Genetic determinants of bone mass.

A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1alpha1, TGF-beta1, interleukin-6, calcitonin receptor, alpha2-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, beta3-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.     

Fast-atom-bombardment mass spectra of enkephalins.

The positive- and negative-ion mass spectra of [methionine]enkephalin and [leucine]enkephalin have been obtained by using a fast-atom-bombardment source described previously by Barber, Bordoli, Sedgwick & Tyler [(1981) J. Chem. Soc. Chem. Commun., in the press]. This technique has allowed the spectra to be obtained without conversion of the enkephalins into volatile derivatives. The fast-atom-bombardment spectra show good pseudo-molecular-ion sensitivity and fragmentation that can be interpreted on the basis of the known molecular structure.     

Correlation between skeletal calcium mass and muscle mass in man.

The measurements of total body potassium (TBK) and calcium (TBCa) were made on 317 subjects by the techniques of whole-body counting and total-body neutron activation analysis (TBNAA), respectively. The TBK/TBCa ratios are constant for normals over the age range studied. The males have more cellular mass (TBK) per unit skeletal mass (TBCa) than the females, as indicated by their respective TBK/TBCa ratios, 0.122 +/- 0.008 (1 SD), and 0.100 +/- 0.007 (1 SD). In general, patients with various metabolic disorders tend to follow the physiological trend found in the normals. In a number of metabolic disorders, the loss of TBK was usually approximately 60% of that of the TBCa when expressed in terms of the predicted normal values. This suggests that the mechanism causing the loss of calcium in physiological and altered metabolic states simultaneously involves both the skeleton and its associated musculature.     

An unusual pontine mass lesion.

A 27-year-old Puerto Rican man presented to Yale-New Haven Hospital with a six-week history of left-sided headache, diplopia, and drooping of the left side of his face. Cerebrospinal fluid examination showed a lymphocytic pleocytosis and a CT scan of the brain revealed an unusual intrapontine mass lesion requiring systemic antifungal therapy. This case emphasizes many of the diagnostic and therapeutic considerations required for effective therapy of fungal disease in the central nervous system.     

淡水螺类去壳干重和无灰干重的换算方法

软体动物的生物量常用带壳湿重表示,然而外壳的主要成分是碳酸钙,不宜计为生物量,去壳干重和无灰干重相对更接近真实生物量,但其测量过于繁琐,因此有必要建立一套简单易行的方法对这2种干重生物量进行换算.选择长江流域常见的6种淡水螺类（环棱螺、长角涵螺、纹沼螺、大沼螺、方格短沟蜷和萝卜螺）,对其螺壳的5个形态参数和带壳干湿重与去壳干重和无灰干重的关系进行了研究.结果表明：这6种螺类的5个形态参数与去壳干重和无灰干重的回归关系均为指数式（y=ax^b）,其中,壳宽和壳长的换算效果（预测值与实测值间的百分误差率均值分别为22.0%和22.5%）好于其他参数;带壳湿重可通过方程直接换算为去壳干重和无灰干重（百分误差率均值为21.7%）.从概念的内涵和换算误差表明,无灰干重是表示螺类生物量的最适参数.     

Applications of mass spectrometry to DNA sequencing.

The ability of the mass spectrometer to analyze collectively the masses of DNA fragments that are produced in the Sanger procedure for sequencing may allow the gel electrophoresis step to be eliminated. On the other hand, if gel electrophoresis is required, the use of resonance ionization spectroscopy coupled to a mass spectrometer may enable much faster analysis of DNA bands labeled with stable isotopes. Other combinations of labeling of the DNA and its mass spectrometric analysis with or without gel electrophoresis are also considered. Recent advances in these areas of mass spectrometry are reviewed.     

Characterization of peptide-oligonucleotide heteroconjugates by mass spectrometry.

Two peptide-oligothymidylic acids, prepared by joining an 11 residue synthetic peptide containing one internal carboxyl group (Asp side chain) to amino-linker-5'pdT6 and amino-linker-5'pdT10 oligonucleotides, were analyzed by matrix-assisted laser desorption/ionization (MALDI) on a linear time-of-flight mass spectrometer and by electrospray ionization (ESI) on a triple-quadrupole system. These synthetic compounds model peptide-nucleic acid heteroconjugates encountered in antisense research and in studies that use photochemical crosslinking to investigate molecular aspects of protein-nucleic acid interactions. MALDI and ESI sensitivities for the two hybrid compounds were found to be similar respectively to their sensitivities for the pure oligonucleotide parts. In general, MALDI proved to be less affected by sample impurities and more sensitive than ESI, while ESI on the quadrupole produced greater mass accuracy and resolution than MALDI on the time-of-flight instrument. A hybrid's behavior in a MALDI-matrix or an ESI-spray-solvent was found to be governed mainly by the oligonucleotide. A single positive ESI tandem mass spectrum of the peptide-dT6 accounted for the heteroconjugate's entire primary structure including the point of the oligonucleotide's covalent attachment to the peptide.     

Mutation-tolerant protein identification by mass spectrometry.

Database search in tandem mass spectrometry is a powerful tool for protein identification. High-throughput spectral acquisition raises the problem of dealing with genetic variation and peptide modifications within a population of related proteins. A method that cross-correlates and clusters related spectra in large collections of uncharacterized spectra (i.e., from normal and diseased individuals) would be very valuable in functional proteomics. This problem is far from being simple since very similar peptides may have very different spectra. We introduce a new notion of spectral similarity that allows one to identify related spectra even if the corresponding peptides have multiple modifications/mutations. Based on this notion, we developed a new algorithm for mutation-tolerant database search as well as a method for cross-correlating related uncharacterized spectra.