Biomedical subjects
Publications and source records attributed to C Cash.
This paper describes techniques for the visualization and processing of three-dimensional (3D) ultrasound data. The nature of such data demands specialized algorithms, which differ from those employed for other medical imaging modalities. In this paper, the emphasis is placed on generic processing techniques, which are relevant across a wide range of 3D ultrasound application domains.
OBJECTIVES: To evaluate the accuracy of prenatal ultrasound in the detection of facial clefts in a low-risk screening population and to report on the outcome of these pregnancies. DESIGN: We retrospectively reviewed antenatal ultrasound records from the obstetric ultrasound department, postnatal records from the regional craniofacial unit and autopsy reports of fetuses over 16 weeks' gestational age from the regional pathology department over a 5-year period (1993-97). Cross-referencing between the three data sets identified all cases of facial clefts. RESULTS: Out of 23 577 live and still births, 30 had facial clefts; four were excluded from the study. Of the remaining 26 cases, 10 had associated major anomalies. There were 19 live births and seven terminations. Six of the seven terminations had other major abnormalities. Our detection rate for cleft lip and palate was 93% and the detection rate for isolated cleft palate was 22%. Isolated cleft lip was detected in 67% of cases. The overall detection rate for facial clefts was 65%. CONCLUSION: From our results and a review of the literature it is clear that before standards can be set we need to define which facial clefts are sonographically demonstrable. Our data provide information for effective counseling and setting of standards for clinical practice.
Lipid accumulation within macrophages is a major sequelae of atherosclerosis. Much of this lipid accumulation occurs within large, swollen lysosomes. We analyzed lipid accumulation in cultured macrophages using oxidized or acetylated low density lipoprotein (LDL) as the loading agent. Pigeon macrophages incubated for 48 h with mildly oxidized pigeon LDL (TBARS = 5-10 nmol/mg protein) showed significant increases in cellular cholesterol compared with untreated controls. Forty-eight percent of the increased cholesterol occurred as unesterified cholesterol. Treated cells had lipid-swollen lysosomes similar to those of atherosclerotic foam cells. The increase in lysosomal lipid was accompanied (correlation coefficient of 0.96) by increases in acid phosphatase staining cisternae of the Golgi and trans-Golgi network (TGN). THP-1 macrophages incubated with oxidized LDL showed similar lysosomal loading and Golgi/TGN hypertrophy. In contrast, macrophages incubated with acetylated LDL accumulated significant amounts of cholesterol but the increase occurred as cholesteryl ester (81% in pigeons) within cytoplasmic droplets and there was no associated increase in acid phosphatase-containing cisternae of Golgi or TGN. The correlation in both pigeon and THP-1 macrophages of oxidized LDL-induced lysosomal lipid accumulation and Golgi hypertrophy suggests a linkage of these two phenomena. This implicates intracellular membrane trafficking as a possible defect in foam cells of the atherosclerotic lesion.
The experience of the University of Illinois at Chicago's College of Medicine with implementing a pilot generalist program focuses on institutionalization and management. Various features of the program make it an interesting case study: It is inter-disciplinary, comprising pediatricians, general internists, and family practitioners; students join the program in the autumn of their first year; and it is changing from a voluntary to a required, institutionally ingrained course of study. The difficulties and procedures encountered in making room for an interdisciplinary primary care program in a traditional medical school curriculum are discussed.
Radioactive excreta from nuclear medicine patients can enter solid waste as common trash and medical biohazardous waste. Many landfills and transfer stations now survey these waste streams with scintillation detectors which may result in rejection of a hospital's waste. Our survey indicated that on the average either or both of Boston University Medical Center Hospital's waste streams can contain detectable radioactive excreta on a weekly basis. To avoid potential problems, radiation detectors were installed in areas where housekeepers carting trash and medical waste must pass through to ensure no radioactivity leaves the institution.
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An immunoblot procedure was developed to quantify the amount of tryptophan hydroxylase (TpOH), the rate limiting enzyme in the synthesis of serotonin, in the rat raphe dorsalis nucleus (NRD). Using this method we have studied the time course variations in TpOH protein level after a single p-chlorophenylalanine (PCPA) i.p. injection (300 mg/kg). PCPA provoked a rapid and large decrease of TpOH in the NRD, without affecting neuron-specific enolase in the NRD or TpOH in the locus coeruleus. The decrease in TpOH was maximum (-60% of the control value) 2 days after the drug administration and followed a monoexponential law which allowed us to estimate the half-life of this enzymatic protein as 1.43 days and to postulate that, during these 2 days, TpOH synthesis was inhibited. The neosynthesis of TpOH molecules from 2 to 7 days was estimated to be 57.8 U TpOH/NRD/day which was comparable to the initial steady state of synthesis (48.44 U TpOH/NRD/day). In vivo administration of 6-fluorotryptophan or in vitro incubation of raphe homogenates with either halogenated derivative had no effect on TpOH protein levels. PCPA should be an interesting tool to study the turnover rate of TpOH protein.
A visual half-field presentation technique was used to assess hemispheric asymmetries in young, language-deficient, retarded children who had been taught a nonspeech graphic symbol system. Unlike most tachistoscopic and dichotic listening methods, the present method did not require verbal instruction or verbal responses. In addition, the subjects' explicit understanding of the need to fixate visually prior to stimulus presentation was not necessary. Meaningful graphic symbols were recognized more accurately when presented to the hemisphere associated with the dominant eye and hand. Recognition of meaningless symbols was best when they were presented to the nondominant hemisphere. There was a significant hemispheric specialization effect similar to what would be expected in older, normal subjects using traditional methods.
gamma-Hydroxybutyrate binding sites, first described on crude membranes from rat brain, have been further studied on subcellular fractions. The nerve ending fraction (fraction C) exhibits the maximal capacity for GHB binding. The two classes of binding sites (high and low affinities) described for the crude membrane preparation are enriched in this synaptosomal fraction. This result is further evidence in favor of a role for GHB as a neurotransmitter or neuromodulator in rat brain.
The release of gamma-hydroxybutyrate from preloaded rat brain striatal slices was investigated. K+-induced depolarization caused an efflux of gamma-hydroxybutyrate of about 50 fmol min-1 mg-1 (wet weight), but in a Ca2+-free medium containing Mg2+, the evoked release was reduced by 50-60%. The release was higher when 100 microM veratridine was used as a depolarizing agent. The efflux of gamma-hydroxybutyrate is related to veratridine and K+ concentration, and is strongly inhibited by 10 microM tetrodotoxin. The Ca2+ channel blocker verapamil induces a large decrease in the efflux of gamma-hydroxybutyrate after both K+- and veratridine-induced depolarization. These results are in favour of a possible transmitter function for gamma-hydroxybutyrate in rat striatum.
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The existence of a specific synthesizing enzyme for gamma-hydroxybutyric acid in rat brain has recently been reported. Here, for the first time, we demonstrate the presence of a high affinity, apparently specific binding site for this compound in the same tissue. This binding does not require Na+ and takes place optimally at pH 5.5. The bound gamma-hydroxybutyric acid is not displacable by GABA or baclofen. We report here on some structurally related compounds of GHB with a similar or better binding capacity than GHB itself. The number of binding sites increases with age up to adulthood and differs depending on the brain region. In primary tissue cultures of pure chicken neurones and glia, gamma-hydroxybutyric acid binding occurs exclusively in the neuronal preparations.
The ontogeny and distribution in rat brain of specific succinic semialdehyde reductase is described. This enzyme is probably responsible for the synthesis of gamma-hydroxybutyrate in brain. The highest activities and levels of apoenzyme are found in cerebellum, olfactory bulb, septum and median hypothalamus. During neonatal development, the enzyme activity remains stable at least until 63 days of age. As the levels of other enzymes of the GABA shunt pathway increase during this same period, this result indicates that there is a relative decrease in the reductive pathway of succinic semialdehyde catabolism during development leading to gamma-hydroxybutyrate synthesis, compared to the oxidative pathway leading to succinate.
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Rat brain contains two major NADPH-linked aldehyde reductases that can reduce succinate semialdehyde to 4-hydroxybutyrate. One of these enzymes appears to be fairly specific for succinate semialdehyde and is not significantly inhibited by classic aldehyde reductase inhibitors such as barbiturates. The other enzyme can reduce several aromatic aldehydes and is strongly inhibited by barbiturates and branched-chain fatty acids. Using one such inhibitor, it was possible to distinguish between and measure the two enzyme activities separately in various rat brain regions and in subcellular fractions. Both enzymes are mainly cytoplasmic but there is some activity in the synaptosomal fraction. The activity of the specific succinic semialdehyde reductase is highest in the cerebellum, where it represents 21% of the total activity, and lowest in the cortex, where it represents about 11% of the total activity.
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Two succinic semi-aldehyde reductases (A and B) have been purified to electrophoretic homogeneity. Enzyme A, which is a monomer of molecular weight 40,000 +/- 5,000 reduces a wide range of aldehydes and is inhibited by some barbiturates and certain anticonvulsants. Enzyme B, which is a dimer of molecular weight 80,000 +/- 10,000, is very specific for succinic semi-aldehyde and is not inhibited by the aforementioned compounds.