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Biomedical subjects

H Vogel

Publications and source records attributed to H Vogel.

At least 181 records · Page 10Linked to original sources

Template-assembled melittin: structural and functional characterization of a designed, synthetic channel-forming protein.

Template-assembled proteins (TASPs) comprising 4 peptide blocks, each of either the natural melittin sequence (melittin-TASP) or of a truncated melittin sequence (amino acids 6-26, melittin6-26-TASP), C-terminally linked to a (linear or cyclic) 10-amino acid template were synthesized and characterized, structurally by CD, by fluorescence spectroscopy, and by monolayer experiments, and functionally, by electrical conductance measurements on planar bilayers and release experiments on dye-loaded vesicles. Melittin-TASP and the truncated analogue preferentially adopt alpha-helical structures in methanol (56% and 52%, respectively) as in lipid membranes. Unlike in methanol, the melittin-TASP self-aggregates in water. On an air-water interface, the differently sized molecules can be self-assembled and compressed to a compact structure with a molecular area of around 600 A2, compatible with a 4-helix bundle preferentially oriented perpendicular to the interface. The proteins reveal a strong affinity for lipid membranes. A partition coefficient of 1.5 x 10(9) M-1 was evaluated from changes of the Trp fluorescence spectra of the TASP in water and in the lipid bilayer. In planar lipid bilayers, TASP molecules are able to form defined ion channels, exhibiting a small single-channel conductance of 7 pS (in 1 M NaCl). With increasing protein concentration in the lipid bilayer, additional, larger conductance states of up to 1 nS were observed. These states are likely to be formed by aggregated TASP structures as inferred from a strongly voltage-dependent channel activity on membranes of large area. In this respect, melittin-TASP reveals channel features of the native peptide, but with a considerably lower variation in the size of the channel states. Compared to the free peptide, template-assembled melittin has a much higher membrane activity: it is about 100 times more effective in channel formation and 20 times more effective in releasing dye molecules from lipid vesicles. This demonstrates that the lytic properties are not solely related to channel formation.

Acetylation↗

[X-chromosome dominant chondrodysplasia punctata (Happle syndrome). Lyonization of the eyelashes?].

X-linked dominant chondrodysplasia punctata or Happle syndrome is a rare hereditary disorder. The clinical features include retardation of growth, cataract, and temporary, ichthyosiform erythroderma. Atrophic lesions and hyperkeratotic papules of the skin and disturbances of hair growth follow the lines of Blaschko. A 5-year-old girl with X-linked dominant chondrodysplasia punctata was found to be mentally retarded and to have abnormalities of the eyelashes (growth and pigmentation), which had not previously been described in this condition.

Bone and Bones↗

Biologically addressable monolayer structures formed by templates of sulfur-bearing molecules.

We demonstrate that the combined application of Langmuir-Blodgett and self-assembly techniques allows the fabrication of patterns with contrasting surface properties on gold substrates. The process is monitored using fluorescence microscopy and surface plasmon spectroscopy and microscopy. These structures are suitable for the investigation of biochemical processes at surfaces and in ultrathin films. Two examples of such processes are shown. In the first example, the structures are addressed through the binding of a monoclonal antibody to a peptide. This demonstrates the formation of self-assembled monolayers by cysteine-bearing peptides on gold, and the directed binding of proteins to the structured layers. A high contrast between specific and unspecific binding of proteins is observed by the patterned presentation of antigens. Such films possess considerable potential for the design of multichannel sensor devices. In the second example, a structured phospholipid layer is produced by controlled self-assembly from vesicle solution. The structures created--areas of phospholipid bilayer, surrounded by a matrix of phospholipid monolayer--allow formation of a supported bilayer which is robust and strongly bound to the gold support, with small areas of free-standing bilayer which very closely resemble a phospholipid cell membrane.

Amino Acid Sequence↗

Insulin-like growth factor I correlations to changes of the hormonal status in puberty and age.

IGF-I is considered to be one of the most important growth factors during puberty. Information concerning its correlation to thyroid hormones (T3, T4), adrenal and sex steroids is limited to puberty and the elderly. The presented study included 455 subjects (among them 259 children) ranging in age from newborn to 100 years. Serum IGF-I concentrations increase from childhood to the end of puberty (2 years earlier in girls). There are close positive correlations between IGF-I concentrations and age, height and weight and between IGF-I and estradiol or testosterone concentration in girls and boys respectively, and the DHEA-S level in boys during puberty. Correlations also exist with T3, aldosterone and 17 OH-progesterone in boys and girls in the pubertal stages I-V and with T4 in stages I-IV. Compared to 20-30 year-old subjects IGF-I concentrations amounted to 59% after 60 years, 43% in men and 54% in women after 70 years and 29% after 90 years. It is suggested that increasing adrenal DHEA-S concentrations stimulate IGF-I synthesis and by means of gonadal steroidogenesis, increase the pubertal GH secretion and the further pubertal IGF-I increase. The low IGF-I concentrations in patients > 60 years reflect the more catabolic metabolism of the elderly.

Adolescent↗

[Radiology in the 3d World, illness, hunger, violence].

Parasitoses, perinatal X-ray diagnostics, hunger, war, and torture produce X-Ray findings that are hardly known in Western and Central Europe. X-ray diagnostics in the 3rd world are often decisive for the diagnosis due to the lack of other methods. X-ray diagnostics offers many possibilities but is often not available or available only for few.

Adolescent↗

Structural characterization of membrane insertion of M13 procoat, M13 coat, and Pf3 coat proteins.

A new, simple, and efficient purification method has been developed for the extremely hydrophobic M13 procoat, M13 coat, and Pf3 coat proteins. Homogeneous preparations were obtained in 2-propanol/0.1% TFA, where M13 coat protein is found to be dissolved in a monomeric form, and the two other proteins as dimers or trimers. The conformations of these particular proteins in different environments have been determined by circular dichroism and infrared spectroscopy. In organic solvents, the proteins adopt a conformation with an average helix content of 90%. In lipid bilayers composed of phosphatidylcholine and phosphatidylglycerol lipids, the average helix content is 50% for M13 procoat protein, 60% for M13 coat protein, and 75% for Pf3 coat protein. The orientational order parameter S alpha of the protein helices in planar lipid bilayers have been determined by polarized infrared measurements in the amide I spectral range. The helices of the three proteins are oriented preferentially parallel to the membrane normal, with S alpha = 0.63 for M13 procoat protein, S alpha = 0.58 for Pf3 coat protein, and a distinctly higher value of S alpha = 0.81 for M13 coat protein.

Amino Acid Sequence↗

Structural fluctuations between two conformational states of a transmembrane helical peptide are related to its channel-forming properties in planar lipid membranes.

Putative transmembrane helices of membrane proteins in general and channel proteins in particular often contain proline residues which may induce a bend into an otherwise regular helical structure. Here we show by fluorescence-energy-transfer measurements and molecular-dynamics calculations that, in the case of synthetic bilayer-spanning helical polypeptides, a proline-induced bend in a helix acts as a flexible element mediating rigid body motions of the helical segments. Most important, such structural fluctuations in the transmembrane helices seem to play a functional role in the formation of ionic channels in planar lipid bilayers and biological membranes.

Amino Acid Sequence↗

Filamentous degeneration of neurons. A possible feature of cytosine arabinoside neurotoxicity.

BACKGROUND: The use of high-dose cytosine arabinoside (Ara-C) may be complicated by a characteristic form of cerebellar neurotoxicity. Other reported manifestations of neurologic dysfunction include signs of possible cranial neuropathies, for which a neuropathologic substrate has not been previously reported. METHODS: A 43-year-old man was treated for refractory acute promyelocytic leukemia with a regimen of high-dose Ara-C. He died after dysarthria, ophthalmoplegia, and severe cerebellar neurotoxicity developed. RESULTS: The postmortem examination revealed a peculiar subacute neuronopathy that involved preponderantly brain stem tegmental and spinal motor neurons. The neuronopathy was characterized by hypereosinophilic perikarya and karyolytic nuclei. The perikaryal changes resulted from accumulations of argyrophilic masses of filaments that stained positively with neurofilament antibodies and ultrastructurally were shown to be composed of bundles of intermediate filaments. CONCLUSIONS: This report indicates that Ara-C neurotoxicity, possibly aggravated in our patient by oliguric renal failure, is not confined to the cerebellum but involves cranial nerve and spinal motor neurons, which in turn may explain the cranial neuropathies that sometimes complicate the use of high-dose Ara-C therapy.

Adult↗

[Prevalence of symptoms in selected diagnostic groups in teachers].

In the context of occupational medical screening, teachers in the age groups up to, and older than, 45, were examined under a standardized medical programme in 1987 (22,240) and in 1988 (25,934). The relative risk within these groups for various illnesses was compared with data from investigations with other workers also examined in the former German Democratic Republic (over 400,000 yearly). As was the case for other occupational groups, the most frequently occurring symptoms were related to the musculoskeletal and cardiovascular systems. Teachers in both age categories showed a higher risk for illnesses of the nervous system, especially psychic disturbances and neurosis, and kidney and bladder diseases; male teachers showed a higher risk for cardiovascular diseases, and female teachers for diseases of the respiratory system. Elevated relative risks were already apparent in the group up to 45 years; for diseases of the nervous system the risk increased even further in subjects in the older age category. The proportion of persons overweight was, among female teachers, markedly smaller than in other groups.

Adult↗

[Change in radiation exposure in x-ray diagnosis today?].

The dosage for the single exposure is today from a half to a quarter of the dosage used 20 years ago. The number of diagnostic X-ray examinations performed has increased; this increase concerns mainly patients whose life expectancy is shorter than the latency period to the manifestation of an X-ray induced malignoma and whose reproduction probability is very low. The genetic risk therefore is zero. This was demonstrated for coronary angiography. The dose distribution in the body shows important differences between conventional X-ray diagnostic and computed tomography. One cannot calculate the radiation risk of roentgen diagnostics from a dose applied to the population or from a dose per head of a population. Such a dose is not suitable for comparison with radiation exposure due to natural sources and civilization. The overall risk of disease is not altered by radiation exposure of an adequate roentgen diagnosis method.

Humans↗

[Radiation exposure in computed tomography].

The axial dose profile of various scans of different CTs was determined to obtain specification on radiation geometry by collimation. The dose was measured "free-in-air" by thermoluminescent dosimeters at the axis of rotation. Considerable differences between the various CTs were observed. The scans of different CTs had narrow and wide fields. It seems to be possible to reduce the energy transmitted to the body by appropriate collimation.

Humans↗

A clinical evaluation of frequent replacement contact lenses on patients currently wearing premium reusable daily wear soft contact lenses.

A 3-month clinical investigation was undertaken to evaluate a population of premium reusable daily wear soft contact lens wearers when refitted with soft contact lenses worn on a daily wear schedule and replaced every 2 weeks. In addition to an initial visit, follow-up visits occurred at 2-, 4-, 8-, and 12 weeks. Areas of assessment included vision, lens fitting performance, ocular physiology, subjective comfort and handling responses and lens surface deposits and damage. Of the 51 patients recruited, 50 were successfully trial fit and enrolled. During the course of the investigation, all subjects utilized a multipurpose care regimen without the addition of an enzymatic cleaner. Upon conclusion of the investigation, 75.0 percent of the subjects chose to continue wearing the study lenses on a 2-week frequent replacement basis.

Adult↗

[Acute upper gastrointestinal hemorrhage caused by ruptured aneurysm of the right gastroepiploic artery].

Visceral aneurysms are very rare (0.1% in autopsy-statistics). In our own review of literature we have found only 9 described cases of an aneurysm of the gastroepiploic artery. In the presented case an aneurysm was found when the patient developed an acute upper gastrointestinal bleeding. Due to the high risk of rupture (20% of all visceral aneurysms), which can be either intraperitoneally, intraluminally or into the satellite vein, the treatment should be surgically on finding.

Aged↗

Intracerebral (parenchymal) infusion of methotrexate: report of a case.

This report describes the neuropathological findings in a 32 year old woman with acute myelogenous leukemia (AML) and central nervous system (CNS) involvement, who received a total of 48 mg of methotrexate (MTX) intended to be delivered to the ventricle. At autopsy, the tip of the infusion catheter was found to have been inadvertently placed in the left basal ganglia. The delivery of the MTX at that site caused white matter lesions characteristic of those previously reported in MTX encephalopathy following diverse modes of administration. This case is unusual in that there was the direct infusion of MTX into cerebral parenchyma, circumventing both the blood:brain and cerebrospinal fluid:brain barriers. Axonal abnormalities were widespread in the MTX-infused tissue, frequently but not always accompanied by myelin loss. Since radiation therapy had not been employed, this case permitted the assessment of pathologic changes largely attributable to MTX.

Adult↗

H-CAM expression in the human nervous system: evidence for a role in diverse glial interactions.

H-CAM (CD44/Hermes antigen) is an 85-95 kDa widely-distributed cell surface adhesion molecule that participates in diverse cellular interactions. It is an important cell surface receptor of hyaluronate, and has been implicated in the binding of circulating lymphocytes of endothelial cells in the process of lymphocyte homing. Here we define the immunohistological distribution of H-CAM in the human nervous system as a means of assessing its possible participation in nervous system ontogeny and function. H-CAM is widely expressed in human CNS white matter by subsets of glial cells, and within the neuropil of several grey matter structures. Neurons appear uniformly negative. H-CAM+ cells and processes are first detected at 20 weeks gestation in a diffuse subependymal pattern, and staining of the anchoring processes but not the cortical extensions of radial glia is seen by 24 weeks. Beginning at 26 weeks, H-CAM+ astrocytes also demarcate fascicles of axons in developing white matter tracts, becoming diffusely distributed in all CNS white matter by full term gestation. In the mature CNS, fibrous and subpial astrocytes, glial outlines within the glomeruli of the cerebellar granule cell layer, Bergmann glia, and extraneuronal grey matter matrix in certain locations are H-CAM+. In reactive gliosis occurring in foetal and developed brains, H-CAM is strongly and uniformly expressed by GFAP+ astroglial cells. In the PNS, dorsal roots express substantially higher levels of H-CAM than ventral roots, and there is an accompanying inverse staining pattern displayed by weakly immunoreactive posterior horns and positive anterior horns. Also, there is an abrupt cessation of H-CAM expression at the junction of the central and peripheral segments of cranial nerves. These findings indicate the dynamic regulation of H-CAM expression in the developing human nervous system, and suggest the hyaluronate-binding activity and potentially other cell-cell or cell-matrix adhesive functions of H-CAM may play an important role in development of the nervous system.

Aged↗