Molecular properties of F9 embryoglycan recognized by a unique antibody in sera from patients with germ cell tumors

Human antibody against an embryoglycan present on a mouse teratocarcinoma cell line F9 was found in sera from 16 of 29 patients with embryonal carcinoma, yolk sac tumor, immature teratoma, and choriocarcinoma of gonadal and extragonadal origins by Farr assay. In contrast, none of the sera from patients (77 cases) with dysgerminoma, seminoma, germinoma, and mature teratoma or from patients (118 cases) with nongerm cell types of ovarian tumors contained this antibody. The antigenic embryoglycan was of high molecular weight (Mr greater than 70,000) on Sephacryl S300 column chromatography and carried binding sites for Grifonia simplicifolia agglutinin-1. The antigenic embryoglycan was also found in F9 cell-cultured medium. Absorption of patients' sera with synthetic Blood Group B trisaccharides failed to remove the antibody against F9 embryoglycan. None of these patients' sera showed higher hemagglutination titer to rabbit erythrocytes than the normal range. In contrast, alpha-galactosyl carbohydrates obtained from Ehrlich ascites tumor cells effectively inhibited the binding of patients' sera with F9 embryoglycan. These results indicate that the human antibody against F9 embryoglycan recognizes alpha-galactosyl structures that are distinct from B blood group antigen, but are cross-reactive with alpha-galactosyl structures on Ehrlich ascites cells.     

Effect of concomitant use of anticancer drugs and a Ca2+ antagonist, on human gastric cancer transplanted into nude mice

We examined the effect of concomitant use of anticancer drugs such as Carmofur or 5-FU and Nicardipine, a Ca2+ antagonist, on human gastric cancer transplanted into nude mice, and obtained the following results: 1. Combined administration of Carmofur or 5-FU together with Nicardipine caused potentiation of an antitumor effect. 2. After Carmofur was used together with Nicardipine, the FU level in the tumor tissue was significantly elevated. In conclusion, it was found that in the combined use of Carmofur or 5-FU together with Nicardipine, a Ca2+ antagonist, caused a higher level of the FU in tumor tissue and potentiation of an antitumor effect on human gastric cancer transplanted into nude mice.     

The human antimicrobial peptide dermcidin activates normal human keratinocytes

Background  The skin has evolved an epithelial defence mechanism which is characterized by antimicrobial peptides that inactivate various microorganisms and exhibit stimulatory activities bridging innate and adaptive immunity. Dermcidin (DCD) is a newly isolated antimicrobial peptide produced by the eccrine sweat glands in the skin. Recently, the DCD peptides DCD-1 and DCD-1L have been shown to display in vitro microbicidal activities against bacteria and viruses.
Objectives  Because some skin-derived antimicrobial peptides activate keratinocytes, we investigated whether DCD-1L would also trigger keratinocyte activation.
Methods  Normal human keratinocytes were used in this study. The ability of DCD-1L to induce the production of cytokines/chemokines by keratinocytes was determined by enzyme-linked immunosorbent assay, and various inhibitors were used to investigate the stimulatory mechanism of DCD-1L. Mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB activation were analysed by Western blotting.
Results  DCD-1L stimulated keratinocytes to generate cytokines and chemokines including tumour necrosis factor-α, interleukin-8 (CXCL8), interferon-inducible protein 10 (CXCL10) and macrophage inflammatory protein-3α (CCL20). To determine the molecular mechanism involved, we showed that DCD-1L-mediated cytokine/chemokine production was controlled by both G-protein and MAPK pathways, as evidenced by the inhibitory effects of pertussis toxin and specific inhibitors for p38 and ERK, but not for JNK, on DCD-1L-induced keratinocyte activation. Furthermore, we confirmed that DCD-1L could induce phosphorylation of p38 and ERK, and noticeably upregulated NF-κB activation.
Conclusions  Taken together, the new activity of DCD-1L to stimulate the production of cytokines/chemokines by keratinocytes provides novel evidence for the implication of DCD, beyond its microbicidal ability, in skin immunity.     

Efficacy of pilsicainide for the long-term prevention of paroxysmal atrial fibrillation: analysis based on the time of onset]

OBJECTIVES: This study evaluated the efficacy of long-term pilsicainide therapy to maintain sinus rhythm in patients with paroxysmal atrial fibrillation in terms of the time of onset. METHODS: A total of 81 patients (57 men, 24 women, mean age 65 +/- 11 years) were given pilsicainide (150 mg/day) after cardioversion. Paroxysmal atrial fibrillation was divided into three types by the time of onset: the day type (AM 7:00-PM 5:00, n = 13), the night type (PM 5:00-AM 7:00, n = 12) and the mixed type (n = 56). Mean follow-up period was 35.4 +/- 16.1 months. RESULTS: There was a higher incidence of hypertension in the day type (38.5%) and the mixed type (48.2%) than in the night type (8.3%) (p < 0.05). The periods for maintenance of sinus rhythm in the day type, the night type and the mixed type were 15.7 +/- 5.0, 9.9 +/- 2.7 and 5.7 +/- 1.3 months, respectively, with a significant difference between the day type and the mixed type (p < 0.01). Actuarial event free-rates at 1, 3, 6, 9 and 12 months were 76.9%, 69.2%, 61.5%, 53.8% and 53.8% respectively, in the day type, 83.3%, 66.7%, 58.3%, 33.3% and 33.3%, respectively, in the night type and 58.9%, 37.5%, 26.8%, 25.0% and 21.4%, respectively, in the mixed type. There was a significant difference in the rate at 12 months between the day type and the mixed type (p < 0.05). CONCLUSIONS: These results suggest that pilsicainide has a high degree of efficacy for maintaining normal sinus rhythm in patients with the day type onset of paroxysmal atrial fibrillation.     

Human lymphocytes synthesize C-reactive protein

We obtained evidence for the synthesis and secretion of C-reactive protein (CRP) by peripheral mononuclear cells in culture. Human mononuclear cells isolated from peripheral blood, after depletion of platelets, were cultured in giutamine-depleted RPMI 1640 supplemented with [³H]glutamine in the presence of 10-O-tetradecanoyl-phorbol-13-acetate (TPA). Anti-CRP antiserum was added to the culture medium, and the resultant immunoprecipitate was analyzed in SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The immunoprecipitate consisted of CRP, heavy and light chains of IgG, and only the CRP protein band had radioactivity, indicating that CRP was synthesized by mononuclear cells. In the populations of mononuciear cells, T-cell preparations mainly synthesized CRP, under stimulation of a factor derived from activated monocytes. Studies using the inhibitors of phospholipid metabolism suggested that generation of the monocyte factor was relevant to metabolites of an arachidonate cascade.     

Human striatal D-neurons and their significance]

It has recently been reported that the human striatum, especially its ventral part, the nucleus accumbens, contains numerous neurons immunoreactive for aromatic L-amino acid decarboxylase (AADC; the second-step monoamine synthesizing enzyme), but not for tyrosine hydroxylase (TH; the first-step catecholamine synthesizing enzyme) or tryptophan hydroxylase (TPH; the first-step serotonin synthesizing enzyme). These AADC (+)/TH(-)/TPH(-) neurons are named D-neurons. AADC is also the rate-limiting synthesizing enzyme of phenylethylamine (PEA). Although the functions of striatal D-neurons are yet unclear, their functions were discussed in the present review based on recent findings in the literature. D-neurons may participate in the manifestation of efficacy of pharmacotherapy for Parkinson's disease by uptaking monoamine precursors, including L-dopa or droxidopa (L-threo-DOPS), and by converting them to dopamine (DA) or noradrenaline (NA), respectively. Because the nucleus accumbens is one of the brain regions involved in the pathogenesis of schizophrenia and drug dependence, D-neurons might be related to the etiology of these mental disorders. It has also been suggested that striatal D-neurons are the pluripotential cells that have compensating functions against aging or degeneration. Further studies should be conducted to elucidate the functions of this unique cell group in the human striatum.     

The relation of argyrophilic proteins of nucleolar organizer regions (AgNORs) to the proportions of Ki-67 or DNA polymerase alpha-reacting cells in non-Hodgkin's lymphomas.

In order to examine the relationship between argyrophilic proteins of nucleolar organizer regions (AgNORs) and the proliferation activity of cells, we investigated lymph nodes obtained from 25 untreated non-Hodgkin's lymphoma (NHL) patients. Two monoclonal antibodies (MoAb) (Ki-67 antibody and anti-DNA polymerase alpha antibody) were used for evaluating cell proliferation activity. A linear relation between the mean number of agNORs per nucleus and the proportion of NHL cells reacting with Ki-67 MoAb was observed (r = 0.48, P less than 0.05). A similar relation between AgNORs and DNA polymerase alpha MoAb was also observed (r = 0.51, P less than 0.01). From these data, it was confirmed that AgNORs reflect the proliferation activity of NHL cells. We conclude that the AgNOR staining procedure is one of the simplest and most reliable methods for analyzing cell proliferation potential.