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D Larson

Publications and source records attributed to D Larson.

At least 55 records · Page 3Linked to original sources
PubMed1995

The RNA polymerase I transcription factor UBF is the product of a primary response gene.

Transcription of the ribosomal RNA genes by RNA polymerase I is tightly coordinated with the rate of cell growth. The RNA polymerase I transcription factor, UBF, activates transcription by binding to elements within the promoter and enhancer elements within the intergenic spacer but is not required for basal transcription. To assess the role of UBF in modulating ribosomal DNA transcription, we studied its expression in NIH3T6 fibroblasts when transcription was repressed in response to serum starvation and stimulated following refeeding. Our results demonstrate a correlation between the amounts of UBF protein and the rates of ribosomal DNA transcription in quiescent and serum-stimulated cells. Nuclear run-on assays and Northern blot analyses demonstrated that the UBF gene was a primary response gene, exhibiting characteristics similar to those of c-myc and SRF. These results suggest that the regulation of transcription of the UBF gene by polymerase II represents a pathway by which cells modulate transcription by RNA polymerase I.

3T3 Cells↗
PubMed1995

Evaluation of a novel serotyping system for hepatitis C virus: strong correlation with standard genotyping methodologies.

Direct sequencing and analysis of viral genomes are definitive methods for identifying various hepatitis C virus (HCV) genotypes. However, HCV genome sequencing methods are cumbersome and unsuitable for analyzing large numbers of clinical samples. We have developed a convenient, reliable, and reproducible RIBA strip immunoblot assay system for determining HCV serotype. Briefly, the assay consists of an immunoblot strip on which there are five lanes of immobilized serotype-specific HCV peptides from the nonstructural (NS-4) and core regions of the genomes of HCV types 1,2, and 3. HCV serotype is deduced by determining the greatest intensity of reactivity to the NS-4 serotype-specific HCV peptide band in relation to the intensity of the human immunoglobulin G internal control bands on each strip. HCV core peptide reactivity is used only in the absence of NS-4 reactivity. We used this assay to successfully serotype a high percentage of sera from well-documented HCV-infected patients. Our serotyping results correlated 99% with the findings from the standard restriction fragment length polymorphism genotyping methods. Less than 5% of the serum samples were untypeable. For a selected group of alpha interferon-treated patients we observed that the nonresponders (76.2%) and a majority of the responders who relapsed (72.2%) had type 2 HCV infection. A small population (n= 8) of complete responders was split 3:4:1 as type 1, type 2, and type 3, respectively. Our data indicate that this new serotyping assay has the potential to be a highly specific and reliable method for typing of HCV infection in patients.

Genotype↗
PubMed1995

Stereotactic radiosurgery in children.

The role of stereotactic radiosurgery in the treatment of pediatric patients is still being explored. We report the Gamma Knife treatment of 33 patients under the age of 21, at the University of California, San Francisco, between the years 1991 and 1993. Treatment-related toxicity has been low. 10/14 patients treated for arteriovenous malformation (AVM) with follow-up > 1 month have shown partial or complete AVM obliteration. No patient has had a new hemorrhage after AVM treatment. In children with malignant tumors, treatment was well tolerated, although most patients, ultimately, had progressive disease. Stereotactic radiosurgery is logistically possible in the pediatric population. Its use in selected patients with AVMs seems appropriate, although its role in the treatment of malignant brain tumors remains to be defined.

Adolescent↗
PubMed1994

Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addiction to opioid and stimulant drugs and has been reported to decrease morphine and cocaine self-administration in rats. The present study sought to determine if other iboga alkaloids, as well as the chemically related harmala alkaloid harmaline, would also reduce the intravenous self-administration of morphine and cocaine in rats. Because both ibogaine and harmaline induce tremors, an effect that may be causally related to neurotoxicity in the cerebellar vermis, the temorigenic activities of the other iboga alkaloids were assessed. Lastly, in view of the involvement of the dopaminergic mesolimbic system in the actions of drugs of abuse, the effects of some of the iboga alkaloids on extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum were determined. All of the tested alkaloids (i.e., ibogaine, tabernanthine, R- and S-coronaridine, R- and S-ibogamine, desethylcoronaridine, and harmaline) dose-dependently (2.5-80 mg/kg) decreased morphine and cocaine intake in the hour after treatment; decreases in morphine and cocaine intake intake were also apparent the day after administration of some but not all of these alkaloids (i.e., ibogaine, tabernanthine, desethylcoronaridine, and the R-isomers of coronaridine and ibogamine). In some rats, there were persistent decreases in morphine or cocaine intake for several days after a single injection or after two or three weekly injections of one or another of these alkaloids; R-ibogamine produced such effects more consistently than any of the other alkaloids.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1994

Hard choices: the gynecologic cancer patient's end-of-life preferences.

Few reports in gynecologic literature have addressed patient preferences about terminal care. In light of the current discussions about end-of-life decision-making, a study was designed to assess the desires of patients with gynecologic cancer. A questionnaire was completed by 108 patients under treatment for gynecologic cancer at the University of Michigan Medical Center and by 39 patients from the routine gynecology clinic at the same institution. Participants were asked about their reactions to a poor prognosis, their desires for the location of terminal care, and their preferences for withdrawing or withholding life-sustaining technologies. Five percent of these cancer patients anticipated giving up the fight against their disease. Seventy-eight percent specifically expressed resolve to continue the fight against their disease. Feedback from these patients about their end-of-life preferences served to define the concept "fight." A majority preferred to receive care at home. Ninety percent of these cancer patients could envision their conditions deteriorating to the point that they would not want ventilator support. Thirty-four percent could envision refusing surgery for another life-threatening condition; 37%, a time when artificial nutrition would be refused; 22%, a time when antibiotics would be rejected. This study suggests that limiting the use of artificial respiratory support while continuing the use of artificial nutrition and hydration support would be consistent with the preferences of gynecologic cancer with end-stage disease.

Adult↗
PubMed1994

Family views on sterilization for their mentally retarded children.

Eighty-eight parents of adolescents or adults with mental retardation answered written and/or telephone questionnaires concerning sterilization and reproductive health choices for their children with mental retardation. The 36 parents whose children were still living at home were more concerned about the capacity for sexual activity in their disabled child than were the 52 parents whose children were living outside the home. Otherwise, the two groups of parents were very similar in their attitudes. The reasons for considering sterilization were parental fear of sexual abuse, unwanted pregnancy and failure of birth control methods. Almost all the parents in this study wanted to participate in decisions concerning the sterilization of their disabled child.

Activities of Daily Living↗
PubMed1993

Beta test site report: gamma plan.

We describe our preliminary experience with a beta-test version of the Leksell Gamma Plan (LGP) treatment planning system. During this testing phase we used the LGP system to find an acceptable treatment plan and then transferred coordinates to the KULA system for final calculation. We find that the LGP system offers a fast way of optimizing shot placement and weighting, especially for complex treatments. The ability to display many MR and CT images on screen and to superimpose isodose lines on these images, as soon as the dose distribution has been calculated, allows adjustments to be made more rapidly than with the plotting approach used by the KULA system. This software is in beta-test, and is undergoing modification. Problems relating to our hardware configuration have been addressed with a newer workstation specified for the production system.

Computer Graphics↗
PubMed1992

A specialized home care team does make a difference.

Results of a study done in a large teaching and research facility in Alberta reveal that a specialized home care team can substantially lower the cost of caring for people who are ventilator dependent. With the assistance of a pulmonary physician, the Respiratory Home Care program has shown excellent results. Patients report that they "feel as safe at home as in the hospital", and the savings to the health care system are estimated to be about $2,000,000 per year.

Alberta↗
PubMed1992

Evaluation of a Treponema pallidum western immunoblot assay as a confirmatory test for syphilis.

Tests for the detection of antibodies to Treponema pallidum are recommended for the confirmation of reactive nontreponemal test results and the accurate diagnosis of syphilis. The present-day use of Western blot (immunoblot) technology for the diagnosis of retroviruses prompted the development and evaluation of a Western blot assay with whole-cell T. pallidum as the antigen. The assay detected antibodies in syphilitic serum or plasma from dilutions of specimens incubated overnight with test strips. A test was considered positive when at least three of four major antigens having molecular masses of 15.5, 17, 44.5, and 47 kDa were detected. The Western blot assay had 93.8% sensitivity and 100% specificity for clinically defined samples. The Western blot assay was compared with double-staining fluorescent treponemal antibody absorption [FTA-ABS (DS)], which had a sensitivity and a specificity of 91.7 and 92.0%, respectively. Dilution series studies of syphilis-positive specimens indicated that the Western blot assay has an endpoint of reactivity at least 3 to 4 serial dilutions greater than that for FTA-ABS (DS). Overall, the greater than 95% agreement between the Western blot assay and FTA-ABS (DS) for clinically defined specimens indicates that the sensitivity of the Western blot assay is equal to or greater than that of FTA-ABS (DS). The Western blot assay demonstrated no false-positive or equivocal reactivities for nonsyphilitic specimens, including normal specimens (both plasma and serum), biological false-positives, and specimens with elevated gamma globulin or antinuclear antibody. We conclude that the high sensitivity and specificity of the T. pallidum Western blot assay, together with its simplicity and objectivity, make it a good confirmatory test for syphilis.

Animals↗
PubMed1992

Psychosocial and psychopathologic influences on management and control of insulin-dependent diabetes.

The objective of this research was to explore the relationship of psychosocial variables to management and control of insulin-dependent diabetes, as measured by a scale of reported behavioral adherence and by glycosylated hemoglobin, respectively. The method includes a relatively large sample (127 subjects) drawn from a clinic, a broad range of psychosocial variables (depression, anxiety, family process, health locus of control), and documented reliability and validity of psychosocial measurement (alpha coefficients ranging from .63 to .95). The results show that both anxiety and depression have weak positive correlations with blood sugar. Family process variables also are weakly correlated with blood sugar. The measure of behavioral adherence is moderately correlated with blood sugar. The life stage of the diabetic appears to affect these relationships markedly. The conclusion is that there is no broad strong association of psychosocial variables with blood sugar but that there may be subgroups of diabetics, especially adolescents with recent onset, for whom the relationships may be more powerful.

Adolescent↗
PubMed1991

Regional blood-brain barrier transport of cationized bovine serum albumin in awake rats.

Regional blood-brain barrier permeability-surface area products (PAs) of cationized bovine serum albumin (cBSA) with isoelectric point (pI) approximately 8 or greater than or equal to 11 and of native bovine serum albumin (nBSA;pI approximately 4) were determined in awake male Sprague-Dawley rats after bolus intravenous injection. The albumins were labeled with 125I. Brain uptakes were assessed by autoradiography and by direct assay of radioactivity in brain regions. nBSA uptake into brain was statistically insignificant over 3 h, whereas cBSA uptake was significantly even at 6 min. Mean PA values of cBSA with pI approximately 11 (1.69-2.65 x 10(-5) ml.s-1.g-1) in most brain regions were twofold higher than PAs of cBSA with pI approximately 8 (0.98-1.37 x 10(-5) ml.s-1.g-1), whereas mean PA for nBSA did not differ significantly from zero. Autoradiographs of brain slices and net distributions in brain compartments at 6 and 30 min after injection suggested that cBSA entered the brain parenchyma via blood vessels and cerebrospinal fluid but that the former was the main route. The results quantitate for the first time regional brain PA values for cationized proteins and suggest specific mechanisms at cerebral blood vessels that distinguish transport of cationized from noncationized macromolecules.

Animals↗
PubMed1991

Christian Psychiatry: the impact of evangelical belief on clinical practice.

OBJECTIVE: The authors surveyed psychiatrists in the Christian Psychiatry movement to assess the role of religious belief in their practices. METHOD: The psychiatrists were members of the Christian Medical and Dental Society; questionnaires were sent to 260, and usable responses were received from 193. The subjects were asked about demographic and practice variables, "born again" religious experiences, group cohesion, and beliefs about using the Bible and prayer in treatment. RESULTS: The respondents were somewhat more religious than Americans overall, who are themselves more religious than most psychiatrists. Nearly all reported having been "born again," after which they generally experienced a decrease in emotional distress. There was a significant difference in the respondents' affiliative feelings toward psychiatrists in the Christian Psychiatry movement and other psychiatrists. For acute schizophrenic or manic episodes, the respondents considered psychotropic medication the most effective treatment, but they rated the Bible and prayer more highly for suicidal intent, grief reaction, sociopathy, and alcoholism. Whether or not a patient was "committed to Christian beliefs" made a significant difference in whether the respondents would recommend prayer to the patient as treatment. About one-half said they would discourage strongly religious patients from an abortion, homosexual acts, or premarital sex, and about one-third said they would discourage other patients from these activities. CONCLUSIONS: Many studies have suggested a need for more sensitivity to religious issues by psychiatrists, and this study provides systematic findings on one approach. It remains important to evaluate ways in which a religious perspective can be related to clinical practice and what benefits and problems may derive from such a relationship.

Adult↗
PubMed1990

A CT-based computerized treatment planning system for I-125 stereotactic brain implants.

A computer program has been developed at the University of California, San Francisco, as an aid in planning and evaluating stereotactic brain implants made with 125I seeds. The program allows images of seeds and catheters to be positioned in the target volume revealed by CT. It then generates and displays the resulting isodose distributions. Catheters may be changed interactively until an optimum implant is achieved. From the geometry of a stereotactic implant frame as measured by CT, the program calculates the approach angles of the catheters in the frame coordinate system. After the seeds are implanted, films made with a fiducial marker box can be used to generate true seed positions and hence true isodoses. This paper describes mathematically the geometrical transformations used by the program, and also outlines its many features and options. In its first 2 years of use the program has proved to be a valuable contributor to improved patient care.

Brachytherapy↗
PubMed1990

Prognostic factors for positive surgical staging in patients with Hodgkin's disease.

Staging laparotomy was performed as part of the routine recommended diagnostic evaluation following clinical staging (CS) in 692 patients presenting with supradiaphragmatic Hodgkin's disease (HD). Various clinical factors were analyzed by multivariate analysis for prediction of abdominal involvement. Factors that were statistically significant for predicting disease below the diaphragm included CS III-IV disease (P less than .001), B symptoms (P less than .001), mixed cellularity (MC) or lymphocytic depletion (LD) histology (P = .017), number of supradiaphragmatic sites greater than or equal to 2 (P = .001), male sex (P = 0.034) and age greater than or equal to 40 years (P = .004). Separate analyses were performed for various subgroups of CS IA-IIA, CS IB-IIB, CS IIIA-IVA, and CS IIIB-IVB patients. Upstaging was seen in 0% to 55% of CS I-II patients based on subgroup. Male sex, B symptoms, and number of sites above the diaphragm greater than or equal to 2 all independently predicted for positive surgical staging in CS I-II patients. Sixty-four percent of CS I-II patients who were upstaged had extensive abdominal disease by positive lower abdominal nodes or multiple splenic nodules (greater than or equal to 5). Downstaging (to pathological stage [PS] I-II) was seen in 9% to 68% of patients with CS III-IV disease based on subgrouping. Age greater than or equal to 40, MC or LD histology, and B symptoms all independently predicted for positive surgical staging in CS III-IV patients. Downstaging was more frequently seen in CS IIIA-IVA patients (55%) than in patients who were CS III-IVB (22%). Four subgroups of patients who had a low probability (less than 10%) of stage or treatment change following laparotomy were identified. These included CS IA female patients, CS IA male patients with lymphocyte predominance histology or high neck presentations, and patients with CS IIIB-IVB disease and account for 21% of the study population. Staging laparotomy altered the stage and treatment of a significant number of the remaining 79% patients and should continue to be recommended for this group of patients.

Abdominal Neoplasms↗
PubMed1989

Treatment patterns for schizophrenia in psychiatric hospitals.

This paper analyzes the patterns of clinical treatments prescribed to patients diagnosed with schizophrenia who were admitted to state and county mental hospitals, private for-profit psychiatric hospitals, and private nonprofit psychiatric hospitals in July 1980. Treatment patterns were specified by examining the distribution of treatment types provided to patients over a 3-month period through standard tabular arrays and matrix analysis that holds constant the number of treatment types received by the patients. Data for this study are based on nationwide patient sample surveys and facility enumerations conducted in 1980 by the Survey and Reports Branch, National Institute of Mental Health. Clear differences and similarities emerged among the three types of hospitals in terms of the number and type of treatments provided to patients with schizophrenia. In general, patients with schizophrenia admitted to private psychiatric hospitals received a more comprehensive care regimen (generally inclusive of individual therapy) than similarly diagnosed patients admitted to state and county mental hospitals; private nonprofit psychiatric hospitals had marginally discernible treatment patterns from private for-profit psychiatric hospitals, especially with respect to assignment of group and self-care skill training.

Activities of Daily Living↗
PubMed1989

Auger electron contribution to bromodeoxyuridine cellular radiosensitization.

Halogenated thymidine analogs become incorporated into the DNA of proliferating cells during S-phase and may be used clinically to radiosensitize tumors that are otherwise poorly responsive to radiation. Although radiosensitization has been studied for years, mechanisms of radiosensitization are poorly understood. One possible mechanism involves the release of short range, high-LET, Auger electrons following photoelectric absorption of an X ray by the K-shell of the incorporated halogen. Such absorption occurs only with X ray energies slightly greater than the K-shell binding energy. We report the results of an experiment designed to measure this effect, in which cultured monolayers of Chinese hamster V79 cells, with 32% replacement of thymidine by bromodeoxyuridine (BUdR), were exposed to monoenergetic X rays just below (13.450 KeV) or above (13.490 KeV) the K-edge (13.475 KeV) of bromine. Enhancement ratios calculated in five different ways were slightly increased (3-12%) above the K-edge compared to below. However, only a calculation using a linear-quadratic fit to the data and a surviving fraction of 0.01 demonstrated a statistically significant increased enhancement ratio (12%) above the K-edge. We conclude that Auger electrons produced following photoelectric absorption of X rays by the K-shell of bromine contribute minimally to observed BUdR cellular radiosensitization.

Animals↗