Search PubMed⌕ Search

Biomedical subjects

J Thorpe

Publications and source records attributed to J Thorpe.

At least 19 recordsLinked to original sources
PubMed2001

Noninvasive quantification of coronary blood flow reserve in humans using myocardial contrast echocardiography.

BACKGROUND: We hypothesized that coronary blood flow (CBF) reserve could be quantified noninvasively in humans using myocardial contrast echocardiography (MCE). METHODS AND RESULTS: Eleven patients with normal epicardial coronary arteries (group I) and 19 with single-vessel coronary stenosis (group II) underwent quantitative coronary angiography, MCE, and CBF velocity measurements at rest and during intravenous adenosine infusion. In group I patients, MCE-derived myocardial blood flow (MBF) velocity reserve (2.4+/-0.08) was similar to CBF velocity reserve using a Doppler flow wire (2.4+/-1.1). Patients with a single risk factor had a significantly higher MBF reserve (3.0+/-0.89) than those with >/=2 risk factors (1.7+/-0.22). In group II patients, significant differences were found in MBF velocity reserve in patients with mild (<50%), moderate (50% to 75%), or severe (>75%) stenoses (2.2+/-0.40, 1.6+/-0.65, and 0.55+/-0.19, respectively; P=0.005). A linear relation was found between flow velocity reserve determined using the 2 methods (r=0.76, P<0.001), and a curvilinear relation was noted between the percent coronary stenosis measured using quantitative coronary angiography and velocity reserve using both methods. CONCLUSIONS: CBF reserve can be measured in humans using MCE. This method may allow the noninvasive assessment of coronary stenosis severity and the detection of microvascular dysfunction.

Adult↗
PubMed2001

Quantification of renal blood flow with contrast-enhanced ultrasound.

OBJECTIVES: The goal of this study was to determine the ability of contrast-enhanced ultrasound (CEU) to quantify renal tissue perfusion. BACKGROUND: The kinetics of tracers used to assess renal perfusion are often complicated by countercurrent exchange, tubular transport or glomerular filtration. We hypothesized that, because gas-filled microbubbles are pure intravascular tracers with a rheology similar to that of red blood cells, CEU could be used to quantify renal tissue perfusion. METHODS: During a continuous venous infusion of microbubbles (SonoVue), regional renal perfusion was quantified in nine dogs using CEU by destroying microbubbles and measuring their tissue replenishment with intermittent harmonic imaging. Both renal blood volume fraction and microbubble velocity were derived from pulsing-interval versus video-intensity plots. The product of the two was used to calculate renal nutrient blood flow. Renal arterial blood flow was independently measured with ultrasonic flow probes placed directly on the renal artery and was increased using dopamine and decreased by placement of a renal artery stenosis. RESULTS: An excellent correlation was found between cortical nutrient blood flow using microbubbles and ultrasonic flow probe-derived renal blood flow (r = 0.82, p < 0.001) over a wide range (2.5 fold) of flows. CONCLUSIONS: Ultrasound examination during microbubble infusion can be used to quantify total organ as well as regional nutrient blood flow to the kidney.

Animals↗
PubMed1999

A missense mutation in myosin VIIA prevents aminoglycoside accumulation in early postnatal cochlear hair cells.

Myosin VIIA is expressed by sensory hair cells in the inner ear and proximal tubule cells in the kidney, the two primary targets of aminoglycoside antibiotics. Using cochlear cultures prepared from early postnatal Myo7a6J mice with a missense mutation in the head region of the myosin VIIA molecule we show that this myosin is required for aminoglycoside accumulation in cochlear hair cells. Hair cells in homozygous mutant Myo7a6J cochlear cultures have disorganized hair bundles, but are otherwise morphologically normal and transduce. However, and in contrast to hair cells from heterozygous Myo7a6J cultures, the homozygous Myo7a6J hair cells do not accumulate [3H]gentamicin and do not exhibit an ototoxic response on exposure to aminoglycoside. Possible roles for myosin VIIA in the process of aminoglycoside accumulation are discussed.

Animals↗
PubMed1999

Identification of eukaryotic parvulin homologues: a new subfamily of peptidylprolyl cis-trans isomerases.

We report here the existence of a subfamily of eukaryotic parvulin proteins that have strong sequence homology with E. coli parvulin, but lack the WW domain found in previously described eukarytoic parvulins. We hence term members of this subfamily EPVH (eukaryotic parvulin homologue). We describe the characterisation of hEPVH (human eukaryotic parvulin homologue). Immunogold labelling transmission electron microscopy reveals that hEPVH is preferentially localised in the mitochondrial matrix. The homology of hEPVH with its prokaryotic ancestor supports the hypothesis that this protein may have a mitochondrial function. An essential role in this organelle may explain the need for a high degree of conservation of this protein between distantly related species.

Amino Acid Sequence↗
PubMed1998

Detection and identification of cannabis by DNA.

The unambiguous identification of illicit substances, including Cannabis sativa, is a major concern of law enforcement agencies. Current methods of cannabis identification involve the use of techniques such as HPLC and GC to identify cannabinoids. A method for the identification of cannabis using DNA-specific primers has been developed and is described here. The nucleotide sequences between the trnL and trnF genes in the chloroplast of Cannabis sativa have been determined and Cannabis sativa-specific nucleotide sequences within the intergenic spacer between the trnL 3' exon and trnF gene identified. Primers, made to these sequences, have been tested on a range of different plant extracts but only give a PCR product in the presence of Cannabis sativa. The successful production of a PCR product using these primers identifies the presence of cannabis.

Cannabis↗
PubMed1998

Respiratory insufficiency due to high anterior cervical cord infarction.

OBJECTS AND METHODS: Respiratory dysfunction may occur as a result of lesions in the upper cervical spinal cord disturbing the descending pathways subserving automatic and volitional ventilatory control. Four patients are described who presented with acute respiratory insufficiency caused by infarction of the anterior portion of the upper cervical cord due to presumed anterior spinal artery occlusion. RESULTS: Two patients presented after respiratory arrests; they were ventilated and there was no automatic or volitional respiratory effort. Both had signs of an extensive anterior spinal cord lesion at the C2 level and this was confirmed by MRI. One patient presented with a C4 infarction and required ventilation for three months. Ventilatory recovery was characterised by the development of an automatic respiratory pattern. The fourth patient required ventilation for two months after infarction at the C3 level. On attempted weaning he had prolonged periods of hypoventilation and apnoea during inattention and sleep indicating impairment of automatic respiratory control. CONCLUSION: Infarction of the spinal cord at high cervical levels may be due to fibrocartilaginous embolism and involvement of the descending respiratory pathways may occur. Extensive lesions at C1/2 cause complete interruption of descending respiratory control leading to apnoea. Partial lesions at C3/4 cause selective interruption of automatic or voluntary pathways and give rise to characteristic respiratory patterns. The prognosis depends on the level and extent of the lesion.

Adult↗
PubMed1997

Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium enhanced magnetic resonance imaging.

OBJECTIVE: To assess whether serial serum levels of soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) are useful as surrogate markers of disease activity in multiple sclerosis (MS). BACKGROUND: Increased levels of sICAM-1 and sVCAM-1 have been described in cross-sectional, but not longitudinal, studies of patients with MS. Although they appear to correlate with clinical and MRI markers of disease activity, their role as potential surrogate markers remains undefined. METHODS: Serial serum levels of sICAM-1 and sVCAM-1 were measured in patients with MS undergoing monthly gadolinium-enhanced MRI studies of the brain (462 gadolinium-enhanced MRI in 57 patients) and in 12 normal control subjects. Ten patients had primary progressive (PP), 22 relapsing remitting (RR), and 25 secondary progressive (SP) disease. RESULTS: Levels of sICAM-1 and sVCAM-1 were increased intermittently in patients with all subtypes of MS. Median levels of sICAM-1 were elevated in patients with MS compared with normal controls (normal controls median [interquartile range] = 176[119-209] compared with PP = 502[194-1768], RR = 419[158-481], and SP = 352[196-469] ng/mL; p = 0.04). After excluding patients with PP MS, patients with high sICAM-1 levels had a greater number of gadolinium-enhancing lesions per study (1.9[0.9-4.3]) than patients with normal levels (0.4[0-2.7], p = 0.03), and patients with MRI studies with no gadolinium-enhancing lesions had lower associated sICAM-1 levels (200 ng/mL[85-561]) than patients with only persistent (349 ng/mL[82-615]) or new enhancing lesions (497 ng/mL[108-667], p = 0.03). Patients with RR or SP disease that progressed clinically during the study had a greater number of gadolinium-enhancing lesions per MRI study (3.5[0.4-5.5]) than did patients in whom disease did not progress (1.2 [0.3-2.7], p = 0.03). The patients with progressive disease tended to have higher sICAM-1 levels (469 ng/mL [196-1019]) than patients in whom disease did not progress (353 ng/mL [171-469], p = 0.07). Although MS patients tended to have higher sVCAM-1 levels than did normal controls, this finding was not significant. No correlation could be found between levels of sVCAM-1 and gadolinium enhancement on MRI. CONCLUSIONS: Patients with MS have elevated levels of sICAM-1, which correlate with gadolinium enhancement on MRI and possibly short-term disease progression. Soluble ICAM-1, and not sVCAM-1, may therefore be suitable as a long-term surrogate marker of disease activity in MS.

Adult↗
PubMed1996

Quantification of MRI lesion load in multiple sclerosis: a comparison of three computer-assisted techniques.

Several computer-assisted techniques for measuring multiple sclerosis lesion load on MR images have been developed to provide a quantitative and sensitive means for monitoring disease activity, particularly in the context of treatment trials. We have evaluated three techniques: manual outlining (similar to that of the North American interferon beta-1b trial), semiautomated lesion contouring (local lesion based threshold), and intensity-based thresholding for the whole brain. Contiguous, 5 mm-thick, axial, T2-weighted images of the brain were obtained on a 1.5T MR imager in eight patients with clinically definite multiple sclerosis. Analyses of the scans were performed twice, independently by three operators, using the three different techniques. The coefficient of variation of the measurement techniques was: (a) intrarater precision, 9.0 +/- 5.2 (mean +/- SD) (range 0.4-18.5) for the manual outlining, 2.5 +/- 2.1 (0.1-7.7) for the contour technique, and 7.5 +/- 6.9 (0.2-22.0) for the global threshold technique; (b) interrater precision, 11.0 +/- 5.8 (4.9-21.7) for the manual outlining, 4.5 +/- 1.6 (1.8-6.6) for the contour technique, and 11.4 +/- 4.9 (2.8-19.2) for the global threshold technique (0.0 = perfect precision). The absolute lesion loads measured were very similar using the manual outlining and the contour techniques but were significantly smaller using the global threshold technique. We conclude that the contour technique is a promising tool for use in treatment trials. Further studies are needed to assess sensitivity to changes in lesion load over time.

Brain↗
PubMed1996

CAMPATH-IH in multiple sclerosis.

In a pilot study, seven patients with multiple sclerosis were treated with CAMPATH-IH which targets the CD52 antigen present on lymphocytes and monocytes. There was a substantial reduction in disease activity as measured by gadoliunium-enhancing lesions on MRI. Encouraged by this result a further seven patients have been treated with CAMPATH-IH; four also received anti-CD4 antibody. Lymphopaenia developed rapidly and was sustained for at least one year. In 12 patients, the first infusion of antibody was characterised by significant exacerbation or re-awakening of pre-existing symptoms lasting several hours. These clinical effects of antibody treatment correlated with increased levels of circulating cytokines. Peak levels of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) occurred at 2 h whereas the rise in interleukin-6 (IL-6) was significantly delayed and peaked at 4 h after starting antibody treatment. The neurological symptoms could not be attributed directly to pyrexia and were not provoked (in one patient) by an artificial rise in temperature. In the remaining two patients, a single pre-treatment with intravenous methylprednisolone (500 mg) prevented both the transient increase in neurological symptoms and the cytokine release. Our results suggest that soluble immune mediators contribute to symptom production in multiple sclerosis by directly or indirectly blocking conduction through partially demyelinated pathways.

Adrenal Cortex Hormones↗
PubMed1996

Encore, a gene required for the regulation of germ line mitosis and oocyte differentiation during Drosophila oogenesis.

During Drosophila oogenesis, a stem cell daughter undergoes precisely four rounds of mitosis to generate a cyst of 16 cells interconnected by cytoplasmic bridges. One of the cells becomes the oocyte while the remaining 15 cells differentiate as nurse cells. We hve identified a gene, encore, that is involved both in regulating the number of germline mitoses and in the process of oocyte differentation. Mutations in encore result in exactly one extra round of mitosis in the germline. Genetic and molecular studies indicate that this mitotic defect may be mediated through the gene bag-of-marbles. The isolation and characterization of multiple alleles of encore revealed that they were all temperature sensitive for this phenotype. Mutations in encore also affect the process of oocyte differentiation. Egg chambers are produced in which the oocyte nucleus has undergone endoreplication often resulting in the formation of 16 nurse cells. We argue that these two phenotypes produced by mutations in encore represent two independent requirements for encore during oogenesis.

Alleles↗
PubMed1995

Mapping of the linear site on the Fas/APO-1 molecule targeted by the prototypic anti-Fas mAb.

Fas/APO-1 is a member of the nerve growth factor/tumor necrosis factor (TNF) family of receptors and has been shown to mediate apoptotic cell death upon binding of specific mAb. We report here that the prototypic anti-human Fas mAb (clone CH-11) induces apoptosis by binding to a linear epitope present on the extracellular domain of the Fas/APO-1 protein. Synthetic peptides corresponding to this epitope blocked the apoptotic effect of the antibody in a susceptible Jurkat T cell line. Based upon the similarity between the Fas/APO-1 protein and the recently crystallized soluble TNF receptor type I, we generated a molecular model of Fas/APO-1, Our computer modeling indicates that the antibody binding region forms a hairpin loop on the surface of the Fas/ APO-1 protein. These findings further our understanding of the Fas/APO-1-mediated apoptotic signal and may provide a useful tool in future investigations of programmed cell death.

Amino Acid Sequence↗
PubMed1995

High resolution magnetic resonance imaging of the anterior visual pathway in patients with optic neuropathies using fast spin echo and phased array local coils.

High resolution MRI of the anterior visual pathways was evaluated using frequency selective fat suppressed fast spin echo (FSE) sequences in conjunction with phased array local coils in patients with optic neuropathies. Fifteen normal controls and 57 patients were examined. Coronal T2 weighted fat suppressed FSE images were obtained in 11 minutes with an in plane resolution of 0.39 x 0.39 mm. The optic nerve and its sheath containing CSF were clearly differentiated. Central retinal vessels were often visible. In demyelinating optic neuritis and in anterior ischaemic optic neuropathy high signal within the nerve was readily delineated. Meningiomas and gliomas involving the optic nerve were precisely visualised both in the orbit and intracranially. Extrinsic compression of the optic nerves was readily visualised in carotid artery ectasia and dysthyroid eye disease. Enlarged subarachnoid spaces around the optic nerves were demonstrated in benign intracranial hypertension. High resolution MRI of the anterior visual pathway represents an advance in the diagnosis and management of patients presenting with optic neuropathy.

Adult↗