Long-term survivors in stage IV non-small cell lung cancer

BACKGROUND AND OBJECTIVES: To determine the prognostic factors for long-term survivors (LTS) with stage IV non-small cell lung cancer (NSCLC) who had undergone various treatments. PATIENTS AND METHODS: From 1990 to 1999, 222 NSCLC patients with stage IV disease, who had been treated in our department, were reviewed. As the initial treatment, 135 patients (48%) were treated with chemotherapy alone, 52 patients with a combination of chemotherapy and radiotherapy, 19 patients underwent an operation with or without any other therapeutic modalities and 16 were received radiotherapy alone. RESULTS: Seventeen (7.7%) patients survived for more than 2 years, and all but one had adenocarcinoma. Among these LTS, eight patients received surgery as the initial therapy, and 16 (94.1%) received some type of local-control therapy, including surgery or radiotherapy, during the course of their disease. Regarding the clinical characteristics between LTS and others (non-LTS), an early N status, a single metastatic site, a good performance status, and surgery for initial therapy were all found to be significantly important factors for LTS. A multivariate analysis using a logistic regression model also showed an early N status and surgical treatment to be significantly associated with LTS. CONCLUSIONS: Selected patients with an early N status may be appropriate candidates for aggressive multimodality treatment including surgery, in order to provide a long-term survival for stage IV NSCLC.     

Activity of gelatins to induce secretion of a variety of cytokines from murine peritoneal exudate macrophages

Previously, we observed that liquid form bovine bone (BB) gelatin stimulates murine spleen cells to proliferate in vitro. In this study, activity of BB gelatin to stimulate murine-adherent peritoneal exudate cells (PEC) to secrete cytokines has been examined. Quantitatively, BB gelatin stimulated adherent PEC of C3H/HeN mice to secrete interleukin (IL)-12 (+p40), TNF-alpha, and IL-6 but not IL-1beta, IL-2, IL-10, and IFN-gamma. Qualitatively, BB gelatin-induced secretion of KC, MIP-2, MCP-1, RANTES, and MIP-1a as well as IL-6 but not 6Ckine, CTACK, Eotaxin, G-CSF, GM-CSF, IL-2,-3,-4,-5,-9,-10,-12,-13,-17, Leptin, IFN-gamma, SCF, sTNFri, TARC, TNF-alpha, TIMP-1, Tpo, and VEGF. BB gelatin acted on adherent PEC of C3H/HeN mice but not C3H/HeJ mice, which lack Toll-like receptor 4. Polymyxin B, a LPS antagonist, did not inhibit the activity of BB gelatin. Lipopolysaccharide (LPS) but not BB gelatin induced secretion of an appreciable amount of mIL-1beta. These results suggest that the activity of BB gelatin is not attributed to contamination of LPS but BB gelatin itself. It was also suggested that BB gelatin stimulated adherent PEC to newly produce and secrete cytokines.     

Expression of the JAK/STAT signaling pathway in the ligamentum flavum of patients with lumbar spinal canal stenosis

Background

Ligamentum flavum (LF) hypertrophy is an important cause of lumbar spinal canal stenosis (LSS), one of the most common spinal disorders in the elderly. Although many cytokines are reported to be associated with LF hypertrophy, the intracellular signaling system is rarely discussed. The purpose of this study was to identify the JAK/STAT signaling pathway and to examine the role of the JAK/STAT systems in the hypertrophied LF.

Cdc7-Drf1 is a developmentally regulated protein kinase required for the initiation of vertebrate DNA replication

Cdc7, a protein kinase required for the initiation of eukaryotic DNA replication, is activated by a regulatory subunit, Dbf4. A second activator of Cdc7 called Drf1 exists in vertebrates, but its function is unknown. Here, we report that in Xenopus egg extracts, Cdc7-Drf1 is far more abundant than Cdc7-Dbf4, and removal of Drf1 but not Dbf4 severely inhibits phosphorylation of Mcm4 and DNA replication. After gastrulation, when the cell cycle acquires somatic characteristics, Drf1 levels decline sharply and Cdc7-Dbf4 becomes the more abundant kinase. These results identify Drf1 as a developmentally regulated, essential activator of Cdc7 in Xenopus.     

Visco-elastic properties of cartilage tissue regenerated with fibroin sponge

The mechanical properties of regenerated cartilage tissue were measured to evaluate changes in their visco-elastic properties during cultivation. An indentation test and dynamic visco-elasticity measurements were carried out on cartilage tissue cultured with rabbit chondrocytes that had been inoculated into the fibroin sponge. A 1.5-mm-diameter porous indentor was used for the indentation test, in which time-dependent strain curves were derived from measurements taken under several loading conditions. Dynamic visco-elasticity measurements were performed under compressive loading to evaluate the load-bearing function of the articular cartilage. Although the amount of permanent deformation was not influenced by the duration of cartilage regeneration, the amount of creep deformation increased with longer cultivation. The E' value of the regenerated cartilage increased and the peak value of tan delta and the frequency at the peak became lower with longer cultivation. It is suggested that the changes in the time-dependent strain curves and dynamic visco-elastic properties of the regenerated cartilage were caused by maturation of the cultured cartilage tissue.     

WSX-1 over-expression in CD4(+) T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation

WSX-1 is a component of the IL-27R. Analyses of WSX-1 knockout (WSX-1(-/-)) mice have shown that IL-27/WSX-1 signaling is essential for the proper development of T(h)1 responses and that WSX-1 can suppress cellular activation and pro-inflammatory cytokine production. We have generated transgenic mouse lines over-expressing the WSX-1 gene under the control of the T cell-specific CD2 promoter (WSX-1 Tg mice). Unexpectedly, like activated CD4(+) T cells from WSX-1(-/-) mice, activated CD4(+) T cells from WSX-1 Tg mice showed increased proliferation, augmented IL-2 production and up-regulated surface expression of activation markers. IL-27-mediated tyrosine phosphorylation of STAT1 was also enhanced in WSX-1 Tg CD4(+) T cells, but STAT3 activation was normal. Exogenous IL-27 supported the proliferation of wild-type CD4(+) T cells but suppressed that of WSX-1 Tg cells. WSX-1 over-expression increased IFN-gamma production in T(h)1-polarized CD4(+) T cells, but also promoted T(h)2 cytokine production under T(h)1-polarizing conditions. Importantly, WSX-1 over-expression failed to suppress T(h)2 cytokine production under T(h)2-polarizing conditions. Cytokine hyperproduction was also observed in vivo in WSX-1 Tg mice injected with Con A. Our data suggest that WSX-1 plays a pivotal role in regulating T cell responsiveness to TCR stimulation and that the correct balance of STAT1/STAT3 activation downstream of IL-27R engagement is crucial for the physiological function of IL-27.     

Two XX male brothers

Two brothers with XX male syndrome with penoscrotal hypospadias are reported. Chromosomal analysis of cells from the peripheral blood, skin, and testes revealed a normal female karyotype in both subjects. Biopsy of both testes in the brothers showed histological features of normal immature testes and no evidence of ovarian structures. Neither vagina, uterus nor fallopian tubes could be detected either by exploratory laparotomy or retrograde urethrography. Results of endocrine studies on serum gonadotropins (LH and FSH) and testosterone levels as well as their responses to LH-RH and hCG stimulation tests were normal for age. Studies of various genetic markers, including the Xg blood type and erythrocyte enzymes, were performed in the probands and their parents. Possible explanations for the paradoxical occurrence of testes in XX males and for the familial occurrence are discussed.     

Hearing impairment, undescended testis, circumferential skin creases, and mental handicap (HITCH) syndrome: a case report

Association of the pink-eye-dilution gene (P) with hypopigmentation is seen in patients who have oculocutaneous albinism type 2 (OCA2) and Prader-Willi syndrome (PWS) or Angelman syndrome (AS). However, it remains unknown whether duplication or amplification of the P gene causes hyperpigmentation. We previously reported a woman who had hyperpigmentation with a duplication of the proximal part of 15q, including the P gene. Here, we describe an additional patient with mosaicism of inv dup(15) and clinical manifestations of severe psychmoter retardation, epilepsy, and pigmentary dysplasia showing mottled and linear patterns of hyperpigmentation. His karyotype was 47,XY,+idic(15)(pter-->q14::q14-->pter)[38]/46,XY[12] de novo. Chromosomal fluorescence in situ hybridization (FISH) showed six copies of the P gene. Therefore, his cutaneous mosaicism might be caused by the presence of both normal and hyperpigmented skin due to multicopies of the P gene.