Absence of retroviral vector-mediated transformation of gene-modified T cells after long-term engraftment in mice.

There is considerable concern regarding the transforming potential of retroviral vectors currently used for gene therapy, with evidence that retroviral integration can lead to leukemia in recipients of gene-modified stem cells. However, it is not clear whether retroviral-mediated transduction of T cells can lead to malignancy. We transduced mouse T cells with a Moloney murine retroviral gene construct and transferred them into congenic mice, which were preconditioned to enhance the engraftment of transferred T cells. Recipients were then observed long-term for evidence of cancer. Transferred T cells persisted in mice throughout life at levels up to 17% with gene copy numbers up to 5.89 x 10(5) per million splenocytes. Mice receiving gene-modified T cells developed tumors at a similar rate as control mice that did not receive T cells, and tumors in both groups of mice were of a similar range of histologies. Hematological malignancies comprised approximately 60% of cancers, and the remaining cancers consisted largely of carcinomas. Importantly, the incidence of lymphomas was similar in both groups of mice, and no lymphomas were found to be of donor T-cell origin. This study indicates that the use of retroviral vectors to transduce T cells does not lead to malignant transformation.

Presence of angiotensin converting enzyme in the adventitia of large blood vessels.

BACKGROUND: Angiotensin converting enzyme (ACE) is present in the endothelial cells of all vascular beds. There are, however, many reports of converting enzyme activity in blood vessels not associated with the endothelium. METHODS: ACE was localized in large blood vessels of a number of mammals by in vitro autoradiography using the radioligand 125I-351A. To characterize this binding further, immunohistochemistry was performed on rabbit aorta using polyclonal antisera raised to two different preparations of rabbit lung ACE. RESULTS: In all of the blood vessels studied, which included the rabbit pulmonary artery, rabbit, dog and sheep aorta, human internal mammary artery and human saphenous vein, high levels of radioligand binding were found in endothelial cells, as expected. In addition, a very high density of punctate binding was observed interspersed between diffuse moderate labelling in the adventitia. Immunoreactivity was confined to the endothelium of both the intima and the vasa vasorum of the adventitia. The immunostaining correlated well with the autoradiography. The ACE inhibitors lisinopril and perindoprilat displayed similar high affinities in competing for the binding of 125I-351A to the endothelium and adventitia of the sheep aorta, suggesting that at these two sites the radioligand was binding to ACE. CONCLUSIONS: We find that ACE in the adventitia of large blood vessels is confined to the vaso vasorum. The results of this study help to explain the findings of many studies that ACE activity persists in endothelium-denuded blood vessels and also reveals a source of ACE distant from the luminal endothelial surface.

Improved glucose control in nonhospitalized pregnant diabetic patients.

Methods for management of diabetic pregnancy in the outpatient setting require strict glucose control. To assess the effect of diet and injection of short and intermediate acting insulin on glucose, diabetic patients tested their urine daily for glucose and had biweekly serum glucose tests. A brief metabolic ward study in 9 diabetic patients during the third trimester yielded hourly glucose determinations. These results defined the range of serum glucose over a 24-hour period. Glucose data on 6 normal third trimester women also came from hourly glucose values. Glucose results of normal and diabetic subjects were similar. A 16th subject with diabetic eye, renal, and foot complications is included as a case report to illustrate management technics. Infants of the diabetic women had no perinatal mortality, morbidity, or macrosomia and thus differ from an earlier study where glucose was not strictly controlled. The data suggest hospitalization can be short and low perinatal morbidity and mortality are possible with this outpatient method of management of the pregnant diabetic patient.

Renal aspergilloma--a case illustrating the problems of medical therapy.

The second documented case of renal aspergilloma due to Aspergillus flavus is presented. The merits of the medical therapy that failed are discussed. Pathological examination showed a nidus of aspergillus around suture material persisting from a pyelolithotomy operation 2 years before in India. We argue that this was the reason for the failure of the medical therapy. This is the first case of its kind reported.

Circadian variation of serum glucose, C-peptide immunoreactivity and free insulin normal and insulin-treated diabetic pregnant subjects.

To examine differences among pregnant diabetic and nondiabetic subjects, serum glucose, and immunoreactivity of C-peptide, free and total insulin were measured at hourly intervals during a 24--h third trimester metabolic ward evaluation. Six normals, three mild, and four juvenile-onset type diabetics were studied. Diets were identical for all subjects. Mild diabetics differed from juvenile diabetics by having significant residual pancreatic B-cell function, as measured by C-peptide immunoreactivity. Short and intermediate acting insulins given once or twice daily to diabetics maintained serum glucose levels within the normal range throughout the 24 h. Despite wide variation in serum total insulin levels, peripheral free insulin concentrations in well-controlled diabetics fell within a relatively narrow range that was higher than in controls. Infants of the diabetic subjects were comparable to the offpsring of the control women.