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PubMedDate not supplied

Design of beam-modulating devices for charged-particle therapy.

The computer modeling program used to design beam-modulating devices for charged-particle therapy at Lawrence Berkeley Laboratory has been improved to allow a more realistic description of the beam. The original program used a single calculated Bragg peak to design the spread Bragg peak. The range of this curve was shifted so that Bragg curves of varying ranges could be superimposed. The new version of the program allows several measured Bragg curves with different ranges to be used as input, and interpolates between them to obtain the required data for the superposition calculation. The experimental configuration for measuring these input curves simulated therapy conditions. Seven beam-modulating propellers with spread Bragg-peak widths ranging from 2.2 to 14.4 cm were designed and constructed for a 215-MeV/u helium beam using this new design program. Depth-dose distributions produced by these new propellers were in good agreement with predicted distributions, and these propellers are currently being used clinically.

Equipment Design↗
PubMed1994

An automated image-registration technique based on multiple structure matching.

A new image-registration technique that matches multiple structures on complementary imaging data sets (e.g., CT and MRI) has been developed and tested with both phantom and patient data. The algorithm assumes a rigid-body transformation and is suitable for correlating structures within the cranium or at the skull base. The basic premise of the new technique is that an optimum transformation is achieved when the relative volume lying outside of the intersection between a structure and its transformed counterpart is a minimum. This relative volume is calculated numerically using a random sampling approach, and a binary searching algorithm was used to step through the nine-dimensional parameter space consisting of three rotation angles, three scaling factors and three components of a translation vector. For the nine tests using phantom data, the automated structure-matching technique was able to predict the correct rotation angles to within +/- 1 degree. The expected clinical performance of the new technique was assessed by comparing results obtained with the new method to those obtained using other techniques for 12 patients who were treated with charged particles at Lawrence Berkeley Laboratory (LBL) and who had image-registration studies performed as part of their treatment plan. For 9 of the 12 patients considered, the new structure-matching technique produced a significantly better registration than the older methods, as measured by the resultant average relative volume lying outside of the intersection between any structure and its transformed counterpart. For the other three patients, results were not significantly different for the new structure-matching method and the older techniques.

Algorithms↗
PubMed1999

Boron neutron capture therapy (BNCT): implications of neutron beam and boron compound characteristics.

The potential efficacy of boron neutron capture therapy (BNCT) for malignant glioma is a significant function of epithermal-neutron beam biophysical characteristics as well as boron compound biodistribution characteristics. Monte Carlo analyses were performed to evaluate the relative significance of these factors on theoretical tumor control using a standard model. The existing, well-characterized epithermal-neutron sources at the Brookhaven Medical Research Reactor (BMRR), the Petten High Flux Reactor (HFR), and the Finnish Research Reactor (FiR-1) were compared. Results for a realistic accelerator design by the E. O. Lawrence Berkeley National Laboratory (LBL) are also compared. Also the characteristics of the compound p-Boronophenylaline Fructose (BPA-F) and a hypothetical next-generation compound were used in a comparison of the BMRR and a hypothetical improved reactor. All components of dose induced by an external epithermal-neutron beam fall off quite rapidly with depth in tissue. Delivery of dose to greater depths is limited by the healthy-tissue tolerance and a reduction in the hydrogen-recoil and incident gamma dose allow for longer irradiation and greater dose at a depth. Dose at depth can also be increased with a beam that has higher neutron energy (without too high a recoil dose) and a more forward peaked angular distribution. Of the existing facilities, the FiR-1 beam has the better quality (lower hydrogen-recoil and incident gamma dose) and a penetrating neutron spectrum and was found to deliver a higher value of Tumor Control Probability (TCP) than other existing beams at shallow depth. The greater forwardness and penetration of the HFR the FiR-1 at greater depths. The hypothetical reactor and accelerator beams outperform at both shallow and greater depths. In all cases, the hypothetical compound provides a significant improvement in efficacy but it is shown that the full benefit of improved compound is not realized until the neutron beam is fully optimized.

Biophysics↗
PubMed2003

Focusing on the big picture.

As a postdoc in cognitive neuroscience who's also a neurology fellow, Adam Gazzaley is a meld of basic science expertise and clinical experience: He studies brain aging in people by using functional magnetic resonance imaging at the University of California (UC), Berkeley, and he also sees patients at UC San Francisco's Memory and Aging Center. The 34-year-old native New Yorker dives with equal fervor into scientific research and nature photography, two lenses for viewing a single world of discovery. Growing up in Queens, Gazzaley knew from age 7 that he wanted to become a scientist, and as a teenager, he commuted long hours to attend the Bronx High School of Science. He earned an M.D.-Ph.D. from the Mount Sinai School of Medicine in New York City. Gazzaley's hobby as a shutterbug periodically takes him on backpacking trips to document the beauty of the great outdoors. He sells fine-art prints of his photographs to individuals, hospitals, and clinics through his company, Wanderings Inc.

Brain↗
PubMed2001

Correction of sickle cell disease in transgenic mouse models by gene therapy.

Sickle cell disease (SCD) is caused by a single point mutation in the human betaA globin gene that results in the formation of an abnormal hemoglobin [HbS (alpha2betaS2)]. We designed a betaA globin gene variant that prevents HbS polymerization and introduced it into a lentiviral vector we optimized for transfer to hematopoietic stem cells and gene expression in the adult red blood cell lineage. Long-term expression (up to 10 months) was achieved, without preselection, in all transplanted mice with erythroid-specific accumulation of the antisickling protein in up to 52% of total hemoglobin and 99% of circulating red blood cells. In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect.

Anemia, Sickle Cell↗
PubMed1950

Molecular orientation and intracellular photometric analysis.

In reference to the article "Chromatographic Analysis of a Mixture of Proteins from Egg White" (Science, 1949, 110, 564), the cation exchange resin Dowex 50 employed in the experiment cited was obtained in February, 1949, from the Microchemical Specialties Company, Berkeley 3, California, under the name of Ion-X, and not from the Dow Chemical Company as reported in the footnote. We have thus far not obtained satisfactory results with a sample of Dowex 50, (24427), obtained from the Dow Chemical Company on August 8, 1949.

California↗
PubMed1983

Small RNA.

The illustration that accompanied the review by C. C. Albritton, Jr., of W. H. Goetzmann and K. Sloan's Looking Far North (Viking, New York, 1982) in the issue of 10 December, page 1109, should have been credited to the Bancroft Library, University of California, Berkeley, as well as to the book under review.

Base Sequence↗
PubMed1991

Variants of Aspergillus alutaceus var. alutaceus (formerly Aspergillus ochraceus) with altered ochratoxin A production.

The present studies, using Aspergillus alutaceus var. alutaceus Berkeley et Curtis (formerly A. ochraceus Wilhelm) NRRL 3174 along with three other wild-type strains, were undertaken in an attempt to understand the effects of irradiation and other treatments on mycotoxin production in grain. Bedford barley was inoculated with spores of NRRL 3174, gamma irradiated, and incubated at 28 degrees C and 25% moisture. After 10 days of incubation, two colony types, ochre (parental) and yellow (variant), were isolated from the grain. Further culturing of the yellow variant resulted in the spontaneous appearance of a white variant that exhibited greatly enhanced fluorescence under UV light. In subsequent work, we have also isolated variants producing a soluble red pigment. In addition, in model experiments involving irradiation (1 kGy) of pure cultures, induction frequencies ranging between 2 and 4% (survival basis) were observed for the yellow and red variants. Inoculation of these variants into wheat and incubation for 14 days at 28 degrees C and 32% moisture resulted in ochratoxin A production in the relative amounts of 0.09:1:4.6:9.3 for the red, ochre (parental), yellow, and white variants, respectively. Additional characteristics of these isolates are described. Confirmation that the white high-ochratoxin-A-producing variants were derived from the parental strain was demonstrated by obtaining revertant sectors in monoclonal cultures of the variants.

Aspergillus ochraceus↗
PubMed1961

Complement fixation test in experimental clinical and subclinical melioidosis.

Nigg, Clara (University of California, Berkeley), and Margaret M. Johnston. Complement fixation test in experimental clinical and subclinical melioidosis. J. Bacteriol. 82:159-168. 1961.-Soluble stable antigens prepared from Pseudomonas pseudomallei gave 4+ complement fixation reactions in a dilution of 1 to 8,000 when tested with specific rabbit antiserum diluted 1 to 10,000. The complement fixation reaction was positive in 100% of experimentally infected rabbits 9 to 11 days postinfection. Infected guinea pigs and monkeys showed similar results. Monkeys inoculated with very small infecting doses of P. pseudomallei developed positive complement fixation reactions in the absence of clinical manifestation of infection. An anamnestic complement-fixing antibody response could be induced in such monkeys, after the titer had dropped to approximately the preinfection level, by inoculating very small doses of viable P. pseudomallei or larger doses of killed melioidosis vaccine. The complement fixation test described appeared to be both sensitive and specific, and should be of value in human melioidosis which cannot be diagnosed on the basis of clinical manifestations alone. It is suggested that subclinical infections may play a role in the epidemiology of human meliodosis. The potential application of the complement fixation test to serological surveys in areas where melioidosis occurs endemically is discussed.

Animals↗
PubMed1961

Lysis of brucellae by the combined action of glycine and a lysozyme-like agent from rabbit monocytes.

Ralston, Doris J. (University of California, Berkeley), B. S. Baer, and S. S. Elberg. Lysis of brucellae by the combined action of glycine and a lysozyme-like agent from rabbit monocytes. J. Bacteriol. 82:342-353. 1961.-An acid-extractable lytic material was obtained from rabbit monocytes. It acts on a substrate in the walls of brucellae and has properties similar to egg-white lysozyme. Brucella melitensis strain Rev Is is completely resistant to this agent and also to crystalline lysozyme, but when the cells are exposed to sufficient amounts of glycine, the surface is rendered susceptible to these lytic agents. Rough type Rev Is cells are more susceptible than smooth, and the virulent B. melitensis strain 6015 is most resistant.

Animals↗
PubMed1961

Polysaccharide of Coccidioides immitis.

Pappagianis, D. (University of California, Berkeley), E. W. Putman, and G. S. Kobayashi. Polysaccharide of Coccidioides immitis. J. Bacteriol. 82:714-723. 1961.-Soluble polysaccharide from mycelia or culture filtrates of Coccidioides immitis was found to consist mainly of mannose, but also included small quantities of galactose and another reducing sugar. Isolation of the polysaccharide by ethanol precipitation provided accompanying nitrogenous material. There was 3 to 4% nitrogen, present in amino acids, but in a nondialyzable (possibly protein or peptide) form. The average molecular weight of the complex was 31,700. Attempts to separate the nitrogenous and polysaccharide materials by chemical methods or by moving boundary electrophoresis were unsuccessful; ultracentrifugation showed a single peak. Despite these findings, there appeared to be several antigenic species present, as indicated by multiple lines of precipitation in double diffusion and quantitative precipitin tests. In the latter, polysaccharide-containing fractions gave precipitates without measurable carbohydrate, suggesting separability of nitrogenous and polysaccharide components.

Antigens, Fungal↗
PubMed1961

Growth of shigellae in monolayer tissue cultures.

Gerber, Dolores F. (University of California, Berkeley) and H. M. S. Watkins. Growth of shigellae in monolayer tissue cultures. J. Bacteriol. 82:815-822. 1961.-The influence of environment on virulence, antigenicity, and antibiotic susceptibility of infectious agents is well recognized. The development of tissue culture monolayer techniques has stimulated new interest in manifestations of these attributes at the cellular level. Shigella flexneri and S. sonnei were grown intracellularly in Henle epithelial cell monolayer tissue cultures; uptake of the bacteria was induced by 50% normal horse serum in the infection medium. Since preliminary experiments indicated that streptomycin in the extracellular fluid depressed intracellular multiplication of these organisms, the antibiotic was later omitted from the tissue culture growth fluid. Extracellular multiplication of shigellae was controlled by thorough washing of the infected monolayers and replacement with fresh medium at 2-hr intervals during incubation. Intracellular growth patterns of two S. flexneri and two S. sonnei strains were established. Differences in the capacity of strains to adapt to the intracellular environment was reflected in the number of organisms subsequently produced, and appeared to be associated with the degree of intracellular resistance to streptomycin. No such variation was seen in cultures grown in broth. Microscopic examination of stained monolayers showed that intracellular bacterial growth was confined to the cytoplasm, which became filled with organisms prior to cellular disintegration.Biological implications of the variable response of Shigella strains to the intracellular environment are discussed.

Anti-Bacterial Agents↗
PubMed1962

Transduction of the attached sex factor of Escherichia coli.

DeWitt, Susanne K. (University of California, Berkeley) and Edward A. Adelberg. Transduction of the attached sex factor of Escherichia coli. J. Bacteriol. 83:673-678. 1962.-The linkage of the sex factor to one extremity of the chromosome in Hfr cells of Escherichia coli has been confirmed by transduction experiments. In Hfr P4x-6, lac is the last marker to penetrate the female during conjugation. When lac(+) was transduced from P4x-6 into a lac(-) strain by phage Plkc, 5% cotransduction of the sex factor was observed. No cotransduction of the sex factor was observed when markers other than lac(+) were selected.The transduced males resembled the Hfr parent with respect to the site of attachment and orientation of the sex factor, the order of genetic markers transferred, and the gradient of recombination frequencies produced with a given female. When the lac(-) recipient used in the transduction carried an sfa locus in a different region of the chromosome, the over-all rate of cotransduction was tenfold lower, but the transduced males again resembled the Hfr parent in their sexual behavior.

Chromosomes↗
PubMed1962

Nutritional effects on frequencies of bacterial recombination.

Riley, Monica (University of California, Berkeley) and Arthur B. Pardee. Nutritional effects on frequencies of bacterial recombination. J. Bacteriol. 83:1332-1335. 1962.-The number of recombinant colonies obtained from mated Escherichia coli is highly dependent on the composition of the medium, both during and after mating, and of the agar medium on which the bacteria are plated. Many bacteria appear to participate in mating, but the efficiency with which they carry out subsequent events leading to recombinant colony formation depends on the physiological state of the zygotes and the challenge to which they are subjected on the selective plates. These findings are reminiscent of the factors which influence the frequency of production of mutants from irradiated bacteria, the survival of bacteria irradiated with ultraviolet light, lysogenization by bacteriophage, or transformation by deoxyribonucleic acid. As a practical measure, care must be taken to hold conditions of plating constant to obtain reproducible numbers of recombinant colonies in mating experiments. For instance, traces of nutrients in agar can greatly affect recombination frequencies.

Acridines↗
PubMed1962

Sporulation of Clostridium botulinum. I. Selection of an aparticulate sporulation medium.

Tsuji, Kiyoshi (National Canners Association Research Laboratory, Berkeley, Calif.) and William E. Perkins. Sporulation of Clostridium botulinum I. Selection of an aparticulate sporulation medium. J. Bacteriol. 84:81-85. 1962.-The thermal resistances of Clostridium botulinum spores produced in seven different liquid media were compared. A 5% solution of a commercially produced mixture of dehydrated enzymatic hydrolyzates of casein and animal tissues yielded spores of maximal thermostability. Sporulation in this medium was almost complete under the conditions employed. The suspensions were essentially free of vegetative cells and sporangia and could be thoroughly washed. The incubation time at 30 C was found to have a negligible effect on thermal resistance for periods between 4 and 21 days. Supplementing the medium yielding the most thermolabile spores with various divalent cations did not enhance the thermal resistance of the spores produced. The identical amino acids and related compounds were found in spores exhibiting the maximal and minimal thermal resistance when they were analyzed chromatographically. The more thermostable spores contained a higher concentration of glucosamine.

Amino Acids↗
PubMed1962

Sporulation of Clostridium botulinum. II. Effect of arginine and its degradation products on sporulation in a synthetic medium.

Perkins, William E. (National Canners Association Research Laboratory, Berkeley, Calif.) and Kiyoshi Tsuji. Sporulation of Clostridium botulinum. II. Effect of arginine and its degradation products on sporulation in a synthetic medium. J. Bacteriol. 84:86-94. 1962.-A synthetic medium which supports spore germination, vegetative cell multiplication, toxin production, and sporulation of Clostridium botulinum strain 62A is described. Arginine has been shown to play an important role in sporulation. Experiments involving the substitution of citrulline and ornithine for arginine, together with amino acid analyses of culture supernatant fluids and cells, indicate that most of the arginine is broken down by a dihydrolase enzyme system through citrulline to ornithine. The second step in this reaction series, the degradation of citrulline, appears to be essential to sporulation. The absence of citrulline or ornithine in either growing cells or spores suggests that another product of the arginine dihydrolase system, adenosine triphosphate, may be responsible for the observed stimulation of sporulation.

Amino Acids↗
PubMed1963

Phosphorylation by extracts of Nitrosomonas europaea.

Burge, W. D. (University of California, Berkeley), E. Malavolta, and C. C. Delwiche. Phosphorylation by extracts of Nitrosomonas europaea. J. Bacteriol. 85:106-110. 1963.-Cellfree preparations of Nitrosomonas europaea are capable of oxidizing hydroxylamine, but not ammonium ion, to nitrite. The quantity of nitrite formed by our preparations was, at most, equivalent to only 70% of the hydroxylamine added. Although the preparations had a strong phosphatase activity, resulting in a net loss of organic phosphate during the experimental period, P(32)-labeled inorganic phosphate was found to be incorporated into the organic fraction, including adenosine triphosphate (ATP) and adenosine diphosphate (ADP). The provision of hydroxylamine as substrate resulted in the formation of nitrite and an increased incorporation of P(32) into the organic fraction. It is concluded that the chemosynthetic autotroph Nitrosomonas, in common with certain other autotrophic organisms and heterotrophs, is capable of converting energy released in the oxidation of its inorganic substrate into high-energy phosphate units (ATP and ADP) for the mediation of other energy-requiring reactions. The simultaneous formation of ATP and ADP is interpreted as evidence for an adenylate kinase activity. The preparations used exhibited a considerable endogenous incorporation of P(32) into organic phosphate in the absence of added hydroxylamine. Cyanide inhibited both phosphorylation and the oxidation of hydroxylamine. Both the supernatant and particulate fractions of a Nitrosomonas extract subjected to centrifugal fields of 100,000 x g were active in phosphorylation and nitrite formation, but these activities appeared to be uncoupled in the particulate fraction and only partially coupled in the supernatant solution. This most likely reflects a significant endogenous respiration, and not a real lack of coupling between the two reactions.

Cyanides↗