In vitro behavior of human nonfertile semen in isoosmotic and hyperosmotic media

High-ionic-strength media are known to favor rapid capacitation and acrosome reaction of spermatozoa in vitro. The influence of isoosmolar (N-BWW) and hyperosmolar (H-BWW) media on the percent motility, forward progression, and zona-free hamster egg penetration has been investigated for 148 semen from patients consulting for male or idiopathic sterility. After 15 h of incubation, the hyperosmotic medium had no significant detrimental effect on the percent motility of spermatozoa, although the forward progression was better maintained in the isoosmolar medium. In general egg penetration was increased when spermatozoa were treated with the hypertonic medium, and in particular 5 patients whose semen showed no penetration when treated with N-BWW scored greater than 12% when treated with H-BWW. For the 23 subjects who had an IVF at the same period, a good agreement with zona-free egg penetration was found in 70% of the cases.     

Sclerosed liver hemangioma mimicking malignant tumor at MR imaging: Pathologic correlation

This case report illustrates atypical magnetic resonance (MR) imaging findings in a liver hemangioma mimicking a malignant lesion—lower signal intensity than cerebrospinal fluid on T2-weighted spin-echo images and lack of early enhancement on dynamic contrast material—enhanced gradient-echo images. Pathologic analysis demonstrated nearly total replacement of the vascular cavities by dense fibrous tissue. In this rare, sclerosed form, this lesion could not be defined as a hemangioma with MR imaging.     

Platelet receptor expression on three human megakaryoblast-like cell lines.

Platelets, the progeny of bone marrow megakaryocytes, are nonnucleated cells; many platelet proteins, including platelet membrane receptors, are believed to be derived from megakaryocytes. Several hematopoietic cell lines that exhibit megakaryocytic characteristics have been established as models for the study of megakaryocyte biology. We report here the screening of platelet receptor expression, in terms of functional coupling with the formation of two second messengers, calcium and cAMP, in three cell lines exhibiting megakaryoblastic properties: HEL, MEG-01, and DAMI. We show that all these cell lines respond to thrombin, ADP, epinephrine, and prostaglandin E1 (PGE1). However, transmembrane signaling pathways appear partly different from those present in mature platelets, because the action of thrombin was found to be positively coupled with the cAMP pathway, in addition to that of calcium, and because PGE1, which interacts with the cAMP pathway, also raises intracellular calcium levels in the three cell lines studied. Furthermore, an endothelin-1-induced increase in intracellular calcium level was observed in MEG-01 cells, strongly suggesting the expression of endothelin receptors on platelet precursors cells, whereas the presence of such receptors is controversial on platelets. These cell lines should prove useful in further studies of the expression and molecular pharmacology of platelet receptors on platelet precursor cells, as well as for the investigation of functional roles for platelet receptors on megakaryoblastic cells.     

Benzo(a)pyrene inhibits epidermal growth factor binding and receptor autophosphorylation in human placental cell cultures

Studies investigated the effects of benzo(a)pyrene (BP) treatment on epidermal growth factor (EGF) receptor binding and kinase activity in human placental cell cultures. Specific binding of 125I-EGF to cells from early gestation placentae was significantly decreased by 37 and 60% following exposure to 1 and 10 microM BP, respectively, for 24 hr. In contrast, cells cultured from term placentae showed no inhibitory effect of either concentration of BP. Specific binding of 125I-labeled insulin and insulin-like growth factors-I and -II to early gestation cells was decreased only 15-18% at 10 microM BP, which indicates that loss of membrane receptors appears to be selective for EGF. Scatchard analysis of early gestation cells revealed that BP was associated with a dose-dependent loss in the number of high affinity EGF binding sites. Evidence from cross-linking and autophosphorylation experiments confirmed that the Mr 170,000 binding protein was decreased in a dose-dependent manner following BP treatment. In comparison, term placental cells exhibit a 26% loss of EGF receptor autophosphorylation without alteration in binding following exposure to 10 microM BP. Thus, early gestation cells exhibit a BP-related down-regulation of EGF receptors, whereas term placental cells show receptor desensitization. No adverse effect of BP treatment was observed on the incorporation of [35S] methionine into proteins secreted by early gestation cells. Further experiments compared the effects of BP with the related poly-cyclic compounds beta-naphthoflavone, alpha-naphthoflavone, and 3-methylcholanthrene. In early gestation cells, EGF binding and receptor autophosphorylation were measurably decreased at 10 microM concentrations of these polycyclic compounds, but to a lesser extent than observed with BP. In term placental cells, however, EGF binding was unchanged or increased, whereas receptor autophosphorylation was decreased 10-26%. Thus, exposure of term placental cells to these polycyclic compounds leads to a dissociation between EGF binding and receptor protein kinase activity. Finally, aryl hydrocarbon hydroxylase activity was induced 20- to 200-fold in early placental cells exposed to BP, beta-naphthoflavone, and 3-methylcholanthrene. In summary, the direct effects of BP and related compounds observed on placental EGF receptors may indicate altered function of EGF in the regulation of cell growth and differentiation in the human placenta.     

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.     

Primary health care in a multi-level perspective: towards a research agenda

The authors propose to view primary health care (PHC) from a multi-level perspective. Studying how PHC is conceived and implemented at different levels of social organization (e.g. in international agencies, national governments, regional centres of health care and local communities) will reveal which interests may be competing in the planning and execution of what broadly and conveniently is called 'PHC'. Mapping out these conflicting views and interests will contribute towards a better understanding of how PHC works or why it does not work and provide suggestions for a more effective and equitable PHC. Five themes are proposed for a multi-level research approach: (1) vertical versus horizontal organization of PHC: (2) the role of medical personnel in PHC; (3) the distribution of pharmaceuticals; (4) the integration of traditional medicine in PHC; and (5) family planning.     

Evaluation of the end-expiratory lung volume as an indirect index of bronchial constriction in asthma

The purpose of this study was to evaluate the merits of the end expiratory lung volume as an indirect ventilatory index of bronchial obstruction and to show an application of continuous monitoring of lung volume in asthmatic patients. The accuracy of the external measurements (IS) of functional residual capacity (FRC) was controlled by comparing them with the helium measurements (DS) obtained during nine methacholine tests (IS = 0.06 + 1.065 DS in litres: R2 = 0.99). Seven asthmatics (18-48 yr) were monitored by measuring rib cage and abdominal perimeter variations. This was done in basal condition, after methacholine-induced bronchoconstriction and after bronchodilation by either salbutamol or oxytropium bromide inhalation. All the subjects were investigated on two separate days and were their own control. Bronchoconstriction produced a significant increase (p less than 0.01) of tidal volume (VT: + 67%), external minute ventilation (VE: + 58%), mean inspiratory flow (VT/TI: + 78%) and FRC (+ 26.5%) while frequency (f) and fractional inspiratory time (TI/TT) fluctuated non significantly. In the group of seven tested subjects, there was a significant correlation (p less than 0.01) between forced expiratory volume in one second (FEV1) and VE, FEV1 and VT/TI, FEV1 and FRC. However, the individual regression line showed a significant relationship only between FEV1 and FRC (R2 = 0.80 +/- 0.04). We therefore conclude that the variation of the end expiratory level can be chosen as an indirect index of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.