Ward managers. Too hot to handle?
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Biomedical subjects
Publications and source records attributed to C Laurent.
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Catechol-O-methyltransferase is a candidate in the predisposition to schizophrenia both because of its function and the position of its gene. A multipoint non-parametric linkage analysis and a transmission disequilibrium test were performed on 42 multiplex families genotyped for Pml I and Bcl I polymorphisms using two definitions of the affected phenotype. Neither linkage nor preferential transmission of any allele or haplotype was detected, failing to replicate previous positive findings.
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Most studies investigating the symptom dimensions of schizophrenia utilising the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) favour a three factor model. This study sought to investigate the factor structure of both the global and individual items of the SANS and SAPS in a large sample of South African Xhosa patients with schizophrenia. A total of 422 subjects participated. Both principal components and factor analytical procedures were applied. For the global items, a two-factor solution representing positive and negative symptoms accounted for 59.9% of the variance. Alternatively, the three-dimensional model of negative, psychotic and disorganisation factors was supported by a five-factor solution if the more heterogeneous items of attention and alogia were ignored. Analysis of the individual items yielded a five-factor solution with the negative symptoms splitting into diminished expression and disordered relating, and the positive symptoms separating into factors for psychosis, thought disorder and bizarre behaviour. Our findings are very similar to those from other parts of the world, providing evidence that the factor structure for the symptoms of schizophrenia is relatively resistant to cultural influences. This is particularly true for negative symptoms.
This article argues that therapist empathy is both an essential context and an active intervention for addressing the emotion regulation problems common among adult survivors of child abuse. We define healthy emotion regulation, the role of parental empathy in the development of these capacities, and the results of abuse and neglect as empathic failures. We define therapeutic empathy and outline how it functions both to modulate arousal and to increase client awareness of emotional experience, thus facilitating emotional processing of trauma memories.
Many polypeptides overexpressed in bacteria are produced misfolded and accumulate as solid structures called inclusion bodies. Inclusion-body-prone proteins have often been reported to escape precipitation when fused to maltose-binding protein (MBP). Here, we have examined the case of HPV 16 oncoprotein E6. The unfused sequence of E6 is overexpressed as inclusion bodies in bacteria. By contrast, fusions of E6 to the C-terminus of MBP are produced soluble. We have analyzed preparations of soluble MBP-E6 fusions by using three independent approaches: dynamic light scattering, lateral turbidimetry, and sandwich ELISA. All three methods showed that MBP-E6 preparations contain highly aggregated material. The behavior of these soluble aggregates under denaturating conditions suggests that they are formed by agglomeration of misfolded E6 moieties. However, precipitation is prevented by the presence of the folded and highly soluble MBP moieties, which maintain the aggregates in solution. Therefore, the fact that a protein or protein domain is produced soluble when fused to the C-terminus of a carrier protein does not guarantee that the protein of interest is properly folded and active. We suggest that aggregation of fusion proteins should be systematically assayed, especially when these fusions are to be used for binding measurements or activity tests.
Resection of liver colorectal metastases allows a 5-year survival in 25% to 35% of patients. The outcome of patients with noncolorectal metastases is unknown because of the heterogeneity of this group. The aim of this retrospective study was to evaluate predictive factors of survival in patients who underwent resection of noncolorectal and nonneuroendocrine (NCRNE) liver metastases. From 1980 to 1997, 284 patients underwent hepatectomy for liver metastases of whom 39 (25 men and 14 women, mean age 55 years) had curative resection for NCRNE liver metastases. No patients had extrahepatic disease. The primary tumors were gastrointestinal (n = 15), genitourinary (n = 12) and miscellaneous (n = 12). The mean number of metastases was 1.8, and the mean size of the lesions was 51 mm. The median disease-free interval was 27 months. Twenty patients had a major hepatectomy and 19 a minor resection, with simultaneous resection of the primary in 6 cases. Overall survival was evaluated using the Kaplan-Meier method. There was no operative mortality, and 8% morbidity. The survival at 1, 3, and 5 years was 81, 40, and 35%, respectively. Patients with a disease-free interval higher than 24 months had a greater survival rate than those with a disease-free interval of less than 24 months (100% vs. 10%; p = 0.0004). Survival was not significantly influenced by age, sex, type of primary tumor, number, size and localization of metastases, type of hepatectomy, or blood transfusion. Resection of NCRNE liver metastases should be justified for patients without extrahepatic disease and resectable metastases, especially for those who have a disease-free interval of more than 24 months.
Several studies have compared loop ileostomy with loop colostomy to defunction colorectal anastomoses. The discordant results may be due to the heterogeneity of the indications. We therefore performed a retrospective study to compare the two procedures in a homogeneous group of patients operated on electively for rectal cancer. Among 462 consecutive patients undergoing rectal resection for cancer during 1986-1998, 60 had a loop colostomy and 107 a loop ileostomy to defunction a low anastomosis. The two groups were similar with respect to age, gender, obesity, tumor stage, and duration before closure (109 vs. 104 days; p = 0.28). All the stoma-related complications that occurred after construction and after closure of the stoma were recorded. There were no stoma-related deaths in the two groups. After stoma construction, the morbidity rate was significantly higher following loop colostomy than after loop ileostomy (35% vs. 19%; p = 0.02). After stoma closure the complication rate was significantly higher in the colostomy group than in the ileostomy group (34% vs. 12%; p = 0.004). The risk of surgical reintervention related to the morbidity of both construction and closure of the stoma was twice as high after loop colostomy than after loop ileostomy (22% vs. 9%; p = 0.03). The results of this study showed that, in our experience, the overall stoma-related morbidity and risk of reoperation were significantly lower after loop ileostomy than after loop colostomy. This suggests that loop ileostomy is the best procedure for defunctioning colorectal anastomoses electively. We therefore recommend using a loop ileostomy during rectal cancer surgery.
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Polycyclic aromatic hydrocarbons (PAHs) are lipophilic organic pollutants occurring widely in the terrestrial environment. To study the transfer of PAHs in the food chain, pigs have been fed with milk spiked either with [(14)C]phenanthrene or with [(14)C]benzo[a]pyrene. The analysis of blood radioactivity showed that both PAHs were absorbed with a maximum concentration at 5--6 h after milk ingestion, similar to fat metabolism. The blood radioactivity then decreased to reach background levels 24 h after milk ingestion. Furthermore, the blood radioactivity was higher for phenanthrene (even if the injected load was the lowest) than for benzo[a]pyrene, in agreement with their solubility difference. These findings suggest that milk fat and PAHs were absorbed during the same time period.
OBJECTIVE: The aim of this study was to describe the distributions of major extracellular matrix components, such as proteoglycans, collagen and hyaluronan, in the fetal membranes at term. STUDY DESIGN: Fetal membranes were obtained from elective cesarean deliveries at term. Guanidinium extracts were analyzed for proteoglycans with alcian blue precipitation, sodium dodecyl sulfate- polyacrylamide gel electrophoresis, and Western blotting and for hyaluronan with a radioimmunoassay. Collagen was measured by estimating hydroxyproline content. Tissue sections were immunostained for decorin and biglycan and stained for hyaluronan with a biotin-labeled hyaluronan-binding protein. RESULTS: The fetal membranes contained predominantly smaller proteoglycans, such as biglycan and decorin. The amnion consisted of typical fibrous connective tissue with a high concentration of collagen. The amnion was dominated by decorin located in close connection with the collagen fibrils. The chorion was composed of a fibroblastic part containing collagen and decorin and a trophoblastic part mainly containing biglycan. In addition, large amounts of hyaluronan were found, especially in the amnion and in the decidual cell layers. CONCLUSION: The distributions of proteoglycans, collagen, and hyaluronan in human fetal membranes may explain the biomechanical properties of this tissue. We suggest that changes in the relative proportions of these extracellular molecules are crucial for the proposed maturation process in the fetal membranes during the last weeks of pregnancy.
PURPOSE: To investigate the incidence of translocations induced by iodine-131 therapy in thyrotoxicosis patients 1 year after the administration of the radiolabelled compound. MATERIALS AND METHODS: Tricolour FISH with whole-chromosome-specific probes for chromosomes 2, 4 and 8 was used for scoring translocations. From the genomic translocation frequencies, derived using the Lucas formula, equivalent whole-body doses were calculated, based on the in vitro (60)Co gamma-ray dose-response curve. RESULTS: A total of 101 translocations were observed in 4864 metaphases, 63% being of the two-way type. In the control group used for obtaining dose-response data, nine translocations were observed in 5278 metaphases, 55% being two-way translocations. No correlation was found between the observed frequency of translocations and administered radioactivity. Using the in vitro dose-response, an estimated average dose for the group of nine patients of 0.79 +/- 0.22Gy was obtained. Compared with frequencies following the assumption that the involvement of a particular chromosome in a two-break exchange-type aberration is proportional to its DNA content, chromosome 4 was more frequently involved and chromosomes 2 and 8 less frequently involved in chromosomal rearrangements. CONCLUSION: This study shows that (131)I therapy for thyrotoxicosis patients induced translocations, especially in chromosome 4, which could be detected 1 year after the administration of the radiolabelled compound.
BACKGROUND: Studies conducted mainly in industrialized countries have shown that the transmission of hepatitis C virus (HCV) is mainly parenteral, and have emphasized the role of nosocomial transmission. In Equatorial Africa, the respective contributions of parenteral and non-parenteral routes of transmission are unknown. The potential role of sexual transmission in this area of high HCV endemicity, where sexually transmitted infections (STI) are frequent, is suggested by the fact that HCV infection is rare in infants and young adolescents, but increases thereafter with age. The present study, conducted in Democratic Republic of Congo, was designed to determine the prevalence of HCV infection and associated sexual risk factors in two female populations with different sexual behaviour. METHODS: Cross-sectional studies conducted among commercial sex workers (CSW; n = 1144) and pregnant women (n = 1092) in the late 1980s in Kinshasa showed a high frequency of at-risk sexual behaviour, STI and human immunodeficiency virus (HIV) infection, particularly among CSW. We screened samples collected during these epidemiological studies for antibodies to HCV using a second-generation ELISA with confirmation by a third-generation LIA. We also assessed sociodemographic variables, medical history, STI markers and sexual behaviour, and their potential association with HCV infection. RESULTS: The overall prevalence of anti-HCV was 6.6% (95% CI : 5.2-8.2) among CSW and 4.3% (95% CI : 3.2-5.7) among pregnant women (age-adjusted OR = 1.5, 95% CI : 1.0-2.1, P = 0.05). Multivariate analysis showed that the presence of anti-HCV among CSW was independently associated with a previous history of blood transfusion (P < 0.001), age >30 years (P < 0.001) and the presence of at least one biological marker of STI (P < 0.03). No such links were found among pregnant women (although the history of blood transfusions was not investigated in this group). Anti-HCV was not associated with sociodemographic variables or sexual behaviour in either group, or with individual markers of STI. Despite the high-risk sexual behaviour and the higher prevalence of STI in CSW, the difference in HCV seroprevalence between CSW and pregnant women (6.6% versus 4.3%) was small, particularly when compared with the difference in the seroprevalence of HIV (34.1% versus 2.8%). CONCLUSION: The role of sexual transmission in the spread of HCV seems to be limited. Parenteral transmission (including blood transfusion and injections), possibly related to the treatment of STI, probably plays a major role.
Recombinant production of HPV oncoprotein E6 is notoriously difficult. The unfused sequence is produced in inclusion bodies. By contrast, fusions of E6 to the C-terminus of carrier proteins such as maltose-binding protein or glutathione-S-transferase are produced soluble. However, it has not yet been possible to purify E6 protein from such fusion constructs. Here, we show that this was due to the biophysical heterogeneity of the fusion preparations. We find that soluble MBP-E6 preparations contain two subpopulations. A major fraction is aggregated and contains exclusively misfolded E6 moieties ('soluble inclusion bodies'). A minor fraction is monodisperse and contains the properly folded E6 moieties. Using monodispersity as a screening criterion, we optimized the expression conditions, the purification process and the sequence of E6, finally obtaining stable monodisperse MBP-E6 preparations. In contrast to aggregated MBP-E6, these preparations yielded fully soluble E6 after proteolytic removal of MBP. Once purified, these E6 proteins are stable, folded and biologically active. The first biophysical measurements on pure E6 were performed. This work shows that solubility is not a sufficient criterion to check that the passenger protein in a fusion construct is properly folded and active. By contrast, monodispersity appears as a better quality criterion. The monodispersity-based strategy presented here constitutes a general method to prepare fusion proteins with optimized folding and biological activity.