Biochemical bone marrow markers and their significance in postmenopausal osteoporosis--a new method in the diagnosis of osteoporosis?]

This study analyzes the qualification of biochemical markers in the diagnosis of osteoporosis and evaluates the potential of a multiparametric classification of premenopausal and non-osteoporotic as well as osteoporotic postmenopausal women, which is based on biochemical marker profiles. For this evaluation data of 29 women in the age between 28-74 years were used. The classification of osteoporosis was done by the trabecular density of the lumbar spine using qCT-measurements. The biochemical markers of formation and resorption AP, bAP, OC, ucOC, PICP, PYD, DPD, NTX, BSP and vitamin K were analyzed on day 1 and 42 in all patients. For vitamin K we found significant distribution differences between non-osteoporotic and osteoporotic women (p<0.005). The crosslinks PYD and DPD showed weakly significant differences. All other parameters exhibited non-significant results. Vitamin K acted with a sensitivity of 64% and a specificity of 82%. The used multiparameter classification process improved sensitivity and specificity considerably. The parameter profiles of OC/PYD, vitamin K/PYD and vitamin K/bAP revealed the highest sensitivities with specificities of more than 82%.     

Seven New Mutations in hMSH2, an HNPCC Gene, Identified by Denaturing Gradient-Gel Electrophoresis

Hereditary nonpolyposis colorectal cancer (HNPCC) is a relatively common autosomal dominant cancer-susceptibility condition. The recent isolation of the DNA mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) responsible for HNPCC has allowed the search for germ-line mutations in affected individuals. In this study we used denaturing gradient-gel electrophoresis to screen for mutations in the hMSH2 gene. Analysis of all the 16 exons of hMSH2, in 34 unrelated HNPCC kindreds, has revealed seven novel pathogenic germ-line mutations resulting in stop codons either directly or through frameshifts. Additionally, nucleotide substitutions giving rise to one missense, two silent, and one useful polymorphism have been identified. The proportion of families in which hMSH2 mutations were found is 21%. Although the spectrum of mutations spread at the hMSH2 gene among HNPCC patients appears extremely heterogeneous, we were not able to establish any correlation between the site of the individual mutations and the corresponding tumor spectrum. Our results indicate that, given the genomic size and organization of the hMSH2 gene and the heterogeneity of its mutation spectrum, a rapid and efficient mutation detection procedure is necessary for routine molecular diagnosis and presymptomatic detection of the disease in a clinical setup.     

Coaction of three factors controlling chlorophyll and anthocyanin synthesis

In a three-factor analysis the rate of chlorophyll a (Chl) accumulation in excised mustard cotyledons was studied as a function of kinetin, light (operating through phytochrome, P _fr) and an excision factor. It was found that the three factors operate additively provided that the P _fr level is high enough. When the P _fr level is below approximately 1 per cent (<0.01) the effectiveness of the excision factor decreases while the effect of kinetin remains additive. The observed additivity is explained by a model where the three factors operate independently through a common intermediate (presumably 5-aminolevulinate) in the biosynthetic chain leading to Chl. With regard to the coaction of the excision factor and phytochrome it is concluded that the production of the excision factor requires the operation of phytochrome (even though saturated at a low P _fr level) while the action of the excision factor is independent of phytochrome. This conclusion was confirmed by experiments in which the rate of light-mediated anthocyanin synthesis was measured in excised mustard cotyledons. The effect of excision in the case of anthocyanin formation differs kinetically from the effect of excision on Chl formation.Abbreviations Chl chlorophyll(ide) a - P _fr far-red absorbing form of phytochrome - P _fr/P _tot ratio at photoequilibrium - RL red light - FR far-red light - GL green light - RG9 light long wavelength far-red light - WL white light     

Different handling of parathyrin by basal-lateral and brush-border membranes of the bovine kidney cortex.

The two parts of the bovine kidney cortex plasma membrane, the basal-lateral and the brush-border membrane, were simultaneously prepared from the same organ. Both types of membrane bound parathyrin, but only from the basal-lateral fraction was the hormone displaceable by its bioactive N-terminal fragment. In parallel, parathyrin-stimulated adenylate cyclase was predominantly found in basal-lateral membranes. The hormone was fragmented by both membrane types. Basal-lateral membranes generated fragments with a rather uniform size distribution (somewhat smaller than the intact peptide) and apparently preferred the hormone itself as a substrate. In contrast, the fragments produced by brush-border membranes were numberous small peptides.     

The interaction of methemoglobin and modified poly-(hydroxyethylmethacrylates) studied by spectroscopic methods

The interaction between methemoglobin (MetHb) and macroporous matrices on the basis of polymethacrylates was investigated by means of optical and e.p.r. spectroscopy. The spectroscopic data show that the adsorption of MetHb to imidazole-containing matrices occurs by complex formation between matrix-bound imidazole and the iron of the prosthetic group, with all 4 polypeptide chains of the MetHb molecule being included in the interaction. The adsorption to hydrophobic side chains containing matrices leads, via the protein-matrix interaction, to considerable disturbances of iron protoporphyrin IX in equilibrium or formed from protein-contacts, which are of general importance with respect to the functional variablity and control, respectively, of iron porphyrins in hemoproteins. In case of matrix containing n-hexyl groups deoxyHb is oxidized by O2 to MetHb, instead of being oxygenated to HbO2. Not all prosthetic groups are able to bind N-3. With the increase in hydrophobicity of the matrix a conformational change is enforced leading in the beta-chains to the direct interaction between iron and sulfur of cysteine (beta-cys 92), as it is proved in all cytochrome P-450 and other model compounds.     

Opsonizing effect of serum and albumin gland extracts on the elimination of human erythrocytes from the circulation of Helix pomatia

The removal of human erythrocytes of the A₁ and B types from the circulation of the gastropod Helix pomatia follows an exponential curve. The elimination of the nonself particles is apparently dependent on serum opsonins as preincubation of A₁ and B erythrocytes in Helix serum increases the rate of their clearance. This conclusion is supported by our finding that secondary doses of nonsensitized A₁ erythrocytes injected 12–19 hr after a similar primary dose are cleared very slowly; however, the clearance rate returns to normal if erythrocytes comprising the second dose are preincubated with Helix serum. Furthermore, the elimination of second-dose A₁ erythrocytes is strongly enhanced after their pretreatment with agglutinating extracts of the albumin glands from H. pomatia and Cepaea (Helix) nemoralis. On the other hand, no opsonizing effect was obtained by pre-incubating A₁ erythrocytes in the agglutinating extract of the sponge Aaptos papillata.     

Continuous Synthesis of (R)-(+)-Benzaldehydecyanohydrin Using (R)-Oxynitrilase in Lyotropic Liquid Crystals

The possibility of using the enzyme (R)-Oxynitrilase in a biphasic lyotropic liquid crystal/dibutylether system has been demonstrated. This reaction system is applicable for the continuous production of (R)-benzaldehydecyanohydrin in a fixed bed reactor. The optical purity was between 94 and 96% ee and independent of the flow rate. The space time yield was maximal (2650 g/(1*d)) at a flow rate of 1.6 ml/min.     

Digital roentgen analysis as a tool for kinematic studies of the shoulder--a study of radiation dosage

The radiation exposure during biomechanical investigation of the shoulder joint done with a digital radiography system (Polytron 1000 VR - Siemens) was measured experimentally. Total radiation dose and surface dose were determined by phantom measurements. The radiation exposure per image is about 1/6 to 1/7 of that of a conventional study. The digital radiography system used is thus suitable for kinesiologic studies of large joints in healthy volunteers.