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Biomedical subjects

D Norris

Publications and source records attributed to D Norris.

At least 19 recordsLinked to original sources
PubMed1992

T1 snapshot FLASH measurement of rat brain glioma: kinetics of the tumor-enhancing contrast agent manganese (III) tetraphenylporphine sulfonate.

The ultrafast inversion recovery snapshot FLASH technique was used to determine the kinetics of the contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS) in experimental brain tumors in rats. In the first part of the investigation this technique was validated with the conventional inversion recovery spin-echo method by comparing in vivo T1 data of a normal rat brain. Agreement between T1 values obtained from both techniques was complete, as tested for a large number of pixels in identical coronal slices. In the second part the fast IR snapshot FLASH method was applied to study the effect of the NMR contrast agent MnTPPS on the T1 relaxation time of experimental gliomas in rat brains. T1 of normal brain tissue (1024-1035 ms), tumor (1217 ms), and edema (1199 ms) was determined with the inversion recovery version of the snapshot FLASH imaging technique. After intraperitoneal injection of MnTPPS (0.25 mmol/kg body wt) T1 decreased exponentially to 56% of control in tumor and to 62% in muscle. In normal and edematous brain tissue no significant changes in T1 were observed up to 5 h after injection of the contrast agent. Once the T1 contrast between tumor and peritumoral brain tissue had reached a saturation, the enhancement persisted for several hours to days. Therefore application of this contrast agent resulted in a sharp demarcation between glioma and peri-tumoral edema.

Animals↗
PubMed1992

The monolingual nature of speech segmentation by bilinguals.

Monolingual French speakers employ a syllable-based procedure in speech segmentation; monolingual English speakers use a stress-based segmentation procedure and do not use the syllable-based procedure. In the present study French-English bilinguals participated in segmentation experiments with English and French materials. Their results as a group did not simply mimic the performance of English monolinguals with English language materials and of French monolinguals with French language materials. Instead, the bilinguals formed two groups, defined by forced choice of a dominant language. Only the French-dominant groups showed syllabic segmentation and only with French language materials. The English-dominant group showed no syllabic segmentation in either language. However, the English-dominant group showed stress-based segmentation with English language materials; the French-dominant group did not. We argue that rhythmically based segmentation procedures are mutually exclusive, as a consequence of which speech segmentation by bilinguals is, in one respect at least, functionally monolingual.

Adult↗
PubMed1992

Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study.

PURPOSE: The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS: The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS: The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION: Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.

Adolescent↗
PubMed1990

Purification of a strand exchange stimulatory factor from Saccharomyces cerevisiae.

The SEP1 strand exchange protein of Saccharomyces cerevisiae catalyzes the formation of heteroduplex DNA joints between single-strand circles and homologous linear duplexes in vitro. Previous work [Kolodner, R., Evans, D. H., & Morrison, P. T. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5560-5564] showed that the optimal stoichiometry of SEP1 in this reaction was 1 SEP1 monomer per 12-14 nucleotides of single-stranded DNA. The work presented here describes the purification and characterization of a 33,000-dalton yeast protein that permits SEP1 to catalyze joint molecule formation at much lower stoichiometries. In the presence of this second factor, which has been designated SF1 for stimulatory factor 1, the optimal amount of SEP1 dropped to 1 SEP1 monomer per 725 nucleotides of single-stranded DNA. At this concentration of SEP1, the rate of joint molecule formation increased approximately 3-fold over that seen in the unstimulated reaction (no SF1). Titration experiments indicated that when the concentration of SEP1 was reduced over 300-fold to 1 SEP1 molecule per 5800 nucleotides of single-stranded DNA, the stimulated reaction had the same rate and extent of joint molecule formation as the unstimulated reaction. The optimal amount of SF1 was 1 molecule of SF1 per 20 nucleotides of single-stranded DNA. Electron microscopic analysis showed that a bona fide strand exchange reaction produced the joint molecules in the stimulated reaction. The stimulated reaction had requirements that were essentially identical with those seen in the unstimulated reaction, including a lack of dependence on ATP. SF1 aggregated single-stranded and double-stranded DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA, Fungal↗
PubMed1990

Interaction of a Saccharomyces cerevisiae strand exchange stimulatory factor with DNA.

In the preceding paper (Norris & Kolodner, 1990), we described the purification of a Mr 33,000 polypeptide which dramatically stimulated the activity of SEP1, the yeast mitotic strand exchange protein. In this paper, we characterized this new protein, which was designated SF1, in the absence of SEP1. SF1 had a sedimentation coefficient of 1.7 S and a Stokes radius of 30 A, which was consistent with a calculated native molecular weight of 31,000, indicating that SF1 existed in solution as a monomer. Filter binding assays showed that SF1 bound preferentially to single-stranded rather than double-stranded DNA. Fluorescence spectroscopy analysis indicated that SF1 occluded approximately eight nucleotides when bound to single-stranded DNA and exhibited a dissociation constant, KD, of 2.83 x 10(-6) M. The binding of SF1 to single-stranded DNA was noncooperative and appeared to involve at least one tyrosine residue. SF1, in the absence of SEP1, stimulated the renaturation of homologous single-stranded DNA, suggesting that it might act directly in some phase of the strand exchange reaction.

DNA↗
PubMed1990

Effect of histocompatibility factors on pulmonary retention of indium-111-labeled granulocytes.

Granulocyte transfusions are associated with a number of side effects including febrile transfusion reactions and occasionally pulmonary infiltrates. There is evidence that the presence of preformed antibodies may be a cause of these complications. In this study, allogeneic 111Indium-labeled granulocytes were used to evaluate the pulmonary retention of radioactivity in alloimmunized and non-alloimmunized patients in an attempt to assess antibody effect on granulocyte migration. After injection of labeled allogeneic granulocytes into neutropenic patients, the ratios of lung to heart activity were calculated for the first 30 min of scanning. There was significantly greater retention of radioactivity from cells in the lungs of patients who were alloimmunized, having both lymphocytotoxic (anti-HLA) and leuko-agglutinating antibodies, compared to the activity in the lungs of non-alloimmunized patients (P less than .001) or of patients receiving autologous granulocytes (P less than .001). This study demonstrates that labeled, mismatched granulocytes may be retained in the lungs for a significantly longer time in patients with preformed antibodies. This implies that transfusion of large numbers of such mismatched granulocytes, i.e., granulocyte transfusions, may also be retained in the lungs of alloimmunized patients, which could lead to pulmonary compromise. Therefore, granulocyte transfusions from random donors should not be given to alloimmunized patients.

Blood Transfusion↗
PubMed1990

Aziridinylbenzoquinone (AZQ) in the treatment of recurrent pediatric brain and other malignant solid tumors. A Pediatric Oncology Group phase II study.

To assess the response rates and toxicity of AZQ in children with recurrent brain and other malignant solid tumors, a phase II study was implemented by the Pediatric Oncology Group. Eligible patients received AZQ 18 mg/M2/week i.v. for 4 doses followed by a 2 week rest period. Each dose was given over four hours (1/3 over the initial 20 minutes). After the first year, the dosage was reduced to 13 mg/M2 due to myelotoxicity resulting in treatment delays. No objective responses were observed in 73 evaluable children with various non-central nervous system tumors. Of the 91 patients with brain tumors, there were 4 CR's and 2 PR's in patients with astrocytoma, ependymoma, glioblastoma multiforme, oligodendroglioma, brain stem glioma and intracranial yolk sac tumor (median duration, 10 months; range, 2-20+ months). Three of 4 CR's were achieved with a dosage of 18 mg/M2/week. An additional 13 children with brain tumors experienced stable or improved disease (duration, 2-36 + months; median 7.5 months). The principal toxicity was myelosuppression which was cumulative but there were also 3 allergic reactions to AZQ. We conclude that for selected brain tumors, the rates of objective response and stable disease plus the duration of responses support further assessment of AZQ in combination with other agents. Furthermore, the 18 mg/M2 dosage may provide better responses.

Adolescent↗
PubMed1990

How to build a connectionist idiot (savant).

This paper describes the development of a connectionist model of an idiot savant date calculator using a multi-layer back-propagation network. The model mimics the behaviour of idiot savant date calculators in learning to perform the date calculation task without the need either to develop arithmetical skills or to encode explicit knowledge about regularities in the structure of dates. However, the performance of the model highlights limitations on the use of back-propagation as a general-purpose learning algorithm in complex problem domains. Even with a relatively simple problem like date calculation back-propagation can only succeed when forced to take a highly structured and modular approach to learning.

Algorithms↗
PubMed1990

Renal sarcomas of childhood.

Renal sarcomas in infants and children are extremely uncommon. Previously classified as Wilms tumors with unfavorable histology, these tumors were thought to be variants of Wilms tumors but in general have a worse prognosis. Our recent experience with 4 cases of renal sarcomas indicate that these tumors must be approached individually and treated appropriately. Their histologic picture and their varying response to surgery and chemotherapy suggest that these unusual tumors are not variants of Wilms tumors but instead sarcomas unrelated to the classic Wilms tumors.

Child↗
PubMed1990

A yeast H2A-H2B promoter can be regulated by changes in histone gene copy number.

The two divergently transcribed H2A-H2B gene pairs in yeast are differentially regulated as a function of the copy number of histone genes. Transcription of an HTA2-lacZ reporter gene is independent of histone gene copy number. Transcription of an HTA1-lacZ gene can be repressed or derepressed, depending on the number of HTA plus HTB genes in cells. Regulation by histone gene dosage is dependent on a negative site in the HTA1-HTB1 promoter and the products of regulatory genes that act through this site. The level of H2A plus H2B protein in the cell may signal the response to histone gene copy number, suggesting that transcription of the HTA1-HTB1 locus can be autogenously regulated. This phenomenon may be used, in part, to maintain the balanced synthesis of histones, a critical parameter in nucleosome assembly.

Cell Cycle↗
PubMed1989

Limits on bilingualism.

Speech, in any language, is continuous; speakers provide few reliable cues to the boundaries of words, phrases, or ther meaningful units. To understand speech, listeners must divide the continuous speech stream into portions that correspond to such units. This segmentation process is so basic to human language comprehension that psycholinguists long assumed that all speakers would do it in the same way. In previous research, however, we reported that segmentation routines can be language-specific: speakers of English do not. French has relatively clear syllable boundaries and syllable-based timing patterns, whereas English has relatively unclear syllable boundaries and stress-based timing; thus syllabic segmentation would work more efficiently in the comprehension of French than in the comprehension of English. Our present study suggests that at this level of language processing, there are limits to bilingualism: a bilingual speaker has one and only one basic language.

England↗
PubMed1989

Granulocyte transfusion therapy and amphotericin B: adverse reactions?

One hundred twenty-five granulocyte transfusions were given concurrently with amphotericin B to 31 granulocytopenic patients with acute leukemia during a four year period. Twenty-six patients had culture-documented, and 5 had presumed fungal infections; pulmonary infiltrates were present in 26 patient courses. Eight patients developed pulmonary deterioration temporally related to therapy with amphotericin, granulocyte transfusions, or both. One event occurred following amphotericin alone. Three additional reactions occurred in alloimmunized patients with antibodies to human leukocyte antigens (HLA) who received random donor granulocytes, which may indicate a potential mechanism for the pulmonary reactions. Two reactions potentially represent an adverse interaction between amphotericin and granulocytes, but these were reversible and were not unlike reactions expected with each modality alone. Our data fail to document a specific detrimental interaction between granulocyte transfusions and amphotericin beyond the reactions associated with each modality, and the data suggest that other clinical factors, particularly infection and alloimmunization, also contribute to pulmonary decompensation. We nevertheless recommend great care and attention be given to administering these modalities in the setting of severely ill patients.

Adolescent↗
PubMed1989

Artificial intelligence in the prediction of operative findings in low back surgery.

In a prospective trial of 150 patients undergoing first time low back surgery for sciatica, the performance of a computer was compared to that of clinicians in predicting the likely operative findings. The results indicate that artificial intelligence techniques implemented on a computer can be used for predicting operative findings in low back surgery, can out-perform clinicians and can be used to develop better methods of human prediction.

Adult↗
PubMed1988

The effect of histone gene deletions on chromatin structure in Saccharomyces cerevisiae.

As a way of studying nucleosome assembly and maintenance in Saccharomyces cerevisiae, mutants bearing deletions or duplications of the genes encoding histones H2A and H2B were analyzed. Previous genetic analysis had shown that only one of these mutants exhibited dramatic and pleiotropic phenotypes. This mutant was also the only one that contained disrupted chromatin, suggesting that the original phenotypes were attributable to alterations in chromosome structure. The chromatin disruption in the mutant, however, did not extend over the entire genome, but rather was localized to specific regions. Thus, while the arrangement of nucleosomes over the HIS4 and GAL1 genes, the telomeres, and the long terminal repeats (delta sequences) of Ty retrotransposons appeared essentially normal, nucleosomes over the CYH2 and UBI4 genes and the centromere of chromosome III were dramatically disrupted. The observation that the mutant exhibited localized chromatin disruptions implies that the assembly or maintenance of nucleosomes differs over different parts of the yeast genome.

Centromere↗
PubMed1988

Hyperfractionated radiotherapy in brain stem tumors: results of a Pediatric Oncology Group study.

Between September 1984 and January 1986, 38 patients were entered onto the first phase of a Pediatric Oncology Group study designed to test the feasibility of treating children with brain stem tumors with hyperfractioned (twice daily) radiotherapy, to assess the early and late morbidity and efficacy of such treatment, and to test the feasibility of dose escalation in this group of patients. Of the 34 patients considered eligible after neuroradiology review, two did not complete planned radiotherapy because of progressive disease; both died of disease at 4 weeks and 9 months following initiation of treatment. The remainder were treated with 1.1 Gy twice daily, with an interval of 4 to 6 hours, to a total dose of 66 Gy in 60 fractions over 6 weeks. The majority of patients (24/34, 71%) improved clinically during the course of treatment; two remained stable, seven deteriorated, and for one the clinical response was unknown. By CT scan and/or MRI, no patient showed complete regression of disease; five showed a partial response to treatment, twenty fell into a stable disease category, eight patients developed progressive disease by the time of their first follow-up radiologic examination, and one patient was not evaluable for response, having been lost to follow-up immediately after completion of treatment. All five patients who achieved partial response and 17/20 patients in the stable, disease category subsequently progressed, after a median interval of 6.5 months. The median survival time was 11 months and survival at 1 year was 48% (SE 0.08). Morbidity of treatment consisted of an enhanced skin reaction in three patients, otitis media and/or externa in nine, and complications related to steroid intake in four, including diabetic ketoacidosis (two patients), Pneumocystis pneumonia (one patient), and disseminated varicella (one patient). Protracted use of steroids in 13 patients was associated in all instances with non responding or progressive disease. No patient developed signs or symptoms suggestive of CNS damage, and tissue obtained by biopsy at the time of progression in three patients and at autopsy in five failed to demonstrate any evidence of injury attributable to the radiotherapy. A dose escalation to 70.2 Gy in 60 fractions over 6 weeks was implemented as planned.

Adolescent↗
PubMed1988

Artificial intelligence in the diagnosis of low-back pain and sciatica.

In a prospective trial of 200 patients with low-back pain or sciatica, the diagnostic performance of a computer was compared with that of a clinician in a variety of clinical settings. The results indicate that artificial intelligence techniques can be used for the differential diagnosis of low-back disorders, can outperform clinicians, and can be used to develop better methods of human differential diagnosis.

Back Pain↗
PubMed1988

Changes in histone gene dosage alter transcription in yeast.

Chromatin structure is believed to be important for a number of cellular processes, including transcription. However, the role of nucleosomes in transcription is not well understood. We have identified the yeast histone locus HTB1-HTB1, encoding histones H2A and H2B, as a suppressor of solo delta insertion mutations that inhibit adjacent gene expression. The HTA1-HTB1 locus causes suppression either when present on a high-copy-number plasmid or when mutant. These changes in HTA1-HTB1 after transcription of the genes adjacent to the delta insertions. On the basis of this result, we have examined the effects of increased and decreased histone gene dosage for all four yeast histone loci. From the types of histone gene dosage changes that cause suppression of insertion mutations, we conclude that altered stoichiometry of histone dimer sets can alter transcription in yeast.

DNA Transposable Elements↗