A non-T, non-B human leukemia cell line (NALM-1): establishment of the cell line and presence of leukemia-associated antigens.

A permanent hematopoietic cell line, designated NALM-1, was established from the peripheral blood of a patient who was in blastic crisis of Ph1-positive chronic myleocytic leukemia. By means of a panel of specific xenoantisera, the NALM-1 cells were found to express a specific antigen of acute lymphoblastic leukemia and blast leukemia-associated antigen. The cells exhibited no cell-surface receptors for sheep erythrocytes, IgG, or complement; neither cell-surface immunoglobulins nor cytoplasmic immunoglobulin were observed. Furthermore, normal T-cell or B-cell antigens, detectable by the antisera used in this study, were not found in the NALM-1 line.     

Antitumor and antimetastatic actions of eicosapentaenoic acid ethylester and its by-products formed during accelerated stability testing

The aim of the present work was to compare the effects of eicosapentaenoic acid (EPA) ethylester and EPA derivatives (EPAD) on tumor growth and metastasis to the lung in tumor-bearing mice. Because EPA is very unstable during long-term storage, the EPAD were subjected to accelerated testing under storage conditions of 60 +/- 5% relative humidity at 37 degrees C for 30 days. EPAD are composed of a mixture of a newly identified EPA ethylester dimer and EPA hydroxyethylester, and known EPA and EPA ethylesters. The inhibitory effects of EPAD, the EPA ethylester dimer and EPA hydroxyethylester on Matrigel-induced capillary-like network formation were stronger than the effect of EPA ethylester. The oral administration of EPAD (300 or 1000 mg/kg) inhibited angiogenesis in gels containing Matrigel supplemented with vascular endothelial growth factor (VEGF) and heparin in an in vivo model, but EPA ethylester had no effect. EPA ethylester (300 or 1000 mg/kg) or EPAD (1000 mg/kg) inhibited tumor growth in mice with subcutaneously implanted LLC. Furthermore, EPAD inhibited metastasis to the lung in mice implanted with LLC subcutaneously, but EPA had no effect. EPAD increased the CD8(+) T-cell population in the spleen compared with mice with subcutaneously implanted LLC. EPA ethylester increased the natural killer cell population in the spleen. Thus, it is suggested that the mechanisms of the antitumor and/or antimetastatic actions of EPAD and EPA ethylester involve different immune functions, and that the EPA ethylester dimer and the EPA hydroxyethylester of EPAD may contribute to these actions.     

Cytogenetic and immunoglobulin markers of human leukemic B-cell lines.

This study describes the establishment of two permanent leukemic B-cell lines (BALM-1 and -2) originating from the blood cells of a patient with a B-cell type of acute lymphoblastic leukemia. The cells of BALM-1 and -2 exhibited cell surface markers compatible with B-cell origin. The identity between the leukemic cells in vivo and those of the BALM lines was established on the basis of the karyotypic picture, including marker chromosomes 14q+ and t(12;17;?) and cell surface immunoglobulins (K, delta, and mu chain determinants).     

Epidemiologic characteristics of definite Ménière's disease in Japan. A long-term survey of Toyama and Niigata prefectures

To identify epidemiologic characteristics of definite cases of Ménière's disease (DMD), we conducted retrospective surveys of the period 1990-2004 of the Nishikubiki district and of the period 1980-2004 of Toyama Medical and Pharmaceutical University. Three hundred and seventy-five patients (50 from Nishikubiki, 325 from Toyama) were diagnosed with DMD according to the diagnostic criteria proposed by the Japanese Society for Equilibrium Research. There was a slight increase in the prevalence of DMD during the period 1990-2004. However, incidence did not change significantly over time. The average annual prevalence and incidence were 34.5 and 5.0, respectively, per 100,000 population. Incidence and prevalence predominated in females. With respect to age at disease, the incidence in elderly patients was increased when we corrected for age distribution in the overall population.     

Hypotensive effect of des-acyl ghrelin at nucleus tractus solitarii of rat

Ghrelin is a gut-brain peptide and its endocrine activities are mediated by GH secretagogue receptor (GHSR)-1a. Des-acyl ghrelin does not activate GHSR-1a and is devoid of endocrine activities. While the microinjection of ghrelin into rat nucleus tractus solitarii (NTS) elicited hypotensive effects, this was not the case upon injection into GHSR-expressing rostral ventrolateral medulla or caudal ventrolateral medulla. To make clear the reason of the discrepancy between receptor distribution and neuronal responses, we examined the cardiovascular response of rats microinjected with des-acyl ghrelin into NTS. Intra-NTS injection of des-acyl ghrelin significantly reduced mean arterial pressure and heart rate. The hypotensive and bradycardic activity evoked by des-acyl ghrelin was not significantly different from that of native ghrelin. These results suggest that des-acyl ghrelin contribute to the regulation of cardiovascular control and that a receptor other than GHSR-1a exists in NTS.     

Visualization of newly deposited tau in neurofibrillary tangles and neuropil threads

Neurofibrillary tangles (NFTs) and neuropil threads (NTs), the major hallmark of Alzheimer disease (AD), are composed of the microtubule-associated protein tau that has undergone posttranslational modifications, including deamidation and isomerization on asparaginyl or aspartyl residues. Because such modifications represent protein aging, we generated 2 antibodies, TM4, specific for Asp-387 of tau, and iD387, specific for isoAsp-387 of tau, to investigate the evolution of NFTs and NTs. On Western blots of Sarkosyl-insoluble fractions, TM4 strongly labeled paired helical filament-tau (PHF-tau), whereas iD387 preferentially labeled PHF smear. Thus, it is reasonable to postulate that TM4-labeled tau (unmodified tau species) represents more recent deposition, and iD387-labeled tau (modified tau species) represents earlier deposition. Unexpectedly, TM4 immunostained even highly evolved NFTs, suggesting that deposition of newly produced tau continues until neuronal death. iD387 labeled the whole profile of NFTs up to distal dendritic branches, whereas TM4 staining was localized to particular portions of NFTs in proximal dendrites and neuronal perikarya. In NTs, TM4 preferentially labeled the outer portion, whereas iD387 intensely labeled the core portion. Based on TM4-positive NFT counts and total NFT counts, we speculate that NFTs in the human hippocampus are produced at a constant rate irrespective of the disease stage.     

Effects of fasting and refeeding on jejunal morphology and cellular activity in rats in relation to depletion of body stores

BACKGROUND: Intestinal mucosa atrophy following a period of starvation characterized by the mobilization of fat stores for energy expenditure (phase II) worsen after a long fast marked by an increase in protein catabolism (phase III). However, the morphology of the jejunum is completely restored after 3 days of refeeding. The aim of this study was to determine the mechanisms involved in the rapid jejunal restoration following the critical phase III. METHODS: Jejunal structure was observed through conventional and environmental scanning electron microscopy, whilst cellular dynamics were studied using classical optic microscopy tools and immunohistochemistry. RESULTS: Mucosal structural atrophy during fasting proved to worsen over the two phases. During phase II, apoptosis is still present at the tip of the villi, the number of mitosis in crypts showed a 30% decrease and a transient drop in cell migration is observed. During phase III, however, an 85% rise in mitosis was noticed along with an increase in cell migration and the disappearance of apoptotic cells at the villus tips. This increased cell renewal continues after food ingestion. CONCLUSIONS: Starved rats appeared to be in a phase of energy sparing in phase II, with depressed cellular events in the intestinal mucosa. In phase III, however, the preservation of functional cells and the early increase in crypt cell proliferation should prepare the mucosa to refeeding and could explain why jejunal repairs are complete after 3 days of refeeding following either phase II or phase III.     

Division of the Pulmonary Ligament After Upper Lobectomy is Less Effective for the Obliteration of Dead Space than Leaving It Intact

Purpose To investigate whether division of the pulmonary ligament after upper lobectomy obliterates dead space.Methods Thirty-five patients scheduled to undergo upper lobectomy (23 right, 12 left) were randomly assigned to two groups, according to whether the inferior pulmonary ligament was divided (11 right, 12 left) or preserved (6 right, 6 left). To assess upward movement of the nonoperated lobes, plain chest X-ray films (posterior-anterior) were done at end-inspiration preoperatively and 1 month postoperatively, and the ratio of dead space in the longitudinal axis was measured. To assess the change in the angle of the main bronchus, chest X-ray tomography films were done preoperatively and 1 month postoperatively. The angles formed by the main bronchus and the truncus intermedius on the right side, and by the main bronchus and the lower bronchus on the left side, were measured, and the postoperative changes were calculated.Results The dead space ratio did not differ significantly between the divided group and the preserved group (3.5% vs 5.5%) or between sides. The change in the angle of the main bronchus did not differ significantly between the two groups on either the right (36.4° vs 36.3°) or the left side (72.5° vs 60.0°).Conclusion Division of the pulmonary ligament after upper lobectomy is less effective for the obliteration of dead space than leaving it intact.