Immunohistochemical analysis of centromere protein F expression in buccal and gingival squamous cell carcinoma

Centromere protein F (CENP-F) expression (localization and characteristics) in relation to tumor clinicopathological parameters was immunohistochemically examined and evaluated in 47 archival biopsy specimens of buccal and gingival squamous cell carcinomas (SCC). Centromere protein F expression was detected in 79% of the samples. An increase in the labeling index (LI) with WHO grading was obtained ( P  < 0.05). Correlations were obtained between the CENP-F LI and tumor size ( P  < 0.05). Immunoelectron microscopy showed CENP-F nuclear staining as punctate or fine dots. The present study shows that CENP-F expression and detection of a more specific cell subpopulation presents a theoretical advantage for the analysis of the precise cell cycle of G₂ to M cells, compared to Ki-67.     

Frequent allelic loss at the TOC locus on 17q25.1 in primary breast cancers

Sporadic breast cancers often show allelic losses on the long arm of chromosome 17. Since the BRCA1 gene lies at 17q21.1 and the TOC locus, associated with esophageal cancer, lies at 17q25.1, either gene could be the target of those losses. We examined both loci in 178 primary breast cancers, using microsatellite markers covering the relevant regions of 17q, and observed allelic losses in 97 tumors (55%). Losses were most frequent at markers around the TOC locus (48% at D7S1839 and 43% at D17S1603), where we identified a distinct commonly deleted region within a I -cM interval. Another larger, separate commonly deleted region including the BRCA1 gene was also identified, which exhibited 45% of allelic loss (at D17S934). Allelic loss on 17q was more frequent in tumors of the solid-tubular histologic type (P = 0.0129) and in estrogen-negative and progesterone-negative tumors (P = 0.0281 and 0.0196, respectively). The results indicated that BRCA1 and TOC are independent targets of allelic loss on 17q in primary breast cancers, and that inactivation of the TOC locus in particular may play an important role in the genesis of sporadic breast tumors.     

Enhancement of lipopolysaccharide-stimulated cyclooxygenase-2 mRNA expression and prostaglandin E2 production in gingival fibroblasts from individuals with Down syndrome

It is well known that Down syndrome (DS) is a premature ageing syndrome. Periodontal disease in individuals with DS develops rapidly and extensively in a relatively younger age bracket compared with that in healthy controls. The mechanisms involved in the periodontal inflammatory processes in DS patients are not fully understood. In the present study, the non-inflamed gingival fibroblasts isolated from seven patients with DS (DGF) and seven healthy controls (NDGF) were stimulated with lipopolysaccharide (LPS) derived from Actinobacillus actinomycetemcomitans (A. a.). We measured the level of prostaglandin E2 (PGE2) production by DGF and NDGF by radioimmunoassay, and also measured the mRNA expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) by using the real-time PCR method. We found the higher levels of LPS-stimulated COX-2 mRNA expression and PGE2 production in DGF when compared with those in NDGF. This study may indicate that overexpression of LPS-stimulated COX-2 induced a greater ability of DGF to produce PGE2, and that these phenomena may be responsible for the severer periodontal disease in DS patients.     

Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients

A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.     

Education of medical technologists in North America

The increasing complexity of diseases and advancing medical technologies have recently raised the number of test items and their use. This has caused each department to ask for clinical support by medical technologists, including consultation services on clinical laboratory tests in Japan. Under these circumstances, we think it is necessary to consider a Japanese education system for medical technologists to foster people with advanced ability capable in providing adequate clinical support. It is important that we study medical technologist systems and education systems superior to than ours. Therefore, to investigate the state of the Japanese education system for medical technologists, we conducted a comparison between the medical technologist systems and education systems in foreign countries and those of Japan. The social background in which medical technologists are positioned, their scope of work, and the education systems overseas are different from Japan on many points and we were given many suggestions for what a system in Japan should be like.     

Morphogenesis of the secondary palate in mouse embryos with special reference to the development of rugae

Morphological studies of secondary palate formation, with special reference to the development of rugae, were carried out on Jcl:ICR mouse embryos. Three rugae were observed on the anterior part of the future oral surface of the vertically developing palatal shelves in 13-day embryos. Rugae increased in number as the development of the palatal shelves proceeded, and five to six prominent rugae were observed in 14-day embryos just prior to shelf elevation. The folding of these five to six rugae progressed in conjunction with the formation of a sharp, valley-like groove at the base of the anterior two-fifths of the vertical palatal shelves. As palatal shelves elevated, the groove disappeared gradually, and, accordingly, the folding of rugae loosened. In the groove region, the superficial epithelial cells were roundish, while the basal ones were elongated. Such characteristic features were no longer observed when the disappearance of the groove was completed. Eight rugae were observed on the future hard palate of 14-day embryos with already completed palatal fusion. An additional ruga was frequently found in 15-day embryos, and the pattern then was almost the same as that of an adult. Epithelial thickening and condensation at the rugae region, as well as mesenchymal condensation under the epithelium of the rugae, were confirmed in embryos both before and after elevation of the palatal shelves. There is a possibility that these structural characteristics observed in the epithelial and mesenchymal cells of the rugae and groove regions may be related to palatal shelf elevation.     

Decreased interleukin 1 activity in culture supernatant of lipopolysaccharide stimulated monocytes from patients with liver cirrhosis and hepatocellular carcinoma.

Immunoregulatory function of peripheral blood monocytes was studied in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC), by assaying interleukin 1 (IL-1) and prostaglandin E2 (PGE2) in the culture supernatant of lipopolysaccharide-stimulated monocytes. IL-1 activity of the monocyte culture supernatant without indomethacin was decreased in patients with HCC and LC, compared with that of controls. The activity was lower in patients with HCC than that in those with LC. The PGE2 content of the culture supernatant of monocytes from patients with LC and HCC was increased, compared to normal controls. To avoid the effect of PGE2 on the IL-1 assay, we cultured the monocytes with addition of indomethacin and assayed IL-1 activity in the culture supernatant. As a result, monocyte IL-1 production was increased in patients with HCC and LC, compared with normal controls. The decrease in IL-1 activity of the supernatant without indomethacin of patients with LC and HCC was considered to be due to increased secretion of PGE2 by the monocytes. Therefore, monocytes from patients with HCC and LC had an increased capacity of secreting both IL-1 and PGE2 over normal controls, but the effect of the suppressor function (PGE2 secretion) dominated in these patients.     

Increased peripheral blood Ia positive T cells and their effect on autologous mixed lymphocyte reaction in chronic active liver disease.

We measured Ia antigen bearing peripheral blood T cells, as an index of immunological stimulation, of patients with chronic active liver diseases (CALD) by the rosette assay method. We also examined the role of Ia antigen which represents the products of the genes of the major histocompatibility complex on the autologous mixed lymphocyte reaction (AMLR) since this reaction may reflect self regulation of immune responses. The percentages of Ia positive T cells of 29 patients with CALD (17.1 +/- 4.3%, P less than 0.001) and of 12 patients with other liver diseases (12.9 +/- 2.4%, P less than 0.05) were increased when compared with that of normal individuals (10.7 +/- 2.0%). However, levels of Ia positive T cells activated by phytohaemagglutinin-P in patients with CALD and other liver diseases did not differ from normal subjects. Ia positive cells in OKT8 positive cells were markedly elevated (P less than 0.001), whereas those in OKT4 positive cells were decreased (P less than 0.01) in CALD. The impaired values for the AMLR correlated inversely (P less than 0.01) with the increased percentages of Ia positive T cells in patients with CALD. Further analysis showed that there was no suppression of the proliferation of Ia and OKT4 positive cells by Ia and OKT8 positive cells although the culture of increasing numbers of Ia and OKT8 positive cells and decreasing numbers of Ia and OKT4 positive cells gave a lesser AMLR value. These data suggest that the increase in Ia positive T cells and the alteration of Ia positive cells in the T cell subsets reflect an activation of immune system and provide further evidence in favour of an abnormality of the immunoregulatory system in CALD.     

Soluble Fas and soluble Fas L levels in patients with acute pancreatitis

The FasL-Fas system is an apoptosis induction system and plays an important role in homeostasis and biophylaxis. The present study was conducted to investigate soluble Fas (sFas), soluble Fas ligand (sFasL), and tumor necrosis factor alpha (TNF-alpha) in patients with acute pancreatitis. As acute pancreatitis became severe, the levels of sFas in the serum increased significantly, while those of sFasL decreased significantly. A significant inverse correlation was observed between the serum levels of sFas and those of sFasL. Also, a significant positive correlation was observed between the levels of TNF-alpha and sFas. A greater increase in serum sFas and decrease in serum sFasL levels was observed in patients with complicating multiple organ dysfunction syndrome (MODS) than in those without it. The results of the study suggest that the pathological aggravation of acute pancreatitis could be related to changes in the Fas-FasL system.     

Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs

Background: Histamine N-methyltransferase (HMT) modulates histamine- and antigen-induced bronchoconstriction. However, it is unclear whether vascular permeability evoked by an allergic reaction can be exaggerated by inhibition of HMT activity. Methods: We studied the effects of intravenously injected SKF 91488, a specific HMT inhibitor, on increases in plasma extravasation induced by intravenously injected histamine in unsensitized guinea pigs and by intravenously injected ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue dye as a marker. Results: Pretreatment with SKF 91488 shifted, in a dose-dependent fashion, the dose-response curves of the leakage of dye to histamine to lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise, pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the leakage of dye induced by ovalbumin antigen (200 μg/kg intravenously) in three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg intravenously), did not alter the leakage of dye induced by histamine (from 0.001 μg/kg to 10 μg/kg intravenously) (p > 0.20). HMT activities were observed in the nasal mucosa, as well as in the trachea and main bronchi, as shown in a previous study. Conclusion: These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine induced by antigen challenge on plasma extravasation in the airway in guinea pigs in vivo. (J ALLERGY CLIN IMMUNOL 1995;96:910-6.)