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Carcinoma within urethral diverticula.

Because diagnosis of urethral diverticulum is often elusive the presence of a tumor within the diverticular cavity may be overlooked until it has grown beyond the confines of the diverticulum. A search of the medical records from 1940 to 1975 at the University of California Medical Center in San Francisco and Alta Bates Hospital in Berkeley has revealed only 3 cases of carcinoma within a urethral diverticulum. Two are presented here and the third was reported by Hinman in 1960. The paucity of cases in the literature reflects the rarity of such location for the tumor--or, perhaps, rather its evasive diagnostic nature. Undoubtedly, many cases are unreported but the important message for the clinician is that he suspect a urethral diverticulum (with the possibility of underlying neoplasm) in any patient with unexplained persistent irritative symptoms of the lower genitourinary tract.

Adenocarcinoma↗

Immunoglobulin composition of three commercially available intravenous immunoglobulin preparations.

To evaluate whether significant differences in immunoglobulin composition exist among the three commercially available intravenous immunoglobulin (IVIG) preparations, we compared three of these products in terms of their quantitative immunoglobulin concentration, IgG subclass concentration, and the presence of IgG aggregates. Three different lots were tested for each of the IVIG formulations, and the IgG subclass assays were performed by three different laboratories. Differences were found among the three formulations in subclass concentration and aggregate content. Sandoglobulin (Sandoz Pharmaceuticals, East Hanover, N.J.) contained a significantly higher amount of IgG2 (p less than 0.002) compared to the other formulations. All the formulations tested were found to be deficient in IgG4 relative to the World Health Organization standards, with Gammagard (Hyland Therapeutics, Glendale, Calif.) demonstrating only negligible amounts. Immunoglobulin aggregate content was different among manufacturers with Gamimmune N (Cutter Biological, Berkeley, Calif.) containing the highest amount of monomer IgG (99.8%). Significant differences were found in the subclass results obtained by the ICN ImmunoBiologicals assay (Lisle, Ill.), compared to the two reference laboratories. This difference among the subclass assays raises the question as to the use of these assays in the evaluation of patients with suspected subclass deficiencies. The differences in subclass concentration and aggregate content in IVIG preparations were great, and future clinical trials with these formulations would be indicated to determine the clinical significance of these findings.

Chromatography, High Pressure Liquid↗

Compartmentalized assembly of oligosaccharides on exported glycoproteins in yeast.

Temperature-sensitive secretory mutants (sec) of S. cerevisiae have been used to evaluate the stages and localization of glycoprotein oligosaccharide synthesis. At the nonpermissive growth temperature (37 degrees C), the sec mutants accumulate secretory organelles and glycoproteins. Histochemical staining and thin-section electron microscopy reveal that the secreted glycoprotein, acid phosphatase, is contained within one of three distinct organelles that accumulates in different mutants: ER; Golgi-like structures called Berkeley bodies; and 80--100 nm vesicles. When produced at 37 degrees C, invertase and acid phosphatase have less carbohydrate in the mutants that accumulate ER than in other mutants, or than in the wild-type strain. External invertase migrates on SDS-polyacrylamide gels as a heterogeneous species with an apparent molecular weight of 100 to 140 kd. Radiolabeled invertase, immunoprecipitated from extracts of ER-accumulating mutant cells, migrates as a set of three discrete protein species with apparent molecular weights of 79, 81, and 83 kd; the other mutants produce a form more like the secreted enzyme. In each case, removal of N-glycosidically linked oligosaccharides by treatment with endoglycosidase H produces a discrete species that migrates as a protein of 61 kd. Immunochemical analysis of bulk glycoprotein accumulated in the mutants suggests that a major portion of the N-linked oligosaccharide, the outer chain, is added after material passes from the ER.

Acid Phosphatase↗

Predicting rejection of her infant from mother's representation of her own experience: implications for the abused-abusing intergenerational cycle.

Child-battering parents are described in the literature as having three primary behavioral characteristics: a general difficulty with the control of aggression; an aversive, unsympathetic response to distress in others; and self-isolating tendencies. Here we review recent studies of young abused children which show the development of similar behavioral characteristics as early as 1-3 years of age. Surprisingly, these same three behavioral characteristics also develop in relatively maternally rejected children in normal samples. Taken together, these findings seem to suggest a continuum of psychological process from the experience of "normal" rejection to the experience of actual abuse by the parent. Studies of normal samples can then enrich our understanding of the psychological processes involved in child abuse. The second half of this article presents preliminary findings taken from our own ongoing study of social development in normal (nonabusive) families. Our study of the transcripts of 30 Berkeley Adult Attachment Interviews shows that a mother's apparent experience of her own mother as rejecting is systematically related to her rejection of her own infant (as observed in our laboratories) and at the same time to systematic distortions in her own cognitive processes (as taken from our study of adult attachment interviews). These distortions (idealization of the rejecting parent, difficulty in remembering childhood, incoherency in discussing attachment) are each significantly related to the mother's rejection of her own infant. Distortions in representation of an abusing parent may play a positive role in the perpetuation of child abuse.

Adult↗

Detection of induced mitotic chromosome loss in Saccharomyces cerevisiae--an interlaboratory study.

The diploid yeast strain D61.M was used to study induction of mitotic chromosome loss. The test relies upon the uncovering and expression of multiple recessive markers reflecting the presumptive loss of the chromosome VII homologue carrying the corresponding wild-type alleles. The underlying 'loss event' is probably complex since the predicted centromere-linked lethal tetrad segregations for chromosome VII are not recovered. Instead, the homologue bearing the multiple recessive markers is patently homozygous. An interlaboratory study was performed in which 16 chemicals were tested under code in 2 laboratories. The results generated by the Berkeley and Darmstadt laboratories were in close agreement. Acetonitrile, ethyl acetate, 4-acetylpyridine, propionitrile and nocodazole were identified as potent inducers of mitotic chromosome loss. Acetone, dimethyl sulfoxide and 2-methoxyethyl acetate either elicited weak responses or yielded ambiguous results. Water, carbon tetrachloride, 4-fluoro-D,L-phenylalanine, amphotericin B, griseofulvin, cadmium chloride, ethyl methanesulfonate and methylmercury(II) chloride failed to induce chromosome loss. These data suggest that the system described herein represents a reliable assay for chemically induced chromosome loss in yeast.

Alleles↗

Neuronal mechanisms of color categorization in areas V1, V2 and V4 of macaque monkey visual cortex.

A landmark study conducted by Berlin and Kay (Basic Color Terms, University of California Press, Berkeley, 1969, pp. 1-12) demonstrates that well-developed languages contain exactly 11 basic color terms. The basic colors (8 chromatic and 3 achromatic) are situated in specific locations of color space, suggesting a fixed relationship between specific hue and luminance. To determine the physiologic origins of the basic colors, we have studied the responses of cells in visual cortical areas V1, V2 and V4 of the behaving macaque monkey, using chromatic and achromatic stimuli of varying luminance. A total of 569 cells (291 from V1, 205 from V2, 73 from V4) were obtained, and classified as 'B' (bright; 43-50% of the total cells in each area), 'D' (dark; 6-12% of the total), and 'B/D' (bright/dark; 27-28% of the total) color or non-color cells according to each cell's color/luminance preference in relation to the neutral gray background. About two thirds of 'B' cells in each area were color specific, whereas the proportion of color cells in 'B/D' and 'D' categories was lower. In all three areas (v1, V2, V4), color cells with preferences for midspectral colors (such as yellow, lime and green) also preferred high luminance levels, while color cells with preferences for endspectral colors (such as red and blue) responded preferentially to luminance levels closer to background. The date provide evidence for categorical color perception within the visual system, as well as providing a physiological basis for the increased saliency of endspectral contours observed at equiluminance in psychophysical studies.

Action Potentials↗

Nonlinear SPICE models for physiologic systems.

Most biological systems are nonlinear but investigators interested in modeling them often make linear approximations to avoid performing tedious manual calculations. SPICE (Simulation Program with Integrated Circuit Emphasis, developed at the University of California, Berkeley, CA), an electrical circuit simulation program, is frequently used for creating and analyzing linear network models of physiologic and pathophysiologic processes. However, few investigators use the full capabilities of the program by modeling nonlinear elements. We developed six nonlinear SPICE elements, allowing simplified modeling of most commonly encountered physiologic processes. These are provided as subcircuits that can be easily incorporated into existing SPICE models. Included are voltage and current controlled nonlinear resistors, capacitors and inductors. In addition, we describe adders, multipliers, powers, inverse, and derivative functions.

Computer Simulation↗

Nonlinear waveform generation.

We developed three analog logic SPICE (Simulation Program with Integrated Circuit Emphasis, developed at the University of California, Berkeley, CA) subcircuits, a voltage comparator and a nonlinear waveform generator to compliment the previously derived functions (Goldstein and Rypins, Comput. Methods Programs Biomed. 29 (1989) 161-172) that simplify modeling of physiologic systems. The logic elements are the 'AND', 'OR' and 'NOT' Boolean functions. In addition, we derived a voltage comparator for use in our composite waveform generator. All the circuits are analog so they can be incorporated into existing analog circuits while performing digital functions.

Analog-Digital Conversion↗

Recruitment in the Coronary Artery Disease Risk Development in Young Adults (Cardia) Study.

Coronary Artery Disease Risk Development in Young Adults (CARDIA) is a longitudinal study designed to trace the development of risk factors for coronary heart disease in 5100 individuals 18-30 years old. The study will compare, by cross-sectional and longitudinal analyses, trends and processes involved in risk factor development by sex, race, age, and other sociodemographic characteristics. Participants for the approximately 4 1/2-hour baseline examination were randomly selected and recruited by telephone from census tracts in Minneapolis and Chicago, by telephone exchanges within the Birmingham city limit, and from lists of the Kaiser-Permanente Health Plan membership in Oakland and Berkeley. A major issue was the desirability of sampling approximately equal numbers by age, race, sex, and education as compared with sampling numbers representative of the population base. The recruitment goal of 5100 was achieved on schedule.

Adolescent↗

The evolving microlesion concept.

The "microlesion concept", introduced by D. Grahn in the 1970's, was further explored using published quantitative carcinogenesis data. Laboratory experiments performed by T. C. H. Yang and co-workers and by R. J. M. Fry and co-workers using the Fe ion beam of the Lawrence Berkeley Laboratory Bevalac have resulted in quantitative data on in vitro and in vivo (respectively) carcinogenesis in mouse systems. These data sets were interpreted on the basis of track calculations, and it was found that the action cross section for tumor induction in cultured cells is approximately 0.032 micrometer2 and that it is about 1/1000th as great in mouse Harderian gland cells. This great difference in carcinogenic sensitivity is a reflection of the biological differences between these two highly promoted systems, neither of which may be quantitatively applicable to humans in space.

Animals↗

Mutagenic effects of heavy ions in bacteria.

Various mutagenic effects by heavy ions were studied in bacteria, irradiated at accelerators in Dubna, Prague, Berkeley or Darmstadt. Endpoints investigated are histidine reversion (B. subtilis, S. typhimurium), azide resistance (B. subtilis), mutation in the lactose operon (E. coli), SOS chromotest (E. coli) and lambda-prophage induction (E. coli). It was found that the cross sections of the different endpoints show a similar dependence on energy. For light ions (Z < or = 4) the cross section decreases with increasing energy. For ions of Z = 10, it is nearly independent of energy. For heavier ions (Z > or = 26) it increases with energy up to a maximum or saturation. The increment becomes steeper with increasing Z. This dependence on energy suggests a "mutagenic belt" inside the track that is restricted to an area where the density of departed energy is low enough not to kill the cell, but high enough to induce mutations.

Azides↗

Sexual communication in the age of AIDS: the construction of risk and trust among young adults.

Sexually transmitted diseases are extremely prevalent among youth, and it is only by understanding the processes involved in negotiating sexual relationships that effective prevention and intervention programs can be designed. This study explores sexual communication among young adults, how gender and sexual orientation influence negotiation for safer sex, the strategies employed for risk reduction, and the barrier to safer sex. It assumes sexual behavior as a communicative form, both reflective and reflexive, subject to interpretation, and created interactively within and between sexual partners. Data from in-depth interviews with 30 undergraduates at the University of California, Berkeley were triangulated with questionnaires (n = 159), secondary sources and informal interviews with university officials. Participants were representative of arts and science students, ethnically diverse and of varying sexual orientations. Interviews focused on the normative influences of family, school and friends regarding sexuality; and how relationships and sex were negotiated. They investigated how strategies for risk reduction, attitudes about HIV and testing, and contraceptive practices were managed differently by gender and sexual orientation and what the barriers to safer sex were in various situations. Interviews focused on the normative influences of family, school and friends regarding sexuality; how relationships were negotiated, and how trust and risk were constructed within relationships; how strategies for risk reduction, attitudes about HIV and testing, and contraceptive practices were managed differently be gender and sexual orientation; and what the barriers were to safer sex. Friends, the social culture at university, and the interaction of the two with the developmental tasks characteristic of the period between adolescence and adulthood were more important influences than parents or high school sex education classes in how sexual relationships were managed. How and whether friends talked about sex and practiced safe sex were strong normative influences in predicting safer sex among individuals. Negotiating for safer sex contains elements of impression management, requires assertiveness and takes constant effort, even among those who have made the most progress in incorporating it. Practicing safer sex involves a complicated process of sexual negotiation, requiring a degree of open communication about sexual desire and intent that is not widely available in this culture, and still less among young people. Risk and thus how sex is negotiated is assessed differently by gender, and varies further according to the degree of intimacy in the relationship or the sex act being contemplated. How sex is negotiated depends on the construction of risk and trust which differ by the type of relationship or sexual encounter being contemplated.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

In vivo radiobiology of heavy ions.

The radiobiology of heavy charged particles has been investigated with various animal systems in vivo at the Lawrence Berkeley Laboratory using the helium beam from the 184" synchrocyclotron and the carbon, neon, and argon beams from the BEVALAC. Tumor experiments were carried out using the R1 sarcoma in rats and the EMT6 mouse mammary carcinoma, comparing X rays, carbon ions, neon ions, and argon ions. In vivo normal tissue experiments have been carried out with a wide range of tissues including testis, bone marrow, intestinal crypt cells, lens of the eye, esophagus, lung, and the spinal cord. The induction of dominant lethal mutations after irradiation of the testis was assayed by in vitro embryo culture after in vivo irradiation. Experiments were also done with the Harderian gland tumor induction system.

Animals↗

A phase I-II trial of heavy charged particle irradiation of malignant glioma of the brain: a Northern California Oncology Group Study.

Thirty-nine patients with primary or recurrent glioma of the brain were irradiated wholely or in part with heavy charged particle beams at the University of California Lawrence Berkeley Laboratory in a Phase I-II clinical trial of the Northern California Oncology Group. During the course of this trial, treatment techniques have been developed and tumor doses have been escalated in order to obtain data on normal brain toxicity and response of malignant glioma of the brain. Toxicity has been acceptable with a low level of brain injury. Survival and tumor control has been approximately the same as historical results in glioma of the brain. Further dose escalation is planned together with possible trial of combined modality therapy.

Adult↗

Dose volume histogram analysis of liver radiation tolerance.

Eleven patients with carcinoma of the pancreas or biliary system received heavy charged particle radiation treatments and whole liver heavy charged particle radiation at Lawrence Berkeley Laboratory. Doses to the whole liver ranged from 10 to 24 Gray-equivalent (the biological equivalent of 10 to 24 Gray of low-LET photon radiation), whereas the dose to the primary lesion ranged from 53.5 to 70 Gray-equivalent (GyE). The fraction size was 2 to 3 GyE. The liver received partial as well as whole organ irradiation. Integral dose volume histograms for the liver were obtained in all 11 patients. An integral dose volume histogram displays on the ordinate the percentage of liver that was irradiated in excess of the dose specified on the abcissa. In this study, the clinical liver radiation tolerance of these patients is correlated with the information contained in an integral dose volume histogram. One patient developed radiation hepatitis. The integral dose volume histogram of this patient differed from the dose volume histograms of the other 10 patients. This difference was greatest in the range of doses between 30 and 40 GyE. Our results suggest that liver doses in excess of 30 to 35 GyE should be limited to 30% of the liver or less when 18 GyE of whole liver radiation is delivered at 2 GyE per fraction in addition to primary radiation of the pancreas or biliary system.

Helium↗

Charged particle radiotherapy of selected tumors in the head and neck.

For selected tumors in some sites in the head and neck region, charged particles such as protons or helium, carbon, neon and silicon ions provide improved dose distributions, higher tumor doses, and an increased chance of local control and prolonged survival. In tumors with "radioresistant" histologies, slow growth kinetics and/or hypoxic cells, the high-LET component of neon or silicon ions may also offer and added potential for increased effect on tumors. Sixty-seven (67) evaluable patients with tumors in the head and neck region having a histology other than squamous carcinoma received partial or full treatment with charged particles at the University of California Lawrence Berkeley Laboratory. The tumor sites included base of skull or cervical spine, salivary glands, paranasal sinuses, nasopharynx, and miscellaneous sites such as lacrimal gland, soft tissues of the neck, or thyroid. Follow-up ranges from 1-9 years with a mean of 36 months and a median survival (Kaplan-Meier technique) of 50 months. The actuarial local control rate is 60% at 24 months post-treatment. Thirty-one (31) patients with squamous carcinoma of various sites in the head and neck have also been treated using charged particle irradiation; local control was lower (11 of 31 pts) and survival shorter (mean: 9 months) in this group of patients with advanced squamous carcinoma.

Adult↗

Development of a hospital-based proton beam treatment center.

Radiation oncologists recognize a continuing need to improve the radiation dose distribution between a cancer and the surrounding normal tissue. A most promising method of accomplishing this goal is the use of charged particle beam irradiation, the clinical use of which has been investigated for the past 40 years. Since the first clinical studies began at the Lawrence Berkeley Laboratory in 1954, more than 5,000 patients have been treated with protons, using accelerators designed for physics laboratories. Superior results are reported for the control of selected diseases by the ten facilities which are currently investigating proton radiation therapy. The findings have resulted in expansion plans in several of these facilities, and in the formulation of plans for two new facilities. We report on the planned development of a new facility at Loma Linda University, which has contracted with Fermi National Accelerator Laboratory for the design and fabrication of a 250 MeV synchrotron and its beam transport and delivery systems. This facility will be the first in the world to employ a proton accelerator dedicated to medical service and research. As such, it will be available as an international resource to develop and improve the modality.

California↗

Radiosensitization produced by iododeoxyuridine with high linear energy transfer heavy ion beams.

Little is known about radiosensitization produced by iododeoxyuridine (IUDR) with high linear energy transfer radiation. Likewise, the effect of IUDR on repair of sublethal or potentially lethal damage is unclear. A series of in vitro experiments was performed examining these aspects of IUDR radiosensitization. Human T1 cells were grown in the presence of 3.0 micromolar IUDR for 72 hours (approximately three doubling times), an exposure which resulted in minimal cytotoxicity to unirradiated cells. As the cells entered plateau phase they were exposed to X rays and a variety of heavy ion beams. Sensitization was found to decrease as linear energy transfer (LET) increased. No sensitization took place in an extremely high LET Lanthanum ion beam (1000 keV/micrometer). However, IUDR produced significant sensitization in the Neon ion beam currently used to treat cancer patients at Lawrence Berkeley Laboratory. Sensitization enhancement ratios at the 40% cell survival level were found to be 1.8 for X rays, 1.5 for the proximal Bragg peak of the clinical Neon beam, and 1.3 for the distal peak of the clinical Neon beam. Cell survival curves fitted to the linear-quadratic model showed IUDR significantly increased the value of the linear component (alpha) in beams with LETs below 40 keV/micron. The value of the quadratic component (beta) was unaffected by IUDR, regardless of LET. Split-dose experiments with both X rays and proximal peak Neon ions revealed IUDR did not affect sublethal damage repair. Similarly, delayed-plating experiments showed IUDR did not affect repair of potentially lethal damage. In contrast to cells unexposed to IUDR, IUDR-treated cells showed near-equal levels of cell killing throughout the extended Bragg peak of the clinical Neon beam. These findings suggest that the addition of IUDR to Neon ion radiotherapy could enhance the therapeutic ratio of the clinical Neon beam.

Cell Survival↗