Class II defective avian sarcoma viruses: Comparative analysis of genome structure

The genomes of class II avian sarcoma viruses PRCII, PRCII-p, PRCIV, and Fujinami sarcoma virus (FSV), were studied by oligonucleotide fingerprinting, heteroduplex mapping, and nucleic acid hybridization. All of these viruses are genetically defective and have a small RNA genome between 4.5 and 6.1 kilobases (kb) in length. They contain helper-related sequences at both the 5′- and 3′-ends, but most of the retroviral sequences in the middle of the genome are deleted. In place of this deleted information, a contiguous stretch of transformation-specific sequences, termed fps, is found. These putative oncogenic sequences are about 1.2 kb in PRCII, and those in PRCII-p and PRCIV are roughly 2.9 kb. From the analysis of oligonucleotides, it appears that the fps sequences of PRCII represent a subset of those of PRCII-p. Most of the additional sequences present in PRCII-p but absent from PRCII are at the 5′-half of fps. The helper-related sequences in PRCII and PRCII-p are almost indistinguishable, except that PRCII-p contains slightly more retroviral information at the 3′-end of the genome. Therefore, it is possible that PRCII has been derived by deletion from PRCII-p. By contrast, PRCII-p and PRCIV were found to contain identical fps sequences, but their helper-related sequences have diverged substantially. These two sarcoma viruses either represent two independent isolates or, if derived from a single isolate, they have undergone extensive mutation and recombination with diverse avian retroviruses. FSV was found to differ to a greater extent from other class II sarcoma viruses in both helper-related and fps sequences. The difference in fps sequences is localized in the 5′-half of that region. Considering the variation in fps among all members of class II avian sarcoma viruses, it appears that the 3′-half of that genetic region is more conserved than the 5′-half.     

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.     

Impact of cadaveric organ donation on Taiwanese donor families during the first 6 months after donation

OBJECTIVE: Organ donation is a complex decision for family members of Asian donors. The impact of cadaveric organ donation on both Chinese and Western donor families has not been well investigated within a cultural framework. The purposes of this study were to follow Chinese family members' appraisal of their decision to donate organs, to explore the possible negative and positive impacts of organ donation on their family life, and to determine what help they expected from healthcare providers during the first 6 months after donation. METHODS: Twenty-two family members (10 men and 12 women) of cadaveric organ donors who signed consent forms at an organ transplant medical center in Taiwan participated in this project and completed in-depth interviews during the sixth month after donation. RESULTS: Participants were 25 to 56 years old (mean = 48.15 +/- 8.31 years). The type of kinship of the participants included the donor's parents, older sister, and spouse. Subjects reported several negative impacts: worry about the donor's afterlife (86%), stress due to controversy among family members over the decision to donate (77%), and stress due to others' devaluation of the donation (45%). Positive impacts reported by the subjects included having a sense of reward for helping others (36%), having an increased appreciation of life (32%), having closer family relationships (23%), and planning to shift life goals to the study of medicine (9%). Subjects expected the transplant team to provide information about organ recipients (73%), to submit the necessary documents so that family members could receive healthcare payments from the insurance company (68%), to help resolve legal proceedings and settlements associated with accidents (64%), and to not overly publicize their decision to donate (64%). CONCLUSIONS: Although all of the subjects reported that organ donation was the right decision, the decision to donate did not protect Taiwanese donor families from negative psychocognitive bereavement. The impacts of organ donation were affected by the subject's social cultural, spiritual, and legal context and the nature of their bereavement.     

Adeno-associated virus-mediated vascular endothelial growth factor gene therapy in skeletal muscle before transplantation promotes revascularization of regenerating muscle

Successful clinical transplantation of whole skeletal muscles can be limited by impaired muscle revascularization and regeneration. The aim of this study was to enhance the revascularization (and hence speed of regeneration) of transplanted whole muscles by transducing muscles with the vascular endothelial growth factor (VEGF) gene before transplantation, using a recombinant adeno-associated virus (rAAV). The rAAV encoding VEGF and green fluorescent protein (GFP) (rAAV.VEGF.GFP) was injected into the tibialis anterior muscles of adult BALB/c mice. One month after injection whole muscle autotransplantation was performed. Muscles were sampled 7 days after autografting. GFP expression was examined as an indicator of persistent transgene expression after grafting, and immunohistochemistry was used to identify VEGF, blood vessels, and newly formed myotubes. After grafting, GFP expression persisted only in a few surviving myofibers in the periphery of rAAV.VEGF.GFP-pretreated muscles, although abundant VEGF expression was seen in myogenic cells in all grafted muscles. Quantitative analysis demonstrated that, although only small numbers of rAAV.VEGF.GFP-transduced myofibers were present, whole muscle grafts preinjected with rAAV.VEGF.GFP were significantly more vascular than saline-injected and uninjected control muscle grafts. Furthermore, rAAV.VEGF.GFP-injected whole muscle transplants were further advanced in terms of regeneration (myotube formation) compared with the uninjected control muscle transplants. This study clearly shows that rAAV-mediated VEGF expression persists only in myofibers that survive the necrosis induced by muscle transplantation; however, this amount of VEGF results in significantly increased revascularization and regeneration of whole muscle transplants.     

Evolution of neurotransmitter receptor systems

The presence of hormones, neurotransmitters, their receptors and biosynthetic and degradative enzymes is clearly not only associated with the present and the recent past but with the past several hundred million years. Evidence is mounting which indicates substantial conservation of protein structure and function of these receptors and enzymes over these tremendous periods of time. These findings indicate that the evolution and development of the nervous system was not dependent upon the formation of new or better transmitter substances, receptor proteins, transducers and effector proteins but involved better utilization of these highly developed elements in creating advanced and refined circuitry. This is not a new concept; it is one that is now substantiated by increasingly sophisticated studies. In a 1953 article discussing chemical aspects of evolution (Danielli, 1953) Danielli quotes Medawar, "... endocrine evolution is not an evolution of hormones but an evolution of the uses to which they are put; an evolution not, to put it crudely, of chemical formulae but of reactivities, reaction patterns and tissue competences." To also quote Danielli, "In terms of comparative biochemistry, one must ask to what extent the evolution of these reactivities, reaction patterns and competences is conditional upon the evolution of methods of synthesis of new proteins, etc., and to what extent the proteins, etc., are always within the synthetic competence of an organism. In the latter case evolution is the history of changing uses of molecules, and not of changing synthetic abilities." (Danielli, 1953). Figure 4 outlines a phylogenetic tree together with an indication of where evidence exists for both the enzymes that determine the biosynthesis and metabolism of the cholinergic and adrenergic transmitters and their specific cholinergic and adrenergic receptors. This figure illustrates a number of important points. For example, the evidence appears to show that the transmitters and their associated enzymes existed for a substantial period before their respective receptor proteins. While the transmitters and enzymes appear to exist in single cellular organisms, there is no solid evidence for the presence of adrenergic or cholinergic receptors until multicellular organisms where the receptors appear to be clearly associated with specific cellular and neuronal communication (Fig. 4). One can only speculate as to the possible role for acetylcholine and the catecholamine in single cell organisms.(ABSTRACT TRUNCATED AT 400 WORDS)