Epstein-Barr-based episomal chromosomes shuttle 100 kb of self-replicating circular human DNA in mouse cells.

We describe the microcell fusion transfer of 100-200 kb self-replicating circular human minichromosomes from human into mouse cells. This experimental approach is illustrated through the shutting of the latent 170 kb double-stranded DNA genome from the human herpesvirus, Epstein-Barr virus, into nonpermissive rodent cells. Using this interspecies transfer strategy, circular episomes carrying 95-105 kb of human DNA were successfully established at low copy number in mouse A9 cells. Selected episomes were stably maintained for 6 months, and unselected episomes were characterized by a 95% episomal retention per cell division. The establishment of a mouse artificial episomal chromosome system should facilitate evolutionary and therapeutic studies of large human DNA in rodent genetic backgrounds.

Kinetics of D-xylose absorption in patients with human immunodeficiency virus enteropathy.

D-Xylose absorption was studied in 12 patients with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex who had had diarrhea for more than 8 weeks, averaged an 11% (range, 3% to 21%) body weight loss during the previous 6 months, and had had negative stool examinations for enteric pathogens. Patients were evaluated by duodenal aspiration and biopsy and received both 25 gm oral and 10 gm intravenous doses of D-xylose. Kinetic analysis of D-xylose absorption was characterized by an absorption rate constant (ka) and a rate constant (ko) reflecting nonabsorptive loss. Extent of D-xylose absorption averaged 18.4% +/- 9.3% (+/- SD) in the 12 patients (normal greater than 60%). Percentage of weight loss during the previous 6 months was negatively correlated with ka (r = -0.69; p = 0.018) in the 11 patients in whom this parameter was reduced but was not correlated with either ko or extent of D-xylose absorption. In these patients with human immunodeficiency virus enteropathy, ka was reduced out of proportion to the minor histologic changes present in the duodenal biopsy specimens.

Chromosomal aneuploidy in proliferative breast disease.

Although some forms of proliferative breast disease have been associated with increased risk of breast cancer, substantial confirmatory evidence that the lesions are biologically premalignant has not been presented. Our intent was to identify cytogenetic aberrations in proliferative breast disease using fluorescence in situ hybridization probes selected for their relationship to aberrations previously reported in breast cancer. Application of fluorescence in situ hybridization techniques to paraffin tissue sections using pericentromeric probes for chromosomes 1, 16, 17, 18, and X revealed chromosome aneuploidy in proliferative and malignant lesions of the breast. Sectioning artifact that may result in nuclear truncation was controlled by establishing expected baseline frequencies for gain and loss in normal tissues from the same breast. Localization of chromosomal aberrations to proliferative breast disease lesions with concomitant retention of a normal chromosome complement in corresponding normal breast tissues indicates biologic significance of the results. The similarities of losses involving chromosomes 16, 17, and 18 in hyperplastic lesions and in malignant breast lesions suggest that some hyperplasias may be part of a sequence of progression to malignancy in breast cancer. Gains of chromosome 1 in both in situ and invasive carcinoma are consistent with reports of polysomy 1q as a common cytogenetic change in breast cancer. Its localization to advanced lesions suggests that this trisomy is probably not the initial cytogenetic change in breast cancer tumorigenesis.

Chromosome abnormalities and oncogenesis in cat leukemias.

Chromosome abnormalities are found in feline leukemia virus (FeLV)-infected tumor cells as well as in tumor cells free of the virus. Three cell lines derived from tumors in the domestic cat (Felis catus), two of thymic origin and one of multicentric lymphoma origin, were analyzed cytogenetically to determine whether the FeLV virus was associated with chromosomal abnormalities in these tumor cell lines. One thymic tumor and the multicentric lymphoma were FeLV infected. The other thymic tumor cell line was FeLV-free. The normal diploid number in the domestic cat is 38. All three cell lines had numerical chromosome abnormalities with modal numbers of 37, 38 (pseudodiploid), and 39, respectively and had consistent structural chromosome abnormalities. Three markers in the virus-free cell line (S markers) were shared with one or the other of the virus-positive cell lines. The two FeLV-positive cell lines did not have S markers in common. The finding of chromosome abnormalities in both the virus-infected and the virus-free cell lines suggests that these abnormalities may be important in oncogenesis. The FeLV virus could not be considered the only causative agent of the abnormalities observed.

[Relation between cytomegalovirus infection and the so-called intolerance to azathioprine in renal transplantation]. / Rapporto tra infezione da virus citomegalico e la cosiddetta intolleranza all'azatioprina nel trapianto renale.

Renal transplant recipients can develop hepatic function abnormalities or severe leucopenia after transplantation. Generally it is thought to be due to azathioprine intolerance and patients are treated by curtailment of immunosuppressive therapy, being subsequently at risk to lose their allograft because of rejection. Evidence of Cytomegalovirus (CMV) infection is also common after renal transplantation. It is generally thought that the majority of these infections are asymptomatic, but they can be accompanied by leucopenia and/or hepatic function abnormalities. Sixty-nine renal transplant recipients have been studied for at least three months in order to investigate the relationship between CMV and azathioprine intolerance after transplantation. Twenty-five out of 58 patients who underwent seroconversion to CMV (a fourfold or greater rise in titer of CMV antibodies) after transplantation or who had a high CMV titer (greater than or equal to 1 : 16) prior to transplant, developed azathioprine intolerance. None of 11 patients who before renal transplantation had low CMV titers and who did'nt underwent seroconversion did not tolerate azathioprine. Therefore the Authors advance the hypothesis that azathioprine intolerance following renal transplantation can be often due to an asymptomatic and unknown CMV infection.

[Urologic complications in kidney transplants: experience in 274 transplants]. / Le complicanze urologiche nel trapianto renale: esperienza su 274 trapianti.

The urological complications after a renal transplantation still represent an event anything but rare, ranging, according to the different statistics, from 0.9% up to 23%, with a mortality between 0 and 25%. In this work done by the Verona Centre the experience on 274 transplantations is reported. The urological complications weighed with 6.2% and absence of mortality among the patients. The importance of the prevention and precocious diagnosis is confirmed.

[Occupational exposure to formaldehyde at a service of pathologic anatomy]. / Esposizione occupazionale a formaldeide in un servizio di anatomia patologica.

OBJECTIVE: Aim of the present study is to evaluate the air pollution produced by formaldehyde in pathological anatomy. METHODS: This study was made with instrumental approach based on environmental evaluation of 10% formaldehyde used in pathological anatomy, by an infrared gas analyser (Brüel & Kjaer), and clinical approach of pathological anatomy personnel. RESULTS: The final result is not very comforting because we found values of formaldehyde during specific activities which exeeded the current limits proposed by industrial hygienist, infact we found in a different settings 1.81 ppm, 3.78 ppm, 8.3.05 ppm. The personnel exposed reported subjective symptoms as reactive airway symptoms, headache, skin problems. CONCLUSIONS: To reduce air pollution we have indicated technical precautions as forced ventilation which is a major engineering control for reducing risk from chemical agents, use of personal protective equipment (PPE) as last resort for protection, behavioral rules and health surveillance.

[Techniques for administering inhalation anesthetic agents, professional exposure, and early neurobehavioral effects]. / Tecniche di somministrazione di agenti anestetici per inalazione, esposizione professionale ed effetti neurocomportamentali precoci.

BACKGROUND: Occupational exposure to high concentrations of anaesthetic gases can cause neurobehavioral effects in operating room personnel. The measures taken to reduce waste gas exposures, including the installation of active scavenging devices and airconditioning systems, are not effective, so that the NIOSH recommendations for maximum exposure are currently unattainable in practice. OBJECTIVES: The aim of the present study was to measure operating room pollution and neurobehavioral functions in a group of anaesthesiologists during open-system and low-flow anaesthesia. METHODS: Environmental concentrations of N2O and isoflurance were measured by an infrared gas analyzer (Brüel & Kjaer) in open system and in low flow anaesthesia. Under the same stress condition, but with different exposure levels to anaesthetic gases, psychomotor vigilance and response speed were evaluated four times with the Reaction Time Test at the beginning and at the end of the first weekday shift and at the beginning and at the end of the last weekday shift. Exclusion criteria were considered excessive alcohol and coffee intake and use of CNS medication. RESULTS: Concentrations of N2O and isoflurane in the operating room were 4.83 ppm and 0.4 ppm respectively, which are lower compared with open systems: 301 ppm and 11.1 ppm respectively. The mean of the Reaction Time was significantly higher (p < 0.01) during work with the open system compared to work in low flow at the end of the first weekday shift and at the end of the last weekday shift. CONCLUSIONS: Low-flow anaesthesia appears to be effective in reducing waste gas exposure: lower flows produced lower values and protect the integrity of neurobehavioral functions.

Mosaic pattern of hepatocellular carcinoma: histologic basis for a characteristic CT appearance.

PURPOSE: The mosaic pattern is a characteristic CT appearance for hepatocellular carcinoma (HCC). This study was designed to assess the tissue composition responsible for the CT mosaic pattern. METHOD: Gross and whole-mount histologic sections of 10 HCC tumors from eight patients were prepared at identical levels as preoperative CT sections. CT features of the mosaic tumor pattern were spatially registered with the corresponding pathologic sections. RESULTS: CT of mosaic HCC demonstrated enhancing nodules (9/10), low attenuation areas (9/10), and internal septa (3/10). Spatial registration of CT and microscopic sections showed that enhancing tissue was viable tumor in nine of nine. Low attenuation areas were either necrotic (4/9) or of mixed tissue (5/9), including areas of necrosis, fibrosis, and hemorrhage. CONCLUSION: The variable tissue composition of HCC accounts for the mosaic CT pattern. In most patients, enhancing nodules indicate viable tumor cells, and low attenuation areas represent necrosis, fibrosis, or hemorrhage.