The effect of partial portacaval transposition on the canine liver

The influence of nonhepatic splanchnic venous blood on dog liver morphology and biochemical content was investigated by performing partial portacaval transposition, anastomosing the supra-adrenal inferior vena cava to either the right or left branch of the main portal vein. In the resulting preparation, nonhepatic splanchnic venous blood supplies one portion of the liver and systemic venous blood perfuses the remaining fraction,. Seven dogs were studied for 70 to 94 days, 3 with right and 4 with left transposition. No clinical abnormalities were noted. Transient enzyme elevations were seen early after operation but reverted to normal. The most striking feature was the gross and microscopic atrophy and deglycogenation which occurred in the part of the liver receiving systemic venous blood. Blood flow studies were performed in 8 additional dogs with an electromagnetic square wave flowmeter. Flow was measured in both right and left portal vein branches before and 1 to 4 hours after partial transposition to either the right (4 dogs) or left (4 dogs) main branch. Flow rates were increased in 11 instances and remained essentially the same in 5. In 2 more dogs, a jugular venous autograft was placed between the abdominal aorta and the right or left main portal vein branch. Atrophy and deglycogenation in the portion receiving arterial blood was comparable to that described above in liver fractions perfused with systemic venous blood. The evidence from these and earlier experiments that splanchnic venous blood contains a hepatotrophic substance is discussed. © 1967

Portal diversion in glycogen storage disease

Two children with glycogen storage disease were treated with portacaval transposition. The first is alive and in good health more than 5 years later. She underwent a rapid increase in growth after the operation, while the liver remained the same size. The second patient died within 2 days after the transposition, apparently because the portal system of the swollen liver was unable to transmit the vena caval inflow. © 1969

Liver transplantation for type I and type IV glycogen storage disease

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1–5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types T and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting

Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.

MYC-driven lymphomas, especially those with concurrent MYC and BCL2 dysregulation, are currently a challenge in clinical practice due to rapid disease progression, resistance to standard chemotherapy, and high risk of refractory disease. MYC plays a central role by coordinating hyperactive protein synthesis with upregulated transcription in order to support rapid proliferation of tumor cells. Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found that this class of compounds can overcome eIF4A abundance by stabilizing target mRNA-eIF4A interaction that directly prevents translation. Proteome-wide quantification demonstrated selective repression of multiple critical oncoproteins in addition to MYC in B-cell lymphoma including NEK2, MCL1, AURKA, PLK1, and several transcription factors that are generally considered undruggable. Finally, (-)-SDS-1-021, the most promising synthetic rocaglate, was confirmed to be highly potent as a single agent, and displayed significant synergy with the BCL2 inhibitor ABT199 in inhibiting tumor growth and survival in primary lymphoma cells in vitro and in patient-derived xenograft mouse models. Overall, our findings support the strategy of using rocaglates to target oncoprotein synthesis in MYC-driven lymphomas.P30 CA036727 - NCI NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHS; LB506 - Nebraska Department of Health and Human Services (Nebraska DHHS)Accepted manuscriptSupporting documentatio

Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells

After exposure to DNA-damaging agents that block the progress of the replication fork, monoubiquitination of proliferating cell nuclear antigen (PCNA) mediates the switch from replicative to translesion synthesis DNA polymerases. We show that in human cells, PCNA is monoubiquitinated in response to methyl methanesulfonate and mitomycin C, as well as UV light, albeit with different kinetics, but not in response to bleomycin or camptothecin. Cyclobutane pyrimidine dimers are responsible for most of the PCNA ubiquitination events after UV-irradiation. Failure to ubiquitinate PCNA results in substantial sensitivity to UV and methyl methanesulfonate, but not to camptothecin or bleomycin. PCNA ubiquitination depends on Replication Protein A (RPA), but is independent of ATR-mediated checkpoint activation. After UV-irradiation, there is a temporal correlation between the disappearance of the deubiquitinating enzyme USP1 and the presence of PCNA ubiquitination, but this correlation was not found after chemical mutagen treatment. By using cells expressing photolyases, we are able to remove the UV lesions, and we show that PCNA ubiquitination persists for many hours after the damage has been removed. We present a model of translesion synthesis behind the replication fork to explain the persistence of ubiquitinated PCNA

Stellar kinematics and populations out to 1.5 effective radius in the elliptical galaxy NGC4636

We present high quality long slit spectra along the major and minor axes out to 1.5 effective radius ($R_e$) of the massive galaxy NGC4636 taken by Hobby-Eberly Telescope (HET). Using Fourier Correlation Quotient (FCQ) method, we measured the stellar line-of-sight velocity distribution along the axes. Furthermore, six Lick/IDS indices ($H\beta,Mgb,Fe_{5015},Fe_{5270},Fe_{5335},Fe_{5406}$) are derived from the clean spectrum. By comparing the measured absorption line strengths with the predictions of Simple Stellar Populations (SSP) models, we derived ages, total metallicity and $\alpha$ abundance profiles of the galaxy. This galaxy presents old and $[\alpha/Fe]$ over abundant stellar populations. Indeed, using the SSP model, we obtained the broadband color profiles. The theoretical colors match well with the measured colors and present red sharp peaks at the galaxy center. The sharp peaks of the colors are mainly shaped by the high metallicity in the galaxy center. Interestingly, the galaxy has steep negative metallicity gradients, but trend flattens outwards. This result likly suggests that the center and outer regions of the galaxy formed through different formation process.Comment: 14 pages, 7 figures, accepted by RA

Morphological and allozyme variation in a collection of Cucumeropsis mannii Naudin (Cucurbitaceae) from Côte d'Ivoire

peer reviewe

Phylogenetic and Molecular Characterization of H9N2 Influenza Isolates from Chickens in Northern China from 2007–2009

The repeated transmission to pigs and humans, and the long-term endemicity in terrestrial poultry of H9N2 viruses in China lend urgency to the study of their ecology and pathogenicity. In the present paper, we reported an H9N2 virus sublineage isolated from chickens in northern China from 2007 to 2009 has high lethality for mice. Phylogenetic analysis of the full genome indicated that six representative H9N2 isolates shared high homology to each other, and they clustered in the same sublineage with other H9N2 viruses isolated recently in northern China. The isolates were double-reassortant viruses containing M genes similar to A/Quail/Hong Kong/G1/97 (H9N2) and the other seven gene segments from A/Chicken/Shanghai/F/98 (H9N2). These six isolates were capable of replicating in the lungs of infected chickens without producing observable clinical signs of disease or death. However, they were highly lethal to mice with mortality rates as high as 100% (14/14) without prior adaptation. The affected mice exhibited severe respiratory syndromes and diffuse lung injury. The H9N2 viruses could be detected in multiple organs of the infected mice, including hearts, livers, spleens, lungs and kidneys. Our findings demonstrated that H9N2 viruses isolated from the chickens in northern China have established a stable sublineage with enhanced pathogenicity to mice, suggesting that urgent attention will need to be paid to the transmission of H9N2 viruses from chickens to mammals

Thermal Hadron Production in High Energy Heavy Ion Collisions

We provide a method to test if hadrons produced in high energy heavy ion collisions were emitted at freeze-out from an equilibrium hadron gas. Our considerations are based on an ideal gas at fixed temperature $T_f$, baryon number density $n_B$, and vanishing total strangeness. The constituents of this gas are all hadron resonances up to a mass of 2 GeV; they are taken to decay according to the experimentally observed branching ratios. The ratios of the various resulting hadron production rates are tabulated as functions of $T_f$ and $n_B$. These tables can be used for the equilibration analysis of any heavy ion data; we illustrate this for some specific cases.Comment: 12 pages (not included :13 figures + tables) report CERN-TH 6523/92 and Bielefeld preprint BI-TP 92/0