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Biomedical subjects

C S Barker

Publications and source records attributed to C S Barker.

At least 19 recordsLinked to original sources

Can spontaneous spinal epidural haematoma be managed safely without operation? A report of four cases.

The presentation, investigation, and management of four patients with spontaneous spinal epidural haematoma is presented. In each case the diagnosis was made by MRI. At the time of diagnosis spontaneous recovery had started in each patient and therefore they were all treated conservatively. In each case follow up MRI confirmed rapid reduction in the size of the haematoma and no underlying cause was demonstrated. The presentation, diagnosis, and rationale for treatment are discussed. Conservative treatment is safe in some cases of spinal epidural haematoma if early neurological recovery has started.

Adult↗

Generation of retroviral vector for clinical studies using transient transfection.

Transient transfection of 293T cells was utilized to produce high-titer murine recombinant retroviral vectors for clinical studies. This system was initially optimized by gene transfer using different retroviral envelope proteins into activated human CD4+ T lymphocytes in vitro. Higher titer and infectivity were obtained than with stable murine producer lines; titers of 0.3-1 x 10(7) infectious units per milliliter for vectors encoding the green fluorescent protein (GFP) were achieved. Virions pseudotyped with envelope proteins from gibbon ape leukemia virus or amphotropic murine leukemia virus resulted in gene transfer of > or = 50% in CD4+ human T lymphocytes with this marker. Gene transfer of Rev M10 with this vector conferred resistance to HIV infection compared with negative controls in the absence of drug selection. Thus, the efficiency of transduction achieved under these conditions obviated the need to include selection to detect biologic effects in T cells. Finally, a protocol for the production of large-scale supernatants using transient transfection was optimized up to titers of 1.9 x 10(7) IU/ml. These packaging cells can be used to generate high-titer virus in sufficient quantities for clinical studies and will facilitate the rapid, cost-effective generation of improved retroviral, lentiviral, or other viral vectors for human gene therapy.

Animals↗

Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication.

We report the development and isolation of a cell line, termed HepAD38, that replicates human hepatitis B virus (HBV) under conditions that can be regulated with tetracycline. In the presence of the antibiotic, this cell line is free of virus due to the repression of pregenomic (pg) RNA synthesis. Upon removal of tetracycline from the culture medium, the cells express viral pg RNA, accumulate subviral particles in the cytoplasm that contain DNA intermediates characteristic of viral replication, and secrete virus-like particles into the supernatant. Since the HepAD38 cell line can produce high levels of HBV DNA, it should be useful for analyses of the viral replication cycle that depend upon viral DNA synthesis in a synchronized fashion. In addition, this cell line has been formatted into a high-throughput, cell-based assay that permits the large-scale screening of diverse compound libraries for new classes of inhibitors of HBV replication.

Cell Line↗

Magnetic resonance imaging of intracranial cavernous angiomas: a report of 13 cases with pathological confirmation.

The magnetic resonance imaging features of 13 pathologically confirmed cavernous angiomas were retrospectively reviewed. T2-weighted images were found to be the most useful, the commonest appearance being a mixed signal intensity core with a complete peripheral rim of marked hypointensity. These appearances relate largely to various stages in the evolution of haemorrhage, although the presence of calcium and slowly flowing blood also contribute.

Adolescent↗

Specific growth stimulation by linoleic acid in hepatoma cell lines transfected with the target protein of a liver carcinogen.

The hepatic carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene) was shown previously to interact specifically with its target protein, liver fatty acid binding protein (L-FABP), early during hepatocarcinogenesis in rats. In search of the significance of the interaction, rat L-FABP cDNA in the sense and antisense orientations was transfected into a subline of the rat hepatoma HTC cell line that did not express L-FABP. After the transfections, the basal doubling times of the cells were not significantly different. However, at 10(-5)-10(-7) M, linoleic acid, which is an essential fatty acid, a ligand of L-FABP, and the precursor of many eicosanoids and related lipids, stimulated the incorporation of [3H]thymidine in three randomly isolated and stably transfected cell clones that expressed L-FABP, but virtually did not stimulate the incorporation of [3H]thymidine in three L-FABP-nonexpressing clones transfected with the antisense DNA. Linoleic acid at 10(-6) M increased cell number almost 3-fold (38% vs. 14%; P less than 0.0001) and thymidine incorporation nearly 5-fold (23.2% vs. 4.9%; P less than 0.001) in the L-FABP-expressing cells compared to that in the transfected nonexpressing cells. L-FABP acted specifically and cooperatively with linoleic acid, inasmuch as all the proteins other than L-FABP in the transfected L-FABP nonexpressing cells and four other fatty acids (gamma-linolenic acid, dihomo-gamma-linolenic acid, arachidonic acid, and palmitoleic acid) were unable to effect a significant elevation or difference in the level of DNA synthesis that was attributable to the transfection. Metabolism of the linoleic acid to oxygenated derivatives was apparently necessary, since the cyclooxygenase inhibitor indomethacin partly inhibited and the antioxidant lipoxygenase inhibitors nordihydroguariaretic acid and alpha-tocopherol completely abolished the growth stimulation. The evidence supports the idea that L-FABP, the target protein of the liver carcinogen, acts specifically in concert with oxygenated metabolites of linoleic acid to modulate the growth of hepatocytes.

Animals↗

Peripheral cerebral aneurysm associated with a glioma.

This 42-year-old man with acute subarachnoid, intraventricular and parenchymal hemorrhage from an angiographically and surgically confirmed successfully clipped, right splenial artery aneurysm, subsequently manifested a grade 3 astrocytoma at the site of the aneurysm. Intracranial aneurysms are recognized in association with metastases from cardiac myxoma and choriocarcinoma, but are rarely seen with primary brain tumors. In patients with nontraumatic peripheral aneurysms it would seem prudent to biopsy the aneurysm and/or surrounding necrotic tissue at the time of surgical clipping.

Adult↗

Activation of the prolactin receptor gene by promoter insertion in a Moloney murine leukemia virus-induced rat thymoma.

The prolactin receptor (Prlr) and growth hormone receptor (Ghr) genes and the Moloney murine leukemia virus integration-2 (Mlvi-2) locus were mapped to mouse chromosome 15 and human chromosome 5 bands p12-p14. To examine the potential relationship between Mlvi-2 and the genes encoding the growth hormone receptor and the prolactin receptor, we determined the chromosomal location of all three loci in the rat, using a panel of rat-mouse somatic cell hybrids, and in the mouse, using a panel of (C57BL/6J x Mus spretus)F1 x C57BL/6J interspecific backcross mice. These analyses revealed that Ghr, Prlr, and Mlvi-2 map to chromosome 2 in the rat and to chromosome 15 in the mouse, in close proximity with each other. Pulsed-field gel electrophoresis of rat genomic DNA showed no overlaps between the gene encoding the prolactin receptor and the remaining loci. Moreover, expression of the prolactin receptor was not affected by provirus insertion in Mlvi-2. During these studies, however, we detected one T-cell lymphoma line (2779) in which the prolactin receptor gene was activated by provirus integration. Sequence analysis of polymerase chain reaction-derived cDNA clones showed that the prolactin receptor RNA message initiates at the 5' long terminal repeat and utilizes the splice donor site 5' of the gag gene to splice the viral sequences onto exon 1 of the prolactin receptor. This message is predicted to encode the intact prolactin receptor protein product. Exposure of the T-cell lymphoma line 2779 to prolactin promoted cellular proliferation.

Animals↗

Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer's disease.

A combination of medial temporal lobe atrophy, shown by computed tomography, and reduced blood flow in the parietotemporal cortex, shown by single photon emission tomography, was found in 86% (44/51) of patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT). The same combination of changes was found in four out of 10 patients with other clinical types of dementia and in two out of 18 with no evidence of cognitive deficit. Of the 12 patients who died, 10 fulfilled histopathological criteria for Alzheimer's disease, nine of them having a clinical diagnosis of SDAT, and one a clinical diagnosis of multi-infarct dementia. All 10 patients with histopathologically diagnosed Alzheimer's disease had shown a combination of hippocampal atrophy and reduced parietotemporal blood flow in life. In 10 patients (nine with SDAT) out of 12 in whom the hippocampal atrophy was more noticeable on one side of the brain than on the other the parietotemporal perfusion deficit was also asymmetrical, being greater on the side showing more hippocampal atrophy. These results suggest that the combination of atrophy of the hippocampal formation and reduced blood flow in the parietotemporal region is a feature of dementia of the Alzheimer type and that the functional change in the parietotemporal region might be related to the loss of the projection neurons in the parahippocampal gyrus that innervate this region of the neocortex.

Aged↗

Ultrasound of the palpable abdominal mass.

A retrospective study was made of adult patients with a palpable abdominal mass referred by Hospital Practitioners to the ultrasound department over an 11 month period. One hundred and four patients were included in the study. Sixty-nine patients had an abnormality responsible for the clinically palpable mass and 35 patients did not . There was one false positive ultrasound diagnosis and one false negative. The correct organ of origin was suggested in 60 patients and the correct pathological diagnosis in 53 patients. The high positive predictive value (99%) and negative predictive value (97%) for the presence or absence of a lesion in these patients compare very well with the investigation of such patients by computed tomography and we suggest that ultrasound should be the initial investigation.

Abdomen↗

Spontaneous thrombosis of a cerebral arteriovenous malformation.

We report a patient who presented acutely to a neurosurgical unit with a mild left hemiparesis following mild trauma and an episode of hypotension. Computed tomography of the brain showed fresh partial thrombosis of a right parietal arteriovenous malformation. Subsequent angiography confirmed partial obliteration of an arteriovenous malformation. The malformation had completely thrombosed on follow up computed tomography, and disappeared angiographically.

Adult↗

Epistaxis as an unusual presentation of an antrochoanal polyp.

Antrochoanal polyps rarely present with severe epistaxis. We present the case of a young male patient who presented in such a manner, thus leading to the suspicion of an angiofibroma as the underlying pathology. The radiological investigations, treatment and pathological features are discussed.

Adult↗

Grading for angioplasty.

An increasing proportion of patients with lower limb arterial disease are being treated by transluminal angioplasty. There have been various estimates of the numbers of potentially treatable patients, but none have been accompanied by detailed selection criteria. Based on patients' arteriograms, we present a clear grading system of suitability for angioplasty aimed at allowing ready interpretation and comparison of data. We have used these grades to examine prospectively the suitability for angioplasty of 118 consecutive patients undergoing arteriography for the first time. Thirty-five per cent of patients with claudication, and 30% of those with rest pain or trophic lesions appeared suitable for angioplasty. Forty-five per cent of claudicants and 40% patients with rest pain or trophic lesions could have their symptoms relieved by appropriate angioplasty of aortoiliac disease alone in the presence of distal disease, or of isolated femoropopliteal lesions. These figures have important implications for the provision of interventional radiological services throughout the United Kingdom.

Adult↗