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Biomedical subjects

M Lowe

Publications and source records attributed to M Lowe.

At least 37 records · Page 2Linked to original sources

The behaviour of the f2-f1 acoustic distortion product: lack of effect of brainstem lesions in anaesthetized guinea pigs.

Two tones of frequency f1 and f2 (the primary tones), when presented simultaneously to the ear, generate acoustic distortion products in the external ear canal. One of these distortion products, of frequency f2-f1, has been shown to undergo a reversible change in amplitude when the primary tones generating distortion are presented continuously to the test (ipsilateral) ear (Brown, 1988; Kirk and Johnstone, 1993). The effect is apparent for low and moderate primary tone intensities and has been postulated to be caused by the action of a neural feedback loop via the superior olivary complex. We have carried out a series of studies of this phenomenon in anaesthetized guinea pigs, making brainstem lesions positioned so as to interrupt the known medical and/or lateral efferent projections to the cochlea from the superior olivary complex. We could not demonstrate any consistent change after lesioning, either in the baseline level of f2-f1 or in the alteration of f2-f1 caused by continuous monaural primary tones. These results are not consistent with the suggestion by others that a neural feedback loop involving either the medial (Brown, 1988) or lateral (Kirk and Johnstone, 1993) olivocochlear efferents may be responsible for the effect. We therefore conclude that either 1) the changes in f2-f1 produced by continuous low-level primary tones reflect the operation of intrinsic hair cell mechanisms and do not involve efferent feedback via brainstem nuclei or 2) a neural feedback loop does play a role, but this loop involves an unknown pathway that was not interrupted by our lesions.

Acoustic Stimulation

'These sorts of people don't do very well': race and allocation of health care resources.

Recent literature has highlighted issues of racial discrimination in medicine. In order to explore the sometimes subtle influence of racial determinants in decisions about resource allocation, we present the case of a 53-year-old Australian Aboriginal woman with end-stage renal failure. The epidemiology of renal failure in the Australian Aboriginal population and amongst other indigenous peoples is discussed. We show that the use of utilitarian outcome criteria for resource allocation may embody subtle racial discrimination where consideration is not given to issues of justice, race, culture and gender. It is only where the processes by which resources are allocated are transparent, clearly defined and based upon consultation with individual patients that issues and justice are likely to be adequately addressed.

Americas

COPs regulating membrane traffic.

Cytosolic coat proteins (COPs) regulate membrane traffic in eukaryotic cells. Three classes of coat protein complexes have so far been identified: clathrin and its adaptor proteins, coatomer (COPI), and COPII. Coatomer (composed of seven different subunits) and ADP-ribosylation factor (ARF), which form the COPI coat, are required for budding of coated vesicles from membranes. COPI has been implicated in several steps of transport from the intermediate compartment to the cis-Golgi network, through cisternae of the Golgi stack, and is essential for retrieval to the endoplasmic reticulum (ER) of membrane proteins containing the carboxy-terminal dilysine ER-retention motif. A family of structurally and functionally related COPs may regulate all membrane traffic steps in eukaryotic cells.

ADP-Ribosylation Factors

Structure of the human pancreatic cholesterol esterase gene.

The gene for human pancreatic cholesterol esterase consists of 11 exons and 10 introns and is 9.2 kb in length. The last and longest exon (841 nucleotides) is unique to the human gene. Functional amino acids are encoded on separate exons. The leader sequence is encoded by a single exon which carries two additional N-terminal amino acids of the mature functional protein. A positive TATA element is identified 43 nucleotides from the start codon. Pulse-field gel electrophoresis and hybridization with various cDNA probes and direct sequence data revealed the existence of a CEase-like gene. Partial sequence analysis of this gene from a human cosmid library and human genomic DNA showed a premature stop signal in exon 10, shortly after the codon for the active-site histidine. Both the functional gene and the CEase-like gene have a polyadenylation signal in the 3'-untranslated region. Thus, the complex gene structure for this intestinally active enzyme may provide in part a potential molecular explanation for the well-known heterogeneity of the intestinal absorption of cholesterol.

Base Sequence

Preliminary report: penile vein occlusion therapy: selection criteria and methods used for the transcatheter treatment of impotence caused by venous-sinusoidal incompetence.

Penile vein occlusion therapy is a fluoroscopic guided technique developed for treating venous-sinusoidal incompetence in patients with erectile dysfunction. We report our experience with 22 patients who have been followed for greater than 1 year. Catheterization of the veins draining the penis was technically possible in 20 of 22 patients (91%). Of these 20 patients 5 (25%) were cured and 9 (45%) had significantly improved erectile function. All 5 patients (100%) with venous-sinusoidal incompetence plus normal cavernous arterial flow, no glans or corpus spongiosal shunts, and bilateral complete coil occlusion of the crural and common crural veins were cured. No deterioration of function was noted at 1 and 2 years. Patient selection and bilateral occlusion of the penile veins are essential to achieve successful penile vein occlusion therapy.

Adult

Assessment of normal and abnormal erectile function: color Doppler flow sonography versus conventional techniques.

The penile arteries were studied with color Doppler flow sonography in 10 subjects with normal and 39 patients with abnormal erectile function. The relationships of systolic and diastolic velocities to spectral waveform changes in the penile arteries in response to tumescence were studied before and after intracorporal injection of vasoactive medications that induce erection. In normal subjects, a characteristic spectral waveform pattern corresponded to increasing intracorporal pressure. Patients with abnormal arterial inflow and/or abnormal venous sinusoidal leakage demonstrated deviation from the patterns noted in normal subjects. Patients with abnormal arterial inflow had lower mean peak systolic velocities than normal subjects. Patients with severe venous sinusoidal incompetence had an arrest of waveform progression with evolution to but not beyond phases 1 or 2 (diastolic flow remained positive). Patients with abnormal arterial inflow and abnormal venous sinusoidal outflow had waveform changes that reflected both processes. Systolic/diastolic velocity and waveform relationships can be used to define the integrity of both the cavernosal artery inflow and venous sinusoidal outflow occlusion mechanisms.

Adult

Molecular cloning and expression of a cDNA encoding the membrane-associated rat intestinal alkaline phosphatase.

Rat intestinal alkaline phosphatase (IAP) has been purified and proteolytic fragments sequenced. A cDNA library was constructed from duodenal poly(A) + RNA and screened for IAP positive clones by a full-length cDNA clone-encoding human IAP. A full length rat IAP clone (2237 bp) was isolated and sequenced, revealing a predicted primary sequence of 519 amino acids (61.974 kDa) with an additional signal peptide of 20 amino acids. 80% of amino acids from residues 1-474 were identical when compared with the human IAP, but there was only 31% identity in the COOH-terminal 45 amino acids. The homology diverges just before the putative binding site for the phosphatidylinositol-glycan (PI-glycan) anchor. The resulting peptide in rat AP contains five hydrophilic amino acids not present in the primary structure of human IAP. Binding of a synthetic 48-mer encoding a portion of this unique and divergent region (residues 476-491) was compared with that of the full-length clone on Northern blots of rat intestinal RNA. Two mRNAs, 3.0 and 2.7 kb, were detected by both probes, confirming earlier results, but the 48-mer bound preferentially to the 3.0 kb mRNA. The protein product of the full-length cDNA in a cell-free system was 62 kDa, corresponding with the smaller of the two IAP proteins produced by rat duodenal RNA. The cDNA transfected into COS-1 cells produced a membrane-bound IAP that was released by phosphatidylinositol-specific phospholipase (PI-PLC). These data provide definitive evidence that IAP is anchored by PI-glycan and conclusively demonstrate that the unique COOH-terminal structure encoded by this rat mRNA supports the addition of a PI-glycan anchor.

Alkaline Phosphatase

Bilateral macular holes in sporadic posterior microphthalmos.

The authors report an unusual sporadic case of bilateral posterior microphthalmos in an 8-year-old Chinese girl. Cycloplegic refraction showed hyperopia of 12.5 diopters in both eyes. Anterior segment examination showed normal corneal diameters, open angles, and normal lens thicknesses. Ultrasonography showed short vitreous compartments resulting in short axial lengths of 17.2 mm. Fundoscopy showed full-thickness macular holes associated with radiate retinal striae. This is the first report of bilateral macular hole formation in sporadic posterior microphthalmos. The literature is reviewed.

Child

Glutamate release from guinea-pig synaptosomes: stimulation by reuptake-induced depolarization.

Glutamate (10-100 microM) reversibly depolarizes guinea-pig cerebral cortical synaptosomes. This does not appear to be because of a conventional autoreceptor. Neither kainate at 1 mM, 100 microM N-methyl-D-aspartate (NMDA), 100 microM L-2-amino-4-phosphonobutanoate (APB), nor 100 microM quisqualate affects the Ca2+-dependent release of glutamate from suboptimally depolarized synaptosomes. However, kainate, quisqualate, and the quisqualate agonists beta-N-oxalylamino-L-alanine and alpha-amino-3-hydroxy-5-methylisoxazole propionate cause a slow Ca2+-independent release of glutamate from polarized synaptosomes. However, unlike kainate, quisqualate does not inhibit the acidic amino acid carrier. APB, NMDA, and the NMDA receptor-mediated neurotoxin beta-N-methylamino-L-alanine do not influence Ca2+-independent release at 100 microM. The depolarization of the plasma membrane by glutamate can be mimicked by D-aspartate, can be blocked by the transport inhibitor dihydrokainate, and is accompanied by the net uptake of acidic amino acids. L-Glutamate or D-aspartate at 100 microM increases the cytoplasmic free Ca2+ concentration. D-aspartate at 100 microM causes a Ca2+-dependent release of endogenous glutamate, superimposed on the Ca2+-independent heteroexchange with glutamate through the acidic amino acid carrier. The results suggest that the glutamatergic subpopulation of synaptosomes can be depolarized by exogenous glutamate.

Amino Acids

Evaluation of normal erectile function with color flow Doppler sonography.

To understand better the vascular events that occur during normal erection, we used color flow Doppler sonography to examine the erectile process in seven normal subjects. The relationship of systolic/diastolic velocities and spectral waveform changes in the penile arteries was studied in response to increasing pressure within the corpora cavernosa (tumescence) before and after the intracorporal administration of drugs to induce erection. A characteristic spectral waveform pattern was identified throughout the erectile cycle, and the pattern was correlated with increasing pressure. Both systolic and diastolic velocities were elevated during the initiation of erection, at which time the pressure within the corpora cavernosa was low (11-25 mm Hg). Systolic velocities remained elevated until the last phase of erection (83-106 mm Hg). Diastolic velocity decreased as the intracorporal pressure increased from 25 to 40 mm Hg. Between 40 and 63 mm Hg, diastolic velocity approximated zero. With increasing pressure (63-83 mm Hg), diastolic flow reversed. As the corpora cavernosa approached full erection (83-105 mm Hg), both the forward systolic and reverse diastolic flow components diminished. At approximately 106 mm Hg (systolic occlusion pressure), flow ceased. Systolic/diastolic velocity and waveform phase relationships could be used to define the integrity of both the cavernosal artery inflow and the venous sinusoidal outflow occlusion mechanisms. Color flow Doppler sonography enhanced our ability to observe and quantify dynamic erectile events and provided new insights into understanding normal erectile function.

Adult