A female case with Down syndrome and non-neurogenic neurogenic bladder

Although the prevalence of a learned voiding dysfunction and non-neurogenic neurogenic bladder (NNB), which is one type of dysfunctional elimination syndrome, is considered to be relatively rare, the association of NNB with Down syndrome (DS) has been elucidated in male patients. We herein describe the occurrence of NNB in an adult female with DS. The diagnosis was confirmed after completely ruling out any neurological or anatomical anomalies that could be related to a lower urinary tract dysfunction. She had renal dysfunction and multiple obstructive uropathies for which clean intermittent catheterization was successfully introduced.     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.     

Prognostic value of N-myc oncogene amplification and S-100 protein positivity in children with neuroblastic tumors.

Data on 43 neuroblastic tumors (30 neuroblastomas and 13 ganglioneuroblastomas) obtained from 22 untreated and 21 pretreated children, were analyzed to determine the correlation between N-myc oncogene amplification and immunohistochemically identified S-100 protein positivity. Sixteen patients in whom the tumor showed significant amplification of N-myc (more than ten copies) died, irrespective of S-100 protein positivity and other conventional factors. Among 27 patients with low amplification of N-myc (less than ten copies), the estimated progression-free survival for those whose tumors had numerous S-100 protein-positive cells (P group), and few or no positive cells (N group) was 75% and 17%, respectively (p < 0.0001). Thus, in addition to N-myc oncogene amplification as a reliable indicator of outcome, S-100 protein positivity should be useful for prediction of prognosis in children with neuroblastic tumors showing low amplification of N-myc. Correlations among these results and other clinical factors are briefly discussed.     

Expression and function of galectin-3, a beta-galactoside-binding protein in activated T lymphocytes

A soluble beta-galactoside-binding lectin, galectin-3 has been shown to be involved in cell adhesion and activation of immune cells. Although galectin-3 is known to be expressed in various types of cells, it has not been shown whether galectin-3 is expressed in T lymphocytes. We present evidence here that galectin-3 is expressed in activated murine T lymphocytes including CD4+ and CD8+ T cells but not in resting T cells. Galectin-3 expression was induced by anti-CD3 mAb or mitogen and enhanced by common gamma-chain signaling cytokines, IL-2, IL-4, and IL-7, in activated T lymphocytes, whereas the inflammatory cytokines including TNF-alpha and IFN-gamma did not. Galectin-3 expression and proliferation were down-regulated by withdrawal of IL-2 and gamma irradiation. Antisense but not sense phosphorothioated oligonucleotides for galectin-3 inhibited galectin-3 expression and blocked proliferation of T cells significantly. This study suggests that up-regulation of galectin-3 plays an important role in proliferation of activated T lymphocytes.     

Phenotypic assortative mating vs. social homogamy among Japanese and Chinese parents in the Hawaii Family Study of Cognition

Among the subjects of Japanese and Chinese ancestries in the parent generation in the Hawaii Family Study of Cognition were 47 pairs of siblings. Since data were available on the spouses of these siblings, this allowed for tests of whether spouse correlations of educational and occupational attainment and cognitive abilities were due to active phenotypic assortment and/or shared social background (social homogamy). Comparisons of sibling correlations, spouse correlations, and correlations between the spouse of one sibling and the spouse of the other sibling, as well as the results of model-fitting analyses, suggest that spouse correlations for education are determined by both phenotypic assortment and social homogamy, spouse correlations for occupational attainment by phenotypic assortment, and spouse correlations for verbal ability mostly by social homogamy.The results reported here were made possible by a collaboration of a group of investigators (G. C. Ashton, R. C. Johnson, M. P. Mi, and M. N. Rashad at the University of Hawaii and J. C. DeFries, G.E. McClearn, S. G. Vandenberg, and J. R. Wilson at the University of Colorado) supported by NSF Grant GB-34720 and Grant HD-06669 from the National Institute of Child Health and Human Development.     

Familial Transmission of Alcohol Use Norms and Expectancies and Reported Alcohol Use

Members of 183 families (biological parents and one adult offspring) completed questionnaires on their quantity and frequency of alcohol use, what they would consider a "normal" quantity-frequency of alcohol use, "problem" quantity-frequency of use, flushing after alcohol use, and other expected physiological and subjective responses to alcohol. Within individuals, own quantity-frequency of alcohol use was moderately negatively correlated with flushing after one drink or less ("fast flushing"), but more highly positively correlated with judged normal alcohol use and with expected subjective effects. Spouse resemblances were low for quantity-frequency of alcohol use and flushing, but high for alcohol use norms and expected physiological and subjective responses. Parent-offspring resemblances were low to moderate for own alcohol use and flushing, but moderate to high for expected physiological and subjective effects. These results were discussed in terms of the effects of genetically transmitted flushing after alcohol use and culturally transmitted alcohol norms and expectations on alcohol use.     

Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat

The vasodilator peptide adrenomedullin (AM) elicits diuresis and natriuresis and inhibits aldosterone secretion. The aim of this study was to better understand the role of AM in maintaining water and electrolyte balance during chronic salt loading. Male Wistar rats were divided into a high salt (HS) group that received a diet containing 8% sodium chloride (NaCl) and a normal salt group that received a diet containing 0.4% NaCl. Plasma AM concentrations as well as expression of AM mRNA in the adrenal gland and kidney were then measured after 3, 7, 14, and 28 days. After 28 days, sodium and water excretion were significantly higher in HS rats than in control, although blood pressure and fluid volume were not significantly affected. Moreover, although plasma AM remained unchanged for up to 14 days, it was increased 2.5-fold in HS rats after 28 days on a high salt diet, and there were corresponding 3-fold and 1.5-fold increases in the levels of AM mRNA in the adrenal gland and kidney, respectively. At the same time, expression of calcitonin receptor-like receptor mRNA was significantly upregulated in both kidney and adrenal gland, as was expression of receptor activity-modify protein 1 (RAMP1) and RAMP2 mRNA in the adrenals and expression of RAMP3 in kidneys. Taken together, these results suggest that AM plays a role in the regulation of water and electrolyte balance in animals chronically ingesting high levels of salt.     

Investigational drugs for the treatment of spinal cord injury: review of preclinical studies and evaluation of clinical trials from Phase I to II

Introduction: Efforts in basic research have clarified mechanisms involved in spinal cord injury (SCI), and resulted in positive findings using experimental treatments including cell transplantation and drug administration preclinically. Based on accumulated results, various clinical trials have begun for human SCI.

Areas covered: In this review, the authors focus on five investigational drugs: riluzole, minocycline, Rho protein antagonist, magnesium chloride in polyethylene glycol formulation, and basic fibroblast growth factor. All drugs have established safety and tolerability from Phase I clinical trials, and are now in Phase II. They have been proven to have neuroprotective and/or neuroregenerative effects in animal models of SCI.

Expert opinion: To date, diverse drugs have been translated into clinical trials, but none have reached clinical application. A key gap was the lack of reliable biomarkers for SCI to fast-track Phase I/II trials. Furthermore, problems were often due to lack of adequate outcome assessments for both animal models and SCI patients. In order to advance clinical trials more quickly and with greater success, more clinically relevant animal models should be used in basic research. Clinically, it is indispensable to use appropriate outcome measurements and to construct a wide network among clinical centers to validate the efficacy of drugs.