Geriatric medicine--spanning the generations.
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Biomedical subjects
Publications and source records attributed to M Lowe.
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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.
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.
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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.
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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.
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.
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.
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.
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The internal concealment of cocaine and other drugs in packets by "body packers"--those who swallow packets of drugs or hide them in their vagina or rectum--to avoid detection by customs officials has been increasing in both the United States and Europe. The types of package and how they are concealed are changing as the traffickers become more sophisticated in their methods. The latest parcels are less likely to burst, but obstruction of the bowel may occur. Awareness of the problem is important for staff of emergency medical services near international ports of arrival.
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Comparison of the amino acid sequences of the deoxythymidine kinases of herpes simplex (HSV) and of marmoset herpes viruses (MHV) suggests a divergence time of 8 to 10 million years ago for HSV-1 and -2. Like MHV, HSV-1 and -2 cause local infections in their natural hosts, and direct contact between two individuals during the brief period of infectivity is needed for transmission. Because B virus, a nearer relative of HSV, depends on both oral and genital routes of transmission, we postulate that ancestral HSV (aHSV) was similar, and that for HSV-1 and -2 to diverge, genital and oral sites had to become microbiologically somewhat isolated from each other, while oral--oral and genital--genital contact had to be facilitated to maintain both aHSV strains. We propose that acquisition of continual sexual attractiveness by the ancestral human female and the adoption of close face-to-face mating, two hallmarks of human sexual behavior, provided the conditions for the divergence.
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