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PubMed1996

Undervaccination for Hepatitis B among young men who have sex with men--San Francisco and Berkeley, California, 1992-1993.

The evaluation of efforts to prevent hepatitis B virus (HBV) infection in the United States requires accurate measures of hepatitis B vaccination coverage among children and adults at risk for infection. Although vaccination coverage among children is obtained by nationwide surveys, vaccination coverage among adults at risk for HBV infection has not been well characterized. To estimate hepatitis B vaccination coverage among young men who have sex with men (MSM) (a group known to be at high risk for HBV infection and for whom hepatitis B vaccine has been recommended since 1982), CDC analyzed serologic data from the 1992-1993 Young Men's Survey (YMS) conducted by the San Francisco Department of Public Health. This report summarizes the results of that analysis, which indicate low hepatitis B vaccination coverage among young MSM in the San Francisco Bay area.

Adolescent↗
PubMed2004

Which cannulae fit the Ipas manual vacuum aspiration syringe?

BACKGROUND: The Ipas double-valve manual vacuum aspiration (MVA) syringe is an alternative to electrical vacuum aspiration. METHODS: This study determines which US cannulae (flexible, rigid-straight and rigid-curved) work with the Ipas MVA syringe. Cannulae from Ipas, MedGyn, Berkeley and Milex, in sizes 6-12 mm, were randomized and affixed to the MVA syringe. A pressure gauge was attached to the cannula with rubber tubing. Pressure readings were recorded initially and over 30 s. RESULTS: Milex cannulae were not compatible. For the remaining brands, initial vacuum pressures ranged from 55 to 65 mmHg. Flexible cannulae from Ipas, Berkeley and MedGyn maintained initial pressures without leaks, as did the 6-12-mm straight- and curved-rigid cannulae by Berkeley. Eight of the 13 tested MedGyn rigid cannulae lost >10% pressure over 30 s. CONCLUSION: Several US manufacturers produce cannulae that fit on the Ipas MVA syringe without a leak, including Ipas flexible cannula; Berkeley flexible, rigid-straight and rigid-curve cannulae and MedGyn flexible cannula, but not their rigid cannulae.

Abortion, Induced↗
PubMed1976

Hereditary and environmental determinants of growth in height in a longitudinal sample of children and youth of Guatemalan and European ancestry.

The effects of hereditary and environmental factors upon the growth in stature of children living in Guatemala City has been studied. Heights at yearly examinations were fitted, by individual, to a double logistic curve in samples of Guatemalan and European children attending a private school in Guatemala City. These two samples differed genetically yet shared the same environment. Their growth was compared, by a multivariate analysis of the parameterized curves, to that of children from the Berkeley Growth Study, genetically similar to the European sample, yet living in different environments. The European children in Guatemala grew, before adolescence, more similar to Guatemalan and differed significantly from the Berkeley sample children. However, the amount of growth during the adolescent years experienced by the European children was similar to that of the Berkeley sample and differed from their Guatemalan counterparts.

ABO Blood-Group System↗
PubMed1993

Definitive postoperative irradiation of bile duct carcinoma with charged particles and/or photons.

PURPOSE: To determine the rates of survival and local control in patients with bile duct adenocarcinomas treated with post-operative photons and/or charged particles. METHODS AND MATERIALS: A retrospective study was performed analyzing all patients with bile duct adenocarcinomas who received radiotherapy through the University of California San Francisco and at Lawrence Berkeley Laboratory between 1977 and 1987, a total of 62 patients. University of California San Francisco patients received photon therapy (median dose 5400 cGy), and Lawrence Berkeley Laboratory patients were treated with the charged particles helium and/or neon (median dose 6000 cGyE). Forty-eight patients were treated post-operatively with curative intent, 30 with photons and 18 with particles. Thirty-six patients in the study had gross residual disease; none had microscopically negative margins. RESULTS: The overall two-year actuarial survival was 28%: 44% for particle-treated patients and 18% for patients treated with photons (p = .048). Median actuarial survival was 23 months in particle patients and 12 months in photon patients. Local control was also improved, though less significantly, in patients treated with particles (median disease-free survival 20 months vs. 4.5 months, p = .054). A univariate and multivariate analysis was performed and revealed that only extent of residual disease predicted local failure and overall survival; no other prognostic factors were identified. CONCLUSION: Compared to conventional photon radiotherapy, treatment with post-operative charged particle irradiation at Lawrence Berkeley Laboratory appeared to offer a survival advantage in this non-randomized series. Additional investigation into protection of surrounding normal tissue with better dose localization through the use of charged particles is planned.

Adenocarcinoma↗
PubMed1996

Radioiodine and thyroid disease: the beginning.

In 1936, Karl Compton, then president of the Massachusetts Institute of Technology (MIT) and the thyroid group of the Massachusetts General Hospital (MGH), undertook a joint study that led to the production of small amounts of short-lived radioiodine (iodine 128, half-life, 25 min). The original intent was to use it for diagnosis and treatment of thyroid disease, but in order to explore the underlying physiology, their first work was performed in rabbits and published in 1938. It clearly showed that the radioiodine was selectively and avidly taken up by the thyroid gland. It was immediately apparent to the MGH-MIT group and another team working at the Berkeley, CA cyclotron that longer-lasting iodine isotopes were needed, and soon both developed procedures for cyclotron-produced 130 (half-life, 12.5 hr) and 131I (half-life, 8 d). In 1939, the Berkeley group, using 131I, was the first to show that the normal human thyroid gland accumulated radioiodine. By 1941, the MGH-MIT team, using mainly 130I, was able to successfully treat a few patients with hyperthyroidism, and so achieved their original goal. The Berkeley group did the same a few months later, using mainly 131I. Both presented results at the same meeting of the American Society for Clinical Investigation in Atlantic City, NJ in the spring of 1942. This was in the midst of World War II and it was not easy to get much 130I or 131I, so experience was limited. Although effective, radioiodine treatment of hyperthyroidism had not been widely adopted by the end of the war in 1945, partly because radioiodine remained in short supply and partly because another medical therapy for hyperthyroidism, antithyroid drugs, had been invented. However, by 1946, fission-derived radioiodine became readily available as a by-product of the Manhattan project in Oak Ridge, TN; hundreds of patients were treated within a few years, both for hyperthyroidism and for thyroid cancer. A new treatment, based on the physiological application of a radioisotope of iodine, was then a reality.

Animals↗
PubMed1997

Radioiodine and the treatment of hyperthyroidism: the early history.

Little was known about iodine metabolism in the mid-1930s, but when Saul Hertz and his chief, J. Howard Means, at the Massachusetts General Hospital (MGH) realized in 1936 that radioiodine could be made and used as a tracer, they arranged with physicists Robley Evans and Arthur Roberts at the Massachusetts Institute of Technology (MIT) to make the short-lived 128I and study its physiology in rabbits. By 1938, they showed that the rabbit's thyroid gland rapidly took up 128I, especially when there was only a little non-radioactive iodine present. There was, however, no hope of using 128I as a treatment because of its brief half-life (25 minutes). In 1939, Joseph Hamilton and Mayo Soley, working with Ernest Lawrence's cyclotron in Berkeley, California, were able to make several radioiodines; one was 130I (12-hour half-life) and another 131I (8-day half-life). They were the first to give these radioiodines to humans to study iodine physiology. The MGH-MIT group also built a cyclotron and by 1940 had generated these two new radioiodines. One of the goals of both groups was the treatment of hyperthyroidism. Hertz and Roberts were the first to do so on March 31, 1941; Hamilton and John Lawrence, Ernest's brother, began on October 12, 1941. By 1942, the United States was actively fighting in World War II. That year both Boston and Berkeley groups have preliminary data on the treatment of hyperthyroidism in Atlantic City; both showed that it was effective and went on to treat more patients. In Berkeley the therapy was viewed cautiously, and, in many case, the physicists were mainly occupied with work for the Manhattan District. In Boston Hertz used the therapy as often as he could, emphasizing the use of 130I, until he joined the U.S. Navy in 1943. Earle Chapman, a clinician on the voluntary staff of the MGH, took over Hertz's practice in 1943; their later differences over the precise treatment and who was in charge led to their falling out. After Hertz's release from the Navy he was not permitted to return to the MGH and became quite bitter; Chapman stayed on at the MGH. After the war was over, both had acquired a sufficient number of patients--there was then no such thing as a controlled trial--and wrote up the results for publication. Each wrote a different physicist, Hertz with Roberts and Chapman with Evans. When Hertz learned that Chapman's paper was being considered by the Journal of the American Medical Associations, he quickly sent his manuscript to JAMA as well. Although the editor of JAMA was puzzled by two papers on the same topic from the same institution, both papers appeared in the same issue of JAMA on May 11, 1964, and announced the new therapy was effective treatment for hyperthyroidism.

Animals↗
PubMed1998

Radiobiology with heavy charged particles: a historical review.

Radiobiological studies using heavy charged particles followed closely the development of accelerators to produce beams of ever-increasing energy, driven primarily by the aspirations of physicists and chemists interested in the structure of matter. An impressive share of this development took place at Berkeley, beginning with the invention of the cyclotron by Ernest Lawrence in 1930. There followed a series of cyclotrons, synchrotrons and linear accelerators, culminating in the BEVALAC, which provided the first source of very heavy ions (helium to argon) to be used clinically, beginning in 1975. Other early entrants (1950's-1960's) in the clinical use of heavy ion beams (protons only) included Uppsala, Harvard/MGH and several facilities in the USSR. During the 1970's negative pi-meson (pion) beams for clinical use were developed in the US (LAMPF), Switzerland (SIN/PSI) and Canada (TRIUMF). Although the first accelerator built primarily for medical use, the Crocker Medical Cyclotron, was completed at Berkeley in 1939 (it was used primarily to produce neutron beams) it was not until 1990 that the next clearly dedicated medical heavy ion facility went into operation: the 3-gantry proton synchrotron at Loma Linda. There are several reasons for this long hiatus: the long time required to complete clinical trials; the need to develop more economic and flexible accelerators and beam handling systems; the early discouraging clinical results obtained with neutron beams at Berkeley in the 1940's, before the dose response differences for early and late effects were fully understood. During the last decade or so there has been a rapid increase in the number of proton beam facilities; heavier ion beams are so far available only at HIMAC in Japan and GSI in Germany. Earlier studies with radioactive alpha-particle sources and plant cells had already shown, by the early 1930's that high LET radiations were biologically more effective than X-rays in producing damage in eukaryotes. The increased penetration of high energy particles from accelerators made it possible to carry out in vivo radiobiological studies in animals, and the publication by Puck of the first radiation survival response for cultured mammalian cells in 1956, provided another valuable tool for radiobiological studies. One of the earliest systematic studies of the dependence of RBE (relative biological effectiveness) and OER (oxygen enhancement ratio) on LET (linear energy transfer) was that by Barendsen in the early 1960's; he irradiated cultured human kidney cells with deuterium and alpha-particles, and showed that RBE reached a maximum at an LET of 100-200 keV/micrometer, the same LET at which the OER decreased to approximately 1.0. More recent studies (Belli, Folkard, etc.) show that the RBE 'peaks' at a LET which is particle-dependent (for protons, RBE maximum is at approximately 30 keV/micrometer), indicating that LET alone does not adequately define the microscopic energy deposition and its influence on biological effect. One of the complications with heavy ion and pion beams is the increase in RBE with depth in the stopping region. Cultured cell techniques were developed to accurately map these RBE changes, which were investigated at each of the heavy ion and pion facilities, allowing physical dose profiles to be shaped to compensate for the change in biological effectiveness. With the heavier ions, RBE is also dependent on dose and on the dose fractionation scheme used. In vivo systems are the most suitable for such measurements and a variety of normal tissue and tumour end-points has been employed for such studies. A review of the published RBE values for proton beams, 1975-1997, shows very good consistency between the various centres, with average in vivo and average in vitro values falling in the range 1.11-1.18. In this article we have, due to space limitations, only been able to review a representative fraction of the extensive literature on heavy ion radiobiology. We have arbitrarily limited our discussion to mammalian systems, except for a few very early experiments of historical interest.

Animals↗
PubMed1996

Transformations of membrane-bound organelles in sec 14 mutants of the yeasts Saccharomyces cerevisiae and Yarrowia lipolytica.

BACKGROUND: In early descriptions of ultrastructural alterations of secretory (sec) mutants of the yeast Saccharomyces cerevisiae, two mutants, sec7 and sec14, were shown to produce cell structures, the so-called Berkeley bodies thought at first to correspond to Golgi structures. In sec7 mutants grown at restrictive temperature, secretion granules soon dis-appeared, whereas networks of Golgi tubules increased in size and transformed into stacks of seven to eight flattened elements. At these time intervals, structures resembling Berkeley bodies appeared to be extensions of the endoplasmic reticulum (Rambourg et al., 1993). It is the purpose of the present study to examine by electron microscopy S. cerevisiae sec14 mutants and to compare the modifications along their secretory pathway with those occurring in a homologous mutant of Yarrowia lipolytica. METHODS: S. cerevisiae sec 14 mutant cells coming from exponentially growing cultures were examined either at 24 degrees C or after shifting at 37 degrees C for 0, 2, 5, 10, 15, 20, 30, 45, 60, 90, and 120 min. Y. lipolytica mutant cells were first cultured in YNB in 5000 medium and then transferred for 0, 6, 8, 12, 20, and 24 hr, in a phosphate-buffered YPD medium, which allows wild cells to differentiate from yeast to mycelian form. In both cases, cells were fixed in 2% glutaraldehyde, treated for 15 min in 1% sodium metaperiodate, post-fixed in reduced osmium, and embedded in Epon. To visualize the three-dimensional configuration of cell organelles, stereopairs were prepared from section stained with lead citrate and tilted at +/- 15 degrees from the 0 degree position of the goniometric stage of the electron microscope. RESULTS: In S. cerevisiae mutant cells shifted for 2 min at the restrictive temperature, faintly stained networks of thin anastomosed tubules were located at close proximity and often continuous with faintly stained ER cisternae. More intensely stained tubular networks with nodular dilations having the size of secretion granules were dispersed throughout the cytoplasm. Later on, the faintly stained ER elements and related tubular networks decreased in number, whereas the intensely stained nodular tubular networks increased in frequency. The incidence of secretion granules also increased and were distributed at random throughout the cytoplasm. Widemeshed, intensely stained fenestrated spheres were often encountered and increased in number, in parallel to the increase in the number of nodular tubular networks. At late time intervals, the fenestrated spheres decreased in number as they seemingly transformed into spherical bodies identical to vacuoles. In contrast to what occurred in S. cerevisiae sec14 mutant, the main ultrastructural modification observed in Y. lipolytica transferred to the YPD medium was the formation of deep plasma membrane invaginations. CONCLUSIONS: It appears that two functionally homologous PI/PC transfer proteins (Sec14psc and Sec14pyl) control distinct physiological processes in the two sec14 mutants examined. Such differences are perhaps related to the regulatory role of these proteins in different target organelles, i.e., the Golgi apparatus in S. cerevisiae or the plasma membrane in Y. lipolytica.

Carrier Proteins↗
PubMed1999

An estimate of the crosstalk matrix in four-dye fluorescence-based DNA sequencing.

Color separation is an essential step of the data processing in the four-dye fluorescence detection strategy used in automated DNA sequencing. In this paper, we propose a model to describe the crosstalk phenomenon, and show how the assumptions of the model are supported by experimental data. The crosstalk matrix is estimated via a reparameterization based on a mapping between the distribution of fluorescence intensities and that of dye concentrations. An iterative algorithm is designed to implement the estimation. To evaluate the color-correction quality of a crosstalk matrix, we propose a quantitative measure based on the distribution of the color-corrected data. We illustrate this method by applying it to a sequencing trace of slab gel electrophoresis obtained at the Human Genome Center at Lawrence Berkeley National Laboratory, and that of capillary electrophoresis provided by the Department of Chemistry at UC, Berkeley. The accuracy of this method is also assessed by the bootstrap method.

Algorithms↗
PubMed1993

Mass screening for endometrial cancer directed in risk groups of patients with diabetes and patients with hypertension.

BACKGROUND: The interest in mass screening programs for the early detection of endometrial cancer (EC) has grown with the rising incidence of this disease. Preliminary programs directed at asymptomatic women with only one risk factor, i.e. age, have not been cost-effective. METHODS: In the current study, 597 asymptomatic women from 45-69 years of age with diabetes and/or hypertension were screened by Vabra (Berkeley Medevices Inc., Berkeley, CA) aspiration. RESULTS: Among the women with diabetes, 6.3% preinvasive lesions of the endometrium were found. This is significantly more than the rate among women with hypertension, which was 1.3% (P < 0.01). CONCLUSIONS: Regular mass screening programs for the early detection of EC should be directed at asymptomatic diabetic women 45 years of age or older. This study does not indicate that similar screenings would be effective for women with hypertension.

Aged↗
PubMed1993

Exploring the HDL likelihood surface.

Using random initial parameter estimates, three segregation analysis models of the inheritance of HDL2 in the Berkeley GAW8 data set were maximized 5000 times each. Initial parameter estimates were assumed to be uniformly distributed on intervals formed by parameter boundaries. The three models were unrestricted, environmental, and Mendelian regressive type A models. Likelihood ratio tests of the global maxima rejected the Mendelian model and accepted the environmental model. However, tests using local maxima accepted the Mendelian model and both rejected and accepted the environmental model. Patterns among the initial parameter estimates of convergent runs were examined to develop empirical rules to increase the frequency of convergence. These rules were tested using data on apoAI in the Berkeley GAW8 data set.

Genetic Predisposition to Disease↗
PubMed2003

Hypercholesterolemia and Dyslipidemia: Issues for the Clinician.

The current state of the art in the diagnosis and treatment of lipoprotein disorders has progressed beyond the standard "lipid profile," which includes total low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, along with fasting triglycerides. Incorporating aspects of the atherogenic lipoprotein profile (ALP) (ALP and LDL subclass distribution), HDL subclass distribution, apolipoprotein E isoforms, lipoprotein (a), homocysteine, and high-sensitivity C-reactive protein provides the clinician with the tools to create a more detailed, accurate, and personalized diagnosis of disorders contributing to coronary artery disease in their patients. Sophisticated laboratory tests are available to clinicians through technology transfer programs as exemplified by the Lawrence Berkeley National Laboratory/Berkeley HeartLab, Berkeley, CA, collaboration and allow clinicians access to research quality laboratory tools. This has significant clinical relevance because the presence of these disorders guides treatment that is specific to the disorder(s). Appropriate treatment has been shown to have significantly greater clinical benefit in patient subgroups exhibiting the disorder the therapy is most likely to correct. A single drug or lifestyle therapy plan is no longer appropriate for all patients. The treatment must match the individual disorder(s).

Journal Article↗