Stability of formal thought disorder and referential communication disturbances in schizophrenia.

This study examined the degree to which different types of communication disturbances in the speech of 48 schizophrenia patients and 28 controls were variable and state related versus stable and traitlike. Clinically rated formal thought disorder and 5 types of referential disturbance showed substantial stability within participants over time. The sixth type of referential disturbance, the vague reference, was not stable over time. Formal thought disorder was associated with the severity of core psychotic symptoms in patients, whereas referential disturbances showed little or no association with positive or negative symptom severity. Furthermore, changes in psychotic symptoms over time were accompanied by corresponding changes in formal thought disorder but not referential disturbances. These results support the idea that some types of referential disturbances are traitlike and may be reflective of vulnerability as well as manifest illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prospects for insulin delivery by ex-vivo somatic cell gene therapy

The principle of insulin delivery by ex-vivo somatic cell gene therapy involves the removal of non-B-cell somatic cells (e.g. fibroblasts) from a diabetic patient, and genetically altering them in vitro to produce and secrete insulin. The cells can be grown in culture and returned to the donor as a source of insulin replacement. Cells modified in this way could be evaluated before implantation, and reserve stocks could be cryopreserved. By using the patient's own cells, the procedure should obviate the need for immunosuppression and overcome the problem of tissue supply, while avoiding a recurrence of cell destruction. Ex-vivo somatic cell gene therapy requires an accessible and robust cell type that is amenable to multiple transfections and subject to controlled proliferation. Special problems associated with the use of non-B-cell somatic cells include the processing of proinsulin to insulin, and the conferment of sensitivity to glucose-stimulated proinsulin biosynthesis and regulated insulin release. Preliminary studies using fibroblasts, pituitary cells, kidney (COS) cells and ovarian (CHO) cells suggest that these challenges could be met, and that ex-vivo somatic cell gene therapy offers a feasible approach to insulin replacement therapy.     

Schizophrenia outpatients' perceptions of their parents: Is expressed emotion a factor?

The factors that mediate the association between expressed emotion (EE) and relapse in schizophrenia patients are still unknown. Many researchers hypothesize that interactions with high-EE individuals are stressful for patients, leaving them vulnerable to relapse. It would be useful to investigate whether patients perceive interactions with high-EE parents as stressful. In this study, associations were examined between levels of EE in parents and the types of personal memories patients had about these parents. EE ratings were obtained for both parents of 27 schizophrenia outpatients, and patients were asked to describe "happy, nonstressful" memories and "unhappy, stressful" memories during 2 interviews. Patients recounted fewer nonstressful memories and more stressful memories about high- versus low-EE parents. Implications of these results are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cancer cell necrosis by autoschizis: Synergism of antitumor activity of vitamin C: Vitamin K3 on human bladder carcinoma T24 cells

Scanning and transmission electron microscopy and fluorescence light microscopy were employed to characterize the cytotoxic effects of vitamin C (VitC), vitamin K₃ (VitK₃) or a VitC:VK₃ combination on a human bladder carcinoma cell line (T24) following 1-h and 2-h vitamin treatment. T24 cells exposed to VitC alone exhibited membranous damage (blebs and endoplasmic extrusions, elongated microvilli). VitK₃-treated cells displayed greater membrane damage and enucleation than those treated with VitC as well as cytoplasmic defects characteristic of cytoskeletal damage. VitC:VitK₃-treated cells showed exaggerated membrane damage and an enucleation process in which the perikarya separate from the main cytoplasmic cell body by self-excision. Self-excisions continued for perikarya which contained an intact nucleus surrounded by damaged organelles. After further excisions of cytoplasm, the nuclei exhibited nucleolar segregation and chromatin decondensation followed by nuclear karryorhexis and karyolysis. This process of cell death induced by oxidative stress was named autoschizis because it showed both apoptotic and necrotic morphologic characteristics.     

Differences in anaerobic performance between boys and men

The purpose of this study was to compare the anaerobic performance of 11-12 year old prepubescent boys (stage 1; n = 18) using a maximal effort 90 s cycling test to that of adult men (n = 19). Performance was separated into short-term anaerobic power (SAP; work in 10 s), intermediate-term anaerobic capacity (IAC; work in 30 s) and long-term anaerobic capacity (LAC; work in 90 s). Resistance on the Monark cycle ergometer was chosen as the highest tolerable load for the 90 s test and set at 2.6 and 3.8 J. rev-1.kg body mass-1 for boys and men, respectively. Power drop-off (%PD) was determined as the change in 5 s power outputs from 0-90 s. Blood lactates were measured at rest (pretest; BL) and at 2 (BL2) and 5 (BL5) min post test. Absolute and relative (to weight or thigh volume) scores for SAC, IAC and LAC were 33-40% lower in the boys compared to the men (p < 0.001). The men demonstrated significantly greater %PD over the 90 s (32.2%) compared to the 25.3% PD of the boys (p < 0.001), suggesting that the development of fatigue was greater in the men even though power and work outputs were high. Resting BL values were similar for both groups. Mean BL2 and BL5 were higher (p < 0.01) in the men (13.5, SD = 3.4; 12.5, SD = 2.8 mmol.l-1) than in the boys (9.1, SD = 1.7; 8.3, SD = 1.6 mmol.l-1). The anaerobic performance of the boys compared to the men cannot be completely explained by the lower resistance setting used. Although the boys were 50% lighter than the men, their resistance was 70% of that used for the men. The results do not support the contention that children and adults have similar abilities in short term, exhaustive work when corrected for size. Prepubescent boys appear to be limited in their ability to perform short-term as well as intermediate and long term anaerobic exercise compared to adult males.     

Development of endothelin receptors in perinatal rabbit pulmonary resistance arteries

1. Contractile responses to endothelin-1 (ET-1) and sarafotoxin S6c (S6c) were studied in pulmonary resistance arteries (approximately 320 microm i.d.) from fetal, 0-24 h, 4 day and 7 day rabbits. The effects of the ET(A)-selective antagonist FR139317, the selective ET(B) receptor antagonist BQ-788 and the non-selective ET(A)/ ET(B) receptor antagonist SB 209670, on these responses, were determined. Acetylcholine-induced vasodilation and noradrenaline-evoked contractions were also examined. 2. ET-1 potency was in the following order (pEC50 values): fetal (8.7) = 0-24 h (8.8) = 4 day (8.6) > 7 day (8.0). The order of potency for S6c was 7 days (11.1) = 4 days (10.8) > 0-24 h (9.7) > fetal (8.6). Hence, S6c and ET-1 were equipotent in the fetus but S6c was increasingly more potent than ET-1 with increasing age, being some 1000 times more potent by 7 days. By 7 days, responses to ET-1 were also resistant to both FR139317 and BQ-788. FR139317 inhibited responses to ET-1 in vessels from 0-24 h and 4 day, but not fetal, rabbits (pKb: 6.4 in 4 day rabbits). BQ-788 inhibited responses to ET-1 at all age points except for 7 days (pKb: 6.7 at 0-24 h; 6.2 at 4 days). BQ-788 inhibited responses to S6c at all age points (pKb: 8.5 at 4 days). SB 209670 inhibited responses to ET-1 and S6c at 0-24 h and 4 days (pKb for ET-1: 8.3 and 8.0 respectively; pKb for S6c: 9.2 and 10.2 respectively). 3. Acetylcholine (1 microM) induced vasodilation at all age points (inhibited by 100 microM L-N(omega)-nitroarginine methylester) although the degree of vasodilation was significantly reduced (approximately 75%) at 0-24 h. Noradrenaline induced contraction at all age points except 7 days and its response was significantly enhanced at 0-24 h. 4. Over the first week of life, the potency of S6c increases whilst that to ET-1 decreases suggesting differential development of responses to ET-1 and S6c and heterogeneity of ET(A)- or 'ET(B)-like' receptor-mediated responses. There is no synergism between ET(A) and ET(B) receptors at birth but this is established by 7 days. Immediately after birth rabbit Pulmonary Resistance Arteries are hyperresponsive to ET-1 and noradrenaline but exhibit impaired nitric-oxide dependent vasodilation.     

Effect of novel mixed ETA/ETB antagonists on responses to ET-1 in human small muscular pulmonary arteries

Selective ETA and ETB receptor antagonists do not fully inhibit responses to ET-1 in human small pulmonary arteries. Here, we have compared the influence of the novel mixed ETA/ETB antagonists SB/217242, SB/234551 and SB/209670 on ET-1-mediated vasoconstriction in these vessels. ET-1 was a potent vasoconstrictor (pEC50: 8.14+/-0.05, n=5) and the concentration-response curve to ET-1 was biphasic in nature. All three mixed antagonists (1 microM) inhibited the responses to ET-1, abolishing the biphasic form of the concentration response curve. The order of potency was SB 209670>SB 234551>/=SB 217242 with estimated pKb values of 8.0+/-0.20, 6.8+/-0.17 and 6. 6+/-0.11 respectively (n=3-5).     

Gelatinase A (MMP-2) and cysteine proteinases are essential for the degradation of collagen in soft connective tissue

Epidermal growth factor (EGF) is a potent mitogen for normal mouse mammary epithelial cells grown in primary culture. EGF activation of the EGF-receptor (EGF-R) induces intrinsic tyrosine kinase activity which results in EGF-R autophosphorylation and tyrosine phosphorylation of other intracellular substrates involved in EGF-R signal transduction. Genistein and erbstatin are anticancer agents which have been shown to be potent tyrosine kinase inhibitors. However, the effects of these compounds in modulating EGF-dependent normal mammary epithelial cell proliferation is presently unknown. Therefore, studies were conducted to determine the effects of genistein and erbstatin on EGF-dependent proliferation, and EGF-R levels and autophosphorylation in normal mouse mammary epithelial cells grown in primary culture and maintained in serum-free media. Chronic treatment with 6.25-100 microM genistein or 1-16 microM erbstatin significantly decreased EGF-dependent mammary epithelial cell proliferation in a dose-responsive manner. However, the highest doses of genistein (100 microM) and erbstatin (16 microM) were found to be cytotoxic. Additional studies showed that acute treatment with 6.25-400 microM genistein did not affect EGF-R levels or EGF-induced EGF-R autophosphorylation, while acute treatment with 1-64 microM erbstatin caused a slight reduction in EGF-R levels, but had no effect on EGF-dependent EGF-R autophosphorylation in these cells. In contrast, chronic treatment with similar doses of genistein or erbstatin resulted in a large dose-responsive decrease in EGF-R levels, and a corresponding decrease in total cellular EGF-R autophosphorylation intensity. These results demonstrate that the inhibitory effects of chronic genistein and erbstatin treatment on EGF-dependent mammary epithelial cell proliferation is not due to a direct inhibition of EGF-R tyrosine kinase activity, but results primarily from a down-regulation in EGF-R levels and subsequent decrease in mammary epithelial cell mitogenic-responsiveness to EGF stimulation.     

Comparative affective reactivity of different types of communication disturbances in schizophrenia.

Twenty-nine schizophrenic outpatients provided speech samples on affectively positive and negative topics. These samples were assessed for several different types of communication failures by using the Communication Disturbances Index. Frequencies of overinclusive references, ambiguous word meanings, and ambiguous referents increased in the affectively negative condition; frequencies of missing referents and instances of syntactic unclarity did not change across affective conditions. Degree of overall affective reactivity of speech was associated with severity of the core positive schizophrenic syndrome. These findings support the idea that different types of schizophrenic communication disturbances are associated with different underlying pathophysiological processes, that some are more reactive to affect than others, and that affective reactivity of these symptoms is associated with the positive schizophrenic process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)