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At least 595 records · Page 33Linked to original sources

Heavy-charged-particle radiosurgery of the pituitary gland: clinical results of 840 patients.

Since 1954, 840 patients have been treated at Lawrence Berkeley Laboratory with stereotactic charged-particle radiosurgery of the pituitary gland. The initial 30 patients were treated with proton beams; the subsequent 810 patients were treated with helium ion beams. In the great majority of the 475 patients treated for pituitary tumors, marked and sustained biochemical and clinical improvement was observed. Variable degrees of hypopituitarism developed in about one-third of patients treated solely with radiosurgery. In the earlier years of the program, 365 patients underwent radiosurgery to treat selected systemic diseases by inducing hypopituitarism. Focal temporal lobe necrosis and cranial nerve injury occurred in about 1% of patients who were treated with doses less than 230 Gy.

Acromegaly↗

Heavy-charged-particle radiosurgery for intracranial arteriovenous malformations.

We have treated over 400 patients with symptomatic inoperable intracranial arteriovenous malformations (AVMs) with stereotactic heavy-charged-particle Bragg peak radiosurgery at the University of California at Berkeley in a collaborative program with Stanford University Medical Center and the University of California Medical Center, San Francisco. A long-term dose-searching clinical trial protocol has been developed and we have followed more than 250 patients for more than 2 years. Initially, radiation doses ranged from 45 to 35 GyE, and now doses of 25, 20, 15 and, under special circumstances, 10 GyE, depending on a number of factors, are being evaluated. The characteristics of charged-particle beams provide a relatively homogeneous dose distribution with the 90% isodose contour to the periphery of the lesion. When the entire arterial phase of the AVM core is included in the treatment field, the rates for complete obliteration 3 years after treatment are: 90-95% for volumes less than or equal to 4 cm3; 90-95% for volumes greater than 4 and less than or equal to 14 cm3; and 60-70% for volumes greater than 14 cm3. The total obliteration rate for all volumes up to 70 cm3 is approximately 80-85%. For complete radiation-induced obliteration there is a relationship of dose and volume primarily, and location secondarily. Results on relationships between dose, AVM obliteration, and complications and sequelae of the radiosurgical procedure are presented and discussed.

Adult↗

A new iridovirus of two species of terrestrial isopods, Armadillidium vulgare and Porcellio scaber.

A new iridovirus, herein named isopod iridescent virus (IIV), was isolated from two species of terrestrial isopods in Berkeley, Calif. Infected individuals of Armadillidium vulgare and Porcellio scaber (Crustacea:Isopoda) appeared purple in color; in thin sections, hemocytes, nerve cells, and fat body cells contained cytoplasmic aggregations of virions. Isolated particles, 135 nm in diameter in negative stain, contained DNA had included at least 19 polypeptide components. The virus was transmitted per os and by injection to healthy isopods, and by injection to larvae of a coleopteran. IIV from the isopod hosts differed from Tipula iridescent virus (TIV) in buoyant density, molecular weights of major polypeptides, and serological reactions with antisera to IIV and TIV.

Antigens, Viral↗

Characterization of nucleic acids associated with Arkansas bee virus.

Arkansas bee virus (ABV) is a 30-nm isometric virus composed of one major species of polypeptide (mol. wt. 43 X 10(3] and one species of single-stranded RNA (mol. wt. 1.8 X 10(6]. The size of the genomic RNA and the lack of evidence for encapsidation or synthesis of a second smaller RNA species exclude further consideration of this virus for inclusion with the physicochemically similar viruses of the Nodaviridae. Several independent isolations of ABV were made from bees, and in each case it was associated in mixed infection with a picorna-like virus termed Berkeley bee picornavirus (BBPV). No evidence for replicative dependence, serological relationship, or genome relatedness by complementary DNA hybridization was obtained between ABV and BBPV.

Animals↗

Sustained effect of glucose-insulin-potassium on myocardial performance during regional ischemia. Role of free fatty acid and osmolality.

To evaluate the influence of glucose infusate administered with insulin and potassium on left ventricular function during 4 h of ischemia, as well as mechanism of action, four groups of intact anesthetized dogs were studied. Acute regional ischemia was induced with a balloon tip catheter in the left anterior descending artery and infusates were begun after 20 min of ischemia. A threefold increase of plasma glucose concentration was associated with improved left ventricular function during ischemia, compared to animals receiving isovolumic saline. There was a significant decline of left ventricular end-diastolic pressure associated with elevation of stroke volume and ejection fraction to control levels, as determined by indicator dilution. In a separate subgroup studied by cineangiography, shortening of the ischemic anterior wall, after an initial decline, was increased in response to glucose but there was no evidence of extension of injury. Ischemic tissue exhibited a smaller gain of water as well as Na+ per gram dry weight as compared to ischemic controls. On precordial electrocardiogram mapping there was a significant decrease in the sigmaST (sum of ST elevation) as well as NST (number of ST segment elevations), but the reduction of R wave amplitude was not different from controls. To further evaluate long-term effects, eight controls and six treated animals underwent myocardial ischemia and were sacrificed after 4 mo. Calculated area and weight of scar, as well as degree of wall thinning, were similar in both groups. The glucose-treated animals had a significant decrease of plasma FFA in contrast to controls which manifested a significant rise. To examine the postulate that the decrease in FFA was important to therapeutic action, a third group was infused with Intralipid (Cutter Laboratories, Inc., Berkeley, Calif.) and heparin, simultaneously with the glucose infusate, to effect an elevation of plasma FFA during ischemia. Changes in myocardial function and electrolyte composition, as well as precordial electrocardiogram mapping, were similar to that of animals receiving glucose alone. Because serum osmolality was increased approximately 40 mosmol during the glucose infusion, the potential role of hyperosmolality was assessed by infusion of 20% mannitol during acute ischemia in a fourth group. After a transient small increase, there was a moderate decline in function by 4 h, suggesting that the response to glucose is not dependent upon extracellular osmolality. Thus, it is concluded that during the initial hours after the onset of myocardial ischemia the glucose infusate improves ventricular performance without evidence of arrhythmia induction or intensification of ischemic injury. Evolution of irreversible necrosis appears to be delayed rather than prevented under the circumstances of this study.

Animals↗

Pulmonary vascular effects of fat emulsion infusion in unanesthetized sheep. Prevention by indomethacin.

Pulmonary diffusing capacity and arterial blood Po(2) decrease in humans when 10% fat emulsion is infused. To study its effects on the pulmonary circulation and lung fluid balance, we infused 0.25 g/kg x h of a 10% fat emulsion (Intralipid, Cutter Laboratories, Inc., Berkeley, Calif.) into an awake sheep lung lymph preparation. The emulsion caused a sustained increase in pulmonary artery pressure to approximately twice base line with little change in left atrial pressure. Pa(O2) decreased an average 13 torr and lung lymph flow increased two- to threefold. Lymph/plasma total protein concentration fell as lymph flow increased; the magnitude of the lymph/plasma protein decrease was similar to that reported previously when lung vascular pressures were mechanically elevated. Heparin infusion (loading dose = 4,000 U, maintenance dose = 2,000 U/h) cleared the serum of triglycerides but did not alter the response to fat emulsion. Indomethacin infusion (loading dose = 5 mg/kg, maintenance dose = 3 mg/kg x h) blocked the rise in pulmonary artery pressure, the increase in lung lymph flow, and the fall in Pa(O2). Neither extravascular lung water nor [(14)C]urea lung vascular permeability surface area products were altered by fat emulsion infusion. We conclude that fat emulsion infusion in sheep increases lung microvascular filtration by increasing vascular pressures, but has no effect on vascular permeability. Since the effects are blocked by indomethacin, they may be prostaglandin mediated.

Animals↗

Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice.

In sickle cell disease, intravascular sickling and attendant flow abnormalities underlie the chronic inflammation and vascular endothelial abnormalities. However, the relationship between sickling and vascular tone is not well understood. We hypothesized that sickling-induced vaso-occlusive events and attendant oxidative stress will affect microvascular regulatory mechanisms. In the present studies, we have examined whether microvascular abnormalities expressed in sickle transgenic-knockout Berkeley (BERK) mice (which express exclusively human alpha- and beta(S)-globins with <1% gamma-globin levels) are amenable to correction with increased levels of antisickling fetal hemoglobin (HbF). In BERK mice, sickling, increased oxidative stress, and hemolytic anemia are accompanied by vasodilation, compensatory increases in eNOS and COX-2, and attenuated vascular responses to NO-mediated vasoactive stimuli and norepinephrine. The hypotension and vasodilation (required for adequate oxygen delivery in the face of chronic anemia) are mediated by non-NO vasodilators (i.e., prostacyclin) as evidenced by induction of COX-2. In BERK mice, the resistance to NO-mediated vasodilators is associated with increased oxidative stress and hemolytic rate, and in BERK + gamma mice (expressing 20% HbF), an improved response to these stimuli is associated with reduced oxidative stress and hemolytic rate. Furthermore, BERK + gamma mice show normalization of vessel diameters, and eNOS and COX-2 expression. These results demonstrate a strong relationship between sickling and microvascular function in sickle cell disease.

Acetylcholine↗

Hemodynamic effects of intravenous fat emulsions in patients with heart disease.

Two intravenous fat emulsions (Liposyn 10%, Abbott Laboratories, North Chicago, IL, and Intralipid 10%, Cutter Laboratories, Berkeley, CA) were evaluated in 13 adult patients following cardiopulmonary bypass procedures in a randomized, prospective, double-blind study to determine their overall hemodynamic effects. The fat emulsions were administered for 30 minutes, and each patient was his own control. Neither intravenous fat emulsion was observed to exert significant changes in left ventricular stroke work, left ventricular filling pressure, cardiac output, systemic vascular resistance, mean systemic arterial blood pressure, central venous pressure, or mean pulmonary artery pressure. This study confirmed that the administration of 10% fat emulsions available in the United States does not exert significant untoward hemodynamic changes, even in patients with severe cardiac impairment recovering from recent open heart surgery.

Cardiopulmonary Bypass↗

Leonard Ralph Braithwaite (1878-1942).

Leonard Ralph Braithwaite lived and worked in Yorkshire all his life, with the exception of service overseas in World War I. He worked with Berkeley Moynihan early in his career, and went on to become a renowned surgeon and teacher in his own right.

England↗

Hospice referral decisions: the role of physicians.

In our study, we collected and evaluated the opinions of physicians in the Lowcountry of South Carolina (Berkeley, Charleston, and Dorchester counties) regarding their referrals to hospice programs and the extent of influence that their patients and families had on the decision. The research questionnaire was sent to 362 physicians who made referrals to hospice (53 percent response rate) and to 337 physicians who did not make referrals (40 percent response rate). Results revealed that medical doctors take the initiative in referrals. They felt that late referrals were due to reluctance on the part of the patient and the patient's family to admit that death was imminent. No differences were found in age, sex, medical specialty percent of terminally ill patients per practice, or initiative taken. However when the age and sex of physicians were evaluated, a statistically significant difference was found; females younger than 45 years of age were more likely to make referrals than younger males. Younger physicians were more likely to perceive that the family's reluctance to admit that death was near was a barrier to hospice referrals.

Adult↗

Reporting on violence: bringing a public health perspective into the newsroom.

The authors present a case study of a collaboration among the Berkeley Media Studies Group, the University of Missouri-Columbia School of Journalism, and journalist Jane Ellen Stevens to introduce to five metropolitan newspapers new violence-reporting techniques that include a public health perspective. A handbook was designed for journalists, and workshops were conducted to explore with editors and reporters how newspapers can report highly unusual crimes and yet avoid misrepresenting the patterns of violence in their communities and creating misguided fear in the public. This case study documents how journalists can be meaningfully engaged on this topic with people from public health despite typical barriers to access faced by public health practitioners and solid resistance from many editors and reporters. The authors describe goals, objectives, and activities across five daily newspapers along with journalists' reactions, concerns, and resistance to the issues that were raised.

Guidelines as Topic↗

Heavy ion therapy: status and perspectives.

Starting with the pioneering work at the University of California in Berkeley in 1977, heavy ion radiotherapy has been of increasing interest especially in Japan and Europe in the last decade. There are currently 3 facilities treating patients with carbon ions, two of them in Japan within a clinical setting. In Germany, a research therapy facility is in operation and the construction of a new hospital based facility at the Heidelberg university will be started soon. An outline of the current status of heavy ion radiotherapy is given with emphasis to the technical aspects of the respective facilities. This includes a description of passive and active beam shaping systems, as well as their implications for treatment planning and dosimetry. The clinical trials and routine treatments performed at the German heavy ion facility are summarized. An overview over the upcoming new facilities and their technical possibilities is given. It is discussed what the necessary improvements are to fully exploit the potential of these facilities. Especially the new Heidelberg facility with the possibility of active beam scanning in combination with the first isocentric gantry for ions and offering beams of protons, helium, oxygen and carbon ions has implications on treatment planning, dosimetry and quality assurance. The necessary and ongoing developments in these areas are summarized. The new facilities also offer the possibilities to perform more extensive clinical studies and to explore future indications for radiotherapy with heavy ions. An overview over the indications and treatment schemes is also given.

Carbon↗

Capacity building in environmental health research in India and Nepal.

The Fogarty International Training and Research Program in Environmental and Occupational Health at UC Berkeley concentrates on two major environmental health issues in the Indian subcontinent: arsenic in drinking water in West Bengal, India, and indoor air pollution in India and Nepal. Local trainees and researchers have had the opportunity to work on related research. Concerning arsenic in drinking water, projects included studies of skin lesions, pulmonary effects, reproductive outcomes, and child development, as well as mitigation approaches to reduce exposures. Activities in the indoor air pollution project have emphasized quantifying exposures to smoke from cooking and heating as well as their associations with tuberculosis and eye disease. Training has focused on developing skills necessary to address these problems. The training emphasizes in-country mentoring of trainees related to their research projects, and intensive short courses at partner institutions. The focus of capacity building in environmental health research in countries in economic and environmental transition should be on country-based research projects with embedded training efforts.

Air Pollution, Indoor↗

Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia.

Overexpression of Bcl-2 is a potential mechanism for chemoresistance in acute leukemia and has been associated with unfavorable clinical outcome. We hypothesized that down-regulation of Bcl-2 would restore chemosensitivity in leukemic cells. To test this hypothesis, we performed a phase 1 study of G3139 (Genasense, Genta, Berkeley Heights, NJ), an 18-mer phosphorothioate Bcl-2 antisense, with fludarabine (FL), cytarabine (ARA-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) salvage chemotherapy in patients with refractory or relapsed acute leukemia. Twenty patients with refractory or relapsed acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) were enrolled. G3139 was delivered by continuous infusion on days 1 to 10. FLAG chemotherapy was administered on days 5 to 10. Common side effects of this combination included fever, nausea, emesis, electrolyte imbalance, and fluid retention that were not dose limiting. Plasma pharmacokinetics of G3139 demonstrated steady-state concentration (Css) within 24 hours. Of the 20 patients, 9 (45%) had disease response, 6 (5 AML, 1 ALL) with complete remission (CR) and 3 (2 AML and 1 ALL) with no evidence of disease but failure to recover normal neutrophil and/or platelet counts or to remain in remission for at least 30 days (incomplete remission). Bcl-2 mRNA levels were down-regulated in 9 of the 12 (75%) evaluable patients. This study demonstrates that G3139 can be administered safely with FLAG chemotherapy and down-regulate its target, Bcl-2. The encouraging clinical and laboratory results justify the current plans for a phase 3 study in previously untreated high-risk AML (ie, age at least 60 years).

Acute Disease↗

The distributed annotation system.

BACKGROUND: Currently, most genome annotation is curated by centralized groups with limited resources. Efforts to share annotations transparently among multiple groups have not yet been satisfactory. RESULTS: Here we introduce a concept called the Distributed Annotation System (DAS). DAS allows sequence annotations to be decentralized among multiple third-party annotators and integrated on an as-needed basis by client-side software. The communication between client and servers in DAS is defined by the DAS XML specification. Annotations are displayed in layers, one per server. Any client or server adhering to the DAS XML specification can participate in the system; we describe a simple prototype client and server example. CONCLUSIONS: The DAS specification is being used experimentally by Ensembl, WormBase, and the Berkeley Drosophila Genome Project. Continued success will depend on the readiness of the research community to adopt DAS and provide annotations. All components are freely available from the project website http://www.biodas.org/.

Base Sequence↗

High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.

BACKGROUND: Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3. METHODS: To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought using a splice site prediction program from the Berkeley Drosophila Genome Project. RESULTS: The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment of SLC26A5 orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of human SLC26A5. CONCLUSION: These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of human SLC26A5 suggests a potential mechanism by which expression of prestin might be maintained in cells carrying the SLC26A5 IVS2-2A>G DNA sequence variation. Additional studies are needed to evaluate the effect of the IVS2-2A>G transition on splicing of SLC26A5 transcripts and characterize the hearing status of individuals homozygous for the IVS2-2A>G variant.

Adenine↗

A Drosophila full-length cDNA resource.

BACKGROUND: A collection of sequenced full-length cDNAs is an important resource both for functional genomics studies and for the determination of the intron-exon structure of genes. Providing this resource to the Drosophila melanogaster research community has been a long-term goal of the Berkeley Drosophila Genome Project. We have previously described the Drosophila Gene Collection (DGC), a set of putative full-length cDNAs that was produced by generating and analyzing over 250,000 expressed sequence tags (ESTs) derived from a variety of tissues and developmental stages. RESULTS: We have generated high-quality full-insert sequence for 8,921 clones in the DGC. We compared the sequence of these clones to the annotated Release 3 genomic sequence, and identified more than 5,300 cDNAs that contain a complete and accurate protein-coding sequence. This corresponds to at least one splice form for 40% of the predicted D. melanogaster genes. We also identified potential new cases of RNA editing. CONCLUSIONS: We show that comparison of cDNA sequences to a high-quality annotated genomic sequence is an effective approach to identifying and eliminating defective clones from a cDNA collection and ensure its utility for experimentation. Clones were eliminated either because they carry single nucleotide discrepancies, which most probably result from reverse transcriptase errors, or because they are truncated and contain only part of the protein-coding sequence.

Amino Acid Sequence↗

An integrated gene annotation and transcriptional profiling approach towards the full gene content of the Drosophila genome.

BACKGROUND: While the genome sequences for a variety of organisms are now available, the precise number of the genes encoded is still a matter of debate. For the human genome several stringent annotation approaches have resulted in the same number of potential genes, but a careful comparison revealed only limited overlap. This indicates that only the combination of different computational prediction methods and experimental evaluation of such in silico data will provide more complete genome annotations. In order to get a more complete gene content of the Drosophila melanogaster genome, we based our new D. melanogaster whole-transcriptome microarray, the Heidelberg FlyArray, on the combination of the Berkeley Drosophila Genome Project (BDGP) annotation and a novel ab initio gene prediction of lower stringency using the Fgenesh software. RESULTS: Here we provide evidence for the transcription of approximately 2,600 additional genes predicted by Fgenesh. Validation of the developmental profiling data by RT-PCR and in situ hybridization indicates a lower limit of 2,000 novel annotations, thus substantially raising the number of genes that make a fly. CONCLUSIONS: The successful design and application of this novel Drosophila microarray on the basis of our integrated in silico/wet biology approach confirms our expectation that in silico approaches alone will always tend to be incomplete. The identification of at least 2,000 novel genes highlights the importance of gathering experimental evidence to discover all genes within a genome. Moreover, as such an approach is independent of homology criteria, it will allow the discovery of novel genes unrelated to known protein families or those that have not been strictly conserved between species.

Animals↗