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PubMed1995

The hydrophobic mannoside Man alpha 1-6Man alpha 1-S-(CH2)7-CH3 acts as an acceptor for the UDP-Gal:glycosylphosphatidylinositol anchor alpha 1,3-galactosyltransferase of Trypanosoma brucei.

The variant surface glycoproteins (VSGs) of Trypanosoma brucei are attached to the plasma membrane via a glycosylphosphatidylinositol (GPI) membrane anchor. This anchor contains the core sequence ethanolamine-PO4-6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol, which is conserved in all GPI anchors, and a unique alpha Gal side chain attached to the 3-position of the alpha Man residue adjacent to the alpha GlcN residue. Here we report that trypanosome membranes can catalyse the transfer of Gal from UDP-Gal to the hydrophobic thioglycoside Man alpha 1-6Man alpha 1-S-(CH2)7-CH3. Characterization of the galactosylated products by electrospray mass spectrometry, exoglycosidase digestion and periodate-oxidation studies revealed that the major product was Man alpha 1-6(Gal alpha 1-3)Man alpha 1-S-(CH2)7-CH3. The similarity of this product to part of the mature VSG GPI anchor suggests that the thioglycoside is able to act as an acceptor for the trypanosome-specific UDP-Gal-GPI anchor alpha 1,3-galactosyltransferase.

Animals↗
PubMed1979

Is a man, a man, a man? (or: is an EEG, an EEG, an EEG?) some remarks on the homogeneity of "normal subjects".

Many studies involving computerized EEG analyses are based on the assumption that normal subjects constitute a homogeneous population, so that under specified conditions across-subject averaging is justified. Quite often EEG signals are processed with little or no concern for the state of the particular person from whom they are obtained. It is the purpose of this discussion to draw attention to the fact that only can normals have different EEG's one from another, but also that the same ones can display markedly different EEGs from recording session to recording session. A consequence of this situation is that there is always a large between-subject variability, and that the source of the signals needs to be carefully documented before generalizations can be made.

Adult↗
PubMed2002

Site-specific discrimination by cyanovirin-N for alpha-linked trisaccharides comprising the three arms of Man(8) and Man(9).

Cyanovirin-N (CVN) is a novel cyanobacterial protein that selectively binds with nanomolar affinities the mammalian oligosaccharides Man(8) and Man(9). Consequently, CVN potently blocks HIV entry through highly avid carbohydrate-mediated interactions with the HIV-envelope glycoprotein gp120, and is under preclinical investigation as an anti-HIV microbicide. CVN contains two non-overlapping carbohydrate-binding sites that bind the disaccharide Manalpha(1-2)Manalpha (which represents the terminal disaccharide of all three arms of Man(9)) with low to sub-micromolar affinities. The solution structure of a 1:2 CVN:Manalpha(1-2)Manalpha complex revealed that CVN recognizes the stacked conformation of Manalpha(1-2)Manalpha through a deep hydrophilic-binding pocket on one side of the protein (site 2) and a semi-circular cleft on the other (site 1). With the prominent exception of the C1 hydroxyl group of the reducing mannopyranose ring, the bound disaccharide is positioned so that each hydroxyl group is involved in a direct or water-mediated hydrogen bond to the polar or charged side-chains comprising the binding pocket. Thus, to determine whether the next-most reducing mannopyranose ring will augment CVN affinity and selectivity, we have characterized by NMR and ITC the binding of CVN to three synthetic trisaccharides representing the full-length D1, D2 and D3 arms of mammalian oligomannosides. Our findings demonstrate that site 1 is able to discriminate between the three related trisaccharides methyl Manalpha(1-2)Manalpha(1-2)Man, methyl Manalpha(1-2)Manalpha(1-3)Man and methyl Manalpha(1-2)Manalpha(1-6)Man with remarkable selectivity, and binds these trisaccharides with K(A) values ranging from 8.1x10(3)M(-1) to 6.6x10(6)M(-1). Site 2 is less selective in that it binds all three trisaccharides with similar K(A) values ranging from 1.7 to 3.7(+/-0.3)x10(5)M(-1), but overall binds these trimannosides with higher affinities than site 1. The diversity of pathogenic organisms that display alpha(1-2)-linked mannosides on their cell surfaces suggests a broad defensive role for CVN in its cyanobacterial source.

Amino Acid Sequence↗
PubMed2001

Solution structure of a cyanovirin-N:Man alpha 1-2Man alpha complex: structural basis for high-affinity carbohydrate-mediated binding to gp120.

BACKGROUND: Cyanovirin-N (CVN) is a novel, 11 kDa cyanobacterial protein that potently inhibits viral entry by diverse strains of HIV through high-affinity carbohydrate-mediated interactions with the viral envelope glycoprotein gp120. CVN contains two symmetry-related carbohydrate binding sites of differing affinities that selectively bind to Man(8) D1D3 and Man(9) with nanomolar affinities, the carbohydrates that also mediate CVN:gp120 binding. High-resolution structural studies of CVN in complex with a representative oligosaccharide are desirable for understanding the structural basis for this unprecedented specificity. RESULTS: We have determined by multidimensional heteronuclear NMR spectroscopy the three-dimensional solution structure of CVN in complex with two equivalents of the disaccharide Manalpha1-2Manalpha, a high-affinity ligand which represents the terminal-accessible disaccharide present in Man(8) D1D3 and Man(9). The structure reveals that the bound disaccharide adopts the stacked conformation, thereby explaining the selectivity for Man(8) D1D3 and Man(9) over other oligomannose structures, and presents two novel carbohydrate binding sites that account for the differing affinities of the two sites. The high-affinity site comprises a deep pocket that nearly envelops the disaccharide, while the lower-affinity site comprises a semicircular cleft that partially surrounds the disaccharide. The approximately 40 A spacing of the two binding sites provides a simple model for CVN:gp120 binding. CONCLUSIONS: The CVN:Manalpha1-2Manalpha complex provides the first high-resolution structure of a mannose-specific protein-carbohydrate complex with nanomolar affinity and presents a new carbohydrate binding motif, as well as a new class of carbohydrate binding protein, that facilitates divalent binding via a monomeric protein.

Amino Acid Sequence↗
PubMed1999

Man alpha1-2 Man alpha-OMe-concanavalin A complex reveals a balance of forces involved in carbohydrate recognition.

We have determined the crystal structure of the methyl glycoside of Man alpha1-2 Man in complex with the carbohydrate binding legume lectin concanavalin A (Con A). Man alpha1-2 Man alpha-OMe binds more tightly to concanavalin A than do its alpha1-3 and alpha1-6 linked counterparts. There has been much speculation as to why this is so, including a suggestion of the presence of multiple binding sites for the alpha1-2 linked disaccharide. Crystals of the Man alpha1-2 Man alpha-OMe-Con A complex form in the space group P2(1)2(1)2(1) with cell dimensions a = 119.7 A, b = 119.7 A, c = 68.9 A and diffract to 2. 75A. The final model has good geometry and an R factor of 19.6% (Rfree= 22.8%). One tetramer is present in the asymmetric unit. In three of the four subunits, electron density for the disaccharide is visible. In the fourth only a monosaccharide is seen. In one subunit the reducing terminal sugar is recognized by the monosaccharide site; the nonreducing terminal sugar occupies a new site and the major solution conformation of the inter-sugar glycosidic linkage conformation is adopted. In contrast, in another subunit the non reducing terminal sugar sits in the so called monosaccharide binding site; the reducing terminal sugar adopts a different conformation about its inter-sugar glycosidic linkage in order for the methyl group to access a hydrophobic pocket. In the third subunit, electron density for both binding modes is observed. We demonstrate that an extended carbohydrate binding site is capable of binding the disaccharide in two distinct ways. These results provide an insight in to the balance of forces controlling protein carbohydrate interactions.

Carbohydrate Conformation↗
PubMed1972

The organization of day-care environments: "zone" versus "man-to-man" staff assignments.

In a large day-care center, measures of group participation were used to compare how much of a child's time is lost from planned activities during the daily transition from lunch, through the bathroom and dressing areas, to the nap area. Participation measures were taken using the "Zone" and "Man-to-Man" staffing procedures, two typical methods for dividing responsibility among teaching staff. In the "Zone" procedure, each teacher was assigned responsibility for a particular area, and for all children who passed through that area. In the "Man-to-Man" procedure, each teacher was assigned responsibility for shepherding a group of designated children through all activity areas during each transition. The Lunch-to-Nap transition using the Zone staffing assignment was accomplished with a smaller decrease in child participation in planned activities than the transition utilizing the Man-to-Man procedure. Thus, other things being equal, it is recommended that the Zone procedure be used in group-care programs with more than one staff member, with each teacher being responsible for specific activity areas, rather than specific children.

Journal Article↗
PubMed1976

Morphological cerebral asymmetries of modern man, fossil man, and nonhuman primate.

Cerebral asymmetries are common in modern and fossil man and the great apes. Those occurring most often are listed here: 1. The left sylvian fissure in man is longer than the right and in both fetal and adult brains the posterior end of the right sylvian fissure is commonly higher than the left. Associated with these findings, the left planum temporale is usually longer than the right. 2. The left occipital pole is often wider and usually protrudes more posteriorly than the right. 3. The left lateral ventricle, and especially the occipital horn, is usually larger than the right. 4. If one frontal pole extends beyond the other it is usually the right. 5. On X-ray computerized axial tomograms (CT) of the brain the right frontal lobe and the central portion of the right hemisphere more often measure wider than the left. 6. The CT studies commonly show a Yakovlevian anticlockwise torque (taking the nose as 12 o'clock), with the left occipital pole longer and often extending across the midline toward the right and a wider right hemisphere in its central and frontal portions and frequent forward protrusion of the right frontal pole. This is found also in newborns. 7. The posterior end of the sagittal sinus usually lies to the right of the midline and the sinus flows more directly into the right transverse sinus than into the left. 8. The right transverse sinus is usually higher than the left. 9. In left-handed and ambidextrous individuals the posterior ends of the sylvian fissures are more often nearly equal in height and the occipital regions are more often equal in width or the right may be wider. 10. The torque of the pyramidal tract and the hemispheral torque cannot at present be related to right- or left-handedness. Statistics concerning left-handedness are somewhat confounded, because it is likely that not a few individuals are left-handed because of an early injury of the left hemisphere in a normally right-handed individual. 11. Cerebral asymmetries are found in fossil man similar to those in modern man. 12. Asymmetries of the sylvian fissures similar to those of modern man have been found in the great apes and are particularly common in the orangutan. 13. The most striking and consistently present cerebral asymmetries found in adult and fetal brains are in the region of the posterior end of the sylvian fissures-- the areas generally regarded as a major importance in language function.

Adolescent↗
PubMed1979

Bismuth toxicity in man II. Review of bismuth blood and urine levels in patients after administration of therapeutic bismuth formulations in relation to the problem of bismuth toxicity in man.

A survey of the leterature on bismuth toxicity in man in relation to blood level data, has revealed the necessity of distinguishing between lipid soluble and water soluble organic complexes of bismuth on the one hand and the simple inorganic salts of bismuth on the other hand. A characteristic feature of the former, illustrated by the water soluble bismuth complex triglycollamate, is the high bismuth levels (due to absorption of the complex as such) and the nephrotoxic properties of the compound in man. Bismuth absorption after administration of the simple inorganic salts of bismuth is postulated to occur in the form of ionic bismuth as such, low bismuth levels being characteristic features of such compounds. Bismuth blood and urine levels obtained from patients after administration of a new anti-ulcer drug (Bicitropeptide) in a well controlled clinical trial are discussed and suggest that that this bismuth containing drug behaves pharmacologically in a manner similar to the inorganic bismuth salts in man, low bismuth blood levels and the absence of toxic side effects being conspicuous features of the drug. Based on these considerations, it is proposed that the pharmacologically active bismuth compounds be divided into four different groups depending on structure, stability and solubility. The question as to what constitutes a "toxic bismuth blood level" can only be discussed in relation to the new proposed sub-division of bismuth compounds and is only meaningful if the term is defined to relate only to ionic bismuth (presumably bound to a large extent to blood proteins). Based on information gleaned from the literature and blood level values reported in the clinical trial referred to, it is suggested that bismuth blood level values below 50 micrograms/ml are highly unlikely to be associated with meaningful toxicity in man. Finally, attention is drawn to the reversibility of bismuth toxicity in man as reported by many authors irrespective of the type of bismuth compound concerned.

Animals↗
PubMed1997

Enzymatic syntheses of GlcNAc beta 1-2Man and Gal beta 1-4GlcNAc beta 1-2Man as components of complex type sugar chains.

GlcNAc beta 1-2Man and GlcNAc beta 1-6Man were synthesized using the reverse hydrolysis activity of beta-N-acetylglucosaminidase from both jack beans and Bacillus circulans. In turn, Gal beta 1-4GlcNAc beta 1-2Man and Gal beta 1-4GlcNAc beta 1-6Man were synthesized regioselectively using the transglycosylation activity of beta-galactosidase from Diplococcus pneumoniae and B. circulans, respectively. These di- and trisaccharides are important components of complex type sugar chains and will be used as intermediates in our synthetic studies.

Acetylglucosaminidase↗
PubMedDate not supplied

Man to Man prostate cancer support groups.

PURPOSE: In this report, the authors describe Man to Man prostate cancer support group characteristics and functioning to identify ways to strengthen the program as it expands nationally and internationally. DESCRIPTION OF STUDY: A mail survey of 38 groups in Florida collected data on group meeting practices, facilitator background, training, and perceived needs, and on participant characteristics and satisfaction with the group. Descriptive statistics and bivariate analyses of survey data were performed. RESULTS: Typical groups included both survivors and significant others, met on a monthly basis, and followed a format that combined educational content with sharing of personal experiences. Facilitators and participants alike were typically retired white men in their 60s and 70s from well-educated professional backgrounds, who joined the groups after undergoing treatment for prostate cancer. High levels of satisfaction with the program's organization and functioning were reported. Perceived needs were in the areas of increasing access to support services, achieving a more diverse membership, and better outreach to newly diagnosed patients. CLINICAL IMPLICATIONS: Healthcare professionals can play a key role in informing newly diagnosed prostate cancer patients about the availability of support groups in their communities. Earlier referral to support groups would enhance patients' access to shared experiences and resources for guidance in treatment decisions. Greater attention to psychosocial issues in Man to Man support groups might better meet the emotional needs of patients and families.

Adult↗