A randomised assessment of the use of a quality of life questionnaire with or without intervention in patients attending a thoracic cancer clinic.

The study examined the impact of using a quality of life (QoL) questionnaire during a clinic to identify QoL issues and to improve QoL. 138 patients were randomised (1:1:1) to either (1) an Intervention group that completed the European Organisation for Research and Treatment of Cancer-Core Quality of Life Questionnaire and Lung Cancer Module (EORTC QLQ-C30 and LC13) at baseline and received feedback during a clinic, (2) an Attention group that completed the questionnaire at baseline without feedback and (3) a Control group that did not complete the questionnaire. All patients completed the same questionnaire 6 weeks later and a contact diary during the study period. There was a significant difference between the Intervention and Control groups for the mean number of QoL issues identified at baseline (4.69 vs. 2.81, P = 0.006) and the mean number of actions taken (4.41 vs. 2.46, P = 0.004). At 6 weeks, there was no difference between the groups in global QoL (Intervention vs. Control group, P = 0.596; Attention vs. Control, P = 0.973). The results suggest that the completion of the EORTC QLQ-C30 LC13 with feedback improves communication and increases the number of QoL issues identified and actions taken. However, the intervention does not impact on QoL per se. Clinicaltrials.gov: NCT01213745.

Behaviour and growth performance of low-birth-weight piglets cross-fostered in multiparous sows with piglets of higher birth weights / Comportamento e desempenho de crescimento de leitões com baixo peso ao nascer uniformizados com leitões de maior peso em fêmeas suínas multíparas

The aim of the study was to evaluate the behaviour, pre-weaning survival rate and growth performance of low birth weight (BW) piglets cross-fostered with piglets of higher weights. Piglets were transferred to 60 foster sows, and divided in three groups (G; n=20): G1- 12 low BW piglets (0.80 - 1.25kg); G2- six low BW piglets and six intermediate BW piglets (1.40 - 1.60kg), and G3- six low BW piglets and six high BW piglets (>1.70kg). For the analysis, groups G2 and G3 were subdivided in LG2 (six G2 light piglets); IG2 (six G2 intermediate piglets), LG3 (six G3 light piglets), and HG3 (six G3 heavy piglets). Behavioural observations were carried out on days 1, 2, 4 and 6 (visual direct observation) and on days 3 and 5 (video recording) after birth. The percentage of missed nursings was higher in LG3 piglets than in LG1, IG2 and HG3 piglets, on days 1 and 2. On day 4, light piglets (LG1, LG2 and LG3) missed more nursings than IG2 and HG3 piglets. On day 3, video recording showed a higher percentage of missed nursings in LG1, LG2, and LG3 piglets as compared to HG3 piglets. On day 1, the number of fights during nursing was higher in IG2 than in LG1 and LG3 piglets. Also on day 1, number of fights and percentage of piglets engaged in fights, during 15min after nursing, were higher in LG1, LG3 and HG3 than in LG2 piglets. More playful behaviours were observed on day 2 in IG2 and HG3 piglets compared to LG1, LG2 and LG3 piglets. Light piglets (LG1, LG2, and LG3) presented similar body weight on days 4, 8, 12 and 16 after birth, regardless of being mixed with piglets of higher weights or not; however, the survival rate until day 16 was most compromised in LG3 piglets compared to the other groups. Despite the lack of influence of littermates' weight on the growth of low BW piglets, their survival rate indicates that they should not be mixed with high BW piglets...

O objetivo do estudo foi avaliar o comportamento, a taxa de sobrevivência pré-desmame e o desempenho de crescimento de leitões leves ao nascer uniformizados com leitões de maior peso ao nascer (PN). Os leitões foram transferidos para 60 fêmeas e divididos em três grupos (G; n=20): G1 - 12 leitões de baixo PN (0,80-1,25kg); G2 - seis leitões de baixo PN e seis com PN intermediário (1,40-1,60kg); e G3 - seis leitões de baixo PN e seis leitões pesados (>1,70kg). Para a análise, os grupos G2 e G3 foram subdivididos em LG2 (seis G2 leitões leves); IG2 (seis G2 leitões de peso intermediário); LG3 (seis G3 leitões leves) e HG3 (seis G3 leitões pesados). Observações de comportamento foram realizadas nos dias 1, 2, 4 e 6 (observações visuais diretas) e nos dias 3 e 5 (gravações) após o nascimento. A porcentagem de mamadas perdidas foi maior no grupo LG3 quando comparado aos grupos LG1, IG2 e HG3, nos dias 1 e 2. No dia 4, leitões leves (LG1, LG2 e LG3) perderam maior número de mamadas do que os grupos IG2 e HG3. No dia 3, a gravação mostrou maior porcentagem de perda de mamadas nos grupos LG1, LG2 e LG3 do que no grupo HG3. No dia 1, o número de brigas durante a mamada foi maior nos grupos IG2 do que nos grupos LG1 e LG3. Também no dia 1, o número de brigas e porcentagem de leitões envolvidos em brigas, durante 15 minutos após a mamada, foi maior nos grupos LG1, LG3 e HG3 do que no grupo LG2. Brincadeiras foram mais observadas no dia 2 nos grupos IG2 e HG3 quando comparado aos grupos LG1, LG2 e LG3. Leitões leves (LG1, LG2 e LG3) apresentaram peso semelhante nos dias 4, 8, 12 e 16 após o nascimento, independentemente de serem misturados ou não com leitões pesados. No entanto, a taxa de sobrevivência até o dia 16 foi mais comprometida nos leitões do grupo LG3 do que nos outros grupos. Apesar da falta de influência do peso das leitegadas no crescimento de leitões de baixo PN, a taxa de sobrevivência indicou que estes não devem ser misturados com leitões de maior PN...

Maturation of dendritic cells leads to up-regulation of cellular FLICE-inhibitory protein and concomitant down-regulation of death ligand-mediated apoptosis.

Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 inhibitory protein cFLIP, whereas only low levels were detected in immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations.

Differential expression of Rel/NF-kappaB and octamer factors is a hallmark of the generation and maturation of dendritic cells.

A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-kappaB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-kappaB factors did not correlate with lower levels of cytosolic NF-kappaB inhibitors, the IkappaBs. One IkappaB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)

The ATPase activity of purified CDC48p from Saccharomyces cerevisiae shows complex dependence on ATP-, ADP-, and NADH-concentrations and is completely inhibited by NEM.

The cell cycle protein CDC48p from Saccharomyces cerevisiae is a member of a protein superfamily (AAA superfamily) characterized by a common region of approximately 200 amino-acid residues including an ATP binding consensus. CDC48p purified to homogeneity showed considerable ATPase activity which could be completely abolished by preincubation with NEM in the absence of ATP. ATP protects the protein from NEM and stabilizes the otherwise labile enzyme. The ATPase activity is reversibly inhibited by NADH and shows cooperativity with its substrate ATP. The application of the in vitro ATPase activity to the identification of physiologically interacting molecules is discussed. By electron microscopy, the enzyme was shown to consist of hexameric ring structures similar to its vertebrate homologue.

The ins and outs of Raf kinases.

Raf kinases are signal-integrating enzymes that have the ability to switch tyrosine kinase signalling to serine/threonine phosphorylation and connect growth factor receptors with transcription factors. The connection involves a cascade of protein kinases that is essential for cellular proliferation and differentiation of species ranging from worms to humans. This cascade also mediates transformation by most oncogenes.

Localisation of hyaluronate (HA) in primary tumors and nude mouse xenografts of human pancreatic carcinomas using a biotinylated HA-binding protein.

A biotinylated hyaluronate (HA)-binding protein isolated from bovine cartilage was used to analyze the distribution of HA in nude mouse xenografts derived from human pancreatic adenocarcinoma cell lines as well as in primary human pancreatic adenocarcinomas. The most reproducible results for the localisation of HA were obtained using cryostat sections. When the biotinylated HA-binding protein was applied to histological sections of nude mouse xenografts, the specific staining found could be inhibited by preincubating the HA-binding protein with an excess of HA or by hyaluronidase treatment of the tissue before staining. The highest HA concentration was found at the tumor boundaries, while in the central part of the tumor staining was slight or absent. In cryostat sections of primary tumors HA was found predominantly in the connective tissue immediately around tumor cells or at the border between the tumor and normal pancreatic tissue.

Yeast cell cycle protein CDC48p shows full-length homology to the mammalian protein VCP and is a member of a protein family involved in secretion, peroxisome formation, and gene expression.

Yeast mutants of cell cycle gene cdc48-1 arrest as large budded cells with microtubules spreading aberrantly throughout the cytoplasm from a single spindle plaque. The gene was cloned and disruption proved it to be essential. The CDC48 sequence encodes a protein of 92 kD that has an internal duplication of 200 amino acids and includes a nucleotide binding consensus sequence. Vertebrate VCP has a 70% identity over the entire length of the protein. Yeast Sec18p and mammalian N-ethylmaleimide-sensitive fusion protein, which are involved in intracellular transport, yeast Pas1p, which is essential for peroxisome assembly, and mammalian TBP-1, which influences HIV gene expression, are 40% identical in the duplicated region. Antibodies against CDC48 recognize a yeast protein of apparently 115 kD and a mammalian protein of 100 kD. Both proteins are bound loosely to components of the microsomal fraction as described for Sec18p and N-ethylmaleimide-sensitive fusion protein. This similarity suggests that CDC48p participates in a cell cycle function related to that of N-ethylmaleimide-sensitive fusion protein/Sec18p in Golgi transport.

The effect of long-term inhibition of mitochondrial protein synthesis on the oxidation capacity of mitochondria for NADH-linked substrates.

Experiments are presented showing that specific inhibition of mitochondrial protein synthesis by tetracyclines decreases the activity of the NADH-dehydrogenase complex in liver mitochondria, if rats are treated for long periods with these antibiotics. The corresponding inhibition of this complex in tumor cells (Zajdela hepatoma) and tumor mitochondria (Leydig cell tumor) is even more pronounced. It is concluded that the mitochondrial genetic system is involved in the assembly of the NADH-dehydrogenase complex, most likely by coding for one or more subunits. It is argued that this information, contrary to the situation for cytochrome c oxidase, the cytochrome bc1 complex and ATPsynthase, has been missed in previous experiments employing differential inhibition of mitochondrial protein synthesis, because of the circumstance that the inhibition did not reach the level at which it became rate-limiting.

Successful induction of follicular maturation and ovulation by prolonged treatment with LH-releasing hormone in women with anorexia nervosa.

Four women with anorexia nervosa were treated with synthetic LH-releasing hormone (LRH) in an attempt to induce ovulation. All the women had very low pretreatment levels of gonadotropins and estrogens. Administration of LRH resulted in significant gonadotropin increases. The FSH response to LRH in relation to the LH response was higher than in regularly menstruating women. LRH (500 mug) was administered parenterally three times daily over about 4 weeks. During this period there were no significant effects on mood, eating behavior, weight, or libido. All the women responded with follicular maturation and ovulation to the prolonged LRH treatment.

Epidemiology of secondary amenorrhea. I. Incidence and prevalence rates.

PIP: The study was designed to investigate the epidemiology of secondary amenorrhea within a county of Sweden. By means of questionnaire data regarding the occurrence of secondary amenorrhea of more than 3 months duration were collected together with background variables such as age, marital status, pregnancy history, use of oral contraceptives, and smoking habits. Subjects consisted of 2000 women of a total population of 30,000 women of age group 18-45 years in Uppsala county. From a computer list of all women born on day 10 or 20 of every month a 1 in 15 sample of the female population in the age group 18 to 45 years was obtained. Eventually 93.1% answered the questionnaire. Women who reported amenorrhea of more than 3 months duration in the past year were sent a second questionnaire asking for information regarding social and medical circumstances considered to be of interest. 258 women (13.8%) of the 1862 gave a history of amenorrhea of more than 3 months duration during the past year. The amenorrhea was due to pregnancy in 183 women (9.8%), secondary to surgical treatment in 13 women (.7%). 62 women, 3.3% were considered to have secondary amenorrhea. No case of primary amenorrhea was found. The age at menarche made no significant difference. 65% of the total group had borne a child. 23% were using oral contraceptives, 1/3 of the youngest and 1/10 of the oldest. 1/2 of the women under age 35 were cigarette smokers as compared to 1/3 of those above age 35. Of the factors considered; age, marital status, residence (city or rural), smoking habits and pregnancy history, only the age factor was found to be significant (t = 2.07; p less than .05). A marked covariation between the use of oral contraceptives and smoking habits was found. A plausible causal relationship between previous use of oral contraceptives and the occurrence of secondary amenorrhea was found in about 16% of the women with amenorrhea. However, findings indicate that the true incidence of secondary amenorrhea due to previous use of oral contraceptive agents is very low, .7% in the present study.^ieng