Structural analysis of substrate binding by the molecular chaperone DnaK

DnaK and other members of the 70-kilodalton heat-shock protein (hsp70) family promote protein folding, interaction, and translocation, both constitutively and in response to stress, by binding to unfolded polypeptide segments. These proteins have two functional units: a substrate-binding portion binds the polypeptide, and an adenosine triphosphatase portion facilitates substrate exchange. The crystal structure of a peptide complex with the substrate-binding unit of DnaK has now been determined at 2.0 angstroms resolution. The structure consists of a beta-sandwich subdomain followed by alpha-helical segments. The peptide is bound to DnaK in an extended conformation through a channel defined by loops from the beta sandwich. An alpha-helical domain stabilizes the complex, but does not contact the peptide directly. This domain is rotated in the molecules of a second crystal lattice, which suggests a model of conformation-dependent substrate binding that features a latch mechanism for maintaining long lifetime complexes.     

A comparison of porosity, fabric and fractal dimension as predictors of the Young''s modulus of equine cancellous bone

Ependymomas are rare neuroectodermal tumors arising from ependymal cells of the ventricular system, choroid plexus, filum terminale, and central canal of the spinal cord (1,2). This review focuses on intracranial ependymomas with special emphasis on pathology, etiology, cytogenetic characteristics, and adjuvant radiation therapy. Recent advances in neurosurgical technique, radiation therapy, and molecular biology have affected management of these tumors and have the potential to increase long-term cure rates. The role of highly advanced radiation therapy techniques such as stereotactic radiosurgery will need to be better defined.     

Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells

Taxoids and other microtubule-damaging drugs are known to induce Bcl2 phosphorylation at the G2-M phase of the cell cycle, with concomitant apoptosis in malignant cells derived from a variety of human malignancies, including leukemia, lymphoma, and breast and prostate cancer. We have investigated the ability of another antineoplastic drug, dolastatin 10, in inducing Bcl2 phosphorylation and apoptosis. We also investigated the effects of a phosphatase inhibitor okadaic acid in the regulation of Bcl2 phosphorylation, cell cycle arrest, and programmed cell death. Moreover, site-directed mutagenesis studies were performed to determine the specific serine residue(s) responsible for drug-induced Bcl2 phosphorylation. Our results indicate that these antimicrotubule agents or okadaic acid can induce posttranslational modification (phosphorylation) of Bcl2 protein at multiple serine residues. Interestingly, mutation of a serine residue at position 70 to alanine can significantly decrease drug-induced posttranslational modification (phosphorylation) of Bcl2 protein. Apparently, Ser70 seems to be a critical site for drug-induced posttranslational modification (phosphorylation) of the Bcl2 protein.     

Factors affecting outcome in hypoxic-ischemic encephalopathy in term infants

Forty-nine term infants were prospectively shown to have hypoxic-ischemic encephalopathy (HIE). All infants survived the neonatal period, and all but two infants (seen at 12 months) were followed up to at least 27 months of age. Factors that significantly correlated with outcome included the Sarnat encephalopathy stage and the occurrence of intractable seizures not controlled by phenobarbital sodium alone. There was no association between the one- or five-minute Apgar score, the need for early ventilation, the EEG, the occurrence of seizures, and the subsequent outcome. There was no significant difference in outcome for those infants who received dexamethasone sodium phosphate (n = 29) v those who did not receive the drug (n = 20). A review of 97 term infants with HIE from a regional perinatal program during a one-year period (1979), including 35 of the 49 infants in the present study, did show a significant increase in morbidity and mortality for transported infants.     

Effect of galactose and sugar substitutes on blood insulin levels in normal and obese individuals

Eighteen male patients between the ages of 25 and 50 were given on a double blind randomized basis (A) 40 gms. galactose (B) 50 gms. arabinogalactan and 0.11 gm. sodium saccharin (C) 2 gm. methyl cellulose and 0.083 gm. sodium saccharin and (D) 4 gm. galactose, all in 200 ml water. Blood glucose, galactose and insulin levels were determined during a six hour period before and after ingestion. The three first mentioned solutions tasted equally sweet, the fourth was essentially tasteless. None of these feedings altered plasma insulin or glucose levels. It appears that in contrast to other conclusions reached by earlier investigators sweet taste is unable to induce insulin secretion through neurogenic pathways.     

Isolation of a spotted fever group rickettsia from the Pacific Coast tick, Ixodes pacificus, in Oregon

A rickettsia of the spotted fever group was isolated on three occasions from Ixodes pacificus in western Oregon. These isolations, and additional evidence furnished by complement fixation tests on guinea pigs inoculated with other Oregon ticks of this species, indicate that the association of this rickettsia with the Pacific Coast tick may be widespread. This is the first isolation of a spotted fever group rickettsia from I. pacificus. Because the Oregon isolates are mildly virulent for guinea pigs they resemble the Western U and Rickettsia montana strains of rickettsiae. However, preliminary evidence from cross-immunofluorescence tests of mouse antisera suggests the Tillamook and Grants Pass strains are antigenically different from all known spotted fever group agents.