Showing papers by "University of California, San Francisco published in 1984"
TL;DR: It is reported here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently and this dynamic instability is a general property of micro Tubules and may be fundamental in explaining cellular microtubule organization.
Abstract: We report here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently. This dynamic instability is a general property of microtubules and may be fundamental in explaining cellular microtubule organization.
3,108 citations
TL;DR: In this article, an approach for deriving net atomic charges from ab initio quantum mechanical calculations using a least squares fit of the quantum mechanically calculated electrostatic potential to that of the partial charge model is presented.
Abstract: We present an approach for deriving net atomic charges from ab initio quantum mechanical calculations using a least squares fit of the quantum mechanically calculated electrostatic potential to that of the partial charge model. Our computational approach is similar to those presented by Momany [J. Phys. Chem., 82, 592 (1978)], Smit, Derissen, and van Duijneveldt [Mol. Phys., 37, 521 (1979)], and Cox and Williams [J. Comput. Chem., 2, 304 (1981)], but differs in the approach to choosing the positions for evaluating the potential. In this article, we present applications to the molecules H2O, CH3OH, (CH3)2O, H2CO, NH3, (CH3O)2PO, deoxyribose, ribose, adenine, 9-CH3 adenine, thymine, 1-CH3 thymine, guanine, 9-CH3 guanine, cytosine, 1-CH3 cytosine, uracil, and 1-CH3 uracil. We also address the question of inclusion of “lone pairs,” their location and charge.
2,976 citations
TL;DR: The equations and methods described in this report are intended to provide a simple but effective means for thermal dose estimation for clinical use and to stimulate efforts to evaluate data in terms of therapeutically useful thermal units.
Abstract: With the rapid development of clinical hyperthermia for the treatment of cancer either alone or in conjunction with other modalities, a means of measuring a thermal dose in terms which are clinically relevant to the biological effect is needed. A comparison of published data empirically suggests a basic relationship that may be used to calculate a "thermal dose." From a knowledge of the temperature during treatment as a function of time combined with a mathematical description of the time-temperature relationship, an estimate of the actual treatment calculated as an exposure time at some reference temperature can be determined. This could be of great benefit in providing a real-time accumulated dose during actual patient treatment. For the purpose of this study, a reference temperature of 43 degrees C has been arbitrarily chosen to convert all thermal exposures to "equivalent-minutes" at this temperature. This dose calculation can be compared to an integrated calculation of the "degree-minutes" to determine its prognostic ability. The time-temperature relationship upon which this equivalent dose calculation is based does not predict, nor does it require, that different tissues have the same sensitivity to heat. A computer program written in FORTRAN is included for performing calculations of both equivalent-minutes (t43) and degree-minutes (tdm43). Means are provided to alter the reference temperature, the Arrhenius "break" temperature and the time-temperature relationship both above and below the "break" temperature. In addition, the effect of factors such as step-down heating, thermotolerance, and physiological conditions on thermal dose calculations are discussed. The equations and methods described in this report are not intended to represent the only approach for thermal dose estimation; instead, they are intended to provide a simple but effective means for such calculations for clinical use and to stimulate efforts to evaluate data in terms of therapeutically useful thermal units.
2,229 citations
TL;DR: N-myc amplification is highly correlated with advanced stages of disease (P less than 0.001) and with the ability to grow in vitro as an established cell line, both of which are associated with a poor prognosis.
Abstract: A domain of DNA designated N-myc is amplified 20- to 140-fold in human neuroblastoma cell lines but not in cell lines from other tumor types. N-myc has now been found to be amplified in neuroblastoma tissue from 24 of 63 untreated patients (38 percent). The extent of amplification appears to be bimodal, with amplification of 100- to 300-fold in 12 cases and 3- to 10-fold in 10 others. Amplification was found in 0 of 15 patients with stage 1 or 2 disease, whereas 24 of 48 cases (50 percent) with stage 3 or 4 had evidence of N-myc amplification. These data indicate that N-myc amplification is a common event in untreated human neuroblastomas. Furthermore, N-myc amplification is highly correlated with advanced stages of disease (P less than 0.001) and with the ability to grow in vitro as an established cell line, both of which are associated with a poor prognosis.
2,168 citations
TL;DR: Antibodies to ARV were found in all 86 AIDS patients and in a high percentage of 88 other homosexual men in San Francisco, indicating the widespread presence of these lymphocytopathic retroviruses and their close association with AIDS.
Abstract: Infectious retroviruses have been detected in 22 of 45 randomly selected patients with acquired immune deficiency syndrome (AIDS) and in other individuals from San Francisco. The AIDS-associated retroviruses (ARV) studied in detail had a type D morphology, Mg2+-dependent reverse transcriptase, and cytopathic effects on lymphocytes. The viruses can be propagated in an established adult human T cell line, HUT-78. They cross-react with antiserum to the lymphadenopathy-associated retrovirus isolated from AIDS patients in France. Antibodies to ARV were found in all 86 AIDS patients and in a high percentage of 88 other homosexual men in San Francisco. This observation indicates the widespread presence of these lymphocytopathic retroviruses and their close association with AIDS.
1,420 citations
TL;DR: The cortical representations of the hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2–8 months after surgical amputation of digit 3, or of both digits 2 and 3.
Abstract: The cortical representations ofthe hand in area 3b in adult owl monkeys were defined with use of microelectrode mapping techniques 2-8 months after surgical amputation of digit 3, or of both digits 2 and 3. Digital nerves were tied to prevent their regeneration within the amputation stump. Suc cessive maps were derived in several monkeys to determine the nature of changes in map organization in the same individuals over time. In all monkeys studied, the representations of adjacent digits and pal mar surfaces expanded topographically to occupy most or all of the cortical territories formerly representing the amputated digit(s). With the expansion of the representations of these surrounding skin surfaces (1) there were severalfold increases in their magnification and (2) roughly corresponding decreases in receptive field areas. Thus, with increases in magnification, surrounding skin surfaces were represented in correspondingly finer grain, implying that the rule relating receptive field overlap to separation in distance across the cortex (see Sur et aI., '80) was dynamically maintained as receptive fields progressively decreased in size. These studies also revealed that: (1) the discontinuities between the representations of the digits underwent significant translocations (usually by hundreds of microns) after amputation, and sharp new discontinuous boundaries formed where usually separated, expanded digital representa tions (e.g., of digits 1 and 4) approached each other in the reorganizing map, implying that these map discontinuities are normally dynamically main tained. (2) Changes in receptive field sizes with expansion of representations of surrounding skin surfaces into the deprived cortical zone had a spatial distribution and time course similar to changes in sensory acuity on the stumps of human amputees. This suggests that experience-dependent map changes result in changes in sensory capabilities. (3) The major topographic changes were limited to a cortical zone 500-700 JIm on either side of the initial boundaries of the representation of the amputated digits. More dis tant regions did not appear to reorganize (i.e., were not occupied by inputs from surrounding skin surfaces) even many months after amputation. (4) The representations of some skin surfaces moved in entirety to locations within the former territories of representation of amputated digits in every
1,327 citations
TL;DR: There is some evidence that suggests that whereas comparator elements are not reset during stress, a comparator element is reset during the course of the circadian rhythm so that different basal levels of steroid are achieved.
Abstract: THE LEVEL of activity within the adrenocortical system is determined by endogenous (circadian) and exogenous (stress) excitatory inputs, by inhibitory neural modulation and also by corticosteroid negative feedback control. Although corticosteroid feedback on (CRF and) ACTH secretion is easily demonstrated by treatment of mammals with exogenous glucocorticoids and subsequent measurement of either basal or stimulated activity in the system, the physiological role of this negative feedback is not so easily discerned. It is likely that most disagreement about feedback regulation of ACTH secretion has arisen because of three characteristics of the system. First, it now appears that there are at least three distinct time domains in which negative feedback by glucocorticoids on ACTH secretion are exerted. These can be distinguished at the level of the corticotrope in vitro by the different cellular effects of glucocorticoid action. Thus, interpretation of results of in vivo experiments is critically dependent on...
1,177 citations
TL;DR: The neurotoxic chemical MPTP is metabolized by rat brain mitochondrial fractions at a rate of 0.91 +/- 0.02 nmoles/mg protein/min, and the major metabolite has been identified as the 1-methyl-4- phenylpyridinium species.
1,111 citations
TL;DR: This study confirms that oral leukoplakia is a precancerous lesion and that certain characteristics indicate greater risks and warrant consideration of more aggressive management.
Abstract: Two hundred fifty-seven patients with oral leukoplakia were studied and followed for an average period of 7.2 years. All lesions were more than one cm in size and had been present and observed for a minimum of 6 months. Of the initial biopsies, 235 revealed a benign hyperkeratosis and 22 others contained some degree of epithelial dysplasia. Seventy-three percent of the patients used tobacco, with cigarette usage being the predominant form. Forty-five patients (17.5%) subsequently developed squamous carcinomas in the hyperkeratotic epithelial site in an average time of 8.1 years. Eight of these malignant transformations came from patients who originally had epithelial dysplasia. High risks for malignant transformation also included non-smoking patients, the clinical presence of erythroplasia (erythroleukoplakia), and a clinical verrucous-papillary hyperkeratotic pattern. Duration of the leukoplakia progressively increased the total number of malignant transformations, with the largest rate occurring in the second year. This study confirms that oral leukoplakia is a precancerous lesion and that certain characteristics indicate greater risks and warrant consideration of more aggressive management.
1,027 citations
TL;DR: When human lymphocytes were cultured with [3H]thymidine, which acts as a source of low-level chronic radiation, and then exposed to 150 rad of x-rays at 5, 7, 9, or 11 hours before fixation, the yield of chromatid aberrations was less than the sum of the yields of aberration induced by [3 H]thcyidine and x-ray separately.
Abstract: When human lymphocytes were cultured with [3H]thymidine, which acts as a source of low-level chronic radiation, and then exposed to 150 rad of x-rays at 5, 7, 9, or 11 hours before fixation, the yield of chromatid aberrations was less than the sum of the yields of aberrations induced by [3H]thymidine and x-rays separately. Often fewer aberrations were found after exposure to radiation from both sources than were found after exposure to x-rays alone. At the same fixation times, nonradioactive thymidine did not affect the yield of x-ray-induced aberrations. The same phenomenon occurred at earlier fixation times, after exposure to 30 or 40 rad of x-rays and [3H]thymidine. This response is analogous to the adaptive response to alkylating agents whereby prior treatment with small doses for a long period reduces the damage occurring from large doses of similar agents given for a short time.
804 citations
TL;DR: The genotype at this locus of 393 unrelated diabetic and nondiabetic individuals is determined and differences were observed in the genotypie and allelic frequencies between groups of different races.
Abstract: A polymorphic region flanking the human insulin gene on the short arm of chromosome 11, the insulin-gene-linked DNA polymorphism, can be described as a locus with at least three classes of alleles: a common small “class 1” allele averaging 570 base pairs, a rare intermediate “class 2” allele of about 1320 base pairs, and a large “class 3” allele averaging 2470 base pairs in size.
We have determined the genotype at this locus of 393 unrelated diabetic and nondiabetic individuals. Differences were observed in the genotypie and allelic frequencies between groups of different races. Asians [17 nondiabetic, 2 with insulin-dependent diabetes mellitus (IDDM), and 8 with non-insulin-dependent diabetes mellitus (NIDDM)] exhibited the least variation in the size of this locus and 98% of the alleles in this group were class 1. A group of American blacks (32 nondiabetic, 5 with IDDM, and 40 with NIDDM) exhibited considerable variation in the size of this locus, and about 22% of the individuals examined had a genotype that included a rare class 2 allele. In neither of these two racial groups were the genotypie or allelic frequencies different between the nondiabetic and diabetic segments of these groups.
However, in a group of Caucasians (83 nondiabetic, 113 with IDDM, and 76 with NIDDM), there was a significantly higher frequency of class 1 alleles and genotypes containing two class 1 alleles in the diabetic patients compared with nondiabetic controls. A strikingly higher frequency of class 1 alleles (P < 0.0001) and genotypes containing two class 1 alleles (P < 0.0001) was observed in the IDDM group compared with nondiabetic Caucasians, whereas the difference between NIDDM and controls was only near the level of statistical significance (P = 0.025). Analysis of the combined data of our Caucasian population and those reported from studies of Caucasians from Denmark and St. Louis, Missouri, continued to show an increased frequency of class 1 alleles and genotypes containing two class 1 alleles in the IDDM group (P = 0.0001) compared with the nondiabetic group; however, there were no longer differences in genotypic or allelic frequencies between NIDDM and nondiabetic groups.
TL;DR: New genetic and functional similarities between divergent organisms have been discovered, providing convincing evidence of the evolutionary conservation of strategies used in the targeting and translocation of polypeptides.
TL;DR: It is reported here that purified centrosomes nucleate the assembly of microtubules with unusual dynamic properties, which may have important implications for the mechanism by which microtubule arrays are organized and stabilized in cells.
Abstract: Microtubules are involved in the morphogenesis of most cells and are the structural basis of the mitotic spindle. We report here that purified centrosomes nucleate the assembly of microtubules with unusual dynamic properties. This may have important implications for the mechanism by which microtubule arrays are organized and stabilized in cells.
TL;DR: This review has attempted to give an account of an afferent vagal input from the lower respiratory tract that has still to be explored fully, and to present experimental evidence that this fine fibre afferent system plays a significant role in the neural control of respiratory function in both normal and pathological circumstances.
Abstract: We have attempted in this review to give an account of an afferent vagal input from the lower respiratory tract that has still to be explored fully, and to present experimental evidence that this fine fibre afferent system plays a significant role in the neural control of respiratory function in both normal and pathological circumstances.
TL;DR: An indirect mechanism appears to activate expression of this putative oncogene within a highly conserved locus on chromosome 15 called int-1 in mammary tumours with proviral insertions positioned on either the 5′ and 3′ sides of the gene.
Abstract: Most mammary carcinomas induced in C3H mice by the mouse mammary tumour virus (MMTV) bear a new proviral insertion within a highly conserved locus on chromosome 15 called int-1. A transcriptional unit within this locus is inactive in all tested normal tissues but expressed at low levels in mammary tumours with proviral insertions positioned on either the 5' and 3' sides of the gene. Transcription of the proviruses proceeds away from int-1; thus an indirect mechanism appears to activate expression of this putative oncogene.
TL;DR: The salivary component of SS should be redefined as the presence of LSG focal sialadenitis, an objective criterion and a more disease-specific feature of SS than xerostomia or any other feature of Salivary disease.
Abstract: Xerostomia is an unsatisfactory diagnostic criterion for the salivary component of Sjogren's syndrome (SS). To determine the diagnostic usefulness of the presence of focal sialadenitis in labial salivary gland (LSG) biopsy specimens, 362 patients suspected of having SS prospectively underwent a unique LSG biopsy procedure. The pattern and severity of LSG inflammation were compared with measurements of parotid flow rate, and the presence or absence of symptomatic xerostomia, major salivary gland enlargement, keratoconjunctivitis sicca (KCS), and other connective tissue diseases (CTD). LSG biopsy focus scores of >1 correlated more closely with the diagnoses of KCS alone and with KCS plus a CTD than did either reduced parotid flow rate or symptoms of xerostomia (P < 0.0005 and P < 0.05, respectively). Focal sialadenitis in an adequate LSG specimen is an objective criterion and a more disease-specific feature of SS than xerostomia or any other feature of salivary disease. The salivary component of SS should be redefined as the presence of LSG focal sialadenitis.
TL;DR: The results show that the trabecular cellularity in NG specimens decreases most rapidly and in a nonlinear manner in the late fetal period and for the first few years of postnatal life, and this rapid decline in cellularity then slows down to proceed in a nearly linear manner for the remainder of the 98 years of life studied.
TL;DR: A significant physiological difference between joints that develop mild and severe arthritis is suggested and indicates that release of intraneuronal substance P in joints contributes to the severity of the arthritis.
Abstract: There is evidence that substance P is a peptide neurotransmitter of some unmyelinated primary afferent nociceptors and that its release from the peripheral terminals of primary afferent fibers mediates neurogenic inflammation. The investigators examined whether substance P also contributes to the severity of adjuvant-induced arthritis, an inflammatory disease in rats. They found that, in the rat, joints that developed more severe arthritis (ankles) were more densely innervated by substance P-containing primary afferent neurons than were joints that developed less severe arthritis (knees). Infusion of substance P into the knee increased the severity of arthritis; injection of a substance P receptor antagonist did not. These results suggest a significant physiological difference between joints that develop mild and severe arthritis and indicate that release of intraneuronal substance P in joints contributes to the severity of the arthritis.
TL;DR: A single N-terminal amino acid sequence for PrP 27-30 was obtained and it does not share homology with any known proteins and knowledge of the amino acids sequence should permit determination of the genetic origin and replication mechanism of prions.
TL;DR: Theoretical calculations for cross-peak intensities obtained in 2D NOE spectra were calculated for a set of three-proton spins and a setof fourproton spin systems in this article, and the influence of specific types of overall and internal motion on the calculated cross peak intensities and the distances determined from them was tested.
TL;DR: Results indicate that the SWI genes function in some way as positive regulators of HO expression and have additional cellular roles.
TL;DR: An outbreak of a new form of oral leucoplakia, found principally on the lateral borders of the tongue, is reported in male homosexuals in the San Francisco area, and may offer clues to the pathogenesis of other forms of oral epithelial hyperplasia and dysplasia.
TL;DR: It is suggested that specific glucocorticoid receptor-DNA interactions may alter the configuration of DNA or chromatin in the vicinity of the binding sites, thereby creating an active transcriptional enhancer.
TL;DR: A specific, sensitive, and rapid bioassay for measuring plasma cholecystokinin in rats is reported, based on their ability to stimulate amylase release from isolated rat pancreatic acini.
TL;DR: It is shown here for one patient that N-myc amplification is confined to the neuroblastoma tumor and is not present in normal tissue, and it is hypothesized that amplification and consequent elevated expression of N- myc may be related to malignant progression.
Abstract: Previous studies had revealed that DNA with partial similarity to the myc oncogene (N-myc) is frequently amplified in human neuroblastoma cell lines and neuroblastoma tumors. We show here for one patient that N-myc amplification is confined to the neuroblastoma tumor and is not present in normal tissue. N-myc mRNA approximately equal to 4.0 kilobases in size is detectable in neuroblastoma cell lines and tumors and in a retinoblastoma cell line. By contrast, appreciable amounts of this RNA were not present in a number of cell lines derived from other human tumors and in fibroblasts from a normal individual and from a neuroblastoma patient. Low levels of N-myc RNA were found in human and murine neuroblastoma cell lines lacking amplification of this gene, up to 80-fold greater levels in all cell lines carrying amplified N-myc. In situ hybridization to sections of neuroblastoma tumors revealed high expression of N-myc predominantly in undifferentiated neuroblasts. We hypothesize that amplification and consequent elevated expression of N-myc may be related to malignant progression.
TL;DR: It is proposed that when occlusion is not ideal, lateral forces cause the teeth to bend and the tensile stresses created during bending disrupt the chemical bonds of the crystalline structures of enamel and dentin, making the disrupted tooth structure more susceptible to loss through dissolution and abrasion.
Abstract: A tensile stress hypothesis for the etiology of idiopathic cervical erosions of human teeth is presented. It is proposed that when occlusion is not ideal, lateral forces cause the teeth to bend. The tensile stresses created during bending disrupt the chemical bonds of the crystalline structures of enamel and dentin. Small molecules may enter between the crystals and prevent the reestablishment of the chemical bonds. As a result, the disrupted tooth structure is more susceptible to loss through dissolution and abrasion and results in the development of the typically wedge-shaped lesions. Patients with lesions typical of hundreds examined by the authors were presented to illustrate the concept. The possible consequences of the proposed hypothesis were discussed. The hypothetical conclusions made in this article will be tested by experimentation.
TL;DR: In Xenopus embryos cell-cycle events of the nucleus, including DNA replication and mitosis, are controlled by the level of MPF activity, which is driven by or may be part of an autonomous cell- cycle oscillator.
TL;DR: The action of baclofen is analysed on the membrane potential of CA1 hippocampal pyramidal cells in vitro and it is reported that it directly hyperpolarizes these cells in a potent, stereoselective manner which is resistant to bicuculline methiodide.
Abstract: Baclofen has been used as an antispastic agent for over a decade1, yet its mechanism of action is still not fully understood. While early iontophoretic studies revealed a depression of neuronal activity2–4, more recent studies have emphasized a presynaptic depression of transmitter release, both in the peripheral5,6 and central nervous sytem7–14, possibly resulting from a blockade of calcium channels15. Although baclofen is structurally similar to the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), none of its actions seem to be antagonized by the GABA antagonist, bicuculline. However, recent experiments have indicated that baclofen binds to a class of bicuculline-resistant GABA receptors, termed GABAB receptors16. Here, we have analysed the action of baclofen on the membrane potential of CA1 hippocampal pyramidal cells in vitro and report that it directly hyperpolarizes these cells in a potent, stereoselective manner which is resistant to bicuculline methiodide. This response is associated with a decrease in neuronal input resistance and may involve an increase in potassium conductance.
TL;DR: Indirect immunofluorescence and subcellular fractionation studies with yeast cells containing the alpha 2-LacZ hybrid proteins indicate that thealpha 2 segment can direct localization of beta-galactosidase to the nucleus, and indicates that theAlpha 2 protein, argued on genetic grounds to be a negative regulator, acts in the yeast nucleus.
TL;DR: Recovery of visual function included a dramatic improvement in ERG and ERP amplitudes over several weeks, and there is no definite evidence of systemic involvement in patients with unilateral ocular findings.
Abstract: • We examined 11 young patients with unilateral ocular findings that included multiple white dots at the level of the retinal pigment epithelium (RPE) or the deep retina, vitreal cells, RPE granularity in the macula, reduced visual acuity, electroretinogram (ERG) and early receptor potential (ERP) amplitudes, and fluorescein leakage from disc capillaries and late staining of the RPE. Recovery of visual function included a dramatic improvement in ERG and ERP amplitudes over several weeks. The etiology of this syndrome remains uncertain; there is no definite evidence of systemic involvement.