The psychosocial burden of Cooley's anemia in affected children and their parents.
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Biomedical subjects
Publications and source records attributed to A Sen.
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Caldesmon inhibits the activation of myosin ATPase activity by actin-tropomyosin. Caldesmon also inhibits the binding of myosin to actin. There is disagreement as to the degree to which competitive displacement of myosin subfragment binding to actin is responsible for the inhibition of ATPase activity. We have examined the possibility that one or more molecules of S1 may bind to actin-tropomyosin-caldesmon without having the normal actin activation of ATPase activity. The effect of caldesmon on the binding and ATPase activity of S1 was measured at several initial levels of saturation of S1 to determine if a fraction of the bound S1 was resistant to displacement by caldesmon. In the case of both unmodified S1 and rhoPDM-modified S1, most, but not all, of the S1 was displaced by caldesmon. The results are consistent with a single molecule of S1 binding with low affinity for each seven actin monomers that are fully saturated with caldesmon and tropomyosin. This single S1 is not necessarily bound directly to actin but may be attached to the NH2-terminal region of caldesmon.
NADPH-cytochrome P450 reductase was purified to electrophoretic homogeneity from detergent-solubilized liver microsomes from the leaping mullet (Liza saliens). The purified reductase was characterized with respect to spectral, electrophoretic, and biocatalytic properties. In addition, effects of pH, ionic strength, and the substrate concentration on the NADPH-dependent cytochrome c reductase activity of the purified fish liver cytochrome P450 reductase were studied. Cytochrome P450 reductase was purified 438-fold with a yield of 17.5% with respect to the initial amount present in the fish liver microsomes. The specific activity of the enzyme was found to be 52.6 mumol cytochrome c reduced per minute per mg protein. The monomer molecular weight of the purified enzyme was calculated to be 77,000 +/- 1000 when electrophoresed on polyacrylamide gels under the denaturing conditions in the presence of SDS. The absorption spectrum of fish reductase showed two peaks at 378 and 455 nm. NADPH-dependent cytochrome c reductase activity of the purified Liza saliens liver cytochrome P450 reductase was found to be maximal when pH was between 7.4 and 7.8. The apparent K(m) of the purified enzyme was found to be 7.69 microM for cytochrome c when the enzyme activity was measured in 0.3 M potassium phosphate buffer, pH 7.7, at room temperature, and the enzyme was fully saturated by its substrate, cytochrome c, when the substrate concentration was at or above the 70 microM. Furthermore, the purified enzyme was biocatalytically active in reconstituting the 7-ethoxyresorufin O-deethylase activity in the reconstituted system containing purified mullet liver cytochrome P4501A1 and lipid. These results suggested that the purified fish liver cytochrome P450 reductase is similar to its mammalian counterparts with respect to spectral, electrophoretic, and biocatalytic properties.
A total of 34 plant species belonging to 18 different families, selected on the basis of folklore medicinal reports practised by the tribal people of Western Ghats, India, were assayed for antibacterial activity against Escherichia coli, Klebsiella aerogenes, Proteus vulgaris, and Pseudomonas aerogenes (gram-negative bacteria) at 1000-5000 ppm using the disc diffusion method. Of these 16 plants showed activity; among them Cassia fistula, Terminalia arjuna and Vitex negundo showed significant antibacterial activity against the tested bacteria. Our findings confirm the traditional therapeutic claims for these herbs.
Cytochrome P4501A1 was purified to electrophoretic homogeneity from the liver microsomes of feral fish leaping mullet (Liza saliens) collected in Izmir Bay, Aegean coast of Turkey. Purification of cytochrome P4501A1 involved anion exchange chromatography of Emulgen 913-cholate solubilized microsomes on first- and second-DEAE-cellulose columns, hydrophobic interaction chromatographies of the partially purified cytochrome P4501A1 on Porapak Q and phenyl-Sepharose CL-4B and further purification on adsorption chromatography on the hydroxylapatite column. Finally, it is further concentrated and purified on the third DEAE-cellulose column. The purified cytochrome P4501A1 was characterized with respect to spectral, electrophoretic, immunochemical and biocatalytic properties. Cytochrome P4501A1, purified 32-fold with a specific content of 15-17 nmoles P450 (mg protein)-1, produced a single band on SDS-polyacrylamide gel electrophoresis having monomer molecular weight of 58,000 +/- 500. Absolute absorption spectrum of the purified cytochrome P4501A1 fractions showed maximal absorption at 417.5 nm and CO-difference spectrum of dithionite-reduced cytochrome P4501A1 gave a peak at 448 nm. Purified P4501A1 was found to be active in the O-deethylation of 7-ethoxyresorufin in the reconstituted system containing purified fish liver cytochrome P450 reductase and synthetic lipid. However, it was unable to catalyze the oxidation of the other monooxygenase substrates such as benzphetamine and aniline known to be specific for the other isozymes. Purified L. saliens liver microsomal cytochrome P4501A1 showed strong cross-reactivity with the antibodies directed against the cytochrome P4501A1 homologues purified from other teleost species such as rainbow trout and scup. Spectral, electrophoretic, immunochemical and biocatalytic properties of the purified cytochrome P4501A1 strongly suggested that it is the CYP1A1 in the L. saliens liver.
Human placental syncytiotrophoblast basal membrane plays an important role in transfer of nutrients from the mother to the growing fetus all throughout gestation. The membrane lipid composition together with the bilayer fluidity is found to be the major index in modulation of these transport processes. In the present study, the effects of changing lipid composition on the placental basal membrane fluidity and the modulating influence of the latter on membrane enzyme and transport functions with progress of gestation,were investigated. Steady-state fluorescence analysis using 1,6-diphenyl- 1,3,5 hexatriene as the probe, indicated a decrease in fluorescence anisotropy of both labeled native membrane vesicles and liposomes prepared from lipids extracted from the basal membrane vesicles, signifying increased bilayer fluidity with progress of gestation. This in turn, was successfully correlated to the lowering of cholesterol content and enhanced phospholipid concentration with a steady decrease in cholesterol/phospholipid ratio during placental development. Enhanced Na+-K+-ATPase activity and steady-state glucose uptake across basal membrane with gestational progress suggested modulation of membrane protein functions by the fluidity, which was further corroborated by the increased bilayer fluidity and enzyme activity in benzyl alcohol treated basal membrane in each gestational age group.
We describe a family of related discrete reliability-growth methodologies potentially applicable to one-shot systems undergoing a test-analyze-and-fix development process. The common feature shared by the models is their connection to Duane's renowned learning-curve property. The major difference, however, lies in their applicability in the context of two intrinsically different sampling schemes. For each model, a summary of the statistical properties of various estimators of the parameters as well as the reliability of the system, are reported. For purposes of assessing model misspecification, a particular text execution scenario conforming to a inverse sampling scheme is adopted. In reliability applications, it is not an uncommon practice to borrow inference results from models which are inappropriate in this setting. A detailed study of the potential impact of such misspecification on the estimation of system reliability is presented.
The structural effect of the presequence of cytochrome oxidase subunit IV (p25) on multilamellar liposomes with different lipid compositions has been investigated using X-ray diffraction and electron microscopy. The presequence causes the disordering of the liposomes containing negatively charged lipids, without destabilizing the bilayer structure or destroying the multilamellar nature of the liposomes. In the systems containing only zwitterionic lipids, a small increase in the d-spacing (lamellar stacking spacing) is observed without any disorder effect suggesting a weaker interaction of the peptide and lipid. Circular Dichroism measurements of the peptide, in the presence and absence of the different lipid systems studied, show that the secondary structure of the peptide is modulated by the lipid environment. Considerable amounts of alpha-helix in the presequence is only observed in the systems containing negatively charged lipids. These are the same systems for which the disordering effect is observed with X-ray diffraction. It is proposed that p25 disorders the bilayer stacking by corrugating the membranes. The results are discussed in terms of the relevance of the specific lipid properties (e.g., electric charge and ability to form inverted phases) in determining how the peptide interacts with the lipid and affects its structural organization. It is suggested that the lipid properties relevant for the disordering effect induced by the peptide are the same as those involved in the formation of contact sites between mitochondrial membranes during the import of nuclear coded proteins.
The actin binding protein caldesmon inhibits the actin-activation of myosin ATPase activity. The steps in the cycle of ATP hydrolysis that caldesmon could inhibit include: (1) the binding of myosin to actin, (2) the transition between any two actin-myosin states and (3) the distribution between inactive and active states of actin. The analysis of these possibilities is complicated because caldesmon binds to both myosin and actin and because each caldesmon molecule binds to several actin monomers. This paper reviews procedures for analysing these interactions and summarizes current information on the stability and dynamics of the interaction of caldesmon with actin and myosin. Possible effects of caldesmon on transitions within the ATPase cycle of actomyosin are also discussed.
Reports of 9 cases with hand dystonia due to stroke are described. The site of the lesion was found to be parietothalamic in 1 patient, posterolateral thalamic in 5 patients, dorsal thalamic in 2 patients and medial thalamic in 1 patient as defined by computerized tomography or magnetic resonance imaging. In addition to the hand dystonia, hemiballism was noted in 1 case, hemichorea in 2 cases, action tremor in 3, anxiety in 3 and pain in 2 cases. The time lapse from the stroke to the manifestation of dystonia was 1 month to 2 years.
We report a 30-year-old woman with periampullary cancer and a large left ovarian cystadenoma presenting during pregnancy with features of duodenal obstruction. She had a right benign ovarian tumor removed a year back. She delivered an intrauterine-growth-retarded live baby. Laparotomy in the postpartum period revealed an unresectable periampullary growth with hepatic metastasis and a left ovarian cystadenoma. The ovarian tumor was removed and a palliative gastrojejunostomy performed.
Placental syncytiotrophoblast while regulating the passage of nutrients from maternal blood to the fetal circulation exposes itself to the risk of oxidative attack by the oxygen free radicals. Extent of lipid peroxidation (LPO) investigated in placental brush border membrane (BBM) and basal membrane (BM) revealed a decreasing trend with gestational progress. Steady-state fluorescence anisotropy measurement of 1,6-diphenyl-1,3,5-hexatriene (DPH)-labeled malondialdehyde treated placental membrane vesicles suggested modulation of BBM and BM fluidity by lipid peroxidation in all gestational ages. alpha-tocopherol content in both the placental membranes which increased as gestation progressed has been proposed to play a significant role in decreasing LPO of placental membranes during intrauterine development.
The effects of stimuli falling outside the 'classical receptive field' and their influence on the orientation selectivity of cells in the cat primary visual cortex are still matters of debate. Here we examine the variety of effects of such peripheral stimuli on responses to stimuli limited to the receptive field. We first determined the extent of the classical receptive field by increasing the diameter of a circular patch of drifting grating until the response saturated or reached a maximum, and by decreasing the diameter of a circular mask in the middle of an extended grating, centred on the receptive field, until the cell just began to respond. These two estimates always agreed closely. We then presented an optimum grating of medium-to-high contrast filling the classical receptive field while stimulating the surround with a drifting grating that had the same parameters as the central stimulus but was varied in orientation. For all but five neurons (of 37 tested), surround stimulation produced clear suppression over some range of orientations, while none showed explicit facilitation under these conditions. For 11 cells (34% of those showing suppression), the magnitude of suppression did not vary consistently with the orientation of the surround stimulus. In the majority of cells, suppression was weakest for a surround grating oriented orthogonal to the cell's optimum. Nine of these cells (28%) exhibited maximum inhibition at the optimum orientation for the receptive field itself, but for 12 cells (38%) there was apparent 'release' from inhibition for surround gratings at or near the cell's optimum orientation and direction, leaving inhibition either maximal at angles flanking the optimum (9 cells) or broadly distributed over the rest of the orientation range (3 cells). This implies the existence of a subliminal facilitatory mechanism, tightly tuned at or near the cell's optimum orientation, extending outside the classical receptive field. For just two cells of 13 tested the preferred orientation for a central grating was clearly shifted towards the orientation of a surrounding grating tilted away from the cell's optimum. The contrast gain for central stimulation at the optimal orientation was measured with and without a surround pattern. For nine of 25 cells tested, surround stimulation at the cell's optimum orientation facilitated the response to a central grating of low contrast (< or =0.1) but inhibited that to a higher-contrast central stimulus: the contrast-response gain is reduced but the threshold contrast is actually decreased by surround stimulation. Hence the receptive field is effectively larger for low-contrast than for high-contrast stimuli. Inhibition from the periphery is usually greatest at or around the cell's optimum, while suppression within the receptive field has been shown to be largely non-selective for orientation. Inhibition by orientations flanking the optimum could serve to sharpen orientation selectivity in the presence of contextual stimuli and to enhance orientational contrast; and it may play a part in orientation contrast illusions.
RATIONALE AND OBJECTIVES: The authors developed a technique to produce high-resolution, three-dimensional images of vasculature from a set of x-ray projections in an attempt to provide detailed anatomic representations of complex vasculature. MATERIALS AND METHODS: Projection images were acquired with a clinical angiographic system by using biplanar rotational digital subtraction angiography. The images were reconstructed with an additive algebraic reconstruction technique. RESULTS: The feasibility of the technique was tested by reconstructing three-dimensional images of several phantoms, including a wire phantom and an anatomic flow phantom. The anatomic phantom allowed replication of contrast material flow and image noise that are characteristic of patient examinations. The reconstruction procedure was then used to examine a carotid artery and a cerebral aneurysm in two patients. CONCLUSION: A method of reconstructing vasculature from x-ray angiograms has been developed and validated with geometric and anatomic phantoms. Preliminary patient applications indicate that this technique enables enhanced visualization of complex vascular relationships and structures.
Three distinct cytochrome P450 isozymes, P4501A1, P4502B and an unidentified P450 isozyme were separated and isolated from beta-NF-treated gilthead seabream liver microsomes. Cytochrome P4501A1 was partially purified from beta-NF-treated gilthead seabream liver microsomes in the presence of detergents Emulgen 913 and cholate and protease inhibitors using two DEAE-cellulose, Porapak Q and two hydroxylapatite column chromatographies. The overall yield of purified P4501A1 was 1.2% with respect to microsomal total P450 with a specific content of 3 nmol/mg protein. The purified P4501A1 was characterized with respect to spectral, electrophoretic, biocatalytic and immunochemical properties, which are found to be similar to P4501A1s purified from other teleost species such as trout, scup, cod and perch suggesting that the P450 we have purified belongs to CYP1A1.
Increased nitric oxide (NO) levels are thought to play an important role in the pathophysiology of the systemic inflammatory response syndrome (SIRS) which is caused by disseminated vascular endothelial damage. Clinical studies have shown that urinary nitrite (NO2-) and nitrate (NO3-) excretions can be utilized as indexes of NO formation. The SIRS and NO relationship was investigated in 15 neonates with SIRS, gestational age 32.5 +/- 4.4 weeks and weight 1,737 +/- 753 g. The control group comprised 18 neonates with a gestational age of 32.8 +/- 3.5 weeks and a weight of 1,778 +/- 538 g. There was no significant difference in birth weights and gestational ages between the two groups (p > 0.05 and p > 0.05). The urinary nitrite levels obtained in the subjects were normalized for urinary creatinine concentrations. The mean urinary nitrite levels in the control group neonates were found to be 4.22 +/- 1.8 micromol/mmol creatinine on the 1st day, 4.09 +/- 2.28 on the 2nd, 3.62 +/- 1.6 on the 3rd, and 4.01 +/- 1.12 micromol/mmol creatinine on the 7th day. There were no statistically significant differences between these levels (p > 0.05). We determined urinary levels of nitrite in neonates in the study group within the first 24 h of SIRS symptoms and found these levels (18.35 +/- 11.16 micromol nitrite/mmol creatinine) to be elevated as compared with those of the control subjects on the 7th day of life (p < 0.0005). In conclusion, urinary nitrite excretion is significantly elevated in neonates with SIRS due to septic events, and these results suggest that NO might play a part in SIRS.
The author examines "the place and role of quality of life in economic evaluation and welfare economics. That exercise certainly involves norms and judgments, but it is also influenced by our reading of factual possibilities, and it influences, in its turn, the nature of prescriptive possibilities we explore and the descriptive statements we choose to make. In this sense, the topic is not confined to welfare economics and involves other branches of economics as well." This essay consists of two lectures, the second of which examines how longevity, life expectancy, and gender- and race-determined mortality differences can contribute to our understanding of quality of life.
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