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Biomedical subjects

G E Turner

Publications and source records attributed to G E Turner.

At least 19 recordsLinked to original sources

Laparoscopic splenectomy: single-centre experience of a district general hospital.

We report the results of 20 consecutive laparoscopic splenectomies performed on haematology patients for a number of indications. Our series includes patients up to 77 years of age at the time of surgery and removal of spleens weighing up to 3530 g. The most significant benefit is the early rate of discharge post-operatively (median 2 d); however, there is a risk of conversion to open laparotomy (in this series 3/20, 15%). We show that laparoscopic splenectomy can be offered as a therapeutic option to patients unfit for conventional laparotomy and that even large and bulky spleens can be removed safely using this approach.

Adolescent

Multiple forms of arginase are differentially expressed from a single locus in Neurospora crassa.

The Neurospora crassa catabolic enzyme, arginase (L-arginine amidinohydrolase, EC 3.5.3.1), exists in multiple forms. Multiple forms of arginase are found in many vertebrates, but this is the only reported example in a microbial organism. The two major forms are structurally similar with subunit sizes of 36 and 41 kDa, respectively. The larger form is produced by mycelia growing in arginine-supplemented medium. Both forms are localized in the cytosol. The structural gene for arginase, aga, has been cloned and sequenced; it contains a 358-codon open reading frame with three in-frame ATGs at the amino terminus. Mutagenesis of these ATGs revealed that the first ATG initiates the 41-kDa protein and the third ATG initiates the 36-kDa protein. Mutation of the second ATG has no effect on translation. Northern analysis demonstrated that a 1.4-kilobase (kb) transcript is synthesized in minimal medium and both a 1.4- and 1.7-kb transcript are produced in arginine-supplemented medium. Primer extension identified the 5' ends of each transcript and demonstrated that the first and third ATG of the open reading frame are the initial AUGs of the 1.7- and 1. 4-kb mRNA, respectively. The results suggest that a basal promoter produces the 1.4-kb transcript and an arginine "activated" promoter is responsible for the 1.7-kb transcript. Tandem promoters are rare in eukaryotic organisms, and they often regulate developmental or tissue-specific gene expression. The possibility that arginase has a role in differentiation in N. crassa is being investigated.

Amino Acid Sequence

Transdural spinal cord herniation: imaging and clinical spectra.

PURPOSE: Transdural herniation of the spinal cord is a rarely reported clinical entity, and many of the existing reports were published before the advent of MR imaging. We describe five current cases and compare them with findings in 25 cases reported in the literature to delineate the clinical and imaging spectra of transdural spinal cord herniation. METHODS: MR imaging, CT myelography, and conventional myelography were performed in five patients with transdural herniation of the spinal cord. These studies, along with clinical findings, are described. Intraoperative photographs are included for one case. The salient features of both the current and previously reported cases are summarized in tabular form. RESULTS: In three cases, transdural spinal cord herniation occurred posttraumatically, in one case the cause was iatrogenic and in the others the herniation occurred spontaneously. Imaging features not previously reported include dorsally directed herniations at thoracolumbar levels (two patients), apparent (lacking surgical confirmation) syringomeyelia (one case), a vertebral body nuclear trail sign (one case), and intramedullary hyperintensities on MR images (two cases). Clinical features not previously reported include unilateral pyramidal-sensory deficits (one case) and isolated unilateral pyramidal signs (one case). Clinical findings similar to previous reports include progressive paraparesis (two cases) and progressive Brown-Séquard syndrome (one case). CONCLUSION: Our five cases illustrate certain clinical and imaging findings not previously reported, and, together with the established features of the 25 cases in the literature, delineate the spectra of transdural spinal cord herniation.

Adult

Overlapping functions for two G protein alpha subunits in Neurospora crassa.

Heterotrimeric G proteins, consisting of alpha, beta and gamma subunits, mediate a variety of signaling pathways in eukaryotes. We have previously identified two genes, gna-1 and gna-2, that encode G protein alpha subunits in the filamentous fungus Neurospora crassa. Mutation of gna-1 results in female infertility and sensitivity to hyperosmotic media. In this study, we investigate the expression and functions of gna-2. Results from Western analysis and measurements of gna-2 promoter-lacZ fusion activity indicate that gna-2 is expressed during the vegetative and sexual cycle of N. crassa in both A and a mating types. Activating mutations predicted to abolish the GTPase activity of GNA-2 cause subtle defects in aerial hyphae formation and conidial germination. Extensive phenotypic analysis of delta gna-2 strains did not reveal abnormalities during vegetative or sexual development. In contrast, deletion of gna-2 in a delta gna-1 strain accentuates the delta gna-1 phenotypes. delta gna-1 delta gna-2 strains have a slower rate of hyphal apical extension than delta gna-1 strains on hyperosmotic media. Moreover, delta gna-1 delta gna-2 mutants have more pronounced defects in female fertility than delta gna-1 strains. We propose that gna-1 and gna-2 have overlapping functions and may constitute a gene family. This is the first report of G protein alpha subunits with overlapping functions in eukaryotic microbes.

DNA, Fungal

A case of mature B-cell ALL with coexistence of t(1;19) and t(14;18) and expression of the E2A/PBX1 fusion gene.

The translocation t(1;19)(q23;p13) is found in 3-5% of all acute lymphoblastic leukaemias (ALL) and results in the expression of an E2A/PBX1 hybrid gene transcript. This translocation is very closely associated with a pre-B phenotype. t(14;18) is associated with follicular B-cell lymphoma and is characterized by over-expression of the bcl-2 oncogene. We describe a case of ALL in an adult with a mature B-cell immunophenotype and a single abnormal cell line with a complex karyotype showing both t(1;19) and t(14;18). Two reports of this phenomenon have been published previously and molecular analysis, where performed, showed the E2A gene was not rearranged, suggesting the t(1;19) was a molecular variant of the established translocation. In contrast, molecular analysis of our case demonstrated expression of the E2A/PBX1 fusion transcript typically associated with t(1;19) in pre-B ALL but showed it to be present at an extremely low level, despite the abnormal karyotype being found in the majority of metaphase cells. Analysis of bcl-2 expression showed a significant up-regulation. A down-regulation of the E2A/PBX1 hybrid gene as a consequence of the enhanced expression of bcl-2 may be a possible mechanism for this finding.

Burkitt Lymphoma

Acetylglutamate synthase from Neurospora crassa: structure and regulation of expression.

A DNA clone which complemented an arg-14 mutation of Neurospora crassa was isolated by sib selection from a cosmid library (pMOcosX). Southern and restriction-fragment-length polymorphism (RFLP) analysis confirmed that the cloned DNA contained the arg-14 gene. The arg-14 gene was identified as the structural gene for acetylglutamate synthase by immunodepletion of enzyme activity with antibodies prepared against an arg-14 fusion protein and by the thermal instability of acetylglutamate synthase in a temperature-sensitive arg-14 mutant. The fungai acetylglutamate synthase has little sequence homology to its bacterial counterpart, unlike other arginine biosynthetic enzymes. Expression of the arg-14 gene is regulated by cross-pathway control similar to many amino acid biosynthetic genes. However, expression of acetylglutamate synthase occurs throughout the developmental growth cycle, unlike other arginine biosynthetic enzymes.

Arginine

The G alpha i homologue gna-1 controls multiple differentiation pathways in Neurospora crassa.

Heterotrimeric G proteins are components of principal signaling pathways in eukaryotes. In higher organisms, alpha subunits of G proteins have been divided into four families, Gi, Gs, Gq, and G12. We previously identified a G alpha i homologue gna-1 in the filamentous fungus Neurospora crassa. Now we report that deletion of gna-1 leads to multiple phenotypes during the vegetative and sexual cycles in N. crassa. On solid medium, delta gna-1 strains have a slower rate of hyphal apical extension than wild type, a rate that is more pronounced under hyperosmotic conditions or in the presence of a cellophane overlay. delta gna-1 mutants accumulate less mass than wild-type strains, and their mass accumulation is not affected in the same way by exposure to light. delta gna-1 strains are defective in macroconidiation, possessing aerial hyphae that are shorter, contain abnormal swellings, and differentiate adherent macroconidia. During the sexual cycle, delta gna-1 strains are fertile as males. However, the mutants are female-sterile, producing small, aberrant female reproductive structures. After fertilization, delta gna-1 female structures do not enlarge and develop normally, and no sexual spores are produced. Thus, mutation of gna-1 results in sex-specific loss of fertility.

Base Sequence

Respiratory and laryngeal function associated with experimental coupling of the oral and nasal cavities.

Three experimental openings (10 mm2, 20 mm2, 30 mm2) were placed one at a time in a man's palatal obturator at a location approximating the junction of the prepalate and the palatal shelves. The man's laryngeal and respiratory function were examined during his production of a series of CV syllables [pa] repeated at a comfortable and loud vocal intensity for each of the three experimental conditions. Two more conditions, in which the subject's obturator was not altered (no hole) and in which no obturator was worn, were also included for study. Laryngeal and respiratory function adjustments were most apparent during the 30 mm2 hole size and no obturator conditions. Laryngeal adjustment, as measured by fundamental frequency, was the most identifiable. A respiratory adjustment, which involved the expenditure of more lung volume as nasal airflow leakage increased, was also observed. These observations imply an active physiologic adjustment rather than a passive response to aberrant oronasal coupling.

Adaptation, Physiological

MR screening for brain stem compression in hypertension.

PURPOSE: To determine the clinical usefulness of MR imaging to screen for vascular compression of the lateral medulla, considered by some to be responsible for neurogenic hypertension. METHODS: MR images and clinical records of 120 adults who had received brain MR imaging for any reason were divided into two groups: group 1 (n = 60) consisted of patients with essential hypertension and group 2 (n = 60) included patients who lacked a diagnosis of hypertension. No patient manifested symptomatic cranial neuralgias. The root entry zone of cranial nerves IX and X into the left lateral medulla was examined by MR imaging for proximity to the ipsilateral vertebral artery or its branches. Images lacking any contact between visible vascular structures and the root entry zone were recorded as normal. Vascular compression was graded according to the degree of proximity to the root entry zone. Lateral medullary contact only (grade I), contact and depression (grade II), or lower brain stem displacement or rotation (grade III) of the root entry zone were recorded in both hypertensive and normotensive patients. Among hypertensive patients, additional data were gathered from electrocardiographic, echocardiographic, and urinary protein reports. RESULTS: We found compression in 34 (57%) of the patients from group 1 and in 33 (55%) of the patients from group 2. Compressions in group 1 were grade I in 22 (37%) of the patients, grade II in 8 (45%), grade II in 4 (7%), and grade III in 2 (3%). There were no statistically significant differences in MR findings between the two groups. Among group 1 patients, MR grading did not predict end-organ changes in the heart (left axis deviation and left ventricular hypertrophy) or kidneys (proteinuria). CONCLUSION: Vascular compression of the root entry zone of cranial nerves IX and X into the left lateral medulla is not an adequate lesion to produce systemic hypertension. This finding is as common among normotensive patients as among hypertensive populations. Neither the presence nor the severity of changes in the root entry zone on MR images increases the occurrence of common end-organ responses in the heart or kidneys among hypertensive patients. MR screening is not warranted among hypertensive patients lacking symptomatic cranial neuralgias.

Adult

Detection of t(14;18) in British follicular lymphoma using cytogenetics, Southern blotting and the polymerase chain reaction.

Cytogenetics, Southern blotting and PCR were used to detect t(14;18) in 72 British patients with follicular lymphoma. The overall incidence of the translocation was 76%. Cytogenetics was the most successful technique, but 10-30% of translocations detected karyotypically were missed by molecular methods, presumably due to break-points falling outside the range of probes and primers used here. Reliance on molecular detection alone may considerably underestimate the incidence of t(14;18) and it is therefore essential to use the most comprehensive range of probes and primers available.

Base Sequence

Transfusion-associated graft-versus-host disease in fludarabine-treated B-chronic lymphocytic leukaemia.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but serious complication of blood component therapy in patients with haematological malignancies. B-chronic lymphocytic leukaemia (B-CLL), however, has rarely been associated with TA-GVHD. We report three patients with advanced B-CLL who developed TA-GVHD. All these had been treated with fludarabine. Suppression of T cells by fludarabine may have contributed to an increased susceptibility to TA-GVHD. The use of irradiated blood products to prevent this complication should be considered for patients with advanced B-CLL treated with fludarabine or other purine analogues.

Antineoplastic Agents

Identification of a G protein alpha subunit from Neurospora crassa that is a member of the Gi family.

Heterotrimeric G proteins, consisting of alpha, beta, and gamma subunits, are implicated in major signal transduction pathways controlling a diversity of functions in eukaryotic organisms. In the filamentous fungus Neurospora crassa, G proteins are implicated in the regulation of several environmental responses. As a first step in studying the role of G proteins in these processes, we have cloned the genes for two alpha subunits, gna-1 and gna-2, from Neurospora. The genes are located on different chromosomes and are differentially regulated during asexual development. The encoded proteins (Gna-1 and Gna-2) are the same size as members of the Gi-alpha family (approximately 40 kDa). The Gna-1 protein sequence is 55% identical overall to members of the Gi family and contains the consensus sequences for ADP-ribosylation by pertussis toxin and incorporation of myristic acid, which are found in this group. These properties make Gna-1 the first identified microbial alpha subunit to be a member of any class. Furthermore, incubation of a N. crassa plasma membrane fraction with pertussis toxin results in ADP-ribosylation of a protein substrate which is the approximate size of Gna-1. The predicted Gna-2 protein sequence does not share a high degree of sequence identity with the Gi class. However, the coding region contains at least one intron in a position conserved in the Gi family. We propose that the Gi family of alpha subunits is ancient and during evolution may have first appeared in filamentous fungi.

Adenosine Diphosphate Ribose

What is marrow fibrosis after treatment of neuroblastoma?

AIMS: To test the hypothesis that the abnormal fibrous stroma of bone marrow found after treatment of disseminated neuroblastoma represents traumatic scarring. METHODS: Twenty six restaging bone marrow biopsy specimens from 14 children with disseminated neuroblastoma were compared with 37 from 37 children with acute lymphoblastic leukaemia. They were assessed independently by two observers for the presence of abnormal fibrous stroma. All biopsies were performed 23 to 50 days after the initial diagnostic biopsy, and from the same iliac crest. A further nine restaging bone marrow biopsy specimens from previously unbiopsied iliac crests from four children with neuroblastoma were examined and the appearances of the diagnostic bone marrow specimens in those with neuroblastoma recorded. Between diagnostic and restaging biopsies, the children received combination chemotherapy regimens. RESULTS: In neuroblastoma abnormal stromal material was observed in 17 of 26 rebiopsied iliac crests as opposed to only 9 of 37 of those with acute lymphoblastic leukaemia (p < 0.005). In addition, four of nine restaging biopsy specimens taken from previously unbiopsied crests in patients with neuroblastoma contained abnormal stroma. All 11 children with neuroblastoma whose restaging specimens contained abnormal stroma had similar abnormalities in one or more biopsy specimens at diagnosis. CONCLUSIONS: Abnormal fibrous stromal material in restaging marrow biopsy specimens of previously biopsied iliac crests occurs much more frequently in neuroblastoma than in acute lymphoblastic leukaemia. We suggest that factors other than traumatic scarring are responsible. This is supported by finding similar abnormalities in previously unbiopsied iliac crests and in the diagnostic biopsy specimens of children with neuroblastoma.

Adolescent

Which lesson components mediate refusal assertion skill improvement in school-based adolescent tobacco use prevention?

Any of three components of current school-based refusal assertion training might mediate improvement of seventh grade students' ability to refuse tobacco use offers: 1) teaching students knowledge of ways to say "no," 2) engaging students in the practice of refusal assertion, or 3) motivating students to perform refusal assertion in a socially skilled way. A 3-condition true field experimental "component study" of the differential effects of these three components yielded improvement in role-played behavioral skill to refuse tobacco offers that was evident in both the Knowledge and Practice conditions but not in the Motivation condition. In these same two conditions, skills training led to a significant decrease in students' intention to use smokeless tobacco in the future but not cigarettes. A focus on engaging students in Knowledge and Practice components of refusal assertion training appears warranted.

Adolescent

Free air in the cavernous sinus as an incidental finding.

Free air within the cavernous sinus was discovered incidentally on a computed tomographic (CT) scan. We suggest that air bubbles were introduced inadvertently when contrast material was injected just prior to CT scanning. On a repeat CT scan 16 days later, the air had disappeared.

Air

Level of accuracy and degree of precision in attempting to maintain steady levels of biting force.

The primary purpose of this study was to assess the level of accuracy (bias) and degree of precision for a group of 24 normal subjects attempting to maintain a constant biting force at levels of 100 gm, 500 gm, 1000 gm and 2000 gm for a period of 10 s each. Accuracy is defined as the difference between subjects' actual level of biting force and the target value they were trying to achieve. Precision is the level or range of variability demonstrated by the subjects while attempting to bite with a constant level of force. Subjects' performance relative to accuracy and precision was also compared when using the central incisors vs. the first permanent molars. Assessment of bite force was measured using a specially designed strain gauge scale which permitted subjects to visually monitor when their biting force equalled a preset resistance. Each subject was instructed to bite on the end of a plastic sheathed steel beam with enough force to activate the indicator needle on the voltage meter to its central position and to try to maintain a constant level of biting force (by attempting to keep the indicator needle steady in its central position). No significant (P > 0.05) differences were found in mean accuracy in bite force for gender or specific teeth used in the biting task. However, a significant difference (P < 0.0001) in mean accuracy in bite force was found to exist between the target levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Fluoroscopy and nasoendoscopy in designing palatal lift prostheses.

Prosthodontists frequently provide prostheses for the management of speech disorders related to palatopharyngeal dysfunction. Optimal prosthetic management of the palatopharyngeal port requires close interaction between the prosthodontist and speech pathologist in the use of videofluoroscopy and videonasoendoscopy for design, placement, and modification of the prosthesis. Function of the palatopharyngeal port during production of controlled samples of connected speech can be observed from multiview fluoroscopy, including lateral and frontal projections. Like fluoroscopy, nasoendoscopy can be used to observe and record function of the palatopharyngeal port during speech. This article provides an overview of the procedures suggested for diagnosing palatopharyngeal disorders. A method for designing and placing a prosthesis to aid in obturating the nasopharynx is also suggested.

Endoscopy