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Biomedical subjects

I Alexander

Publications and source records attributed to I Alexander.

At least 19 recordsLinked to original sources
PubMed2003

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Expression of the gene for transforming growth factor-beta in avian dyschondroplasia.

Previous immunolocalisation studies of dyschondroplasia have indicated that there is a reduction in the number of growth plate chondrocytes containing the protein transforming growth factor beta 3 (TGF-beta 3). The reduction in TGF-beta 3 in dyschondroplasia is likely to be a direct result of a reduction in the expression of the TGF-beta 3 gene. mRNA was extracted from small (0.09 g) samples of growth cartilage from the proximal tibiotarsus of three-week-old broiler chicks. The cartilage samples contained cells from all three zones of the growth plate (proliferative, transitional and upper hypertrophic) and were collected from normal and dyschondroplastic growth plates. The dyschondroplastic growth plates were identified by an accumulation of transitional chondrocytes which were considered to be a result of a failure to differentiate to the hypertrophic phenotype. A semi-quantitative polymerase chain reaction (PCR) was used to estimate the quantity of mRNA specific for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and for each of the three isoforms of TGF beta (TGF-beta 1, TGF-beta 2 and TGF-beta 3) in each of the cartilage samples. The levels of expression of mRNA for GAPDH, TGF-beta 1 and TGF-beta 2 were similar in the two groups, but the expression of TGF-beta 3 mRNA was significantly reduced in the samples from the dyschondroplastic growth plates. The reduction in TGF-beta 3 levels is thought to be associated with the failure of chondrocyte hypertrophy in dyschondroplasia, and provides in vivo evidence that TGF-beta 3 is part of the cascade of events associated with the differentiation of chondrocytes during endochondral ossification in the chick.

Animals↗
PubMed1993

Short-term outcome of mechanically ventilated infants weighing more than 2499 g at birth: a population based study.

Very little data exist describing the neonatal outcome of infants of birthweight 2500 g or more who require mechanical ventilation. Our aim was to collect population-based data on such infants in New South Wales (NSW), and to monitor their neonatal morbidity, mortality to 1 year of age and the associated risk factors. The study group (NICUS infants) comprised all 341 infants weighing > 2499 g who were admitted to the seven neonatal intensive care units in New South Wales and mechanically ventilated for 4 h or more between 1 January and 31 December, 1987. Two groups of infants emerged: those who were preterm and mostly had hyaline membrane disease, and term and post-term infants for whom the most common problem was 'perinatal asphyxia'. The most important factors associated with dying were a birthweight of over 3499 g (OR = 2.6; CI 1.03-6.6) and a 1 min Apgar score < 4 (OR = 4.8; CI 1.4-16.9). Study group mothers were significantly more likely than all NSW mothers to have had a spontaneous abortion in the previous pregnancy (P < 0.01), a pre-existing medical condition or an obstetric complication in this pregnancy, or a Caesarean section for this delivery (P < 0.001). This is the first population-based study of high-risk neonates without congenital anomalies to clearly document the worsening prognosis associated with a birthweight over 3499 g. Further research should be directed towards identifying prenatal and perinatal factors which might minimize the morbidity and mortality in this group of babies.

Apgar Score↗
PubMed1993

Arthrodesis of the first metatarsophalangeal joint: a biomechanical study of internal fixation techniques.

This study compares the strength and rigidity of four methods of internal fixation for arthrodesis of the first metatarsophalangeal joint. Ten matched pairs of cadaveric first rays were harvested and arthrodesis performed by one of four techniques: (1) planar excision of joint surfaces and fixation with crossed Kirschner wires, (2) planar excision of joint surfaces and internal fixation with a dorsal plate and screws, (3) planar excision of joint surfaces and internal fixation with an interfragmentary screw, or (4) excision of the joint surfaces using powered conical reamers and fixation with an interfragmentary lag screw. Biomechanical testing with a Bionix 858 materials testing machine was carried out, applying a plantar force utilizing principles of cantilever loading. Force applied and displacement of the arthrodesis were recorded. Of the four methods tested, bony preparation with power conical reamers and supplementary interfragmentary screw fixation was the most stable.

Arthrodesis↗
PubMed1987

Subcortical arteriosclerotic encephalopathy: Binswanger's disease.

Binswanger, in his 1894 dissertation on the differential diagnosis of general paresis of the insane, described a slowly progressive dementia associated with macroscopic loss of white matter. In recent years interest in Binswanger's disease was rekindled with CT demonstration of extensive white matter low densities in some patients. To define the clinical spectrum, we reviewed 22 consecutive cases in which the CT appearances suggested a diagnosis of Binswanger's disease. Two patients had focal neurological deficits at presentation, but recent anoxic or hypoglycaemic insults could not be excluded as the cause of the CT abnormalities. The 20 remaining patients were demented and showed variable combinations of corticobulbar dysfunction and gait dyspraxia. The duration of symptoms ranged from a few months to several years. Sixty per cent of this group gave a history of discrete stroke events and focal cortical and/or lacunar infarcts were a frequent CT finding. Binswanger's disease is probably due to chronic or acute-on-chronic white matter ischaemia. The association with lacunar and cortical infarctions suggests that a combination of large and small vessel disease produces diffuse ischaemia maximal in white matter watershed zones. Binswanger's disease is clinically differentiated from multi-infarct dementia by its time course.

Aged↗
PubMed1985

P1-purinoceptors mediate relaxation of the bovine bronchial artery.

Adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and adenosine all relaxed the bronchial artery. All four purines tested were more efficacious than isoproterenol. Dipyridamole (10(-6) M) enhanced the relaxations due to adenosine and ATP while theophylline (10(-6) M) inhibited the relaxations due to adenosine and ATP. The results suggest the presence of P1-type purinoceptors in the bronchial artery of cattle.

Adenosine↗
PubMed1985

Comparison of ELISA with virus isolation for the diagnosis of genital herpes.

An enzyme linked immunosorbent assay (ELISA) system which detects and simultaneously types herpes simplex virus antigens in clinical specimens from patients with genital herpes has been compared with standard tissue culture isolation. Although more sensitive than a similar method previously described and also more sensitive than electron microscopy and immunofluorescence, ELISA did not detect all the viruses isolated in tissue culture. Costs were comparable. The speed of obtaining the result together with knowledge of the type causing infection are useful when antiviral chemotherapy is envisaged and when considering the likelihood of recurrences.

Antigens, Viral↗
PubMed1985

Evaluation of a genus reactive monoclonal antibody in rapid identification of Chlamydia trachomatis by direct immunofluorescence.

This study compared the direct visualisation of elementary bodies in urogenital smears by the direct immunofluorescence test with the isolation of Chlamydia trachomatis in McCoy cell cultures treated with cytochalasin B. C trachomatis was isolated from 41 (16.4%) of 250 unselected specimens in McCoy cell cultures treated with cytochalasin B. Of the 41 culture positive specimens 37 (90%) were diagnosed by direct visualisation of elementary bodies in the smears using the direct immunofluorescence test. Four specimens were positive by isolation only and a further seven were positive by the direct immunofluorescence test only. Overall the direct immunofluorescence test had a sensitivity of 90% and a specificity of 97%. The presence of red blood cells or mucus or the use of barrier creams did not appear to interfere with the normal visualisation of elementary bodies using the direct immunofluorescence test.

Antibodies, Monoclonal↗