C cell hyperplasia and carcinoma developing in sheep with experimentally-induced lymphosarcoma.

Two cases of C cell hyperplasia and one case of C cell carcinoma of the thyroid glands were bilaterally recognized in 11 sheep with experimentally-induced lymphosarcoma. The serum calcium concentration in the C cell carcinoma case was slightly increased above the normal concentration of around 9 mg per dl. Bilateral C cell hyperplasia also developed in the thyroid lobes of the C cell carcinoma case. Immunohistochemically, hyperplastic C cells and tumour cells were positive for calcitonin, calcitonin gene-related peptide, chromogranin A and neurone-specific enolase. No amyloid deposition nor multiple endocrine neoplasia was demonstrated in any of the cases. Ultrastructurally, many secretory granules were observed in the cytoplasm of neoplastic cells constituting the C cell carcinoma and in the hyperplastic C cells.     

Heritability of C-Reactive Protein and Association with Apolipoprotein E Genotypes in Japanese Americans

Numerous studies have demonstrated that increased C‐reactive protein (CRP) levels predict coronary heart disease, stroke, peripheral vascular disease, and diabetes, and are associated with features of the metabolic syndrome. Only three previous studies have investigated the heritability of CRP levels, primarily in samples of Caucasian families.The purpose of the present study was to estimate the magnitude of genetic influences on CRP levels, and to examine potential associations between variation in the APOE gene and CRP levels, using a sample of 562 individual Japanese Americans from 68 extended kindreds. In general, correlation coefficients between first‐degree relatives for CRP were approximately 0.2, and spouse correlations did not differ from zero, consistent with genetic influences. Heritability estimates were approximately 0.3 (p < 0.01), even with adjustment for factors known to influence CRP levels. A significant relationship was seen between unadjusted CRP levels and APOE genotypes (p = 0.02), with the highest mean CRP level among ?2 carriers (1.20 mg/L), and nearly the same mean levels among ?3/?3 subjects and ?4 carriers (0.72 and 0.74 mg/L, respectively). However, this relationship was diminished with adjustment for covariates (p = 0.07). These results demonstrate the presence of both genetic and environmental effects on CRP levels among Asian Americans, and additional studies are needed to determine if the APOE gene contributes to these genetic influences.     

Modulation of neuronal histamine in control of food intake

Neuronal histamine affects physiological functions of the hypothalamus. To investigate involvement of histamine receptors in feeding, histamine antagonists were infused into the rat third cerebroventricle. All H1- but no H2-antagonists tested, induced transient feeding during the early light when concentration of hypothalamic histamine was highest. No periprandial drinking was observed. Ambulation concomitantly increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early dark or was decreased by alpha-fluoromethylhistidine (alpha-FMH). Bilateral microinjection indicated that the ventromedial hypothalamus, but not the lateral hypothalamus or the paraventricular nucleus, was a main locus for the induction of feeding by an H1-antagonist. The effect was completely abolished when brain histamine was decreased by pretreatment with alpha-FMH. Hypothalamic neuronal histamine suppresses food intake, at least in part, through H1-receptors in the VMH, and diurnal fluctuations of food intake may mirror neuronal histamine level.     

Sequential compound exocytosis of large dense-core vesicles in PC12 cells studied with TEPIQ (two-photon extracellular polar-tracer imaging-based quantification) analysis

We investigated exocytosis of PC12 cells using two-photon excitation imaging and extracellular polar tracers (TEP imaging) at the basal region of PC12 cells adjacent to the glass cover slip. TEPIQ (two-photon extracellular polar-tracer imaging-based quantification) analysis revealed that most exocytosis was mediated by large dense-core vesicles (LVs) with a mean diameter of 220 nm, and that exocytosis of LVs occurred slowly with a mean latency of ∼7 s even though exocytosis was induced with large increases in cytosolic Ca²⁺ concentration by uncaging of a caged-Ca²⁺ compound. We also found that 97% of exocytic LVs remained poised at the plasma membrane, 72% maintained their fusion pores in an open conformation for more than 30 s, and 76% triggered sequential compound exocytosis of vesicles that were located deeper in the cytosol. Sequential compound exocytosis by PC12 cells was confirmed by electron microscopic investigation with photoconversion of diaminobenzidine by FM1-43 (a polar membrane tracer). Our data suggest that pre-stimulus docking of LVs to the plasma membrane does not necessarily hasten the fusion reaction, while docking and resulting stability of exocytic LVs facilitates sequential compound exocytosis, and thereby allowing mobilization of deep vesicles.     

Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases,Axl and Sky,in human uterine endometrium and ovarian endometriosis

We demonstrated the expression of Gas6, the protein product of the growth arrest-specific gene 6 (gas6) and a member of the vitamin K-dependent protein family, and its receptor tyrosine kinases, Axl and Sky, in human uterine and ovarian endometriotic endometria using RT-PCR-Southern blot analysis and immunohistochemistry. Gas6, Axl and Sky mRNA were detected in all samples analysed. There was no significant difference between the levels of Sky mRNA in normal uterine and endometriotic endometria; however, the levels of Gas6 and Axl mRNA in endometriotic endometria were significantly higher than in normal endometria. These mRNA levels showed no significant alteration during the menstrual cycle. In the immunohistochemical study, Gas6, Axl and Sky were found in endometrial glandular cells and stromal cells in all samples analysed. This study demonstrates the coexpression of receptor tyrosine kinases and their ligand, Gas6, in normal uterine and ovarian endometriotic endometria, and the overexpression of Axl and Gas6 in endometriotic endometria. It is suggested that Gas6 and Axl signal transduction is aberrantly stimulated in endometriotic endometria, and is plausibly related to its growth potential.     

High NK cell activity in early pregnancy correlates with subsequent abortion with normal chromosomes in women with recurrent abortion

PROBLEM: The aim of this study was to assess the role of natural killer (NK) cells in pregnant women with a history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: Consecutive 66 pregnant women with a history of RSA were prospectively assessed for peripheral NK cell activity, percentage of the NK cell subsets, and subsequent pregnancy outcome. RESULTS: NK cell activity in women with subsequent live birth (group I) at 4-5 gestational weeks (GW) (mean +/- SD, 32.5 +/- 12.31%) significantly decreased at 6-7 GW (28.1 +/- 12.1%) and at 8 9 GW (28.0 +/- 11.8%). NK cell activity in women with subsequent abortion with normal chromosomes (group II) at 6 7 GW (41.2 +/- 19.0%) was significantly higher than that in group I women, while NK cell activity at 6-7 GW in women with subsequent abortion with abnormal chromosomes (group III) was the same as the level in group I women. CONCLUSIONS: High NK cell activity at 6-7 GW correlates with subsequent abortion with normal chromosomes.