Population kinetics of chromosomally abnormal human fibroblast subpopulations

The proportion of cells with clonally derived chromosome rearrangements has been recorded at different passage levels in 16 lines of human fibroblast cultures derived from adults. All abnormal clone populations regonized at the lowest passge levels showed a stable or declining frequency relative to the normal cells, although 2 out of the 21 clones detected did show a transient increase. Only 2 clones were found at higher passage levels that were not previously identified at low passge. The observed selection against cells with rearrangements may reflect a general property of chromosome organization which ensures that cytogenetic abnormalities do not normally accumulate in rapidly dividing tissues.     

Treatment of vulvovaginal candidiasis in pregnancy. A comparative study

A carefully controlled comparative study showed miconazole nitrate 2% vaginal cream (Monistat) to be a highly effective agent in the treatment of vaginal candidiasis in pregnant subjects. Miconazole nitrate was significantly more effective than nystatin (Mycostatin) in the treatment of vaginal candidiasis in all three trimesters of pregnancy, and also more effective regardless of whether the candidal infection was primary or recurrent. Observations relating to the safety of this therapy during pregnancy were made and discussed.     

Low-Cycle fatigue properties of a SiC Whisker-reinforced 2124 aluminum alloy

Low-cycle fatigue microcracking leading to failure of smooth specimens of a powder metallurgy (PM) 2124 aluminum alloy reinforced with 20 vol pct SiC whiskers was studied. The crack size near the onset of unstable growth was inferred to be 50 to 70 μm in the stress amplitude range of the present study (400 to 600 MPa,R = −1) from observations of the fracture surfaces of the specimens. This corresponds to stress intensities between 1/3 to 1/2 typical values ofK _1c or 1/4 to 1/9 the critical length predicted fromK _1c values of 12 to 14 MPa√m. The microcrack size distributions and growth data were obtained from the low-cycle fatigue specimens at various stages of fatigue, using a surface replica technique. During continued cycling, microcracks formed and were lost through linkage with other cracks. At the same time, the fraction of small cracks (<5 μm) decreased, while that of larger cracks (>5 μm) increased. The total number of cracks increased with increasing numbers of cycles. Typical microcrack growth rates were determined to bedb/dn = (3.57 to 6.11) × 10⁻¹⁰ (Δ/K)^2.2to2.48 in the lateral direction of the crack, andda/dn = (5.83 to 13.0) × 10⁻¹¹ (ΔK)^{1.54 to 1.60} in the depth direction of the crack.     

Speech processors for cochlear prostheses

The authors review considerations in the design of speech processors for cochlear prostheses. To illustrate issues of processor design, two fundamentally different processing strategies are described in terms of the information that they can convey and in terms of how they might perform under various conditions on nerve survival. A summary is presented of clinical tests comparing these strategies in eight implant patients. Key findings from the comparison studies are that (a) one processor (the interleaved pulse processor) is clearly superior for patients with psychophysical signs of poor nerve survival, (b) another processor (the compressed analog processor) may be superior for patients with signs of good survival, and (c) different processing strategies can produce widely different outcomes for individual patients. Future directions in the future development of speech processors for cochlear prostheses are outlined     

Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product

Single chain Fv chimeric receptors, or T-bodies, are described with intracellular sequences comprising the costimulatory signaling domain of CD28 in series with the zeta-chain from the TCR complex. Using an engineered human single chain Fv derived from P67, an mAb with specificity for human CD33, and a spacer comprising an Ab hinge region with either Fcgamma or part of the CD28 extracellular region, fusion molecules were constructed to test the ability of single chain designs to mediate both primary signaling and costimulation from one extracellular binding event. Constructs with the CD28 signaling domain proximal and the zeta-chain distal to the membrane were found to express more efficiently in Jurkat than constructs with the opposite orientation and were capable of mediating up to 20 times more IL-2 production on stimulation with solid phase Ag when compared with transfectants expressing chimeric receptors with zeta-chain intracellular signaling domains only. IL-2 production was specific to Ag challenge and was completely inhibited by incubation with free Ab of the same specificity as the extracellular binding site of the construct, but not by an isotype-matched control Ab. The CD28 intracellular domain of these fusion proteins was shown to be capable of binding the p85 subunit of phosphatidylinositol 3'-kinase. These constructs represent the first of a new generation of single gene multidomain chimeric receptors capable of mediating both primary and costimulatory signaling specifically from a single extracellular recognition event.     

Thermal conductivity and isotopic impurities in single crystals of helium

We have utilized the enhancement of thermal conductivity by Poiseuille flow of the phonon gas to obtain highly sensitive measurements of phonon scattering by isotopic impurities in single crystals of helium. Crystal orientation, size, and quality may be inferred from the thermal conductivity data themselves. Our hcp ⁴ He crystals were grown at a constant pressure of 85.1 atm using apparatus and techniques that made possible some control over crystal orientation. An isotopic impurity concentration of 1.0×10^–5 decreases the peak conductivity in these crystals by a factor of 1.9 along a direction perpendicular to thec axis. In the Poiseuille region a relaxation time limit has been achieved experimentally that allows our data to be fitted as a function of temperature and concentration with only one parameter. The observed scattering strength is a factor of 2.7 greater than can be explained in terms of mass-defect scattering alone. A number of current theories are examined in the light of this result. Our pure ⁴ He data strongly support aT ^–3 dependence for the normal-process relaxation time. Measurements of the thermal conductivity parallel to thec axis reveal no anisotropy in either the normal-process relaxation time or the isotopic scattering strength.This work was supported in part by the National Science Foundation and the Office of Naval Research.     

Some characteristics of new tissue-binding proteins for metabolites of vitamin D other than 1,25-dihydroxyvitamin D

Protein(s) have been found in a wide range of tissues which have a high affinity for 25-hydroxycholecalciferol. Of the tissues examined only erythrocytes do not have this protein. The properties of the protein have been examined and it has been found that the association constatns range from 2 - 10(9) to 5 - 10(9) M-1 and the sedimentation constants between 5.0 and 6.0 S. It was not possible to distinguish the proteins from the different tissues by their S values, mobility on gel electrophoresis or behaviour on ion-exchange chromatography. These techniques were all used, however, to show that the tissue 25-hydroxycholecalciferol binding protein is distinct from the main plasma binding protein for this steroid and from the intestinal 1,25-dihydroxycholecalciferol-binding protein. A protein has been in the plasma of rachitic animals but not of normals, which is apparently indistinguishable from this new tissue 25-hydroxycholecalciferol-binding protein. The steroid specificity of this new binding protein has been shown to be dependent upon a C-25 hydroxyl group, and an intact conjugated double bond system. Possible functions for this protein have been briefly discussed.