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At least 55 records · Page 3Linked to original sources
PubMed2006

Structural basis of carbohydrate recognition by a Man(alpha1-2)Man-specific lectin from Bowringia milbraedii.

The crystal structure of the seed lectin from the tropical legume Bowringia milbraedii was determined in complex with the disaccharide ligand Man(alpha1-2)Man. In solution, the protein exhibits a dynamic dimer-tetramer equilibrium, consistent with the concanavalin A-type tetramer observed in the crystal. Contacts between the tetramers are mediated almost exclusively through the carbohydrate ligand, resulting in a crystal lattice virtually identical to that of the concanavalin-A:Man(alpha1-2)Man complex, even though both proteins have less than 50% sequence identity. The disaccharide binds exclusively in a "downstream" binding mode, with the non-reducing mannose occupying the monosaccharide-binding site. The reducing mannose is bound in a predominantly polar subsite involving Tyr131, Gln218, and Tyr219.

Binding Sites↗
PubMed1986

Rous sarcoma virus-transformed baby hamster kidney cells express higher levels of asparagine-linked tri- and tetraantennary glycopeptides containing [GlcNAc-beta (1,6)Man-alpha (1,6)Man] and poly-N-acetyllactosamine sequences than baby hamster kidney cells.

The alterations in complex-type N-linked oligosaccharides that can occur when an animal cell line is transformed by two dissimilar viruses were examined by comparing the N-linked oligosaccharides of baby hamster kidney (BHK) cells, metabolically radiolabeled with [2-3H]mannose, to the same class of oligosaccharides from BHK cells separately transformed by Rous sarcoma virus (RS-BHK), an RNA retrovirus, and polyoma virus (PY-BHK), a DNA papovavirus. Based on experiments that utilized serial lectin affinity chromatography, glycosidase digestions, and methylation analyses, both RS-BHK and PY-BHK cells demonstrated a significant increase in the relative amounts of tri- and tetraantennary complex-type N-linked oligosaccharides containing the branching sequence, [GlcNAc-beta(1,6)Man-alpha(1,6)Man], compared to the nontransformed BHK cells. In addition, almost all of the poly-N-acetyllactosamine sequence, [GlcNAc-beta(1,3)-Gal-beta(1,4)], was expressed on the tri- and tetraantennary N-linked oligosaccharides from BHK and RS-BHK cells that contain the sequence, [GlcNAc-beta(1,6)Man-beta(1,6)Man]. The increase in the relative amounts of this latter sequence in the transformed cells, therefore, most likely results in an increase in the amount of poly-N-acetyllactosamine sequence on the N-linked glycopeptides of these cells. The analysis of the degree of sialylation of the complex-type N-linked oligosaccharides from BHK and RS-BHK cells by ion exchange chromatography revealed no apparent differences, and in both of these cell types approximately 3% of the glycopeptide fraction radiolabeled with mannose was recovered in a highly negatively charged fraction that was identified by keratanase digestion to be keratan sulfate.

Acetylglucosamine↗
PubMed1997

Activity of UDP-GlcNAc:GlcNAc beta 1-->6(GlcNAc beta 1-->2) Man alpha 1-->R[GlcNAc to Man] beta 1-->4N-acetylglucosaminyltransferase VI (GnT VI) from the ovaries of Oryzias latipes (Medaka fish).

UDP-GlcNAc:GlcNAc beta 1-->(GlcNAc beta 1-->2)Man alpha 1-R[GlcNAc to Man] beta 1-->4N-acetylglucosaminyltransferase VI (GnT VI) activity was shown to be present in crude homogenates of Medaka fish (Oryzias latipes) ovaries using UDP-[14C]GlcNAc and synthetic GlcNAc beta 1-->6 (GlcNAc beta 1-->2)Man alpha 1-->6Glc beta 1-->octyl as substrates. Characterization of this activity showed a pH optimum at about pH 7.0 and an absolute requirement for divalent cations. The optimum concentration of Mn2+ was at about 25 mM. This finding is the first report on GnT VI activity in fish; the enzyme has previously been described only in avian tissues.

Animals↗
PubMed1981

On the pharmacokinetics of domperidone in animals and man III. Comparative study on the excretion and metabolism of domperidone in rats, dogs and man.

The excretion and metabolism of the novel gastrokinetic and antinauseant drug domperidone were studied after oral administration of the 14C-labelled compound to rats, dogs and man, and after intravenous administration to rats and dogs. Excretion of the radioactivity was almost complete within four days. In the three species, the radioactivity was excreted for the greater part with the faeces. Biliary excretion of the radioactivity amounted to 65% of the dose 24 hours after intravenous administration in rats. Unchanged domperidone as determined by radioimmunoassay, accounted in urine for 0.3% in dogs, 0.4% in man, and in faeces for 9% in dogs and 7% in man. The main metabolic pathways of domperidone in the three species were the aromatic hydroxylation at the benzimidazolone moiety, resulting in hydroxy-domperidone -the main faecal metabolite-, and the oxidative N-dealkylation at the piperidine nitrogen, resulting in 2,3-dihydro-2-oxo-1H-benzamidazole-1-propanoic acid the major radioactive urinary metabolite- and 5-chloro-4-piperidinyl-1,3-dihydro-benzimidazol-2-one. In urine the two first metabolites were present partly as conjugates. A mass balance for the major metabolites in urine, faeces, bile and plasma samples was made up after radio-HPLC (reverse-phase HPLC with on-line radioactivity detection) of various extracts. Only minor species differences were detected.

Adult↗
PubMed1999

The stiff man and stiff man plus syndromes.

Rigidity in the setting of continuous motor unit activity at rest can be caused by a variety of central and peripheral conditions. A central origin is suggested by the presence of painful reflex spasms. Focal spinal lesions and infective causes are relatively easily excluded through imaging, microbiological and serological studies. There then remain a group of patients who may have the classical 'stiff-man syndrome' or a related syndrome. When strict diagnostic criteria are used, patients with the stiff man syndrome uniformly have axial rigidity, and about 90% are found to have antibodies against glutamic acid decarboxylase. Treatment response and prognosis are excellent. Stiff persons with 'plus' signs, particularly those with rigidity of a distal limb, are unlikely to have the classical stiff man syndrome. They have a poorer treatment response and prognosis. Some have a paraneoplastic aetiology, while a non-malignant autoimmune basis seems likely in others. Those in whom post-mortem pathology findings are available usually are seen to have had an encephalomyelitis with prominent involvement of the grey matter. Clinically, stiff persons with 'plus' signs may be divided into three groups according to the aggressiveness of the pathology and its relative distribution. Encephalomyelitis with rigidity follows a relentless subacute course, leading to death within 3 years. Chronic cases may present with predominantly brainstem involvement, including generalised myoclonus (the 'jerking stiff person syndrome') or spinal cord involvement, dominated by stiffness and spasm in one or more limbs (the 'stiff limb syndrome').

Encephalomyelitis↗
PubMed1994

Waardenburg syndrome in man and splotch mutants in the mouse: a paradigm of the usefulness of linkage and synteny homologies in mouse and man for the genetic analysis of human congenital malformations.

The use of chromosomal segments with conserved homologous linkage groups found in different species provides one method of predicting the location of genes causing congenital malformations in man. For example, homology between man and mouse involves 241 homologous autosomal genes spread on 68 homologous chromosomal segments. In addition, the similarities of phenotypic expression of human congenital malformations and mouse mutations indicate the possible involvement of an homologous gene implicated during ontogeny of the two species. The identification of a single gene defect in the mouse and comparative mouse-human gene mapping provides therefore another approach for selecting candidate loci for inborn error of morphogenesis in man. Further molecular studies can then be performed to show that the loci are identical. The human Waardenburg syndrome and the splotch (Sp) mouse mutant represent the first example of the potential of this approach for the understanding of human congenital malformations at the molecular level.

Animals↗
PubMed1998

Identification of Man alpha1-3Man alpha1-2Man and Man-linked phosphate on O-mannosylated recombinant leech-derived tryptase inhibitor produced by Saccharomyces cerevisiae and determination of the solution conformation of the mannosylated polypeptide.

The production of recombinant leech-derived tryptase inhibitor (rLDTI) by two different strains of Saccharomyces cerevisiae resulted in the secretion of non-glycosylated and glycosylated rLTDI. Monosaccharide analysis and a-mannosidase treatment demonstrated that glycosylated rLDTI was exclusively alpha-mannosylated. A trypsin digest of reduced and S-carboxymethylated glycosylated rLDTI was separated on a reverse-phase HPLC column. Glycopeptides identified by a combination of matrix-assisted laser desorption mass spectrometry, amino acid sequence analysis, and monosaccharide analysis revealed the presence of different glycoforms. It was found that Ser24, Ser33 and Ser36 were partially glycosylated with a single mannose residue, whereas Thr42 in glycosylated rLDTI from both strains was fully occupied with manno-oligosaccharides with a degree of polymerization ranging over 1-3 and 1-13 depending on the yeast strain. In phosphorylated rLDTI a single phosphate group was predominantly located at the innermost Man residue of units of mannobiose, mannotriose, mannotetraose and mannopentaose at Thr42. Oligosaccharides released by alkaline treatment were reduced by sodium borohydride and separated by high-pH anion-exchange chromatography on a CarboPac MA1 column, and analyzed by one- and two-dimensional 1H-NMR spectroscopy. Besides the major oligosaccharide Man alpha1-2Man-ol, the (for yeast protein O-glycosylation) unusual Man alpha1-3Man alpha1-2Man-ol was determined. The solution conformation of glycosylated rLDTI was investigated by two-dimensional NMR spectroscopy. Structure calculations by means of distance geometry showed that glycosylated rLDTI is compactly folded and contained small secondary structure elements. Analysis of the chemical shifts showed that amino acids Val32-Ser33, Ser36-Ser39 and Thr42 were affected by the O-mannosylation. In addition, changes in chemical shift were observed within the beta-hairpin peptide regions Val13-Ser16 and Gly18-Tyr21 attributed to direct interactions of the mannose residue at Ser36. Furthermore, the protein-linked oligosaccharides were spatially grouped in a position opposite of the canonical binding loop.

Amino Acid Sequence↗
PubMed1984

Man's man/ladies' man: motifs of hypermasculinity.

Hypermasculine character styles are commonly encountered in clinical practice, popular media imagery and, indeed, in everyday life. Such "hypermasculinity" is readily recognized as an exaggeration and distortion of traditionally masculine traits, and has been studied by Adler (1923), Freud (1937), Reich (1949), Ovesey (1969), and Stoller and Herdt (1982), among others. In this article, I will review those contributions and identify and elucidate two modal forms of hypermasculinity: the Man's Man and the Ladies' Man. I will argue that these two patterns constitute recognizable forms of character pathology with their own understandable developmental paradigms, intrapsychic conflicts and object ties. A developmentally based model for the evolution of hypermasculinity will be proposed, and the implications of these concepts explored.

Adult↗
PubMed1985

Natural and radiation-induced cataracts in man and mouse, and natural macular degeneration in man: proposed mechanisms.

A unified theory of growth and age-dependent disorders is applied to the interpretation of epidemiological data for natural and radiation-induced cataracts and natural macular degeneration in man. Using the same unified theory, mechanisms are also proposed to explain the experimental evidence for natural and radiation-induced lenticular opacities in the lens of the mouse. Epidemiological and experimental data are strikingly consistent with the hypothesis that natural cataract formation is an autoaggressive process but the details of pathogenesis differ greatly between the two species. Radiation dose-response relations reflect these contrasts. Lenticular opacities in the nuclear-bomb survivors at Hiroshima and Nagasaki were probably induced by a 'single-track' mechanism. Radiation-induced generalised opacification in the lens of the mouse results from a 'multi-track' process. The pathogenesis of natural macular degeneration in man happens to have close parallels with that of natural opacification in the mouse. We discuss some implications of these inferences for the phenomenon of radiation-induced lethal disorders in man.

Age Factors↗
PubMed2006

Early midline interactions are important in mouse optic chiasm formation but are not critical in man: a significant distinction between man and mouse.

The optic chiasm is one of the most popular models for studying axon guidance. Here axons make a key binary decision either to cross the midline to innervate the contralateral hemisphere or to remain uncrossed. In rodents, midline interactions between axons from the two eyes are critical for normal development, as early removal of one eye systematically disrupts hemispheric projections from the remaining eye, increasing the crossed projection at the expense of the uncrossed. This is similar to the abnormal decussation pattern seen in albinos. This pattern is markedly different in marsupials where early eye removal has no impact on projections from the remaining eye. These differences are related to the location of the uncrossed projection through the chiasm. In rodents these axons approach the midline whereas in marsupials they remain segregated laterally. We provide anatomical evidence in man suggesting that, unlike in rodents, uncrossed axons are confined laterally and do not mix in each hemi-chiasm, which is a pattern similar to that found in marsupials. Further, we demonstrate electrophysiologically, using visual cortical evoked potentials, that the failure of one eye to develop in man has no impact on the hemispheric projections from the remaining eye. These data demonstrate that the mechanisms regulating chiasmal development in man differ from those in rodents but may be similar to those in marsupials. We suggest that mouse models of the organization and development of the optic chiasm are not common to placental mammals in general.

Adolescent↗
PubMed1998

Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity.

OBJECTIVE: To investigate whether the stiff limb syndrome may be separated from the stiff man syndrome and progressive encephalomyelitis with rigidity on simple clinical grounds, and whether such a distinction has implications for aetiology, treatment, and prognosis. METHODS: Twenty three patients referred over a 10 year period with rigidity and spasms in association with continuous motor unit activity, but without evidence of neuromyotonia, extrapyramidal or pyramidal dysfunction or focal lesions of the spinal cord were reviewed. The patients were divided into those with an acute or subacute illness, leading to death within 1 year, and those with a chronic course. The latter were divided into those in whom rigidity and spasms dominated in the axial muscles, or in one or more distal limbs, at the time of their first assessment. RESULTS: This simple division identified three distinct groups of patients. (1) Progressive encephalomyelitis with rigidity: two patients had a rapidly progressive condition characterised by widespread rigidity which resulted in death within 6 and 16 weeks. One patient had negative anti-GAD and anti-neuronal antibodies, but had markedly abnormal CSF and widespread denervation. The principal pathological findings in this case were a subacute encephalomyelitis which primarily affected the grey matter. In the remaining patient anti-GAD antibodies were not tested, and postmortem was refused. (2) Stiff man syndrome: eight patients had rigidity and painful spasms of the lumbar paraspinal, abdominal, and occasionally proximal leg muscles associated with a lumbar hyperlordosis. There was no involvement of the upper limbs, distal lower limbs, sphincters or cranial nerves. Seven had anti-GAD antibodies and most had additional evidence of autoimmune disease. Neurophysiologically there was continuous motor unit activity with abnormal exteroceptive reflexes, but a normal interference pattern during spasms. The patients all responded to baclofen/diazepam and remained ambulant. (3) Stiff limb syndrome: thirteen patients had rigidity, painful spasm, and abnormal postures of the distal limb, ususphincter or brainstem involvement. Generalised myoclonic jerks were not a feature. Only two had truncal rigidity, and another two had anti-GAD antibodies. Most had no evidence of autoimmune disease. Neurophysiologically they had continuous motor unit activity in the affected limb, abnormal exteroceptive reflexes, and abnormally segmented EMG activity during spasms. The disease ran a protracted course, and most patients had only a partial response to baclofen or diazepam. About half became wheelchair bound. CONCLUSIONS: The stiff limb syndrome seems distinct from the stiff man syndrome or progressive encephalomyelitis with rigidity, and is an important cause of rigidity and spasm in the setting of continuous motor unit activity.

Adult↗
PubMed1983

Description and simulation of a physiological pharmacokinetic model for the metabolism and enterohepatic circulation of bile acids in man. Cholic acid in healthy man.

A multicompartmental pharmacokinetic model based on physiological principles, experimental data, and the standard mathematical principles of compartmental analysis has been constructed that fully describes the metabolism and enterohepatic cycling in man of cholic acid, a major bile acid. The model features compartments and linear transfer coefficients. The compartments are aggregated into nine spaces based on physiological considerations (liver, gallbladder, bile ducts, jejunum, ileum, colon, portal blood sinusoidal blood, and general circulation). The transfer coefficients are also categorized according to function: flow, i.e., emptying of gallbladder or intestinal spaces, and circulation of the blood; biotransformation, i.e., conjugation, deconjugation, or dehydroxylation; and transport, i.e., active or passive transport. The model is made time dependent by introducing meals, which trigger discrete increases in gallbladder emptying and intestinal flow. Each space contains three compartments. For cholic acid, these are unconjugated cholic acid, cholylglycine, and cholyltaurine. The model was then used with all existing experimental data to simulate cholic acid metabolism in healthy man over a 24-h period. Satisfactory agreement was obtained between simulated and experimental results for serum bile acid levels, hepatic bile acid secretion, and bile acid secretion into the intestine. The model was also used to classify 16 clinical instances in which the enterohepatic circulation of bile acids is altered by drugs or disease. The model can be extended to describe completely the metabolism and enterohepatic circulation of any bile acids in man in health and digestive disease. The model should also be broadly applicable to the description of the pharmacokinetics of all other drugs whose metabolism is similar to that of bile acids, i.e., drugs for which there are tissue and bacterial biotransformations, enterohepatic cycling, and appreciable first-pass clearance.

Bile Acids and Salts↗
PubMed1976

The use of a molluscicide in conjunction with chemotherapy to control Schistosoma haematobium at the Barombi Lake foci in Cameroon. II. Urinary examination methods, the use of niridazole to attack the parasite in man, and the effect on transmission from man to snail.

The use of niridazole, in conjunction with snail control, in an attempt to control the transmission of Schistosoma haematobium at 2 Cameroon crater-lake villages is described. Quantitative examinations of urines for S. haematobium eggs were made on the whole population before control began, at intervals during the maintenance of control, and again after control ceased. The methods and difficulties are described, and their accuracy is discussed. After each examination all accessible egg-passers were treated or re-treated with niridazole. The drug was well tolerated and effective. Most treated patients ceased to pass live eggs, and most of those who later became positive again were thought to represent reinfections rather than relapses. During the maintenance of snail control, niridazole treatment of the 'whole' community reduced the total load of S. haematobium eggs passed to less than 1 per cent of the pre-control figure; and repeated subsequent treatments maintained a level of the same order. Despite this, there remained at different times 0.6-50.9 per cent of persons passing small quantities of live eggs, and these were an important source of continuing transmission. The possibility that more than one strain of S. haematobium was involved is discussed. An index of transmission from man to snail is proposed and discussed in relation to determining the level of the "break-point" in transmission. Although combined niridazole/molluscicide control reduced transmission from man to snail by about 3 log cycles, the "break-point", which is thought to lie 4 or more log-cycles lower, was not reached. When control was stopped, transmission built up again, with the prevalence rate in man rising more rapidly than the intensity of infections.

Adolescent↗
PubMed1976

[Experimental inoculation of Leishmaniasis tropical from man to man (author's transl)].

Experimental transformation of leishmaniasis from man to man was demonstrated. The infection occurs through direct inoculation of the leishmania organism in the amastigote form: from an ulcer of a leishmania papule some materials were obtained and were inoculated intradermally in the thigh of one of the authors. Within weeks a red papule has developed in the place of inoculation from which the microorganisms were frequenctly demonstrated. The papule was cured spontaneously within 70 weeks under a formation of a flat pigmented scar. In the electronenmicroscopy the microorganisms were seen to be located intracellular. The microorganism had a double outer membrane, an oval nucleus, and a kinetoplast out of which (in the phlebotomus fly or in the culture) the future flagellum would be formed.

Humans↗
PubMed1976

Evaluation and re-evaluation of genetic radiation hazards in man. II. The arm number hypothesis and the induction of reciprocal translocations in man.

The arm number hypothesis proposed by Brewen and collagues in 1973 has been examined in the light of information thus far available from mammalian studies. In experiments with peripheral blood lymphocytes (radiation in vitro), a linear relationship between dicentric yield and the effective chromosome arm number of the species was obtained in the mouse, Chinese hamster, goat, sheep, pig, wallaby and man. However, the data are not consistent with such a relationship in several primate species (marmoset, rhesus monkey, cynomolgus monkey, squirrel monkey and the slow loris), the cat and the dog. In the rabbit, the data are conflicting. In the mouse and Chinese hamster the frequencies of reciprocal translocations recorded in spermatocytes descended from irradiated spermatogonia are in line with the expectation based on the arm number hypothesis, whereas in the golden hamster, rabbit and the rhesus monkey they are not. In man and the marmoset, the limited data are not inconsistent with a 2-fold higher sensitivity of these species relative to the mouse although they do not rule out a difference as high as 4-fold. In the guinea-pig, the situation is unclear. New data on the transmission of reciprocal translocations in mice suggest that the frequency in the F1 progeny may be close to one-quarter of that recorded in the spermatocytes of the irradiated fathers (spermatogonial irradiation) at an exposure level of 150 R, whereas at higher exposures, the reduction factor is about one-eighth, the latter being in line with the earlier finding. All these results taken together suggest that inter-specific extrapolation from the radiosensitivity of somatic cells (to dicentric induction) to that of germ cells (to translocation induction) is fraught with uncertainity at present. Certain aspects that need to be studied in more detail in the context of induced chromosome aberrations are discussed.

Animals↗
PubMed1990

500-picosecond molecular dynamics in water of the Man alpha 1----2Man alpha glycosidic linkage present in Asn-linked oligomannose-type structures on glycoproteins.

Molecular dynamics simulations of the Man alpha 1----2Man alpha glycosidic linkage found in the N-linked glycans of glycoproteins were performed in vacuo and in the presence of water. In the latter case significant dampening of the molecular fluctuations was found when compared to the in vacuo simulation. A 500-ps dynamics simulation in water showed only occasional short-lived deviations from the minimum-energy conformation, more consistent with carbohydrate "breathing" than flexibility. These studies add further evidence that oligosaccharides can maintain "fixed" geometries with relatively long lifetimes and are in agreement with experimental NMR-derived parameters for the same linkage in oligomannose structures.

Carbohydrate Conformation↗
PubMed1990

A molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man alpha 1-3Man beta 1-4GlcNAc.

A molecular mechanical force field is described for the conformational analysis of oligosaccharides. This force field has been derived by the addition of new parameters to the AMBER force field and is compatible with simulations of proteins. This new parametrization is assessed by comparison of the theoretically predicted conformations of Man alpha 1-3Man beta 1-4GlcNAc with the corresponding crystal structure. Molecular dynamics simulation data are presented for this structure both in vacuo and with the explicit inclusion of water molecules. While the former demonstrate significant torsional oscillations about glycosidic linkages at physiological temperature, in the latter these oscillations are highly damped due to the stabilizing influence of a "cage" of solvent-solvent and solvent-solute hydrogen bonds.

Carbohydrate Conformation↗