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Dissociation of human chorionic gonadotropin into its free subunits is dependent on naturally occurring molecular structural variation, sample matrix and storage conditions.

Measurement of human chorionic gonadotrophin (hCG) is used in many areas of clinical medicine. Recent interest has focused on the stability of this molecule and its fragments during sample storage. In the body hCG is degraded and removed by specific metabolic processes which begin while the molecule is in the bloodstream. In particular, the receptor binding loop of the beta subunit is cut or 'nicked', initiating a catabolic cascade. Furthermore, the extent and nature of glycosylation is believed to have a significant influence on this process. In these studies we incubated seven glycoforms of hCG, each with different degrees of 'nicking', in phosphate-buffered saline, serum, defibrinated blood and urine from healthy non-pregnant women, under varying conditions. Degradation was expressed as the molar increase in free beta subunit. Under all conditions there was a steady dissociation of hCG over time, the process being more rapid at higher temperatures. 'Nicked' hCG dissociated more rapidly than did non-'nicked' hCG. Glycosylation reduced the rate of dissociation. Dissociation was most rapid in urine and buffer solutions, and slowest in serum and defibrinated blood.

Chorionic Gonadotropin↗

A monoclonal antibody recognizes structural variation in cystic fibrosis alpha 2-macroglobulin.

alpha 2-Macroglobulin (alpha 2M) is a major plasma protease inhibitor that has been studied because of its suggested role in the pathology of cystic fibrosis (CF). A panel of monoclonal antibodies specific for human alpha 2M were produced and screened for their ability to bind to a number of human alpha 2M samples. We have used these antibodies to characterize individual antigenic sites in this protein. alpha 2M was purified from plasma by polyethylene glycol precipitation followed by zinc chelate chromatography. A total of 23 alpha 2M samples in the native configuration, as well as the nucleophile-treated configuration, were screened by the panel of 18 monoclonal antibodies in an enzyme-linked immunosorbent assay procedure. Five of the samples tested were from individuals with cystic fibrosis. alpha 2M from family members of two of these patients was subsequently tested for reactivity with the monoclonal antibodies. One antibody, SAM94, exhibited a significant difference in binding to alpha 2M obtained from CF patients as compared with control individuals. This difference was particularly apparent in the binding of SAM94 to the nucleophile-treated CF alpha 2M; SAM94 showed significantly reduced binding to four of five unrelated CF individuals (p less than 0.005) and three of four cystic fibrosis obligate heterozygotes (p less than 0.005).

Antibodies, Monoclonal↗

Effects of structural variation on Young's modulus of non-human cancellous bone.

The modulus of elasticity of cubes of cancellous bone, tested in three orthogonal directions, was measured along with apparent density, fabric (measured using image analysis techniques), connectivity and mineral volume fraction. Multiple regression was used to relate Young's modulus and the explanatory variables. The most important explanatory variable was apparent density; fabric was also important. Connectivity was highly correlated with apparent density, and so it is difficult to assign relative weights to these two variables. However, both have a significant, and separate, effect on Young's modulus. The total variance in Young's modulus explained by these three variables was about 85 per cent. This implies that other explanatory variables are either unimportant or highly correlated with the variables listed above. Mineral volume fraction is shown to be an unimportant variable, and arguments are produced why this is to be expected, even though it is highly important in explaining the variation in Young's modulus of compact bone.

Animals↗

Structural variations in the jugular foramen of the human skull.

The jugular foramen was examined in 300 Anatolian skulls from the 17th and 18th centuries. In 61.6% the foramen was larger on the right and in 26% on the left, with the remainder being of almost equal size. An obvious dome caused by a superior jugular bulb was present bilaterally in 49%, on the right only in 36%, on the left only in 6%; it was absent bilaterally in 10.3%. Complete bony septation occurred in 5.6% on the right and in 4.3% on the left, partial septation was observed in 2.6% on the right and in 19.6% on the left. Another foramen which is completely separated by a spicule of bone and which transmits the inferior petrosal sinus was present in 5.6% of skulls on the right and in 4.6% on the left.

Cranial Nerves↗

[Study on structural variation of nucleolar organizer regions (NOR) and the satellite association (SA)].

To further illustrate the biological significance of variant NOR (including double NOR--dNOR and triple NOR--tNOR) and satellite association (SA) and the relationship to meiotic non-disjunction (NDJ), this study was carried out in the normal population and the parents of patients with Down Syndrome (DS). Of 800 individuals, 4 dNOR carriers, two of them from the control and two from the non-informative experiments were detected. SA data for 3 out of the 4 dNOR carriers showed no statistical significant increase in SA when dNOR was present in the cell even in case 4 where two dNOR were found in one cell. However, ease 3 demonstrated significant decrease in SA when dNOR was present, although it showed that the overall incidence of dNOR was higher in this carrier than that in the other three. It is concluded that dNOR can be detected on any acrocentric chromosome and not be related to NDJ of chromosome, which is a heritable variant that does not affect phenotype and that there are two kinds of dNOR variants, one being from the translocation of the short arm of acrocentric chromosome, the other from non-translocation.

Adult↗

Structural variations and growth potential of Yersinia enterocolitica under different culture conditions.

The growth potential and the polypeptide composition of Yersinia enterocolitica serotype 0:3 isolated from patients with uncomplicated diarrhoea, reactive arthritis or septicemia were evaluated under different culture conditions. The expression of polypeptides varied with presence of the virulence-associated 40-48 Mdal plasmid, growth medium, growth temperature and gas composition of the culture (air, carbon dioxide, oxygen). Also the initial growth medium at 26 degrees C, before temperature shift to 37 degrees C, influenced the subsequent growth potential and expression of polypeptides. The plasmid encoded at least 7 polypeptides. This plasmid also inhibited the multiplication of bacteria under defined culture conditions. The dominating plasmid-encoded polypeptides were optimally expressed in air or oxygen-supplemented growth medium. The majority of the chromosomally encoded polypeptides were expressed independently of presence of the plasmid, whereas the expression of at least 8 were repressed by the plasmid. Five chromosomally encoded polypeptides were expressed only in carbon dioxide and five only in oxygen environment. These results indicate that Y. enterocolitica may express different molecules in different environments in vivo. This may be of importance for host-parasite relationship and immune response.

Bacterial Proteins↗