Phosphorylated KDR is expressed in the neoplastic and stromal elements of human renal tumours and shuttles from cell membrane to nucleus

Vascular endothelial growth factor (VEGF)-A is an important angiogenic factor in establishing the vasculature in renal cell carcinomas (RCCs). Since little is known about VEGF signalling in RCCs, the profile of phosphorylated KDR (pKDR) has been investigated and the intracellular location of the receptor has been examined in the present study. Using two monoclonal antibodies raised against the phosphorylated KDR epitopes (Y1059 and Y1214) known to mediate different VEGF functions, together with a commercial anti-KDR antibody and immunohistochemistry, the expression of pKDR was investigated in a series of normal (n = 25) and neoplastic kidneys (n = 54; clear cell n = 35; papillary n = 10; oncocytomas n = 8). pKDR was present in many tissue elements of both normal and neoplastic renal tissues, with strong expression in the cell membrane, cytoplasm, and nuclei of normal kidney and tumour cells, as well as endothelial cells in tumours of all histological types. Patterns and intensity were similar using both anti-pKDR antibodies. There was no significant correlation in clear cell carcinomas between pKDR expression and age (p = 0.57), tumour size (p = 0.2), gender (p = 0.59), grade (p = 0.2) or histological type (p = 0.36). To delineate further the intracellular processing that might account for the cellular distribution, confocal microscopy was also performed. Antibodies to the different phosphorylated epitopes demonstrated different intracellular staining patterns. This study shows that pKDR is present in a wide variety of renal tumours, suggesting that anti-VEGF therapy might have direct effects on tumour cells. It further suggests that cells traffic pKDR depending on the precise KDR tyrosines that are autophosphorylated in a manner that enables receptor activation to result in different functions.     

APC I1307K and the E1317Q variants are not present in Chinese colorectal cancer patients.

PURPOSE: The APC I1307K and E1317Q variants predispose to colorectal adenomas and carcinomas in Caucasians, but data are lacking in Asians. METHODS AND RESULTS: We sequenced the APC gene from codons 1261 to 1409 and found none of 147 Chinese, 20 Malay, and 11 Indian colorectal cancer patients in Singapore to carry the APC I1307K or E1317Q variants. CONCLUSION: These variants are rare in these Asian populations, and play little role in colorectal cancer causation in Chinese.     

The inversion effect on gaze perception reflects processing of component information

When faces are turned upside-down they are much more difficult to recognize than other objects. This "face inversion effect" has often been explained in terms of configural processing, which is impaired when faces are rotated away from the upright. Here we report a "gaze inversion effect" and discuss whether it is related to configural face processing of the whole face. Observers reported the gaze locations of photographed upright or inverted faces. When whole faces were presented, we found an inversion effect both for constant errors and observer sensitivity. These results were closely replicated when only the eyes were visible. Together, our findings suggest that gaze processing is largely based on component-based information from the eye region. Processing this information is orientation-sensitive and does not seem to rely on configural processing of the whole face.     

Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport

The B cell line 721.174 has lost the ability to present intracellular antigens to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL). This phenotype results from a homozygous deletion in the MHC that includes the peptide transporter genes TAP1 and TAP2, and the proteasome subunits LMP2 and LMP7. Recent work has shown that such cells transfected with TAP genes load their class I molecules with endogenous peptides, and present several viral epitopes to class I-restricted CTL. These data implied that the LMP2 and LMP7 genes were not required for the presentation of most epitopes through class I molecules. By contrast, while confirming the previous reports, we have identified several epitopes that appear to require genes in the MHC in addition to the TAP for their presentation. Further analysis localizes the defect to proteolysis in the cytosol. In one case, presentation could be partially restored by re-expression of full-length LMP7. Control experiments with LMP7, from which the putative pro-region had been removed, failed to restore presentation, and this lack of effect correlated with failure of the shortened LMP7 to incorporate into the proteasome. These results suggest a role for LMP7 in the generation of a viral epitope, but leave open the possibility that additional genes within the .174 deletion are required for full restoration of antigen presentation.     

All-in-one: Conventional versus two different all-in-one solutions for total parenteral nutrition of surgical intensive care patients

Three randomly selected groups of 10 surgical patients under intensive care were prospectively studied concerning the utility and effectiveness of postoperative or posttraumatic parenteral nutrition during 7 days with different solutions: conventional total parenteral nutrition (TPN) with amino acids and glucose (AA/G), or all-in-one solutions with amino acids, fat, and carbohydrates either as glucose (AIO/G) or as a mixture of the polyoles sorbitol and xylitol (AIO/P). The AIO solutions were delivered in stable ready-to-use mixtures and needed no further processing before administration. Efficiency of all regimens in improving nutritional status was documented. Comparing the 3 groups, we found one important difference: the blood glucose level was significantly lower in the AIO/P group than in the other 2 groups with glucose as the carbohydrate (p<0.001). Furthermore, the bilirubin increase observed in all 3 groups, probably a sign of cholestasis, was significantly higher in the AIO/P group versus conventional TPN. We, therefore, conclude that immediate postoperative or posttraumatic nutrition with an AIO solution was safe and its handling simple. In our patients with stress-induced glucose intolerance early after major surgery or trauma, the AIO/P solution without glucose produced less hyperglycemia and compared favorably with conventional TPN or an AIO glucose solution. Both AIO solutions were well tolerated and side effects requiring interruption of the therapy did not occur.

---

Resumen Tres grupos de 10 pacientes de cuidado intensivo seleccionados al azar fueron estudiados en forma prospectiva en relación a la utilidad y efectividad de nutrición parenteral postoperatoria o postraumática en el curso de 7 días, con diferentes soluciones: nutrición parenteral total (NPT) convencional con aminoácidos y glucosa (AA/G), soluciones todasen-una con aminoácidos, grasa y carbohidratos como glucosa (TEU/G) o como mezcla de los polioles sorbitol y xilitol (TEU/P). Las soluciones TEU fueron administradas en forma de mezclas estables y listas para uso, las cuales no necesitan ningún procesamiento adicional antes de ser administradas. El grado de eficiencia, en cuanto a su capacidad de mejorar el estado nutricional, de cada uno de estos regímenes fue determinado. Al comparar los tres grupos encontramos como diferencia importante el que el nivel sanguíneo de glucosa apareció significativamente menor en el grupo TEU/P que en los otros dos grupos que recibieron glucosa como carbohidrato (p<0.001). Además, el aumento de bilirrubina observado en los tres grupos, probablemente como signo de colestasis, apareció significativamenta más alto en el grupo TEU/P en comparación con el regimen de NPT convenional libre de grasa. No se observó diferencia significativa entre las dos soluciones TEU. Hemos llegado a la conclusión de que la nutrición en el estado postoperatorio o postraumático immediato con solución TEU es segura y de fácil manejo. En nuestros pacientes con intolerancia a la glucosa inducida por el estrés de la cirugía mayor o del trauma, la solución TEU/P libre de glucosa produjo menos hiperglicemia y se compara favorablemente con la NPT convencional y con la solución TEU/G. Ambas soluciones TEU fueron bien toleradas y no presentaron efectos colaterales que requirieran interrupción de la terapia.

---

Résumé Trois groupes de 10 malades soumis à des soins intensifs et sélectionnés au hasard ont fait l'objet d'une étude prospective concernant l'utilité et l'efficacité de l'alimentation parentérale pratiquée pendant une période de 7 jours chez des opérés et des blessés. Plusieurs solutions ont été employées: solution classique contenant des amino-acides et du glucose (AA/G), solutions complexes contenant des amino-acides, des graisses et des hydrates de carbone sous la forme soit de glucose (AIO/G) soit de polyoles: sorbitol et xylitol (AIO/P). Les solutions complexes employées étaient préalablement préparées et ne nécessitaient aucune manipulation. L'efficacité de ces diverses solutions sur l'état nutritif fut analysée. Comparant les trois groupes les auteurs ont constaté une importante différence dans le taux du glucose sanguin, ce taux étant significativement diminué dans le troisième groupe (AIO/P). D'autre part, l'élévation du taux de bilirubine constatée dans les trois groupes, un signe de cholestase, était significativement plus marquée dans le group AIO/P par rapport au soluté classique. Ils concluent de ces faits que l'alimentation à l'aide d'une solution complexe (AIO ou all-in-one) en postopératoire ou chez le blessé est dénuée de dangers et facile à pratiquer. Chez leurs patients qui présentaient une intolérance glucidique induite par le stress post-traumatique ou postopératoire, l'emploi d'une solution du 3ème type (AIO/P) ne contenant pas de glucose ne provoqua pas d'hyperglycémie; elle se compare donc favorablement avec la solution classique et la solution complexe de glucose (AIO/G). Les deux solutions complexes furent bien tolérées et ne provoquèrent pas d'effets secondaires nécessitant l'interruption de l'alimentation parentérale.

     

COVID-19 and Infant Hospitalizations for Seasonal Respiratory Virus Infections,New Zealand, 2020

In March 2020, a national elimination strategy for coronavirus disease was introduced in New Zealand. Since then, hospitalizations for lower respiratory tract infection among infants <2 years of age and cases of respiratory syncytial or influenza virus infection have dramatically decreased. These findings indicate additional benefits of coronavirus disease control strategies.