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OBJECTIVES: Interleukin-10 (IL-10) has been implicated in immune deficiency in patients with cancer. The relationship of this cytokine as measured in serum to anti-tumor immunity and prognosis was investigated in unresectable hepatocellular carcinoma. METHODS: This study consisted of 74 consecutive patients with unresectable hepatocellular carcinoma (median age, 65 years). Forty-four healthy age-matched subjects and 32 patients with cirrhosis but no carcinoma served as controls. Patients with hepatocellular carcinoma were divided into those with serum IL-10 concentrations above (high group, n=39) or below (low group, n=35) 10pg/ml. RESULTS: Age, gender, Child-Pugh grade, and tumor stage distributions were similar in high and low groups. The patients of high group showed lower in lymphokine-activated killer (LAK) and natural killer (NK) activities than those of low group (P

Bone marrow (BM) stem cells have been shown to differentiate into liver cells. It remains difficult to sort and culture BM stem cells, and the gene expression of liver-specific proteins in these cells has not been fully investigated. We used a negative selective magnetic cell separation system to obtain stem cell-enriched BM cells. The cells obtained were cultured with hepatocytes or with hepatocyte growth factor (HGF), and the differentiation of BM cells into cells expressing liver-specific genes, hepatocyte nuclear factor (HNF) 1alpha, cytokeratin (CK) 8, alpha-fetoprotein (AFP), and albumin was investigated by the reverse transcription-polymerase chain reaction. We also investigated the gene expressions of Notch receptor-1 (Notch-1) and its ligand Jagged-1 in BM cell differentiation. Sorted BM cells showed positive for Sca-1 (Ataxin-1) by immunofluorescence staining. Fluorescence activated cell sorter analysis showed that 32.6% of sorted BM cells had a high level of expression of the hematopoietic stem cell marker CD90 (Thy-1). When cultured with hepatocytes, these cells expressed the liver-specific genes HNF1alpha and CK8 on culture day 3, AFP and albumin on culture day 7. When cultured with HGF (20ng/ml), the cells expressed HNF1alpha on day 3 and CK8 on day 7. Gene expressions of Notch-1 and Jagged-1 were detected in cultured BM cells on day 3. These results suggest that the negative selective magnetic cell separation system is useful for the rapid preparation of stem cell-enriched BM cells, and that the Notch signaling pathway plays a role in BM cell differentiation into a hepatocyte lineage in vitro.

Rathke's pouch of 12.5-day-old fetal rats was cultured alone or with various fetal organs. After 10 days of culture with the anterior or posterior wall of the basal diencephalon, the size of the pouch was about eight times larger than that in single culture or in combined culture with the telencephalon or liver anlage. There was no chronological difference in the appearance of immunoreactive ACTH and prolactin cells between single and combined cultures. These results suggest that fetal diencephalon promotes the growth of Rathke's pouch but has no potency to promote differentiation of the pituitary cells.

The ontogenesis of immunoreactive (ir) ACTH cells and ir α-MSH cells in rat hypothalamus was studied in vivo and in vitro. Ir ACTH cells first appeared in the neuroepithelial cell layer lining the floor of the third ventricle on Day 13.5 of gestation, whereas ir α-MSH first appeared in the cytoplasm of several ir ACTH cells in the basal part of the arcuate nucleus of the hypothalamus on Day 19.5. When the medial-basal hypothalamus of 12.5-day embryos was cultured alone, a few ir ACTH cells were found after culture for 10 days, but not 3 days, and no ir α-MSH cells were observed in the cultures. When the hypothalamus was cultured with Rathke's pouch (intact or without the intermediate lobe anlage), ir ACTH cells appeared within 3 days. In these cultures on Days 6 and 10, long beaded fibers were seen projecting from cells in the neuronal tissue, and some cells showed immunolabeling for α-MSH. When the hypothalamus was cocultured with oral epithelium instead of Rathke's pouch, the appearance of neuronal ir ACTH cells was like that in cultures of hypothalamus alone. These in vitro findings suggest that stimulus from the anterior lobe anlage of the pituitary is necessary for normal development of ir ACTH α - MSH cells in the hypothalamus.

Although S. Ishii (1977, “Proc. First Int. Symp. Avian Endocrinol.,” Calcutta, Jan. 1977, 50–53) as well as P. Licht and A. R. Midgley, Jr. (1976a, Biol. Reprod., 15, 195–205; reported that specific FSH receptors were not detectable in the gonad of the bullfrog, in this study we found that the testis of the frog, Xenopus laevis, contains specific receptors for FSH at a high concentration. The specific binding of radioiodinated rat FSH to a particulate fraction of homogenate of the Xenopus testis showed the maximum at 37° and pH 7.4. The binding was competitively and quantitatively inhibited by mammalian FSH. Rat LH showed slight competition only at extremely high concentrations. The apparent equilibrium constant of dissociation of the specific binding obtained by a saturation experiment was 0.50 nM. The 95% confidence interval of this value was 0.38 to 0.72 nM. The capacity of the binding was 18.5 fmol/mg of testicular tissue. These properties of the Xenopus FSH receptors are similar to those of mammals and birds, except that Xenopus FSH receptors showed a several-fold higher binding level at 0° than mammalian or reptilian receptors. It is noteworthy that rat thyrotropin showed a significant competitive binding potency, although it was not as high as the potency of mammalian FSH. The radioautographic study revealed that the binding of rat FSH was restricted mostly to the interstitial tissue. This suggests that specific receptors for FSH locate mainly in interstitial cells of the testis in Xenopus laevis.

In an automatic layout design system for masterslice or gate array LSI, a cell library must be provided in advance. Manual preparation of such a cell library requires a considerable amount of design effort and turnaround time. In this paper, an automatic cell pattern generation algorithm and its program implementation for a CMOS transistor-pair array masterslice are presented. The cell pattern generation process consists of the transistor-pair extraction, transistor-pair placement and routing phases. The transistor-pair placement method is based on an iterative improvement algorithm for wiring congestion. For the wiring phase, Lee's maze routing algorithm is modified for application to polysilicon, diffusion and two aluminum layers. Furthermore, a new interconnection ordering algorithm is proposed and its effectiveness for attaining higher wireability is experimentally shown. Finally, it is shown that the proposed cell pattern generation system achieves a significant reduction of cell pattern design time compared to conventional manual design.

The specific binding site of follicle stimulating hormone (FSH) in homogenates of the testes of birds was characterized with respect to its affinity, capacity, and specificity. The usefulness of this system for the radioreceptor assay of lower vertebrate FSH was also studied. The apparent equilibrium constant of dissociation was obtained for the specific binding of rat FSH to homogenates of testis of the Japanese quail. It was 4.1 × 10 −9 M . The binding capacity was 6 fmol/mg of tissue. The former and latter parameters obtained with the fowl testis homogenate were 1.5 × 10 −9 M and 11 fmol/mg of tissue, respectively. These values are in good agreement with those previously reported in testis homogenates of white-crowned sparrows, rats, and cattle. The binding was competitively inhibited at various rates by mammalian gonadotropin preparations. The rates of competition were fully explained by the concentration of FSH contained in the preparations. The binding was also inhibited by adenohypophyseal extracts of the Japanese quail and a chromatographic fraction of bullfrog adenohypophysis but not by a hypophyseal extract of salmon. The FSH activity of acetone-dried adenohypophysis of the Japanese quail estimated from the competition curve was 0.14 × NIAMD-rat FSH-RP-1, and that of the bullfrog adenohypophyseal fraction was 3.0 × FSH-RP-1. The precision index (λ) of the assay was 0.09 ± 0.04 (mean ± SD).

This paper proposes a process/device optimization technique which is well suited for determining optimum process conditions for MOSFETs. After linking process simulator SUPREM II and device simulator FEDAS, process conditions which realize desirable device performance can be obtained by introducing the optimization procedure. The Fletcher-Powell method, one of the most efficient optimization techniques now available, is applied to the present simulator. The validity of the algorithm is successfully demonstrated by the determination of channel doping conditions, such as implanted boron dose and annealing temperature. The present simulator is expected to be an important tool for device design.