PubMed Health⌕ Search

Biomedical subjects

F Drake

Publications and source records attributed to F Drake.

9 recordsLinked to original sources
PubMed2005

Lick Observatory Optical SETI: targeted search and new directions.

Lick Observatory's Optical SETI (search for extraterrestrial intelligence) program has been in regular operation for 4.5 years. We have observed 4,605 stars of spectral types F-M within 200 light-years of Earth. Occasionally, we have appended objects of special interest, such as stars with known planetary systems. We have observed 14 candidate signals ("triple coincidences"), all but one of which are explained by transient local difficulties. Additional observations of the remaining candidate have failed to confirm arriving pulse events. We now plan to proceed in a more economical manner by operating in an unattended drift scan mode. Between operational and equipment modifications, efficiency will more than double.

Astronomical Phenomena↗
PubMed1999

Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization.

Cathepsin K is a cysteine protease expressed predominantly in osteoclasts. Activated cathepsin K cleaves key bone matrix proteins and is believed to play an important role in degrading the organic phase of bone during bone resorption. Mutations in the human cathepsin K gene have been demonstrated to be associated with a rare skeletal dysplasia, pycnodysostosis. The degree of functional activity of the mutated forms of cathepsin K in these individuals has not been elucidated, but is predicted to be low or absent. To study the role of cathepsin K in bone resorption, we have generated mice deficient in the cathepsin K gene. Histologic and radiographic analysis of the mice revealed osteopetrosis of the long bones and vertebrae, and abnormal joint morphology. X-ray microcomputerized tomography images allowed quantitation of the increase in bone volume, trabecular thickness, and trabecular number in both the primary spongiosa and the metaphysis of the proximal tibiae. Not all bones were similarly affected. Chondrocyte differentiation was normal. The mice also had abnormalities in hematopoietic compartments, particularly decreased bone marrow cellularity and splenomegaly. The heterozygous animals appeared normal. Close histologic examination of bone histology revealed fully differentiated osteoclasts apposed to small regions of demineralized bone. This strongly suggests that cathepsin K-deficient osteoclasts are capable of demineralizing the extracellular matrix but are unable to adequately remove the demineralized bone. This is entirely consistent with the proposed function of cathepsin K as a matrix-degrading proteinase in bone resorption.

Animals↗
PubMed1998

Cynomolgus monkey (Macaca fascicularis) cathepsin K: cloning, expression, purification, and activation.

Methodology for the production of recombinant active cynomolgus monkey (Macaca fascicularis) cathepsin K (EC 3.4.22.38) was elucidated. The cDNA encoding the cathepsin K was cloned from female M. cynomolgus monkey mRNA. The deduced amino acid sequence of M. cynomolgus preprocathepsin K from the cDNA sequence showed 94.2% identity to human preprocathepsin K. Sequence differences occurred only in the prepro- domains; the mature domains were identical. The recombinant M. cynomolgus cathepsin K was expressed as a secreted proenzyme using baculovirus-infected SF21 insect cells having the predicted N-terminus (LYPEEILDTH ellipsis ), indicating proper cleavage of the secretion sequence. Purified monkey procathepsin K was activated under autocatalytic conditions at pH 4.0. The mature enzyme was composed of mixture of enzymes having N-termini of Gly113 and Arg114. The molecular weight was determined to be 23,668.3 Da by MALDI-TOF-MS which is consistent with the absence of carbohydrate on the mature enzyme. These results indicate that monkey procathepsin K is able to autoactivate and produces a mature enzyme which is identical to that of human cathepsin K. Since the sequence of monkey and human mature cathepsin K are identical and the in vitro activation mechanisms appear to be indistinguishable, monkeys are predicted to be a good animal model for evaluating cathepsin K inhibitors in vivo as therapeutic agents for diseases characterized by excessive bone loss, such as osteoporosis.

Amino Acid Sequence↗
PubMed1998

Cathepsin K mRNA detection is restricted to osteoclasts during fetal mouse development.

We recently identified a novel cysteine protease, cathepsin K, by random sequencing of an osteoclast cDNA library, and in situ hybridization studies in adult human tissues demonstrated high and specific expression in osteoclasts. To determine whether the expression of cathepsin K mRNA during mouse embryogenesis was more widespread, cryostat sections of early (day 11-13) and late (day 15-17) mouse fetuses were analyzed by in situ hybridization. Serial cross-sections were collected through each fetus, and co-reacted for tartrate-resistant acid phosphatase (TRAP) and nonspecific esterase (NSE), selective markers for the osteoclast, and precursor cells derived from the macrophage/monocyte lineage, respectively. In the 11-13 day fetuses, cathepsin K mRNA was not expressed in any extraskeletal tissue; at this stage of embryogenesis, no osteoclasts are present. However, in the 15-17 day fetuses, a distinctive, developmental stage-dependent pattern of cathepsin K expression was observed in osteoclasts and preosteoclasts at sites of cartilage and bone modeling. Cathepsin K positive osteoclasts differentiated within a peripheral zone of the osteogenic stacked cell layer of the cartilage rudiments (prior to ossification), migrated and/or resorbed the bone collar, and invaded the cartilage core. Furthermore, following the invasive penetration of vasculature into the degenerating cartilage core, the calcified cartilage was resorbed by cathepsin K positive mononuclear osteoclast precursors (NSE+ve, negligible TRAP); cells positive for both enzymes were identified indicative of osteoclast differentiation. The deposition of bone by osteoblasts onto the cartilage remnants is followed by mononucleated and multinucleated osteoclastic resorption; these osteoclasts demonstrated intense cathepsin K expression. Similar expression patterns were observed at sites of intramembranous ossification. No expression was observed in chondrocytes, osteoblasts, marrow, or in any other nonskeletal tissue at these time points. These data indicated that cathepsin K expression during embryogenesis occurred only following the onset of osteoclast differentiation.

Acid Phosphatase↗
PubMed1996

A screening method for occupational reproductive health risk.

Most currently recognized occupational exposure limits do not consider reproductive toxicological end points consistently when establishing recommended exposure limits. In many cases the information is not available, but perhaps as often, existing data is not employed. Further, many manufacturer's material safety data sheets omit reproductive hazard information. A method for identifying potential reproductive toxins and screening levels for associated health risks useful for hazard communication and exposure control is presented. To date, the Registry of Toxic Effects of Chemical Substances lists between 5000 and 6000 chemicals, drugs, and natural substances that show a positive outcome in at least 1 reproductive effects study. This reproductive health risk assessment began with these substances. Using elements of the Environmental Protection Agency's health risk assessment process, the list was reduced to 213 chemicals during the hazard identification step. Occupational reproductive guidelines (ORGs) were developed in the dose-response evaluation step. At the time of this writing, 85% of the chemicals identified in the hazard identification step have had a screening level dose-response assessment completed. Of these, 13% are greater than or equal to a threshold limit value (TLV). The remaining 87% do not have a TLV or ORGs below the TLV. The reproductive toxins list, along with the corresponding dose-response-derived ORGs that have been completed, appears at the end of the text.

Dose-Response Relationship, Drug↗
PubMed1991

Trifluoperazine modulation of resistance to the topoisomerase II inhibitor etoposide in doxorubicin resistant L1210 murine leukemia cells.

Murine leukemia L1210 cells selected for progressive resistance to doxorubicin (DOX) display both the multidrug resistant (MDR) phenotype and reductions in drug induced topoisomerase II-mediated DNA cleavage in nuclear extracts (Ganapathi, R.; Grabowski, D.; Ford, J.; Heiss, C.; Kerrigan, D.; Pommier, Y., Cancer Commun. 1:217-224; 1989). The present study was performed to characterize the results of exposure of the sensitive (S) and progressively DOX-resistant (10-fold, R1, and 40-fold, R2) L1210 cells to the topoisomerase II inhibitor, etoposide, and to investigate the modulating effects of the calmodulin inhibitor, trifluoperazine (TFP). Immunoblotting experiments indicated no apparent decrease in the p170 or p180 isoforms of topoisomerase II in the resistant sublines versus parental sensitive cells. Cross-resistance to etoposide (VP-16) was similar to that of DOX (10- and 40-fold). A non-cytotoxic concentration of 5 microM TFP enhanced cell kill 1.5- fold in the sensitive and 3- to 5-fold in the progressively DOX-resistant cells. Accumulation of VP-16 was 30% to 50% lower in the resistant sublines versus similarly treated sensitive cells, and a marked enhancement of drug uptake in the presence of TFP was observed in the sensitive but not in the resistant cells exposed to equivalent extracellular levels of VP-16. Although equimolar concentrations of VP-16 produced fewer DNA single strand breaks (SSB) and DNA protein crosslinks (DPC) in the resistant versus sensitive cells, similar DNA damage was apparent when S and R1, but not R2, cells were treated at VP-16 concentrations that produced equivalent cell death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

Incidence of salivary gland tumours in Scotland: accuracy of national records.

Statistics on discharge diagnoses in Scotland during 1968-74 show the incidence of all tumours of major salivary glands to exceed 40/million population yearly. This is higher than in any other nationality except Canadian Eskimos. Studies in two hospitals showed that numerous errors occurred in reporting these tumours, but the figures were more likely to be too low than too high. Probably eastern Scotland at least has an unusually high incidence, although in other countries using different methods of analysis the reported figures are likely to be low. Statistics based on discharge diagnoses will continue to be neglected in research until the standard of completion of discharge diagnoses improves.

Diagnostic Errors↗
PubMedDate not supplied

Space missions for SETI.

Radio Telescopes for SETI searches are less demanding than general purpose astronomical radio telescopes. This provides an opportunity to exploit economical approaches in designing SETI systems. Radio Telescopes in low Earth orbit offer no discernible advantages to SETI; indeed, they probably would perform more poorly than a telescope in any other location. Telescopes in geosynchronous orbits would be sufficiently far from Earth to mitigate greatly the deleterious effect of human radio transmissions. Telescopes on the far side of the moon would be superb both from a radio interference standpoint, and from a civil engineering standpoint. Single-reflector telescopes as large as 50 kilometers in diameter could be constructed with conventional materials. However, their costs appear prohibitive. The asteroid belt and the outer solar system are unpromising places to place a large radio telescope. Perhaps the ultimate radio telescope would utilize the sun as a gravitational lens, focusing radiation on free-flying 10-meter class or possibly larger radio telescopes located at distances of the order of 1000 A.U. from the sun. Such a combination has an energy collecting area at 10 centimeters wavelength equivalent to that of a radio telescope about 11 kilometers in diameter, or of the order of 3000 Arecibo radio telescopes. Such a system could detect transmitters with EIRP of the order of a gigawatt at a distance of the order of the distance to the galactic center.

Astronomy↗