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Biomedical subjects

A Moore

Publications and source records attributed to A Moore.

At least 271 records · Page 15Linked to original sources
PubMed1994

Retroviral mediated gene transfer in chronic myelogenous leukaemia.

Gene therapy for chronic myelogenous leukaemia (CML) may provide a therapeutic option for patients who are ineligible for bone marrow transplantation. To determine the feasibility of such an approach we evaluated the transduction efficiency of CML progenitor colonies from seven patients in chronic phase. Vector transduction was optimized using the CML-derived K562 cell line and applied to CML mononuclear cells. After vector exposure, optimal gene transfer was noted when CML mononuclear cell cultures contained stem cell factor, IL-3, GM-CSF and erythropoietin. The addition of IL-6 to this combination decreased transduction efficiency. Using these conditions, 20.4% +/- 2.4 (SE) of erythroid colonies (CFU-GEMM and BFU-E) and 20.2% +/- 4.7 of CFU-GM colonies were G418 resistant. This compares with a transduction efficiency of 5.9% +/- 1.1 and 6.4% +/- 1.5, respectively, for erythroid and CFU-GM colonies using marrow obtained from normal donors. Only a modest increase in gene transfer was noted when CML cells were stimulated with cytokines for the 24 h preceding vector exposure. Vector DNA in colonies expressing the BCR/ABL transcript was documented by performing PCR analysis on individual colonies. The relatively high gene transfer rate in CML suggests that this disease might be very suitable for gene therapy.

Base Sequence↗
PubMed1994

Long-term clinical performance of a central venous oxygen saturation sensor for rate adaptive cardiac pacing.

Rate adaptive ventricular pacemakers using central venous oxygen saturation (O2Sat) to control the pacing rate have been implanted in 14 patients (mean age 71 years), with a mean follow-up period of 44 months (range 2-63 months). In eight patients the pacemakers were replaced due to signs of battery depletion after an implant duration of 39-58 months. During bicycle exercise testing the O2Sat decreased on average from 61% +/- 4% at rest to 36% +/- 4% (P < 0.0001) at peak exercise, and the maximum pacing rate was 122 +/- 5 beats/min. The time delay until the O2Sat had dropped 10%, 65%, and 90% of the total reduction during exercise was 4.8 +/- 0.9 seconds, 39.8 +/- 3.8 seconds, and 71.3 +/- 7.5 seconds, respectively. The O2Sat decreased 9.4% +/- 2% (P < 0.005) from resting supine to resting sitting. Oxygen breathing increased the telemetered O2Sat from the pacemaker by 8.4% +/- 1% (P < 0.001). During follow-up the O2Sats were relatively stable in 50% of the patients, but demonstrated significant fluctuations in the others. At 1-year invasive follow-up O2Sat measured by the pacemaker decreased 22% +/- 2%, and in blood samples from the right ventricle 22% +/- 2% from rest to 3 minutes exercise at 25 watts. There was a significant correlation between O2Sat measured by the pacemaker and in blood samples from right ventricle (n = 105; r = 0.73; P < 0.001). In two patients the O2Sat dropped significantly during pneumonia. In another patient episodes of angina pectoris was associated with low O2Sat and a concomitant fast pacing rate.

Aged↗
PubMed1994

Prospective evaluation of cerebral angiography and computed tomography in cerebral haematoma.

One hundred and two consecutive patients with cerebral haematoma were prospectively allocated to one of two groups according to their CT on admission. Group 1 patients were thought to have a high probability of an underlying structural lesion and underwent cerebral angiography acutely. If normal, this was repeated at three months. Group 2 patients were thought not to have such a lesion and underwent angiography at three months. Patients older than the mean age of the study population, and hypertensive patients were much less likely to harbour an aneurysm or arteriovenous malformation than younger or normotensive patients (p < 0.01; sensitivity 87.9%, specificity 88.6%). An aneurysm or arteriovenous malformation was the cause of haemorrhage in 12.8% of hypertensive patients, in 30.9% of patients with haematoma involving the basal ganglia, and 18.2% of those with posterior fossa haemorrhage. Features of CT in isolation give a sensitivity of 77.2% and a specificity of 84.2%. Follow up angiography in group 1 showed an arteriovenous malformation in one of seven patients in whom the original study was normal. These results contrast sharply with data from previous retrospective studies. The decision to investigate a patient with cerebral haematoma should be primarily based on the patient's clinical condition, rather than on the site of haemorrhage.

Adolescent↗
PubMed1994

Reduced peak aerobic capacity in asymptomatic left ventricular systolic dysfunction. A substudy of the studies of left ventricular dysfunction (SOLVD). SOLVD Investigator. Studies of Left Ventricular Dysfunction.

BACKGROUND: Peak oxygen consumption is reduced in patients with symptomatic congestive heart failure, but functional capacity of patients with asymptomatic left ventricular systolic dysfunction has not been assessed by measurement of peak oxygen consumption attained during graded exercise testing. METHODS AND RESULTS: Peak oxygen consumption, that is, aerobic capacity (VO2, mL/kg per minute), was determined during graded treadmill exercise using the modified Naughton protocol in 40 patients with left ventricular systolic dysfunction (mean ejection fraction ranging from 14% to 35%; mean, 29%) who, while not receiving any cardiac medications, were totally asymptomatic, and in 41 age-matched normal subjects. Peak exercise duration and VO2 were significantly lower in patients with asymptomatic left ventricular systolic dysfunction than in normal subjects (948 +/- 273 versus 1239 +/- 372 seconds, P < .001, and 22.1 +/- 5.9 versus 29.8 +/- 7.7 mL/kg per minute, respectively, P < .001), while asymptomatic patients and normal subjects reached similar respiratory equivalents (1.14 +/- 0.11 versus 1.11 +/- 0.11 [NS]) and level of perceived exertion, using the modified Borg scale (7.4 +/- 2.6 versus 8.1 +/- 1.5 [NS]). Heart rate, systemic blood pressure, and oxygen pulse response to peak exercise were significantly lower in asymptomatic patients than in normal subjects. CONCLUSIONS: Although patients with left ventricular systolic dysfunction can be totally asymptomatic in their daily activities, they have experienced a substantial reduction in peak aerobic capacity when compared with normal subjects of similar age.

Aged↗
PubMed1993

Transcription factors important for starting the cell cycle in yeast.

Unlike early embryonic cleavage divisions in certain animals, cell-cycle progression in yeast and probably also in all metazoan somatic cells requires the periodic transcriptional activation of certain key genes. Thus far, the only clear examples are genes that encode a class of unstable 'cyclin' proteins, which bind and activate the cdc2/Cdc28 protein kinase: the G1-specific cyclins encoded by CLN1 and CLN2, a B-type cyclin implicated in DNA replication encoded by CLB5; and four B-type cyclins involved in mitosis encoded by CLB1, 2, 3, 4. CLN1, CLN2, and CLB5 are transcribed in late G1, as cells undergo Start. A transcription factor composed of Swi4 and Swi6 proteins (called SBF) activates CLN1 and CLN2 transcription via a positive feedback loop in which Cln proteins activate their own transcription. A different but related transcription factor called MBF seems responsible for the late G1-specific transcription of most DNA replication genes including CLB5. We have purified MBF and shown that it contains Swi6 and a 110-120 kDa protein distinct from Swi4 (p120) that contacts DNA. Thus, we propose that SBF and MBF share a common regulatory subunit (Swi6) but recognize their promoter elements via distinct DNA binding subunits.

Base Sequence↗
PubMed1993

Human sperm-egg binding is inhibited by peptides corresponding to core region of an acrosomal serine protease inhibitor.

An antiserum, designated R4 and raised against denatured hamster acrosomes, was shown to localize specifically to the acrosomal region of hamster, rat, mouse, and human spermatozoa, and to inhibit both hamster and human sperm-oocyte binding in vitro. Following screening of a human testis lambda gt11 cDNA expression library with the antiserum R4, a series of cDNA clones were isolated. One (cDNA 134) was selected based on the ability of the beta-galactosidase fusion protein to inhibit human and hamster sperm-zona binding in vitro. The fusion protein was also shown to inhibit the penetration of zona-free hamster oocytes by human spermatozoa. Sequence analysis revealed that cDNA 134 coded for a portion of a serine protease inhibitor (serpin) closely related to plasma Protein C inhibitor. Sequencing of an additional cDNA clone (261) and Northern blot analysis confirmed that a Protein C inhibitor-like mRNA is synthesised in the human testis. Affinity-purified anti-134 antibody specifically localized to the acrosomal region of both hamster and human sperm. Synthetic peptides corresponding to the conserved core region responsible for the interaction of the serpin with its cognate protease also blocked human sperm-zona binding in vitro. The results suggest that this acrosomally located inhibitor plays an important role in the series of binding events that results in human fertilization.

Acrosome↗
PubMed1993

Insulin-like growth factor-I mRNA expression in the interstitial cells of the rat testis.

IGF-I mRNA has been demonstrated in testicular tissue and, more recently, localized specifically to Leydig cells. This study investigated the expression of IGF-I and side-chain cleavage enzyme (SCC) mRNA in two preparations of rat interstitial testicular cells which were separated by buoyant density into Leydig cell-enriched and -depleted fractions. RNA was prepared from interstitial cells obtained from the testes of untreated adult and immature rats and adult rats treated with human chorionic gonadotrophin (hCG) or ethane dimethanesulphonate (EDS; to destroy Leydig cells). IGF-I mRNA was detected in all samples, with five major transcripts ranging from 7.5 to 0.6 kb. Leydig cells (3 beta-hydroxysteroid dehydrogenase-positive and sensitive to EDS) expressed abundant IGF-I and SCC mRNAs, and levels of both were increased following hCG treatment. However, in addition, IGF-I mRNA which was derived from non-Leydig interstitial cells was detected, in the complete absence of SCC message, either in the more buoyant interstitial cells or in both interstitial cell fractions following the destruction of Leydig cells by EDS treatment. IGF-I expression in the Leydig cell-depleted cell fraction was also increased by hCG treatment, and it is therefore suggested that at least part of this non-Leydig interstitial cell IGF-I mRNA originates in Leydig cell precursors. In conclusion, Leydig cells are not the sole origin of IGF-I mRNA in the testis, and the non-Leydig cell expression may be an important component of testicular IGF-I production.

Animals↗
PubMed1993

Paracrine effects via the epidermal growth factor receptor in the rodent testis may be mediated by non-Leydig interstitial cells.

The epidermal growth factor (EGF) receptor is expressed in a wide variety of cell types and is known to be present in the testis of many species including man. In the present study, specific 125I-labelled EGF binding was observed in isolated interstitial cell preparations from both the intact and Leydig cell-depleted rat testis. It was demonstrated that the population of cells to which 125I-labelled EGF binds has a different buoyant density from either of the two adult Leydig cell populations, and remains unchanged in the absence of Leydig cells following in-vivo treatment with ethane dimethane sulphonate (EDS). Cells of this density (1.064 g/ml) identified by electron microscopy were fusiform mesenchymal cells, identical to those suggested by others to be able to differentiate into Leydig cells in vitro, i.e. Leydig cell precursors. In a culture system using two interstitial cell preparations of different buoyant densities from immature rats, both EGF and transforming growth factor-alpha (TGF-alpha) caused increased [3H]thymidine incorporation in the less dense cell preparation. TGF-alpha was more potent than EGF. EGF increased testosterone production in both fractions in amounts which could be related to the amount of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD)-positive cells. This study demonstrated that rat Leydig cells (defined as those cells which bind 125I-labelled human chorionic gonadotrophin, have distinct buoyant densities, are 3 beta-HSD positive and are sensitive to EDS), do not bind 125I-labelled EGF. Rather, EGF binds to a mesenchymal cell without LH receptors which is resistant to EDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The involvement of insulin-like growth factor-I in local control of steroidogenesis and DNA synthesis of Leydig and non-Leydig cells in the rat testicular interstitium.

Insulin-like growth factor-I (IGF-I) peptide, receptors and binding proteins are present in the rodent testis, which strongly implies that IGF-I has one or more testicular functions. In the present study we provide further information to support the concept that IGF-I is an important local mediator in the testis. High concentrations of IGF-I were measurable in interstitial fluid by radioimmunoassay, and IGF-I-binding proteins (IGFBPs) were readily detectable in interstitial fluid by ligand blotting, the predominant type being IGFBP-2. In vitro, IGF-I bound to testicular interstitial cells which did not have 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity and which were resistant to ethane dimethanesulphonate treatment. In vitro, IGF-I receptor-mediated actions increased both steroidogenesis and DNA synthesis. Insulin stimulated DNA synthesis at concentrations appropriate to cross-react with the IGF-I receptor, and this effect was greater in a testicular interstitial Leydig cell-depleted cell population compared with a Leydig cell-enriched cell culture. Furthermore, combinations of epidermal growth factor or transforming growth factor -alpha together with insulin appeared to act synergistically, causing extremely large increases in [3H]thymidine incorporation in the interstitial cells. These results support a paracrine and/or autocrine role for IGF-I in interstitial cell growth and development.

Animals↗
PubMed1993

Management of spinal astrocytoma with conservative surgery and radiotherapy.

Twenty-seven patients with histologically verified spinal astrocytoma were treated at the Royal Marsden Hospital with postoperative radiotherapy. All patients had previous surgery; 10 had partial resection and 17 biopsy alone. All patients received involved field radiotherapy to a median dose of 50 Gy in 33 fractions. Overall 5- and 10-year survival was 59 and 52%, and progression free survival was 38 and 26% at 5 and 10 years, respectively, at a median follow-up of 6.5 years. Following radiotherapy, eight patients showed functional improvement, 15 were unchanged and two deteriorated. Sixteen patients relapsed, eleven at the primary site and five elsewhere in the CNS. Low grade histology, female gender and the presence of intramedullary cysts were favourable prognostic factors for survival on univariate analysis. The extent of surgery was not a significant predictor of survival. It is not possible to define the precise role of radiotherapy. However, all patients had residual tumour prior to irradiation, and 53% of low grade and 33% of high grade gliomas remained controlled locally at 3 years with stabilization or improvement in neurological function in all but two patients. This suggests that radiotherapy may result in temporary disease control analogous to cerebral gliomas.

Adolescent↗
PubMed1992

17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate is a potent odorant in precocious male Atlantic salmon (Salmo salar L.) parr which have been pre-exposed to the urine of ovulated females.

Electrophysiological recordings from the olfactory epithelium have shown that 17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate (17,20 beta-P-sulphate; a conjugate of the oocyte-maturation-inducing steroid in teleosts) is a potent odorant in precocious male Atlantic salmon (Salmo salar L.) parr. However, the olfactory epithelium of these fish only appeared to be responsive to the steroid after stimulation with the urine of ovulated female Atlantic salmon. Immature fish did not respond at any time. Stimulation with urine from immature and precocious male Atlantic salmon parr did not make the olfactory epithelium of precocious male salmon parr responsive to the steroid. 17,20 beta-P-sulphate was found in the urines of ovulated females, precocious male parr and mature male Atlantic salmon. The findings are discussed in relation to the possible role of 17,20 beta-P-sulphate in the physiology of Atlantic salmon.

Animals↗
PubMed1992

Measuring recovery from general anaesthesia using critical flicker frequency: a comparison of two methods.

Critical flicker frequency (CFF) is the frequency at which a flickering light appears steady. It is a sensitive measure for assessing recovery from anaesthesia. The CFF is almost always determined with the method of limits by which the flickering frequency is progressively decreased (or increased) until the patient reports a change from fusion to flicker (or flicker to fusion). This method has two disadvantages: it is influenced by the response bias (i.e., the subjective criterion used by the subject to decide that flicker is present or absent) and by the response delay (i.e., the interval between the perceptual change and the response). To avoid these problems, the method of forced choice is recommended. For each trial, the subject observes the light during two short successive periods. The light flickers during only one period, according to chance. The patient must indicate the period during which flickers occur. If uncertain, the patient has to make a guess. The aim of this study was to compare the two methods for assessing recovery from general anaesthesia. Two induction agents were used to obtain different recovery profiles. Twenty patients undergoing uncomplicated surgery lasting less than two hours were tested. They received either thiopentone or midazolam for induction, according to a randomized design. Vecuronium was used to facilitate tracheal intubation and anaesthesia was maintained with fentanyl, isoflurane and nitrous oxide. The CFF was measured before induction and at 60, 120 and 180 minutes after arrival in the recovery room. The person measuring CFF was unaware of the induction agent used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

An independent application accuracy evaluation of stereotactic frame systems.

The purpose of incorporating stereotactic methodology into neurosurgical procedures is to consistently achieve a high degree of accuracy and precision in localizing intracranial targets. Therefore, the limits of resolution for the therapeutic intervention itself are a function of the accuracy and precision inherent to the particular stereotactic frame system itself. The total clinically relevant error (application accuracy) comprises errors associated with each procedural step, including imaging, target selection, vector calculation and the mechanical errors of stereotactic frames. To evaluate these parameters, a systematic error analysis was carried out in the 4 most commonly used CT-compatible stereotactic devices: the Brown-Roberts-Wells, Cosman-Roberts-Wells, Kelly-Goerss Compass (modified Todd-Wells) and Leksell frames. Over 7,681 independent test measurements were made. The results suggest a potentially significant degree of error in application accuracy of all stereotactic instrumentation which is accentuated by imaging-associated error. These individual error values must be considered with every clinical use of stereotactic frames.

Humans↗