion of EBV-infected multiphenotypic cells.     

Circadian rhythms of pineal melatonin release in the pigeon measured by in vivo microdialysis.

Circadian rhythms of pineal melatonin release were measured in freely moving pigeons (Columba livia) by in vivo microdialysis. The birds were placed in light-dark cycles with 12 h of light and 12 h of darkness (LD 12:12) or continuous dim light (LLdim) after LD 12:12. Although the level of melatonin was various, daily changes of melatonin with higher levels during the dark and lower levels during the light were observed in all of the birds examined. The daily changes of melatonin persisted in LLdim, indicating circadian nature of pineal melatonin release. Moreover pineal melatonin release was inhibited by acute exposure of light during the dark. These results indicate that microdialysis is useful for studying circadian pineal melatonin rhythms of birds.     

In situ telomerase activity in pleural effusions: a promising marker for malignancy

Telomerase activity in 16 pleural effusions was studied using an in situ telomerase repeat amplification protocol (TRAP) assay on cytospin preparations. Six of nine cytologically malignant specimens contained telomerase-positive cells (67%), and in two further specimens, suspicious positive cells were seen. Two of four atypical specimens contained telomerase-positive cells, whereas two benign cases were telomerase-negative. No mesothelial cells showed telomerase reactivity. Thus, telomerase activity was specific for malignancy and it was always found only in malignant cells. The results suggest that telomerase activity measured with this in situ method can be a valuable complement in the assessment of malignancy in pleural effusions.     

Control of B cell production by the adaptor protein lnk. Definition Of a conserved family of signal-modulating proteins

Lnk is an SH2 domain-containing adaptor protein expressed preferentially in lymphocytes. To illuminate the importance of Lnk, we generated lnk(-/-) mice. Whereas T cell development was unaffected, pre-B and immature B cells accumulated in the spleens. In the bone marrow, B-lineage cells were proportionately increased, reflecting enhanced production of pro-B cells that resulted in part from hypersensitivity of precursors to SCF, the ligand for c-kit. Hence, Lnk ordinarily acts to regulate B cell production. Further characterization of lnk(-/-) mice also revealed that full-length Lnk is a 68 kDa protein containing a conserved proline-rich region and a PH domain. Lnk is a representative of a multigene adaptor protein family whose members act, by analogy with Lnk, to modulate intracellular signaling.