THE "BOUND" WATER OF BIOLOGICAL COLLOIDS: A REPLY

The objection by Bull to the estimation of bound water by ultrafiltration, because of an assumed adsorption of the reference substance, has been found invalid for glucose. No adsorption of glucose by the proteins, casein and gelatin, could be detected. The estimation of the bound water of proteins from the probable surface adsorption of water by proteins leads to only a small value.     

Die physikalische Chemie der Eiweissk?rper

Ohne Zusammenfassung(Deutsche Übertragung von FrauElse Asher.)Einige Abschnitte, die für diesen Teil bestimmt waren, mussten wegen Krankheit des Autors, und, um die Veröffentlichung nicht zu verzögern, auf den später erscheinenden zweiten Teil verschoben werden.Die Herausgeber.     

Vereine,Anstalten, Unternehmungen

Ohne Zusammenfassung     

Mental retardation and abnormal skeletal development (Dyggve-Melchior-Clausen dysplasia) due to mutations in a novel,evolutionarily conserved gene

Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC) are similar, rare autosomal recessive osteochondrodysplasias. The radiographic features and cartilage histology in DMC and SMC are identical. However, patients with DMC exhibit significant developmental delay and mental retardation, the major features that distinguish the two conditions. Linkage studies localized the SMC and DMC disease genes to chromosome 18q12-21.1, providing evidence suggesting that they are allelic disorders. Sequence analysis of the coding exons of the FLJ90130 gene, a highly evolutionarily conserved gene within the recombination interval defined in the linkage study, identified mutations in SMC and DMC patients. The affected individuals in two consanguinous DMC families were homozygous for a stop codon mutation and a frameshift mutation, respectively, demonstrating that DMC represents the FLJ90130-null phenotype. The data confirm the hypothesis that SMC and DMC are allelic disorders and identify a gene necessary for normal skeletal development and brain function.     

Polymerase chain reaction detection of Cytauxzoon felis from field-collected ticks and sequence analysis of the small subunit and internal transcribed spacer 1 region of the ribosomal RNA gene

Cytauxzoon felis produces a disease in domestic cats in the Midwest (U.S.A.), which often leads to a fatal outcome. Although the clinical disease process is well described, there are still many unanswered questions about this organism. For example, it is unknown whether species of ticks other than Dermacentor variabilis can serve as vectors for transmission. With recent reports of surviving cats from limited geographic areas, another relevant question is the potential for genetically less virulent organism strains. This study evaluated 352 individual or pooled tick samples (1,362 total ticks) for the presence of C. felis small subunit ribosomal RNA and internal transcribed spacer 1 (ITS-1) region genes using a polymerase chain reaction (PCR). These ticks were collected from dogs and cats in several Missouri counties, including 10 from cats diagnosed with cytauxzoonosis. Only 3 positive C. felis samples were identified in Amblyomma americanum nymphs, and there was very limited genetic variation noted in both genes. The small number of positive samples did not allow the study to determine which PCR analysis was more sensitive. This is the first known report of ITS-1 gene identification and sequencing for C. felis. It is also the first published investigation of genetic variation in C. felis.     

Apolipoproteins C-II and C-III inhibit selective uptake of low- and high-density lipoprotein cholesteryl esters in HepG2 cells

Plasma low- and high-density lipoproteins (LDL and HDL) are cleared from the circulation by specific receptors and are either totally degraded or their cholesteryl esters (CE) are selectively delivered to cells by receptors such as the scavenger receptor class B type I (SR-BI). The aim of the present study was to define the effect of apoC-II and apoC-III on the uptake of LDL and HDL by HepG2 cells. Stable transformants were obtained with sense or antisense strategies that secrete 47-294% the normal level of apoC-II or 60-200% that of apoC-III. Different levels of secreted apoC-II or apoC-III had little effect on LDL and HDL protein degradation by HepG2 cells. However, compared to controls, cells under-expressing apoC-II showed a 160% higher capacity to selectively take up HDL-CE, while cells under-expressing apoC-III demonstrated 70 and 160% higher capacity to take up CE from LDL and HDL, respectively. In experiments conducted with exogenously added apoC-II or apoC-III, no significant effect was observed on lipoprotein-protein association/degradation; however, LDL-CE and HDL-CE selective uptake was significantly reduced in a dose-dependent manner. These results indicate that apoC-II and apoC-III inhibit CE-selective uptake.     

Specific inhibition of the plasmodial surface anion channel by dantrolene

The plasmodial surface anion channel (PSAC), induced on human erythrocytes by the malaria parasite Plasmodium falciparum, is an important target for antimalarial drug development because it may contribute to parasite nutrient acquisition. However, known antagonists of this channel are quite nonspecific, inhibiting many other channels and carriers. This lack of specificity not only complicates drug development but also raises doubts about the exact role of PSAC in the well-known parasite-induced permeability changes. We recently identified a family of new PSAC antagonists structurally related to dantrolene, an antagonist of muscle Ca++ release channels. Here, we explored the mechanism of dantrolene's actions on parasite-induced permeability changes. We found that dantrolene inhibits the increased permeabilities of sorbitol, two amino acids, an organic cation, and hypoxanthine, suggesting a common pathway shared by these diverse solutes. It also produced parallel reductions in PSAC single-channel and whole-cell Cl- currents. In contrast to its effect on parasite-induced permeabilities, dantrolene had no measurable effect on five other classes of anion channels, allaying concerns of poor specificity inherent to other known antagonists. Our studies indicate that dantrolene binds PSAC at an extracellular site distinct from the pore, where it inhibits the conformational changes required for channel gating. Its affinity for this site depends on ionic strength, implicating electrostatic interactions in dantrolene binding. In addition to the potential therapeutic applications of its derivatives, dantrolene's specificity and its defined mechanism of action on PSAC make it a useful tool for transport studies of infected erythrocytes.