A genetic model for undifferentiated cell tumor formation: similar tumors formed by different cell lines transformed by the E1A oncogene

The activation of oncogenes and the mutation/deletion of suppressor genes may be involved in tumor heterogeneity. In an attempt to study tumor heterogeneity, we transformed cell lines from epithelial (PAM 212), mesenchymal (NIH-3T3), or melanocytic origin (L-BIOBR) with the wild type E1a oncogene. To make the cell lines tumorigenic, cells were infected with Harvey sarcoma virus carrying the v-H-ras oncogene. The transformed cells were injected into nude mice and the tumors studied by optical and electron microscopy. The tumors formed by v-H-ras-transformed cells consisted of epitheliod melanomas, spindle cells sarcomas and poorly-differentiated carcinomas, depending on the cell of origin. In contrast, the tumors obtained from cells also carrying the E1a oncogene showed a predominant small and undifferentiated cell pattern regardless of the cell of origin. We conclude that the E1a oncogene products induce a negative control of differentiation, independent of the cell type, and that tumors formed by cells carrying the E1a oncogene display an undifferentiated cell pattern.     

Breast-feeding and the nutritional status of nursing children in Chile

4-Pentafluoroethylumbelliferyl-beta-D-glucoside is proposed as an efficient substrate for human leukocyte acid beta-glucosidase. Its synthesis is described. This substrate was compared directly with 4-trifluoromethylumbelliferyl-beta-D-glucoside synthesized by us earlier and with 4-methylumbelliferyl-beta-D-glucoside which is commonly used for acid beta-glucosidase activity assay. The specific activity of acid beta-glucosidase with 4-pentafluoroethylumbelliferyl-beta-D-glucoside was 3- and 8-fold higher than it was with the substrates mentioned above. The kinetic parameters KM and VMAX for human leukocyte acid beta-glucosidase with the three substrates was determined. One possible application of the newly synthesized substrate is its use in the diagnosis of acid beta-glucosidase hereditary deficiency (Gaucher's disease).     

Comparison of morphologic assessment of hypertrophic cardiomyopathy by magnetic resonance versus echocardiographic imaging

To compare the value of echocardiography and magnetic resonance imaging (MRI) in the assessment of the amount and extent of hypertrophy in hypertrophic cardiomyopathy (HC) and, second, to correlate the degree of hypertrophy, as assessed by MRI, with clinical and electrocardiographic parameters, 30 consecutive patients (16 men and 14 women, aged 20 to 74 years) with HC were studied. Measurements of left ventricular wall thickness were performed at 11 predetermined segments (5 basal, 5 midventricular, and 1 apical) by 2-dimensional echocardiography and MRI. Two parameters derived from MRI studies were considered as indicators of the degree and extent of hypertrophy: (1) mean of the measured wall thickness at the 11 segments, and (2) the number of segments with thickness > 15 mm. Results showed that, from a total of 330 myocardial segments, thickness could be measured by echocardiography in 221 (67%), whereas MRI allowed measurement of 320 segments (97%). When compared with clinical and electrocardiographic data, no correlation was found regarding mean wall thickness and number of hypertrophied segments by MRI except for the presence of an abnormal electrocardiographic repolarization pattern. It is concluded that MRI allows a better assessment of the degree and extension of left ventricular hypertrophy than echocardiography in HC. Despite the precise information on hypertrophy provided by MRI, the amount and degree of hypertrophy bears no correlation with most of the clinical data in these patients.     

Complement resistance of capsulated strains of Aeromonas salmonicida

1. We investigated the effect of exercise on plasma adrenomedullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01). 4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.     

Cellular UDP-glucose deficiency caused by a single point mutation in the UDP-glucose pyrophosphorylase gene

We previously isolated a mutant cell that is the only mammalian cell reported to have a persistently low level of UDP-glucose. In this work we obtained a spontaneous revertant whose UDP-glucose level lies between those found in the wild type and the mutant cell. The activity of UDP-glucose pyrophosphorylase (UDPG:PP), the enzyme that catalyzes the formation of UDP-glucose, was in the mutant 4% and in the revertant 56% of the activity found in the wild type cell. Sequence analysis of UDPG: PP cDNAs from the mutant cell showed one missense mutation, which changes amino acid residue 115 from glycine to aspartic acid. The substituted glycine is located within the largest stretch of strictly conserved residues among eukaryotic UDPG:PPs. The analysis of the cDNAs from the revertant cell indicated the presence of an equimolar mixture of the wild type and the mutated mRNAs, suggesting that the mutation has reverted in only one of the alleles. In summary, we demonstrate that the G115D substitution in the Chinese hamster UDPG:PP dramatically impairs its enzymatic activity, thereby causing cellular UDP-glucose deficiency.     

Ethics of practice: The beliefs and behaviors of psychologists as therapists.

There is an absence of comprehensive, systematically gathered data concerning psychologists' beliefs about and compliance with ethical principles. Furthermore, we know little about which resources are valued as effective in guiding appropriate behavior. Survey data were collected from 456 APA Division 29 members regarding the degree to which they engaged in each of 83 behaviors and the degree to which they considered each behavior to be ethical. These data were categorized and examined in terms of five principles derived from the Hippocratic oath (avoiding harm, competence, avoiding exploitation, respect, and confidentiality) as well as two additional principles (informed consent; social equity and justice). Twelve of the behaviors were very difficult for participants to evaluate on the basis of ethics. Seven of the 83 behaviors were practiced by over 90% of the participants; 16 by fewer than 10%. Colleagues, the APA Ethical Principles, and internship training were rated as the most helpful resources in guiding behavior; state and federal laws, published research, and local ethics committees were rated least helpful. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thyroxine,Triiodothyronine, Reverse-Triiodothyronine,and Other Physiological Characteristics of Periparturient Cows Fed Restricted Energy

Eighty-six cows were assigned to two equal groups with group A fed according to National Research Council recommendations for total digestible nutrients for the 8 wk before parturition and group B was fed 21% higher energy in the first 6 wk and 15% higher in the last 2 preparturient wk. Thyroxine in blood serum decreased in both groups 14 days before and on the day of delivery. It was significantly lower in group A. Findings were similar with triiodothyronine. Blood serum concentrations of reverse-triiodothyronine of group A was significantly higher in group A on day 28 and 14 than group B before delivery. Energy intake had little influence on the serum concentrations of other constituents (albumin, total protein, immunoglobulin G, total and free cholesterol, nonesterified fatty acids). Restricted energy intake that does not alter thyrotropin-thyrotropin-releasing hormone secretion results in higher rate of production of reverse-triiodothyronine and in decreased serum concentration of triiodothyronine. Slight changes of energy balance might be indicated readily by reverse-triiodothyronine concentration in blood serum.