Biomedical subjects
J de Villiers
Publications and source records attributed to J de Villiers.
Transformation of T lymphocytes by the v-fos oncogene.
Activation of T lymphocytes through the T cell antigen receptor has been shown to stimulate a rapid and transient accumulation of c-fos mRNA and protein. Transfection of a normal murine T lymphocyte clone with the FBJ-v-fos oncogene resulted in generation of a cell line that was morphologically transformed, had lost the requirement for IL-2 for proliferation, and was tumorigenic in adult syngeneic mice; however, the transformed cells retained the ability to proliferate in response to IL-2. The transformed cells did not show constitutive expression of IL-2 or c-fos mRNA, although the promoter regions of both IL-2 and c-fos genes contain AP-1 sites that are expected to be targets for binding of Fos/Jun complexes. In contrast, the transformed T cells showed increased constitutive expression of IL-2R alpha and c-myc mRNA; these genes may represent cellular targets for transformation by v-fos and physiologic activation by c-fos. We discuss the possibility that these transformed cells behave as cells partially activated through the TCR, and that transformation occurs through a mechanism independent of IL-2.
Tissue-specific activity of heterologous viral promoters in primary rat hepatocytes and Hep G2 cells.
In preparation for studies using gene transfer, we have identified transcriptional control elements which are active in primary rat hepatocytes. We used plasmids which were constructed so that the promoter or enhancer of interest initiated transcription of the bacterial chloramphenicol acetyltransferase (CAT) gene. Plasmids were introduced into primary rat hepatocytes in culture, into Hep G2 cells and other human and animal cell lines and into bone marrow stromal cells, and CAT activity was assayed after 48 hr. In primary rat hepatocytes, the highest CAT activity was obtained with plasmids carrying the Rous sarcoma virus long terminal repeat (pRSVCAT), or the SV40 early region promoter and enhancer (pSV2CAT). Hepatocytes carrying the murine cytomegalovirus immediate early promoter (pUCRNmCMVX/HCAT) also had appreciable CAT activity. No CAT activity was detected in rat hepatocytes carrying pSVOCAT (a promoterless construct), pUCRNtKCAT (herpes simplex thymidine kinase gene promoter), pLPVCAT (lymphocytotrophic papovavirus promoter) and pHBV1CAT (hepatitis B virus enhancer and core gene promoter). Therefore, for future studies of gene transfer in primary rat hepatocytes, the Rous sarcoma virus long terminal repeat or the SV40 early region promoter and enhancer can be effectively used to drive gene expression. Hep G2 cells carrying pHBV1CAT had high CAT activity. Hep G2 cells carrying pHBV2CAT (similar to pHBV1CAT, but with the hepatitis B virus sequences in reverse orientation with respect to the CAT sequences) and pHBV3CAT (similar to pHBV2CAT, but hepatitis B virus sequences are separated from the CAT sequences by about 700 bases) also expressed CAT activity, but not as strongly as with pHBV1CAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Unexpected natural death of cerebral origin in medicolegal practice.
Due to the rapid evolution of vascular lesions it is not surprising that most causes of sudden death of cerebral origin are due to vascular pathology. Of the traumatic causes extradural haemorrhage is a fairly common clinical entity but as a cause of death declining in its frequency. Sources of diagnostic error can be attributed to the fact that not all patients with extradural haematomas have marked external evidence of trauma and a significant number, particularly children and adolescents, show no radiological, clinical or for that matter, post-mortem evidence of a fracture. Subdural haematomas of a chronic variety are usually produced by minor trauma and occur predominantly in the older person. Acute subdural haematomas are most frequently the result of trauma and may be rapidly fatal due to the associated massive cerebral damage. That intracranial aneurysm or angioma may rupture into the subdural space and cause an acute or chronic subdural haematoma, is less widely appreciated. The acute spontaneous arterial subdural haematoma due to the rupture of a cortical vessel, usually one affected by atheroma, into the subdural space is an uncommon entity. It should be looked for specifically in patients with minimal trauma and the clinical picture of an acute subdural haematoma. Subarachnoid haemorrhage due to aneurysmal rupture is still the common cause of unexpected rapid demise in young adults. There is very little evidence that antecedent trauma or exertion play a part as precipitating factors. Centrally placed aneurysms situated at the anterior communicating artery origin or terminal carotid seem to be particularly malignant in their effects. Cause of death is usually massive extrusion of blood into the intracranial cavity with increasing intracranial pressure, compressive haematoma formation and widespread arterial spasm with ischaemic consequences. Whether aneurysmal rupture can be caused by trauma cannot really be satisfactorily resolved. Intracerebral haemorrhage is most commonly due to hypertension but, as in the case of other haematomas, bleeding disorders may also be a cause. Intracerebral haematoma may, however, also result from rupture of micro-angiomata and the brain should be carefully examined for them in the young patient without evidence of hypertension. Hypertensive crises occurring in people on monoamine oxidase inhibitors should also be remembered as a cause of intracerebral haemorrhage.