The orphan receptor TR4, member of the nuclear hormone receptor family, is related to the orphan receptors TR2, COUP-TFI and ARP-1, and was originally cloned from the adult rat brain. The latter two ...orphan receptors have been implicated in central nervous system (CNS) development. To investigate a possible role for TR4 in brain development, expression of TR4 was studied in rat embryos. At embryonic days 14.5 and 19.5, high expression of TR4 was found in the CNS, while low expression was detected throughout the embryo. In postnatal rats, TR4 was mainly expressed in the hippocampus and cerebellum, resembling the expression pattern found in adult brain. These data show that like COUP-TFI and ARP-1, expression of TR4 becomes restricted to distinct areas. In adult brain, TR4 is predominantly expressed in granule cells of both hippocampus and cerebellum. The data suggest a possible role for TR4 during proliferation and maturation of brain structures.
To investigate how primary care patients interpret the existing terminology used to describe medically unexplained symptoms; to contribute to the current academic discussion on unequivocal ...terminology.
Descriptive cohort study.
We approached patients in the waiting rooms of two general medical practices in the city of Groningen and in the province of Drenthe. Based on a fictitious case, the patients were asked to assign connotations to a number of possible diagnoses for medically unexplained tiredness. The patients could choose from seven predetermined connotations. Among the diagnoses for medically unexplained tiredness were 'functional fatigue', 'chronic fatigue syndrome', 'psychosomatic tiredness', and 'medically unexplained tiredness'. From the seven connotations, we labeled three connotations as being negative. When patients gave at least one negative connotation to a possible diagnosis, the diagnosis was labeled as 'offensive'.
A total of 184 patients participated in the study. From the alternative diagnoses for medically unexplained tiredness, 'psychosomatic tiredness' had the most negative connotations: at least one negative connotation for 65 (35%) patients. 'Chronic fatigue syndrome' and 'functional fatigue' had the fewest negative connotations: at least one negative connotation for respectively 17 (9%) and 24 (13%) patients.
The terms 'chronic fatigue syndrome' and 'functional fatigue' were less offensive. Our results could imply that terms for medically unexplained tiredness that refer less to a psychological basis are most acceptable for the patient.
Prophylactic insulin treatment has been shown to have beneficial effects in type 1 diabetes, both in humans and in various animal models of the disease. In experimental models, the protective effect ...of prophylactic insulin treatment was observed in two parameters: (1) progression of insulitis and (2) diabetes incidence. The mechanism of protection still remains to be investigated. We therefore analysed by immunohistochemistry the effect of prophylactic insulin treatment vs placebo treatment (from 4 to 13 weeks of age) on ER-MP23
+macrophage infiltration in and around pancreatic islets in the non-obese diabetic (NOD) mouse, a spontaneous model for type 1 diabetes. BALB/c mice were used as diabetes-free controls. Using conventional haematoxylin–eosin staining, we detected a protective effect of prophylactic insulin treatment in NOD females on the lymphocytic insulitis, significant at 13 weeks, but not at 9 weeks of age. However, when assessed by immunostaining for early infiltration of ER-MP23
+macrophages around islets, the reduction in severity of insulitis could already be detected as early as 9 weeks of age. With regard to the early accumulation of ER-MP23
+cells, we observed that their numbers per mm
2surface area of the exocrine pancreas and per μm at the circumference of the islet were higher in placebo-treated NODs (197±13.8 and 14±0.9, respectively) as compared to age-matched BALB/c mice (123.1±7.1 and 3.5±0.9, respectively). Prophylactic insulin treatment of NODs lowered the attraction of ER-MP23
+macrophages to the exocrine pancreas and to the circumference of the islets (156.3±8.5 and 7.9±1, respectively). Interestingly also, the islet size was found to be larger in placebo-treated NODs (51% was larger than 10
μm
2) than in age-matched BALB/c mice (9% larger than 10
μm
2). Prophylactic insulin treatment of NODs reduced their islet size to sizes found in the control BALB/c strain. In conclusion, the decrease in islet size by early insulin administration, and the lower attraction of ER-MP23
+macrophages to the islets are morphological indications that prevention of diabetes development by prophylactic insulin treatment results from a downregulation of islet metabolism and growth, with a concomitant decline in the release of islet factors attracting macrophages.
To examine whether HPA-axis activity mediates the relationship between obstetric complications (OCs) and externalizing behavior problems, and to investigate whether this model is different for boys ...and girls. In a population-based cohort of 1,768 10- to 12-year-old early adolescents, we assessed the cortisol awakening response and evening cortisol levels. Externalizing behavior problems were assessed using the Child Behavior Checklist and the Youth Self-Report. OCs were retrospectively assessed in a parent interview. OCs significantly predicted externalizing behavior problems, but OCs did not predict HPA-axis activity. Thus, the mediation model was not supported. In addition to the relationship between HPA-axis activity and externalizing behavior problems, which is specific for girls, there is also a relationship between OCs and externalizing behavior problems. However, these two mechanisms are not related to each other indicating that HPA-axis activity is not a mediator in the relationship between OCs and externalizing behavior problems. Future research should focus on understanding the mechanism through which OCs cause externalizing behavior problems.
PDF