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Biomedical subjects

S Mann

Publications and source records attributed to S Mann.

At least 91 records · Page 5Linked to original sources
PubMed1995

Initial assessment of magnetoferritin biokinetics and proton relaxation enhancement in rats.

RATIONALE AND OBJECTIVES: We evaluated the biokinetics and proton relaxation enhancement of magnetoferritin, a recently developed class of superparamagnetic iron oxides, in rats. METHODS: "Equine" magnetoferritin was administered intravenously at 5 mg protein and 1.4 mg Fe/kg in nude rats carrying subcutaneous xenografted human small-cell lung carcinoma with and without preinjection of 100 mg/kg equine apoferritin. Blood clearance, in vivo biodistribution, and proton relaxation enhancement were assessed by variable field relaxometry, immunohistochemistry, and magnetic resonance (MR) imaging at 1.5 T. RESULTS: Magnetoferritin clearance from blood followed biexponential kinetics, with a short initial half-life of 1.4-1.7 min. A second, longer component lasted for several hours. Histochemical staining, MR imaging, and ex vivo relaxometry revealed rapid uptake of magnetoferritin in the liver, spleen, and lymph nodes. There was no difference in biodistribution after apoferritin preinjection. CONCLUSION: In the rat, equine magnetoferritin is rapidly sequestered by cells of the reticuloendothelial system, with no direct involvement of ferritin receptors. These properties may allow the use of magnetoferritin as an MR contrast agent for the liver and spleen.

Animals↗
PubMed1995

Controlled Biomineralization of Magnetite (Fe(inf3)O(inf4)) and Greigite (Fe(inf3)S(inf4)) in a Magnetotactic Bacterium.

A slowly moving, rod-shaped magnetotactic bacterium was found in relatively large numbers at and below the oxic-anoxic transition zone of a semianaerobic estuarine basin. Unlike all magnetotactic bacteria described to date, cells of this organism produce single-magnetic-domain particles of an iron oxide, magnetite (Fe(inf3)O(inf4)), and an iron sulfide, greigite (Fe(inf3)S(inf4)), within their magnetosomes. The crystals had different morphologies, being arrowhead or tooth shaped for the magnetite particles and roughly rectangular for the greigite particles, and were coorganized within the same chain(s) in the same cell with their long axes along the chain direction. Because the two crystal types have different crystallochemical characteristics, the findings presented here suggest that the formation of the crystal types is controlled by separate biomineralization processes and that the assembly of the magnetosome chain is controlled by a third ultrastructural process. In addition, our results show that in some magnetotactic bacteria, external environmental conditions such as redox and/or oxygen or hydrogen sulfide concentrations may affect the composition of the nonmetal part of the magnetosome mineral phase.

Journal Article↗
PubMed1994

Once daily lisinopril and captopril in hypertension: a double blind comparison using ambulatory monitoring.

AIM: To validate and compare the 24-hour antihypertensive efficacy of the angiotensin-converting-enzyme inhibitors, captopril and lisinopril. METHODS: A randomised, doubleblind, doubledummy crossover study was performed with single-blind placebo run-in and washout periods and titration opportunities during therapeutic phases (captopril 25mg, 50mg and 100mg daily, lisinopril 10mg, 20mg and 40mg daily). The study was monitored using standard office blood pressure measurements, clinical and laboratory assessment. 24 patients of either sex and between 18 and 70 years with essential hypertension were enrolled, 20 met randomisation criteria (of sitting diastolic pressure 95-115mmHg), 3 withdrew from the study during its active phase and one was excluded from analysis having been found retrospectively to have not met randomisation criteria at the appropriate visit. Predetermined endpoints were blood pressure levels during different time periods of ambulatory monitoring performed at the end of each placebo or treatment phase. RESULTS: In the 17 patients who completed the protocol, lisinopril produced a greater reduction of blood pressure at all time periods although the differences were not all statistically significant. The differences were most marked 19-24 hours post dosage time when pressures (systolic/diastolic) during lisinopril therapy were lower than during captopril by 18.0/14.5 mmHg (p < 0.001 for both). As measured by clinic pressures, lisinopril also achieved a considerably higher degree of blood pressure control with less dose titration. CONCLUSION: In this study, lisinopril proved a more effective once daily antihypertensive agent than captopril, especially in the last 6 hours of the 24-hour dosage interval.

Adult↗
PubMed1994

Further characterisation of forms of haemosiderin in iron-overloaded tissues.

The biochemical and biophysical properties of isolated haemosiderins have been compared to that of another iron-containing protein, termed prehaemosiderin, which sediments through chaotropic potassium iodide only after 20 h of ultracentrifugation, in contrast to that of haemosiderin which is recovered after 2 h of ultracentrifugation. The iron/protein ratio and iron/phosphate ratio were less that that of the corresponding haemosiderin, while the elemental composition was also reduced in many of the prehaemosiderin samples. Mossbauer spectroscopy and electron diffraction identified the predominant presence of ferrihydrite in prehaemosiderin species even though the secondary haemochromatosis haemosiderin iron cores were essentially goethite-like. The majority of the prehaemosiderins isolated showed the presence of an additional peptide band at 17 kDa in addition to that at 21 kDa. Further Mossbauer studies of haemosiderin isolated from untreated secondary haemochromatosis patients showed that goethite was the predominant form of iron present, thereby indicating that the presence of this form of ferrihydrite was not wholly attributable to chelation therapy.

Animals↗
PubMed1994

Prenatal diagnosis and post-mortem study of a fetus with mosaic trisomy 14 due to a dic(14)(p11).

Amniocentesis at 17 weeks' gestation revealed a mosaic karyotype--46,XX/46,XX,-14,+dic(14)(p11). No abnormalities were detected on ultrasound. Growth and placentation were normal. The fetus was examined after termination of pregnancy and micrognathia and pulmonary hyperlobation were the only abnormalities detected. Several tissues were set up for cytogenetics, including fetal skin, kidney, ovary, and placenta. The diagnosis was confirmed by these studies. The level of mosaicism varied between tissues, with the trisomy 14 cell line highest in amniotic fluid.

Adult↗
PubMed1994

Self-assembled microstructures from 1,2-ethanediol suspensions of pure and binary mixtures of neutral and acidic biological galactosylceramides.

Optical and electron microscopy were employed to characterize microstructures formed by thermal mechanical treatment of glycol suspensions of various pure and binary mixtures of the brain-derived galactosphingolipids hydroxy fatty acid cerebroside (HFA-Cer), non-hydroxy fatty acid cerebroside (NFA-Cer) and sulfatide (S-Cer). Negative staining indicated some new features of the neutral cerebroside suspensions in glycol. HFA-Cer formed a small fraction of both unilamellar cylinders (ULCs) (lumina ca. 27 nm) and giant multilamellar cochleates in addition to the typical nonhelical multilamellar cylinders (MLCs) (lumina ca. 10-30 nm). NFA-Cer formed a gel composed of a significant fraction of very long ULCs (lumina ca. 17 nm) without helical substructure, in addition to multilamellar helical structures such as ribbons and cylinders (lumina ca. 70 nm). Anisotropic lamellar micelle-shards of NFA-Cer were also detected by negative staining. S-Cer formed short ULCs (lumina ca. 44 nm) with no obvious helical substructure. Complex mixture data are thought to result from thermodynamic and kinetic factors. HFA-Cer is highly insoluble and promotes a network of rigid intralamellar hydrogen bonding that tends to exclude other lipids. NFA-Cer stabilizes helical defects in the lamellae, and S-Cer enhances disorder or micellization. The processes of microstructure nucleation and lipid phase separation were affected by mixtures such that metastable microstructures were trapped or the length of lamellar cylinders was altered.

Animals↗
PubMed1994

Intracellular ionic consequences of dietary salt loading in essential hypertension. Relation to blood pressure and effects of calcium channel blockade.

To study the ionic basis of salt sensitivity in hypertension, 19F-, 13P-, and 23Na-nuclear magnetic resonance techniques were used to measure cytosolic free calcium (Cai), pH (pHi), free magnesium (Mgi), and sodium (Nai) in erythrocytes of essential hypertensive subjects (n = 19). Individuals were studied for 2 mo each on low- (UNaV < 50 meq/d) and high- (UNaV > 200 meq/d) salt diets, with the concomitant administration of nifedipine (10 mg t.i.d.) or placebo tablets for 1 mo of each diet. Salt loading elevated Cai and Nai while suppressing Mgi and pHi; these changes occurred predominantly in salt-sensitive subjects (n = 9). Nifedipine blunted the pressor response to salt loading > 50% (delta diastolic BP [high-low salt vs placebo] = 5 +/- 2 vs 14 +/- 2 mmHg, P < 0.05) and reversed salt-induced ionic changes, lowering Cai and elevating Mgi and pHi. Regardless of the definition of salt sensitivity, continuous relationships were observed between the pressure response to salt loading, the levels of Cai (r = 0.726, P < 0.001), Nai (r = 0.747, P < 0.001), and pHi (r = -0.754, P < 0.001), and the salt-induced change in Mgi (r = -0.757, P < 0.001). Altogether, these results emphasize the reciprocal and coordinate nature of intracellular ionic changes in response to dietary salt loading and calcium channel blockade in essential hypertension. They suggest that salt sensitivity is mediated by cellular calcium accumulation from the extracellular space, in association with magnesium depletion and acidification. Lastly, interpretation of intracellular ion measurements in the future will require concurrent assessment of dietary salt intake.

Analysis of Variance↗
PubMed1993

Overproduction, purification and characterization of the Escherichia coli ferritin.

Recent studies have indicated that Escherichia coli possesses at least two iron-storage proteins, the haem-containing bacterioferritin and ferritin. The ferritin protein has been amplified 600-fold to 11-14% of total cell protein in a bfr mutant and purified to homogeneity with an overall yield of 13%. The cellular ferritin content remained relatively constant throughout the growth cycle and amplification was accompanied by a 2.5-fold increase in cellular iron content. The isolated ferritin contained 5-20 non-haem iron atoms/holomer and resembled the eukaryotic ferritins rather than the prokaryotic bacterioferritins in containing no haem. The 24 subunits of this ferritin (M(r) 19,400) assemble into a spherical protein shell (12 +/- 1 nm diameter, M(r) 465,000) which sequesters at least 2000 iron atoms in vitro to form an electron-dense iron core of 7.9 +/- 1 nm diameter. Electron-microscopic and Mössbauer spectroscopic studies with iron-loaded ferritin showed that the core can be either crystalline (ferrihydrite) or amorphous, depending on the absence or presence of phosphate, respectively. Mössbauer spectroscopy with intact E. coli revealed a novel-high spin Fe(II) component which is enhanced in bacteria amplified for ferritin but not in the parental strain. Western blotting showed that ferritin and bacterioferritin are immunologically distinct proteins. E. coli is thus an organism containing both a ferritin and a bacterioferritin and the relative roles of the two iron-storage proteins are discussed in this study.

Amino Acid Sequence↗
PubMed1993

Structural studies of lipid fibers formed by sphingosine.

The natural product D-erythro-sphingosine and synthetic racemic dihydrosphingosines were examined for their abilities to self-assemble into high-axial-ratio microstructures. When precipitated from methanol/water solution, D-erythro-sphingosine formed a viscoelastic gel composed of 50-nm diameter flexible fibers. These are 'cochleate cylinders' composed of rolls of lamellae. Compared to the biological sphingosine, the DL-erythro- and DL-threo-dihydrosphingosines are much less soluble in methanol/water mixtures. When recrystallized from methanol/water the dihydrosphingosines tend to form irregular lamellar structures or platelets. When higher proportions of methanol are used in the recrystallization solvent, needle-like structures predominate in the DL-erythro-dihydrosphingosine sample, but not in the DL-threo-dihydrosphingosine samples. The needles are mostly very long and narrow crystal platelets often with fracture defects parallel to the long axes. Some curved fiber-like structures are also seen. These results suggest that in comparison to the threo diastereomer, the erythro diastereomer of dihydrosphingosine displays a large differential in intermolecular bonding strengths between divergent orientations within the lamellar sheet. Energy-minimized molecular models indicate that, compared to the threo isomers, intramolecular bonding could bend the erythro headgroup farther toward the hydrocarbon interface of a lamellar microstructure. Moreover, this work illustrates how the erythro headgroup could support a linear pattern of intermolecular hydrogen bonds while the threo could support a two-dimensional network. D-erythro-sphingosine probably displays a similar intermolecular bonding pattern, but as it is optically pure, the molecular packing results in a consistent twist to the neighboring molecules and this is expressed as the bending of the lamellar sheet into a cochleate. The fiber-forming ability of D-erythro-sphingosine may have implications for the reactive and structural properties of biological sphingolipids as well as the design of novel materials based on synthetic high-axial-ratio lipid superstructures.

Crystallization↗
PubMed1993

Structure and composition of ferritin cores from pea seed (Pisum sativum).

Iron cores from native pea seed (Pisum sativum) ferritin have been analysed by electron microscopy and Mössbauer spectroscopy and shown to be amorphous. This correlates with their relatively high phosphate content (Fe: P = 2.83; 1800 Fe, 640 P atoms/molecule). Reconstituted cores obtained by adding iron (2000 Fe atoms/molecule) in the absence of phosphate to pea seed apoferritin were crystalline ferrihydrite. In vitro rates of formation of pea-seed ferritin iron cores were intermediate between those of recombinant human H-chain and horse spleen apoferritin and this may reflect the amino-acid residues of its ferroxidase and putative nucleation centres. The high phosphate content of pea-seed ferritin suggests that this molecule could be involved in both phosphorus and iron storage. The high phosphate concentration found within plastids, from which the molecules were isolated, is a possible source of the ferritin phosphate.

Fabaceae↗
PubMed1993

Gaucher's disease and mesangiocapillary glomerulonephritis in childhood--a coincidence?

A 6-year-old boy, presenting with a nephritic syndrome, was diagnosed as suffering from Gaucher's disease (GD) and mesangiocapillary glomerulonephritis (MCGN). GD was suspected because of aseptic necrosis of the femoral heads on X-ray and later confirmed by bone marrow aspiration and a lack of glucocerebrosidase activity in white blood cells; MCGN was documented on renal biopsy. The child was treated with prednisone, dipyridamole and aspirin, and recovered completely clinically. A second biopsy was not performed. The connection between these two rare diseases, and between nephritis and GD in general, is discussed.

Basement Membrane↗
PubMed1993

Height, occupation and back pain in a national prospective study.

Back pain is an important public health problem but there is a paucity of knowledge about risk factors and causal mechanisms. Previous studies have shown that tall men are more at risk of back pain, although observations in women have been less consistent. This paper presents findings from a national longitudinal study of 3262 men and women aged 43 yr. Standing height and sitting height were related to 18-month reported prevalence of 'sciatica, lumbago or severe backache' in both men and women. The paper investigates explanations for these findings using previously collected data on childhood growth and detailed lifetime occupational histories. Neither greater susceptibility of tall men to heavy lifting, nor the timing of growth, were able to account for these relationships. To assess further the association between height and back pain, information is needed on the relationship between stature and characteristics of spinal structure.

Adult↗
PubMed1993

Human papillomavirus type 6-induced condylomata: an unusual complication of intertrigo.

A 79-year-old virgo intacta presented with a 20-year-history of intertrigo, and a 3-month history of superimposed warty masses beneath both breasts and in the groin and perianal areas. There was no evidence of immunosuppression. Histology of the warty lesions showed squamous papillomata, with evidence of wart virus infection. Human papillomavirus (HPV) type 6 was identified by in situ DNA hybridization, in the submammary lesions. This is an unusual manifestation of both intertrigo and wart virus infection. HPV-6 is classically found in anogenital warts. We assume that these warts were acquired by a non-venereal route and/or by congenital infection some 78 years ago. We suggest that it is the warm, moist environment, rather than the specific site, which encourages HPV-6 to flourish.

Aged↗
PubMed1992

Chemical and structural characterisation of iron cores of haemosiderins isolated from different sources.

The elemental content of the iron cores of haemosiderins isolated from animal and human tissues has been determined to ascertain whether changes in composition are correlated with structural differences previously identified in these mineralisation products. Significant differences were observed in the elemental composition of haemosiderins isolated from patients subjected to desferrioxamine-chelation therapy compared to patients who had been venesected. The P/Fe molar ratio was considerably higher in haemosiderin isolated from treated primary haemochromatosis (0.83), compared to untreated primary haemochromatosis (0.10) and treated secondary haemochromatosis (0.25), and this could account for the amorphous nature of these iron cores. The levels of M/Fe (M = Ca, Cu, Zn) were reduced in the haemosiderins derived from treated secondary haemochromatosis patients, possibly due to the chelation of these ions by desferrioxamine therapy. In an experimentally iron-loaded rat, receiving either desferrioxamine or 1,2-diethyl-3-hydroxypyrid-4-one, selective decreases in these three elements were also observed after two weeks of desferrioxamine therapy. Such changes may be important determinants in the modification of biomineralisation of the iron cores.

Animals↗
PubMed1992

OMA-AML-1: a leukemic myeloid cell line with CD34+ progenitor and CD15+ spontaneously differentiating cell compartments.

OMA-AML-1 was established from a patient with acute myelomonocytic (M4) leukemia at fifth relapse when blasts were greater than 85% CD34+, CD15-. Leukemic cells were established in suspension culture and independently grown as subcutaneous tumors in SCID mice. Cells growing in suspension culture underwent differentiation by phenotypic and morphologic criteria. In contrast, cells grown as subcutaneous solid tumors in SCID mice maintained progenitor cell characteristics with high-density CD34 expression and lack of morphologic differentiation. A tendency toward differentiation to CD15+, CD34- cells in vitro and self-renewal of CD34+, CD15- cells in vivo was consistently demonstrated regardless of whether cells were initially grown in vitro or in vivo. The cell line maintains both a CD34+, CD15- progentitor cell pool and a non-overlapping, CD15+, CD34- differentiating cell compartment after more than 1 year in continuous culture. Cell cycle analysis and cloning experiments were consistent with terminal differentiation occurring in the CD15+, CD34- population. The cell line shows concentration-dependent proliferative responses to interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6, but not to granulocyte CSF (G-CSF). OMA-AML-1 appears to mimic several features of normal myeloid hematopoiesis and should prove useful for the study of normal and malignant myeloid differentiation.

Animals↗
PubMed1992

Magnetoferritin: in vitro synthesis of a novel magnetic protein.

The iron storage protein ferritin consists of a spherical polypeptide shell (apoferritin) surrounding a 6-nanometer inorganic core of the hydrated iron oxide ferrihydrite (5Fe2O3.9H2O). Previous studies have shown that the in vitro reconstitution of apoferritin yields mineral cores essentially identical to those of the native proteins. A magnetic mineral was synthesized within the nanodimensional cavity of horse spleen ferritin by the use of controlled reconstitution conditions. Transmission electron microscopy and electron diffraction analysis indicate that the entrapped mineral particles are discrete 6-nanometer spherical single crystals of the ferrimagnetic iron oxide magnetite (Fe3O4). The resulting magnetic protein, "magnetoferritin," could have uses in biomedical imaging, cell labeling, and separation procedures.

Animals↗