Genetic definition of a new bovine papillomavirus type 1 open reading frame, E5B, that encodes a hydrophobic protein involved in altering host-cell protein processing

We have previously observed that bovine papillomavirus type 1 (BPV-1) induces the appearance of five cellular proteins in C127 mouse fibroblasts, four of which appear to arise by altered processing of resident endoplasmic reticulum proteins. Studies of various cell lines revealed that expression of the 3' end of the BPV early region was sufficient for induction of these changes. To identify the BPV gene responsible, we have utilized the simian virus 40 (SV40)/BPV-1 recombinant virus Pava-1, which expresses the 3' end of the BPV early region behind an SV40 early promoter. C127 cells infected with Pava-1 for 48 h show the expected BPV-associated alterations, as do cells infected with Pava constructs mutated in the E5 or E2 genes. However, a mutation in the start codon of a previously ignored open reading frame extending from nucleotides 4013 to 4170 (E5B) eliminated the BPV-associated changes. Similar results were obtained with COS cells infected with the Pava mutants and C127 cells transformed by full-length mutated BPV. Despite its influence on the processing of cellular endoplasmic reticulum proteins, this mutation in E5B did not alter BPV-transforming efficiency or the ability of transformants to form colonies in soft agar. The E5B open reading frame encodes a hydrophobic 52-amino-acid polypeptide that shares structural similarities with HPV6 E5A and HPV16 E5. Speculations on a role for E5B in the viral life cycle are discussed.     

Psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1,728 patients

We present the first case of esophagogastric devascularization and esophagogastric transection using a stapler through laparoscopic surgery. The procedure was performed in a 71-year-old diabetic woman with alcoholic liver cirrhosis (Child-Pugh B class), portal hypertension, bleeding grade III esophageal varices, and a previous bleeding episode. The surgical technique was carried out without problems, and the patient had an excellent postoperative condition. Esophagogastric devascularization with esophageal transection using a stapler through laparoscopic surgery is a feasible technique that accomplishes the same and all objectives of the open procedure. Operative time in both methods is the same, whereas surgical trauma, inmunologic depletion, amount of transfused blood, pain, use of analgesics, and hospital stay are reduced in the laparoscopic technique.     

Clinical investigation of traumatic injuries of permanent incisors in Izmir, Turkey

470 injured teeth of 370 patients who consulted the Dental Clinic of Ege University, Izmir, Turkey for examination or treatment between 1981-1993 were evaluated. Information concerning sex, age of patients at the time of injury, cause of trauma, number of injured teeth, type of tooth and type of trauma were recorded. More boys suffered traumatic injuries (64.8%) than girls (35.2%). Patients aged 11-15 years old exhibited the highest number of injuries (34.4%) followed by the 6-10 years old group (24.5%). Most injuries involved one tooth (60%) and maxillary central incisors were the most often affected teeth (66.2%). The leading cause of injury was undefined falls (45.1%). At the initial examination, cases seen after a long posttraumatic period showed more complications than those presented within a short time period. Educational programs about the importance of dental trauma, the benefits of immediate attendance and conservation of avulsed and fractured teeth would be very helpful for patients. Additionally improving the knowledge of the dental practitioner about trauma would be another important point in solving the problem.     

Evidence for a tropic role of brain-derived neurotrophic factor in transplanted embryonic retinae

Developing retinal axons must follow a stereotypic course directing them to the subcortical visual centres which on arrival they must recognise. Transplantation studies suggest that local substrate cues close to the surface of the brainstem and diffusible factors emanating from the target region are important. To test a role for diffusible factors, we transplanted retinae to the cerebral cortex and have shown that outgrowth can be promoted by BDNF secreting fibroblasts.     

Measurement of photon beam backscatter from collimators to the beam monitor chamber using target-current-pulse-counting and telescope techniques

Backscattered radiation (BSR) arising from field-defining collimators and entering the beam monitor chamber (BMC) may contribute to observed variations in medical linear accelerator photon beam output with collimator setting. Measuring the magnitude of such contributions for particular accelerators under specified operating conditions is therefore important when attempting to understand and model accelerator head scatter. The present work was conducted to confirm some backscatter measurements for collimating jaws reported previously and to extend these to include other accelerators and a multileaf collimator (MLC). BSR reaching the BMC from the jaws of Clinac 600C, 2100C and 2300CD accelerators and from an MLC on the 2300CD was investigated using both target-current-pulse-counting and telescope methods. Our measurements show that for the Clinac 600C BSR-dependent output variations are negligible. However, for the 2100C and 2300CD BSR-dependent relative output increased in an almost linear fashion, by up to 2.4% for 15 and 18 MV beams, and by up to 1.7% for 6 MV beams, as the field size varied from 5 x 5 cm2 to 40 x 40 cm2. The magnitude of BSR dependent upon collimator location in the head, as expected, thereby contributing to the collimator exchange effect. An earlier study at our centre using the telescope method had reported higher BSR levels. This discrepancy was resolved when corrections for telescope block and room scatter, previously assumed negligible, were made.     

Evaluation of the aortic root by MRI: insights from patients with homozygous familial hypercholesterolemia

Hepatitis C chronically infects approximately 1.5% of Americans and is the most common clinical problem facing hepatologists. Since the virus was initially described in 1989, development of an effective therapy has been challenging. Although several different therapeutic agents have been used, no therapy has been shown to reliably eradicate the virus. Interferon-alpha, a cytokine with immunostimulatory and anti-viral properties, has become the therapy of choice for patients with chronic hepatitis C infection. Trials assessing the efficacy of interferon-alpha have characterized host and viral factors predictive of responses to treatment. A thorough understanding of these predictive factors is requisite to providing cost-effective therapeutic decisions for the patient with chronic hepatitis C infection.     

Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR

The development of 15N, 13C, 2H multidimensional NMR spectroscopy has facilitated the assignment of backbone and side chain resonances of proteins and protein complexes with molecular masses of over 30 kDa. The success of these methods has been achieved through the production of highly deuterated proteins; replacing carbon-bound protons with deuterons significantly improves the sensitivity of many of the experiments used in chemical shift assignment. Unfortunately, uniform deuteration also radically depletes the number of interproton distance restraints available for structure determination, degrading the quality of the resulting structures. Here we describe an approach for improving the precision and accuracy of global folds determined from highly deuterated proteins through the use of deuterated, selectively methyl-protonated samples. This labeling profile maintains the efficiency of triple-resonance NMR experiments while retaining a sufficient number of protons at locations where they can be used to establish NOE-based contacts between different elements of secondary structure. We evaluate how this deuteration scheme affects the sensitivity and resolution of experiments used to assign 15N, 13C, and 1H chemical shifts and interproton NOEs. This approach is tested experimentally on a 14 kDa SH2/phosphopeptide complex, and a global protein fold is obtained from a set of methyl-methyl, methyl-NH, and NH-NH distance restraints. We demonstrate that the inclusion of methyl-NH and methyl-methyl distance restraints greatly improves the precision and accuracy of structures relative to those generated with only NH-NH distance restraints. Finally, we examine the general applicability of this approach by determining the structures of several proteins with molecular masses of up to 40 kDa from simulated distance and dihedral angle restraint tables.     

Direct administration of insulin-like growth factor to fetal rhesus monkeys (Macaca mulatta)

A potential treatment for the amelioration of fetal growth failure is insulin-like growth factor-I (IGF-I). To address concerns of safety and efficacy, IGF-I (80 microg/kg; GroPep Pty.) was administered i.p. to healthy rhesus monkey fetuses via ultrasound guidance every other day between gestational days (GD) 110-120 and 130-140 (third trimester; term = approximately GD 165 +/- 10; n = 6). Pregnancies were monitored sonographically, and fetal/maternal blood samples were collected for complete blood counts, immunophenotyping, and biochemical analyses. Blood samples, external measures of the fetus and newborn, and tissue and organ weights were collected at fetal necropsy (GD 150; n = 2) or at term delivery of neonates (GD 160; n = 4). The results of these investigations have shown no evidence of hypoglycemia in the fetus or dam during the course of treatment. Circulating concentrations of fetal, but not maternal, IGF-I increased with treatment (approximately 80 to approximately 1015 ng/ml), and there was no evidence of a change in serum IGF-II or an increase in IGF binding protein-3 compared with historical control values. Fetal lymphocytes and select red cell parameters increased, and a significant elevation in circulating B cells and CD4/CD8 ratios in fetal lymph nodes was shown. Although no changes were detected in body weights, increases in thymic, splenic, and kidney weights and small intestine lengths occurred. Thus, administration of IGF-I to the fetal monkey is safe and results in 1) transient increases in circulating IGF-I, 2) a significant effect on fetal hematopoietic and lymphoid tissues, and 3) an increase in select fetal organ weights and measures. These data suggest that IGF-I may represent a potential candidate for therapeutic treatment of growth-compromised human fetuses in utero.     

Further studies of the mixed acetals of nucleosides

We reported in 1988 on a new nucleoside modification reaction: the exocyclic amino groups of (d)adenosine and (d)cytidine react rapidly at ambient temperature with acetaldehyde and alcohols to give stable mixed acetals (N-ethylethoxy-acetal). NH2 + O = CH(CH3) + ROH-->NH-CH(CH3)-O-R + H2O. Here we report in detail on the occurrence of this reaction in very dilute aqueous solution (ie under biological conditions), on its mechanism and kinetics, on the mixed acetal formation with other aldehydes and other nucleic acid components, and on the question of whether these adducts are mutagenic.