Automated microscopic image analysis and the prognosis of preneoplasms and carcinomas of the mammary gland

Studies of preneoplasias and carcinomas of the mammary gland have been conducted by means of automated microscopic image analysis, on the basis of previous results as well as with references to the international literature, for 2 purposes: 1. Determination in the context of a clinical follow-up study of the individual carcinoma risk for patients with proliferative fibrocystic breast disease (mastopathy) and 2. Preparation of an objective automated grading of ductal breast carcinomas for better assessment of prognosis. Against the background of the assumption that the majority of carcinomas and precancerous lesions of the breast originate from the terminal ductal lobular unit, an effort is made to determine, independent severity of the mastopathy, the biological valence of solid, cribriform, and papillary ductal epithelial proliferations (no, possible or inevitable preneoplasia). Proliferation patterns without and with atypical features are checked for their similarity with intraductal and invasive carcinomas (similarity principle) and are additionally examined for differences, depending on localization and distance from tumour (topological principle). Automated histological tumour grading is to distinguish with greater subtlety within the large heterogeneous group of moderately differentiated carcinomas and is to objectify and thus facilitate the difficult task of delimitation of moderately and poorly differentiated carcinomas. Nuclear grading will be the major basis for classification along these lines. Objectified and reproducible tumour grading is believed to be extremely helpful in better prognostication of breast cancer.     

Influence of phloem transport, N-fertilization and ion accumulation on sucrose storage in the taproots of fodder beet and sugar beet

To investigate the factors governing the accumulation of sucroseand amino acids in the taproots of sugar beet, their contentswere measured in the leaves, phloem sap and the taproots ofsugar beet, fodder beet and a hybrid between both, grown oneither 3.0 or 0.5 mM nitrate. In the taproots the contents ofmalate, citrate and inorganic ions were also determined. Forthe high sucrose accumulation in sugar beet as compared to theother varieties three factors were found. (a) In sugar beet,less amino acids and more sucrose are taken up into the phloemthan in fodder beet. (b) In sugar beet, the sucrose and aminoacid syntheses are less sensitive to the nitrate concentrationsthat are required for optimal plant growth than in other varieties.In fodder beet, upon raising the nitrate concentration from0.5 mM to 3 mM, the synthesis and storage of sucrose is decreasedand that of amino acids increased. The corresponding valuesin sugar beet (0.5 mM) are similar to those in fodder beet andare not much affected by an increase of nitrate. (c) The sucroseaccumulation is limited by the accumulation of inorganic ionsin the taproots. The sucrose content in the taproots is negativelycorrelated to the total ion content. Whereas sucrose representstwo-third of all solutes in the taproots of sugar beet, it amountsto only one-third of the solutes in fodder beet taproots. Key words: Amino acids, Beta vulgans L, phloem sap, potassium, sucrose storage, sugar beet, taproots, transport     

Molekularbiologie der Mukoviszidose

Mukoviszidose ist eine angeborene Funktionsstörung der exokrinen Körperdrüsen. Sie kommt bei etwa 1 : 2500 Lebendgeborenen in der weißen Bevölkerung Europas und Nordamerikas vor und gehört damit zu den häufigsten lebensbedrohlichen Erbkrankheiten des Menschen. Dennoch sind vollständige Beschreibungen des Krankheitsbildes erst seit etwas mehr als fünfzig Jahren bekannt. Die bei den meisten Mukoviszidosekranken auftretenden fibrotischen Veränderungen (Fibrose - Vermehrung des Bindegewebes) der Bauchspeicheldrüse haben zu der Bezeichnung cystic fibrosis of the pancreas geführt, so daß auch der Name zystische Fibrose (cystic fibrosis, CI) heute synonym gebräuchlich ist. Wir wollen im folgenden in kurzer Form auf die Symptome und Ursachen der Erkrankung eingehen. Eine ausführlichere Darstellung der Mukoviszidose und ihrer molekularbiologischen Grundlagen mit zahlreichen Literaturhinweisen ist kürzlich aktualisiert und erweitert worden [21].     

Kinetics of phospholipid exchange between bilayer membranes

In an accompanying publication by Duckwitz-Peterlein, Eilenberger and Overath ((1977) Biochim. Biophys. Acta 469, 311–325) it is shown that the exchange of lipid molecules between negatively charged vesicles consisting of total phospholipid extracts from Escherichia coli occurs by the transfer of single lipid monomers or small micelles through the water. Here a kinetic interpretation is presented in terms of a rate constant, $\text{k}{}_{\mathrm{?}}$, for the escape of lipid molecules from the vesicle bilayer into the water. The evaluated rate constants are $\text{k}{}_{\mathrm{?}}{}^{\mathrm{<mtext>P</mtext>}}\text{= (0.86 ± 0.05) · 10}{}^{\mathrm{?5}}\text{s}{}^{\mathrm{?1}}$ and $\text{k}{}_{\mathrm{?}}{}^{\mathrm{<mtext>E</mtext>}}\text{= (1.09 ± 0.13) · 10}{}^{\mathrm{?6}}\text{s}{}^{\mathrm{?1}}$ for phospholipid molecules with $\text{trans-}\text{Δ}{}^9\text{-hexadecenoate}$ and $\text{trans-}\text{Δ}{}^9\text{-octadecenoate}$, respectively, as the predominant acyl chain component. The rate constants are discussed in terms of the acyl chain and polar head group composition of the lipids.     

Endosome-lysosome fusion at low temperature

Based on an initial study (Dunn, W. A., Hubbard, A. L., and Aronson, Jr., N. N. (1980) J. Biol. Chem. 255, 5971-5978), low temperature is often used to selectively inhibit fusion between endosomes and lysosomes. Here we have tried to characterize the nature of this inhibition. In addition to endocytic contents markers, we have used a covalent membrane marker to measure the interaction between endosomes and lysosomes over extended periods of time at low temperature. Mouse macrophage cells (P388D1) and human skin fibroblasts were enzymatically labeled with radioactive galactose to provide a covalent marker for plasma-membrane glycoconjugates. Subsequent endocytic membrane traffic for 24 h at 16 degrees C resulted in a significant transfer of membrane marker, as well as of endocytic contents marker, to high density lysosomes, as observed by subcellular fractionation. The kinetics of this transfer have been analyzed for macrophages using the membrane marker, horseradish peroxidase as fluid-phase, and iodinated acetyl low density lipoprotein as receptor-mediated endocytic contents marker. Transfer to lysosomes occurred only about 6 h after application of the respective marker at 16 degrees C. When transfer to lysosomes was initiated by 15 min preincubation at 37 degrees C, subsequent cooling to 16 degrees C did not inhibit ongoing transfer which continued with the same kinetics as when observed after the lag phase. These results show that low temperature delays an unidentified pre-fusion step, but does not inhibit endosome-lysosome fusion as such.