De-coupling of cognitive performance and cerebral functional response during working memory in schizophrenia.

Working memory dysfunction is considered to be fundamental to the cognitive and clinical features evident in schizophrenia. Functional neuroimaging studies have begun to elucidate the neurobiological basis of such deficits, however, interpretation of these studies may be confounded by performance impairment, when the cognitive load exceeds the limited response capacity of patients with schizophrenia. In this study, patients were pre-selected on the basis of intact performance on a relatively low-load verbal working memory task, in order to mitigate against performance confounds. Subjects included 20 right-handed male subjects with chronic schizophrenia, and 20 right-handed, age-matched, male healthy controls, without personal or familial psychiatric history. All subjects underwent fMRI scanning whilst performing a verbal n-back task. There were no significant between-group differences in target identification; the patient group showed a significantly increased mean response latency. Both groups demonstrated robust fronto-parietal activation. In the control subjects, the power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex, however, this coupling of behavioural performance and cerebral response was not evident in the patients. This deficit, apparent within the performance capacity of the patients, may represent a fundamental abnormality in schizophrenia, and may compromise performance at higher cognitive loads.     

Release of soluble transferrin receptor from the surface of human leukemic HL60 cells

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.      

Thymocyte expression of cathepsin L is essential for NKT cell development

CD1d antigen presentation to natural killer T (NKT) cells expressing the semi-invariant T cell receptor V(alpha)14J(alpha)18 requires CD1d trafficking through endosomal compartments; however, the endosomal events remain undefined. We show that mice lacking the endosomal protease cathepsin L (catL) have greatly reduced numbers of V(alpha)14(+)NK1.1(+) T cells. In addition, catL expression in thymocytes is critical not only for selection of these cells in vivo but also for stimulation of V(alpha)14(+)NK1.1(+) T cells in vitro. CD1d cell-surface expression and intracellular localization appear normal in catL-deficient thymocytes, as does the lysosomal morphology; this implies a specific role for catL in regulating presentation of natural CD1d ligands mediating V(alpha)14(+)NK1.1(+) T cell selection. These data implicate lysosomal proteases as key regulators of not only classical major histocompatibility complex class II antigen presentation but also nonclassical CD1d presentation.     

Empowerment versus power: consumer participation in mental health services

Consumer participation is regarded as increasingly important in the effective delivery of mental health services and for the empowerment of mental health consumers. In a qualitative study, 17 consumers and 10 occupational therapists discussed their perceptions of consumer participation in mental health services. These included the advantages and benefits of consumer participation, the barriers to participation and how health workers can facilitate participation. The research brought to light an uncertain relationship between empowerment and power. While empowerment was universally considered to be desirable, opinions about the transfer of power were more ambivalent. It is argued that consumers and health workers need to work together to find creative ways of addressing concerns relating to power so that real power can be shared to benefit all consumers. Limitations of the study included the small sample size and the sampling method, which restricted access to potential participants. Further research is suggested into consumer participation and consumer power. Copyright © 1999 Whurr Publishers Ltd.