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Biomedical subjects

J B Bingham

Publications and source records attributed to J B Bingham.

At least 37 records · Page 2Linked to original sources

Actin-related protein 1 and cytoplasmic dynein-based motility - what's the connection?

The actin-related protein Arp1 works in conjunction with the microtubule-based motor cytoplasmic dynein to drive many types of intracellular motility. In vertebrate cells, Arp1 is present exclusively in the form of a 37-nm filament that constitutes the backbone of dynactin, a 1.2-MDa macromolecular complex containing nine other polypeptides. Dynactin has been proposed to function as the link between dynein and its cargo. Recent work indicates that the dynactin subunit p150(Glued) mediates the interaction of the dynactin molecule with dynein and microtubules, leaving the Arp1 filament as a possible cargo-binding domain. Mechanisms for binding of F-actin to membranes are discussed as models of the Arp1-membrane interaction.

Journal Article↗

Opposing motor activities are required for the organization of the mammalian mitotic spindle pole.

We use both in vitro and in vivo approaches to examine the roles of Eg5 (kinesin-related protein), cytoplasmic dynein, and dynactin in the organization of the microtubules and the localization of NuMA (Nu-clear protein that associates with the Mitotic Apparatus) at the polar ends of the mammalian mitotic spindle. Perturbation of the function of Eg5 through either immunodepletion from a cell free system for assembly of mitotic asters or antibody microinjection into cultured cells leads to organized astral microtubule arrays with expanded polar regions in which the minus ends of the microtubules emanate from a ring-like structure that contains NuMA. Conversely, perturbation of the function of cytoplasmic dynein or dynactin through either specific immunodepletition from the cell free system or expression of a dominant negative subunit of dynactin in cultured cells results in the complete lack of organization of microtubules and the failure to efficiently concentrate the NuMA protein despite its association with the microtubules. Simultaneous immunodepletion of these proteins from the cell free system for mitotic aster assembly indicates that the plus end-directed activity of Eg5 antagonizes the minus end-directed activity of cytoplasmic dynein and a minus end-directed activity associated with NuMA during the organization of the microtubules into a morphologic pole. Taken together, these results demonstrate that the unique organization of the minus ends of microtubules and the localization of NuMA at the polar ends of the mammalian mitotic spindle can be accomplished in a centrosome-independent manner by the opposing activities of plus end- and minus end-directed motors.

Animals↗

Major lectin of alligator liver is specific for mannose/L-fucose.

We surveyed the calcium-requiring (C-type) lectins in alligator liver. The major lectin purified by affinity chromatography was termed alligator hepatic lectin (AHL) and was found to be specific for mannose/L-fucose. AHL contained approximately equal amounts of 21- and 23-kDa bands upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding characteristics of AHL were similar to those of hepatic lectins of other classes in that 1) only terminal monosaccharide was recognized, and 2) the affinity increased exponentially when neoglycoproteins containing increasing numbers of mannose or L-fucose were used as ligand. However, unlike mammalian and chicken hepatic lectins, which exist as hexamers in Triton-containing solutions, AHL was present mainly as monomers, although small amounts of dimer and higher oligomers were present in equilibrium. Mannose-binding proteins and mannose-specific lectins of macrophages bind N-acetylmannosamine, glucose, and N-acetylglucosamine in addition to mannose, indicating that the nature and orientation of the C-2 substituent are not important to these lectins. In contrast, AHL shows a strict requirement for the presence of an axial hydroxyl group at the C-2 position (i.e. mannose).

Alligators and Crocodiles↗

Avascular necrosis of the hamate.

Avascular necrosis of the hamate is a rare condition, only one case having been reported in the literature (Van Demark and Parke, 1992). This reflects the relative rarity of fractures of the body of the hamate and the arrangement of the intraosseous vascular anatomy. A case is presented, which was diagnosed by MR Imaging and treated surgically.

Adolescent↗

MRI in diabetes insipidus due to metastatic breast carcinoma.

Magnetic resonance imaging (MRI) has been established as a valuable imaging modality in the evaluation of pituitary disorders. We describe three women with known carcinoma of the breast, who presented acutely with biochemically proven diabetes insipidus (DI), in whom MRI was used as the primary investigative tool. The patients were studied using a 1.5T superconducting system, with gadolinium enhancement in two cases. All three had thickened pituitary stalks and two had complete loss of the normal high signal from the posterior lobe of the pituitary gland. Two also had enlargement of the anterior pituitary gland. One subject was also noted to have other metastases to the brain. All three had multiple secondary deposits elsewhere in the body and one had metastases to the clivus but without evidence of extension to the pituitary fossa. DI is uncommon in systemic cancers and anterior pituitary dysfunction much more so, due to the separate blood supply of the two lobes. Thickening of the stalk has not been found frequently in large autopsy series. In the clinical context of DI in a patient with a known primary tumour the loss of high signal from the posterior lobe and stalk thickening are indicative of infiltration by metastases. A pituitary mass or metastases to adjacent bones are not necessary for diagnosis.

Acute Disease↗

Magnetic resonance imaging of the parotid gland using the STIR sequence.

The object of this study was to determine the efficiency of the short tau inversion recovery (STIR) sequence in the assessment of salivary disease. Sixteen patients with tumours either in or adjacent to the parotid gland were imaged using a 1.5T Philips Gyroscan, with a standard head coil. T1-weighted spin-echo and STIR sequences were obtained in multiple planes and assessed independently by each of the authors. Positive fine needle aspiration cytology or histological proof of the nature of the imaged lesions was obtained for every patient. T1-weighted spin-echo images were most useful for visualizing anatomical structures and for identification of the facial nerve. All lesions were visible with T1-weighted images but were very much more conspicuous in the STIR sequences, for which a minimal lesion resolution of 6 mm was achieved. No contrast enhancement was required. It was not possible to determine the pathological nature of the lesion by scan appearance only. Our conclusion is that a combination of T1-weighted spin-echo and STIR sequences in the axial and coronal planes is the preferred protocol for salivary gland imaging.

Adolescent↗

Modern imaging methods in oncology.

Modern imaging methods are very important in the management of patients with cancer and of their disease. It is vital that clinicians treating them understand the relevance of different imaging techniques for specific applications, so that the best choice can be made to aid diagnosis and monitor response to treatment. This review briefly covers the development and principles of the diverse imaging methods available, from the discovery of x-rays by Röntgen in 1895 to the recent techniques of magnetic resonance and positron emission tomography. The authors endeavour to point out the strengths and weaknesses of each method, using clinical examples where appropriate. Finally, future developments are discussed. It is hoped that this review will aid clinicians diagnosing and treating cancer patients to choose the most suitable imaging method for their patients from among the vast array available.

Diagnostic Imaging↗

A comparison of CT and MRI in the assessment of the pituitary and parasellar region.

We have carried out a prospective study to compare high resolution thin slice, contrast-enhanced, axial computed tomography (CT) with unenhanced magnetic resonance imaging (MRI) at 1.5T in the assessment of the pituitary and parasellar region. Forty patients with suspected pituitary disease presenting to an endocrine unit were studied. MRI was superior to CT for the identification of the posterior pituitary and pituitary stalk and was better at showing the cystic nature of tumours. Visualization of the optic chiasm and assessment of displacement of the optic chiasm and the carotid arteries were also better with MRI. CT was equally good at showing cavernous sinus displacement or invasion, sphenoid sinus invasion and erosion of the floor of the sella turcica and was the only technique able to show calcification of the gland. More focal abnormalities were seen in the pituitary gland with CT than with unenhanced MRI, but there was a higher false positive rate for microadenoma detection with CT. All the scans were interpreted separately by three observers, two radiologists and one clinician. The percentage agreement between the observers for the identification of pituitary and parasellar structures was better for MRI than for CT and the clinician in particular found interpretation of the MR images easier. MRI thus not only gives more information overall than CT but it is a more reliable technique between different observers for the assessment of the pituitary and parasellar region.

Aged↗

Spectrum of global left ventricular responses to supine exercise. Limitation in the use of ejection fraction in identifying patients with coronary artery disease.

Left ventricular function was evaluated with rest and supine bicycle exercise-multigated blood pool scans in 53 patients who had previously undergone coronary angiography for evaluation of a chest pain syndrome. There were 21 normal patients (less than 25% stenosis in any coronary artery, left ventricular end-diastolic pressure less than or equal to 12 mm Hg, and normal left ventriculography) and 32 patients with coronary artery disease (CAD) (greater than 50% narrowing in 1 or more major coronary arteries). Thirty-two (60%) were receiving propranolol at the time of the study. The normal patient group had a significant increase in mean ejection fraction (EF) during exercise (+0.08 +/- 0.09), while the CAD group had no increase (0 +/- 0.11; p less than 0.05). Mean end-systolic volume decreased significantly in the normal group (-5 +/- 8 ml/m2) but demonstrated no significant change in the CAD group (1 +/- 12 ml/m2; p less than 0.05 compared with normal patients). There was no significant change in mean end-diastolic volume in either group. Mean ejection rate, mean peak systolic pressure/end-systolic volume ratio, and mean pulmonary blood volume ratio also differed in the normal versus CAD patients. Despite mean differences, there was considerable overlap in both groups of individual EF responses: 8 of 21 (38%) of the normal group did not have an increase in EF of 0.05 with exercise, while 15 of 32 (47%) of the CAD group did have an increase in EF of 0.05 with exercise. However, the addition of peak systolic pressure/end-systolic volume ratio and pulmonary blood volume (exercise/rest) ratio improved the sensitivity for detecting CAD from 53 to 84% without adversely affecting specificity. Thus, there is a wide spectrum of left ventricular EF responses to supine exercise. In our patient population, EF alone was an insensitive and nonspecific marker of CAD. The addition of other parameters of global left ventricular function, which may be generated using radionuclide angiography, helps distinguish patients with CAD from normal subjects.

Adult↗

Heart failure in outpatients: a randomized trial of digoxin versus placebo.

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the severity of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P less than 0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound.

Adult↗