Basin boundary metamorphoses in the canonical escape equation

A study is made of the escape boundary, in the space of the starting values of displacement and velocity, for a sinusoidally driven nonlinear oscillator. The oscillator has constant inertia and linear viscous damping, with a restoring force that corresponds to a cubic potential well. This cubic form of the total potential energy has the universal canonical form encountered by all metastable mechanical systems as they approach a generic fold catastrophe under a single control parameter. The basin boundary metamorphoses are observed, and an engineering integrity diagram is proposed, quantifying the rapid erosion of area that is triggered under increasing excitation by a homoclinic tangency. The pictures show clearly the fractal basin associated with the developed homoclinic tangle. The boundary crisis, at which the final chaotic attractor loses its stability, is examined in terms of an accessible saddle point, which is here a directly unstable subharmonic of order six.     

A numerical study of the effect of drive level on the intensity loss from an ultrasonic beam

Knowledge of the spatial distribution of intensity loss from an ultrasonic beam is vital to bioeffect predictions such as heating and streaming. A method for calculating the distribution of intensity loss over a finite-amplitude ultrasonic beam is described. The technique demonstrates that the location of peak intensity loss varies considerably with drive level for a plane circular source, as does the overall distribution of intensity loss across the beam. The effects are shown to be less pronounced but still significant for a focused source.     

Intestinal cell cycle regulations. Interactions of cyclin D1, Cdk4, and p21Cip1

OBJECTIVE: The p21Cip1 protein is a potent stoichiometric inhibitor of cyclin-dependent kinase activity, and p21Cip1 mRNA expression is localized to the nonproliferative compartment of the intestinal villus, suggesting an in vivo growth-inhibitory role in the gut. The authors determined whether nontransformed rat intestinal epithelial cells (IECs) underwent reversible cell cycle arrest by contact inhibition, and determined whether increases in the relative amount of p21 associated with cyclin D/Cdk4 protein complexes were associated with cell growth arrest. METHODS: Density arrest was achieved by prolonged culture IEC-6 in confluent conditions (5 or more days). Release from density arrest was achieved by detaching the cells from the culture plate and reseeding them at a 1:4 ratio. The DNA synthesis was estimated by [3H]-thymidine incorporation and expressed as mean plus or minus standard error of the mean (n = 4). Cyclin D1, Cdk4, and p21 mRNA and protein levels were determined by standard Northern and Western blot analyses, respectively. Cyclin D1, Cdk4, and p21 protein complex formation was analyzed by immunoprecipitating the complexes from cell lysates with an antibody to one of the constituents, followed by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis of the precipitated complexes using antibodies to the other proteins. The kinase activity of the immunoprecipitated Cdk4 was determined using recombinant Rb as substrate. RESULTS: The IEC-6[3H]-thymidine incorporation was decreased 7.5-fold from day 1 confluence to day 7 of confluence. Twenty-four hours after release from density arrest, there was a 43-fold increase in [3H]-thymidine incorporation. Cyclin D1 and Cdk4 mRNA levels remained relatively constant during contact inhibition, whereas immunoblotting showed that the levels of cyclin D1 and Cdk4 proteins decreased by 70.9% and 68.7%, respectively, comparing day 3 with day 9 during density arrest. The levels of cyclin D1 increased 5.8-fold and Cdk4 increased by 4.4-fold by 24 hours after reseeding the day 9 density-arrested cultures, coincident with the increase in DNA synthesis. The amount of p21 associated with the cyclin D1 and Cdk4 complex in the density-arrested cells was 170% of that observed in the reseeded, proliferating cells. More important, the p21::Cdk4 ratio was 6.4-fold higher in the density-arrested (quiescent) cells as compared with rapidly proliferating cells by 24 hours after release from growth arrest. Recovery of Cdk4-dependent kinase activity occurred by 4 hours after release from growth arrest, coincident with decreased binding of p21 to the complex. CONCLUSIONS: Intestinal epithelial cells in culture can undergo density-dependent growth arrest. This process involves downregulation of cyclin D1 and Cdk4 at the level of protein expression, whereas the mRNA levels remain relatively unchanged. Further, during contact inhibition, there is more p21 associated with cyclin D1/Cdk4, which further contributes to the inhibition of the kinase complex. The authors also have shown that the process of contact inhibition is reversible, which may explain partly the ability of the intestinal epithelium to increase proliferative activity in response to injury.     

Chemokine production and adhesion molecule expression by neural cells exposed to IL-1, TNF alpha and interferon gamma

We investigated the effect of TNF alpha, IL-1alpha and IFN gamma on two neuroblastoma (NB) cell lines (SK-N-SH and SK-N-MC). These lines responded differentially to IL-1alpha, TNF alpha and IFN gamma for MCP-1 and IL-8 production and expression of the ICAM-1 and VCAM-1 adhesion molecules. None of the cytokines induced MCP-1 or IL-8 on SK-N-MC cells. Both chemokines were produced in response to IL-1alpha by SK-N-SH cells, while TNF alpha induced mainly MCP-1 production. Addition of IFN gamma decreased IL-8, but not MCP-1 production. These responses correlated with monocyte and neutrophil chemotactic activity in NB culture supernatants. This activity was neutralized by antibodies to IL-8 and MCP-1. The expression of ICAM-1 on SK-N-MC was up-regulated by TNF alpha or IFN gamma, while IL-1alpha also upregulated ICAM-1 on SK-N-SH cells. VCAM-1 expression on SK-N-SH was induced by IL-1alpha and TNF alpha and IFN gamma synergized with TNF alpha in this respect on both NB cell lines. These results suggest that mechanisms for chemokine production and VCAM-1 and ICAM-1 upregulation by inflammatory cytokines differ and IFN gamma, in conjunction with TNF alpha, stimulate neural cell responses (high MCP-1 and VCAM-1 and decreased IL-8) favouring mononuclear cell recruitment.     

Liver selenium and testis phospholipid hydroperoxide glutathione peroxidase are associated with growth during selenium repletion of second-generation Se-deficient male rats

We have previously shown that changes in glutathione peroxidase-1 (GPX1; H2O2:oxidoreductase, EC 1.11.1.9), plasma thyroid hormone and glutathione-S-transferase were not associated with changes in growth observed in second-generation (F2) severely Se-deficient rats; we also found that liver phospholipid hydroperoxide glutathione peroxidase (GPX4; EC 1.11.1.12) activity falls in first-generation (F1) Se-deficient rats to 41% of levels in Se-adequate rats. The purposes of this study were to determine the effect of F2 Se deficiency on GPX4 and to detect early changes in Se parameters associated with growth after single, small Se injections. Se-deficient male F2 weanling rats were randomly divided into two groups and fed a Se-deficient crystalline amino acid (0.003 microg Se/g diet; -Se) diet or that diet supplemented for 14 d with 0.2 microg Se/g diet (+Se) as Na2SeO3. Growth of -Se rats was 55% of the rate of +Se rats. Liver Se, GPX1 activity, GPX4 activity and testis GPX4 activity in -Se rats at 14 d were 1, 2, 23 and 13%, respectively, of levels in +Se rats. In a series of experiments, additional F2 male weanling rats were fed the -Se diet for 14 d and then were given an intraperitoneal single saline injection of 0, 1 or 5 microg Se/100 g body weight (BW) as Na2SeO3 and killed 1 or 7 d later. Rats injected with 1 or 5 microg Se/100 g BW grew 36 or 48%, respectively, above the rate of saline-injected rats. Liver Se concentration increased 367% and testis GPX4 activity doubled in rats 1 d after injection of 1 microg Se/100 g BW compared with saline-injected rats; these parameters were further elevated with 5 microg Se/100 g BW injections. Increases in liver Se and testis GPX4 activity were the parameters best associated with improved growth after Se injection, but the molecular role for Se in growth remains unclear.     

Changes in myocardial A1 adenosine receptor and message levels during fetal development and postnatal maturation

Dysembryoplastic neuroepithelial tumor (DNT) is a recently described rare brain neoplasm with characteristic clinical and morphological features and favorable prognosis. We report here two cases of DNT. The first concerned a 12 years old girl who presented complex seizures preceded by acoustic aura (melodies). Computed tomography revealed a hypodense tumor measuring 2 x 2.5 cm in diameter, located paracortically in the left temporal lobe. The second tumor was removed from a 21-year-old man with partial complex seizures. Nine years earlier patient underwent neurosurgery with partial removal of the tumor The tumor's histopathologic diagnosis is unfortunately lacking. Computed and magnetic resonance imaging showed a mass occupying the cortex and paracortical areas of the anterior pole of the temporal lobe. Histologically, both tumors consisted of small, S-100 protein immunopositive oligodendrocyte-like cells (OLCs) arranged between synaptophysin- and, to a lesser degree, NFP-immunopositive axons (glioneuronal element). In the second case, an area of pilocytic astrocytoma-like appearance was also found, these cells were immunopositive for GFAP. The present study provides clinical, radiological and histological data, which may be helpful in differential diagnosis of this newly recognised brain tumor.     

New treatments for multiple sclerosis: a clinical perspective

A comprehensive screening program was initiated in Saudi Arabia in 1982 to determine the frequency of the sickle cell (Hb S) gene in the different regions of Saudi Arabia. Over a period of 10 years 30,055 samples were collected from 36 areas in the five provinces of Saudi Arabia; these were screened using electrophoretic techniques in alkaline and acid pH for the presence of Hb S in heterozygous and homozygous states. The overall prevalence of Hb AS was 7.36% and Hb SS was 1.06%, giving an Hb S gene frequency of 0.047. The results from the different regions were separated and the prevalence of Hb AS and Hb SS and Hb S gene frequencies were calculated in each province and each region. The prevalence of Hb AS and Hb SS cases ranged from O to 25.88% and O to 5.27%, respectively. No case of Hb AS or Hb SS were identified in certain areas of the central province (Al-Russ, Al-Unaiza, Al-Mesnab and Bkaria) and northern province (Qurayat and Al-Jouf). In the southern province both Hb S homozygotes and heterozygotes were encountered in all regions except Farasan Island. In all other regions the Hb S gene was encountered, but at a variable frequency. Applying Hardy-Weinberg equilibrium it was observed that in the majority of the regions the observed Hb S homozygotes were significantly higher compared to the number expected (p < 0.0001). This was believed to be due to bias as the samples were collected in the hospital. The Hb S gene frequency in the different regions ranged from 0 to 0.17 when the frequency was calculated on the basis of both Hb AS and Hb. SS cases, and 0 to 0.13 if the gene frequency was calculated after eliminating the Hb SS cases. A close correlation was observed between the Hb S gene frequency and malaria endemicity. This study shows that the Hb S gene occurs frequently in several regions of Saudi Arabia and there is an urgent need to implement control and prevention programs to reduce the number of Hb S homozygous cases.     

Metabolites from an Antarctic sponge-associated bacterium, Pseudomonas aeruginosa

In an ongoing survey of the bioactive potential of microorganisms associated with marine invertebrates, the culture media of a sponge-associated bacterial strain of Pseudomonas aeruginosa was found to contain metabolites which inhibit the growth of several Gram-positive microorganisms. A series of diketopiperazines (1-6) including a new natural product (6) and two known phenazine alkaloid antibiotics (7 and 8) were isolated from the culture broth of this bacterium.