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Biomedical subjects

L Marsh

Publications and source records attributed to L Marsh.

At least 19 recordsLinked to original sources
PubMed1992

The clinical application of a non-axial treatment plan for pancreatic and biliary malignancies.

Standard radiation therapy for adenocarcinoma of the pancreas treats a substantial portion of the renal parenchyma. It was hypothesized that rotating the plane of treatment to a non-axial orientation, with the anterior field entering the patient from an inferior oblique direction, would decrease the renal dose of radiation without increasing the liver dose or compromising the target dose. To test this hypothesis, patients referred for radical radiation treatment for tumors of the pancreas or distal common bile duct were prospectively evaluated by performing treatment planning using axial and non-axial field arrangements. Treatment plans were compared using dose volume histograms (DVHs) of both kidneys and the liver. In all 15 cases analyzed, the non-axial plan was superior to the axial plan with respect to renal dose, without significantly increasing the hepatic dose and was used for treatment. Treatment was not significantly more complex nor was gastrointestinal toxicity increased. These findings show that non-axial field arrangements can be used on a routine basis to decrease the renal dose of radiation for the treatment of pancreatic and biliary malignancies. It is anticipated that in the future, a combination of DVH-guided treatment planning and sophisticated renal function studies will be necessary to permit a more accurate prediction of the probability of renal complications resulting from radiation therapy.

Aged↗
PubMed1992

Extensive allelic variation in Cryptococcus neoformans.

The orotidine monophosphate pyrophosphorylase (OMPPase) gene locus of the DNA of 13 Cryptococcus neoformans var. neoformans strains, including 10 recent clinical isolates, was studied by using restriction fragment length polymorphisms and nucleotide sequence analysis. The OMPPase locus (URA5) is highly polymorphic, and at least six alleles were identified. The nucleotide sequences of some alleles differed by up to 5%. The majority of the nucleotide polymorphisms in the protein-coding region occurred at the third codon position and were silent. The low frequency of replacement nucleotide substitutions relative to silent nucleotide substitutions implied that there is strong selection against amino acid changes in OMPPase. The allelic variation suggested that there is extensive genomic diversity among C. neoformans clinical isolates from one geographic area. The various alleles are potentially useful markers in the study of the population structure, epidemiology, and pathogenesis of C. neoformans strains.

Alleles↗
PubMed1992

Substitutions in the hydrophobic core of the alpha-factor receptor of Saccharomyces cerevisiae permit response to Saccharomyces kluyveri alpha-factor and to antagonist.

Mutations in the Saccharomyces cerevisiae alpha-factor receptor that lead to improved response to Saccharomyces kluyveri alpha-factor were identified and sequenced. Mutants were isolated from cells bearing randomly mutagenized receptor gene (STE2) plasmids by an in vivo screen. Five mutations lead to substitutions in hydrophobic segments in the core of the receptor (M54I, S145L, S145L-S219L, A229V, L255S-S288P). Remarkably, strains expressing these mutant receptors exhibited positive pheromone responses to desTrp1,Ala3-alpha-factor, an analog that normally blocks these responses. The M54I mutation appeared to affect only ligand specificity. The other mutations conferred additional effects on signaling or recovery. Two mutants were more sensitive to alpha-factor than wild type (S145L, A229V). One mutant was more sensitive to alpha-factor-induced cell cycle arrest initially, but then recovered more efficiently (S145L-S219L). One mutant (L255S-S288P) conferred positive pheromone responses to alpha-factor as assayed by FUS1-lacZ reporter induction, but did not display growth arrest. The hydrophobic receptor core thus appears to control activation by some ligands and to play roles in aspects of signal transduction and recovery.

Amino Acid Sequence↗
PubMed1991

The influence of linguistic context on young children's understanding of homophonic words.

This study investigates young children's understanding of homophones in two different linguistic contexts. Research has shown that children interpret homophones according to their 'primary' sense even though this is inappropriate to the linguistic context. The present study investigates the influence of different contexts on their interpretations of homophones. A picture test, similar to the British Picture Vocabulary Scale (BPVS), was devised, depicting ten homophones in both their primary and secondary senses. Forty-eight children who were in matched pairs following the BPVS pre-test and whose ages ranged from three to six were asked to select the picture which showed the homophone, first when the homophone was in no linguistic context, and secondly following one of two conditions of the same story which differed according to the richness of context provided. Results showed that those children assigned to story B, the expanded version with full linguistic details and explanations of the words it contained, were more able to identify correctly the secondary meanings of the homophones intended than those children given story A, the unexpanded version. Analyses of variance showed both a significant age trend and a story-type effect. These results are interpreted as showing that the linguistic context is an important factor in young children's understanding of word meaning.

Attention↗
PubMed1988

Vocal quality 10 years after radiotherapy for early glottic cancer.

The voices of 12 patients who had been treated by radiotherapy for Stage I squamous carcinoma of the glottis at least 10 years previously, and who had shown no signs of recurrent disease, were assessed. A speech therapist detected significant abnormalities in all patients, but these did not detract from the overall high satisfaction of the patients with their voice quality.

Aged↗
PubMed1988

STE2 protein of Saccharomyces kluyveri is a member of the rhodopsin/beta-adrenergic receptor family and is responsible for recognition of the peptide ligand alpha factor.

We have cloned the gene for the alpha-factor receptor of the yeast Saccharomyces kluyveri by using the Saccharomyces cerevisiae receptor gene (c-STE2) as a probe. The nucleotide sequence of the S. kluyveri gene (k-STE2) shows that its predicted polypeptide contains seven hydrophobic segments capable of spanning a lipid bilayer and thus that, like c-STE2, it appears to be a member of the rhodopsin/beta-adrenergic receptor family. The k-STE2 polypeptide is 50% identical to that coded by c-STE2, with high conservation (greater than 67%) in the putative membrane-spanning domains. The carboxyl-terminal amino acid sequences are not similar, but both are very hydrophilic and rich in serine and threonine residues. The k-STE2 gene is functional in S. cerevisiae: it reverses the mating defect of an S. cerevisiae mutant defective in its STE2 gene. S. cerevisiae strains expressing k-STE2 rather than c-STE2 exhibit the mating-factor selectivity characteristic of S. kluyveri: better response to S. kluyveri alpha factor than to S. cerevisiae alpha factor. (S. cerevisiae normally responds much better to its own alpha-factor peptide than to the related alpha-factor peptide of S. kluyveri.) This observation demonstrates that the STE2 gene is responsible for ligand selectivity and provides additional evidence that the STE2 protein is the receptor for alpha factor.

Amino Acid Sequence↗
PubMed1988

The early results from a randomised study of radiotherapy versus Nolvadex (tamoxifen) as initial treatment for stage III breast cancer.

Eighty-seven postmenopausal patients have been randomised to receive either radiotherapy or Nolvadex (tamoxifen) as first line treatment for locally advanced (stage III) breast cancer. After a median follow-up of two years no significant differences have been found in the rate of progression of local disease, the time to development of overt metastases or survival.

Breast Neoplasms↗
PubMed1987

New phenotypes associated with mucAB: alteration of a MucA sequence homologous to the LexA cleavage site.

Most mutagenesis by UV and many chemicals in Escherichia coli requires the products of the umuDC operon or an analogous plasmid-derived operon mucAB. Activated RecA protein is also required for, or enhances, this process. MucA and UmuD proteins share homology with the LexA protein, suggesting that they might interact with the RecA protein as LexA does. We used oligonucleotide-directed mutagenesis to alter a site in MucA homologous to the Ala-Gly cleavage site of LexA. The mutation, termed mucA101(Glu26), results in a change of Gly26 of MucA to Glu26. A lexA(Def) recA441 umuC122::Tn5 strain carrying a mucA101(Glu26)B+ plasmid did not exhibit the greatly increased frequency of spontaneous mutagenesis in response to RecA activation that a strain carrying a mucA+B+ plasmid did but retained a basal recA-dependent ability to confer increased spontaneous mutagenesis that was independent of the state of RecA activation. These results are consistent with a model in which RecA plays two distinct roles in mutagenesis apart from its role in the cleavage of LexA. A pBR322-derived plasmid carrying mucA+B+, but not one carrying mucA101(Glu26)B+, inhibited the UV induction of SOS genes, suggesting that MucA+ and MucA(Glu26) proteins may have different abilities to compete with LexA for activated RecA protein. The spectrum of UV-induced mutagenesis was also altered in strains carrying the mucA101(Glu26) mutation. These results are consistent with the hypothesis that activated RecA protein interacts with wild-type MucA protein, possibly promoting proteolytic cleavage, and that this interaction is responsible for facilitating certain mutagenic processes.

Bacterial Proteins↗
PubMed1987

Predictive factors in repeated suicide attempts by adolescents.

A significant number of adolescents treated for attempted suicide have made previous attempts and will make subsequent attempts. These youths have a high risk of actually committing suicide. To find predictive factors of suicide risk, the authors compared 43 adolescent patients who had attempted suicide once with 38 who reported multiple attempts. The repeaters were less successful in school, displayed more hostility, reported more dysphoria, and had undergone more long-term stress. The authors believe assessing suicide risk requires evaluating the repeater's internal state of rage and dysphoria; they recommend that future studies look closely at these internal states as well as at external factors.

Achievement↗
PubMed1986

Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder.

The brains of 232 patients with a case-note diagnosis of schizophrenia or affective disorder who died in one mental hospital over a period of 22 years were weighed, and were assessed in a coronal section at the level of the interventricular foramina. From this sample were eliminated the brains of patients whose illnesses did not meet the Washington University criteria for a diagnosis of definite schizophrenia or primary affective disorder and those brains that showed significant histopathologic evidence of Alzheimer's-type change or cerebrovascular disease. This left a sample of 41 patients with schizophrenia and 29 patients with affective disorder. With age, sex, and year of birth controlled for, the brains of the patients with schizophrenia were 6% lighter, had lateral ventricles that were larger in the anterior (by 19%), and particularly in the temporal, (by 97%) horn cross section, and had significantly thinner parahippocampal cortices (by 11%). The findings provide postmortem confirmation of reports of ventricular enlargement in radiological studies and suggest that such enlargement is associated with tissue loss in the temporal lobe. The changes in schizophrenia were of a lesser degree than those seen in a sample of brains of patients with Alzheimer's-type dementia and Huntington's chorea.

Aged↗
PubMed1985

A double-blind controlled pilot study of plasma exchange versus sham apheresis in chronic progressive multiple sclerosis.

Twenty patients with chronically progressive multiple sclerosis (MS) were randomised in a double-blind controlled study to assess the efficacy of plasma exchange therapy. All patients were immunosuppressed with prednisone and azathioprine and underwent either plasma exchange or sham apheresis. The 10 patients in each group were similar in age, sex, duration of disease and degree of disability. Clinical and laboratory responses were assessed immediately following the course of exchange or sham therapy, and 3 to 6 months later, by individuals blinded to the type of therapy administered. Although modest improvement was suggested on clinical examination in 7 of 10 patients exchanged and 3 of the 10 sham treated group, this was transient and was not accompanied by any change in disability status scores. No differences in abnormal laboratory investigations were demonstrable between the two patient groups following therapy. We conclude that plasma exchange therapy using this protocol is unlikely to be of clinical benefit as an adjunct in the management of chronically progressive M.S.

Adult↗
PubMed1985

umuDC and mucAB operons whose products are required for UV light- and chemical-induced mutagenesis: UmuD, MucA, and LexA proteins share homology.

The products of the Escherichia coli umuDC operon and its plasmid-borne analog, mucAB, are required for mutagenesis caused by UV light and by many chemicals. We have determined the nucleotide sequences of umuDC and mucAB and present comparisons of these sequences. The two operons are 52% homologous at the nucleotide level. Open reading frames corresponding in position and size to the umu and muc genes have been identified. The reading frames of umuD and umuC overlap by 1 base pair, and the reading frames of mucA and mucB overlap by 13 base pairs. The predicted amino acid sequences of the UmuD and MucA proteins are 41% homologous; those of the UmuC and MucB proteins are 55% homologous. Considerable homology has also been detected between UmuD, MucA, and the COOH-terminal domains of the LexA repressor and the repressors of phage lambda, 434, and P22. Complementation analyses reveal that MucA protein cannot substitute for UmuD in a umuD- umuC+ host and that MucB protein cannot substitute for UmuC in a umuD+ umuC- host. Potential regulatory sequences have been identified in umuDC and mucAB.

Amino Acid Sequence↗