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Biomedical subjects

J Lewis

Publications and source records attributed to J Lewis.

At least 163 records · Page 9Linked to original sources
PubMed1998

Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development.

The sensory patches in the vertebrate inner ear are similar in function to the mechanosensory bristles of a fly, and consist of a similar set of cell types. If they are truly homologous structures, they should also develop by similar mechanisms. We examine the genesis of the neurons, hair cells and supporting cells that form the sensory patches in the inner ear of the chick. These all arise from the otic epithelium, and are produced normally even in otic epithelium cultured in isolation, confirming that their production is governed by mechanisms intrinsic to the epithelium. First, the neuronal sublineage becomes separate from the epithelial: between E2 and E3.5, neuroblasts delaminate from the otocyst. The neuroblasts then give rise to a mixture of neurons and neuroblasts, while the sensory epithelial cells diversify to form a mixture of hair cells and supporting cells. The epithelial patches where this occurs are marked from an early stage by uniform and maintained expression of the Notch ligand Serrate1. The Notch ligand Delta1 is also expressed, but transiently and in scattered cells: it is seen both early, during neuroblast segregation, where it appears to be in the nascent neuroblasts, and again later, in the ganglion and in differentiating sensory patches, where it appears to be in the nascent hair cells, disappearing as they mature. Delta-Notch-mediated lateral inhibition may thus act at each developmental branchpoint to drive neighbouring cells along different developmental pathways. Our findings indicate that the sensory patches of the vertebrate inner ear and the sensory bristles of a fly are generated by minor variations of the same basic developmental program, in which cell diversification driven by Delta-Notch and/or Serrate-Notch signalling plays a central part.

Animals↗
PubMed1998

Multiple delta genes and lateral inhibition in zebrafish primary neurogenesis.

In Drosophila, cells are thought to be singled out for a neural fate through a competitive mechanism based on lateral inhibition mediated by Delta-Notch signalling. In tetrapod vertebrates, nascent neurons express the Delta1 gene and thereby deliver lateral inhibition to their neighbours, but it is not clear how these cells are singled out within the neurectoderm in the first place. We have found four Delta homologues in the zebrafish--twice as many as reported in any tetrapod vertebrate. Three of these--deltaA, deltaB and deltaD--are involved in primary neurogenesis, while two--deltaC and deltaD--appear to be involved in somite development. In the neural plate, deltaA and deltaD, unlike Delta1 in tetrapods, are expressed in large patches of contiguous cells, within which scattered individuals expressing deltaB become singled out as primary neurons. By gene misexpression experiments, we show: (1) that the singling-out of primary neurons, including the unique Mauthner cell on each side of the hindbrain, depends on Delta-Notch-mediated lateral inhibition, (2) that deltaA, deltaB and deltaD all have products that can deliver lateral inhibition and (3) that all three of these genes are themselves subject to negative regulation by lateral inhibition. These properties imply that competitive lateral inhibition, mediated by coordinated activities of deltaA, deltaB and deltaD, is sufficient to explain how primary neurons emerge from proneural clusters of neuroepithelial cells in the zebrafish.

Amino Acid Sequence↗
PubMed1998

Clean-catch versus urine collection pads: a prospective trial.

Two methods for collecting urine samples from very young children were compared in a paediatric ward of a busy district general hospital. Samples collected using urine collection pads were compared to the standard clean-catch method using sterile foil bowls. No significant differences were observed in the outcome of tests from samples collected by the two methods over the course of a short nurse-led trial, and the hospital has adopted the urine collection pad for routine paediatric UTI sampling.

Humans↗
PubMed1997

Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the embryonic chick retina.

BACKGROUND: Neurons of the vertebrate central nervous system (CNS) are generated sequentially over a prolonged period from dividing neuroepithelial progenitor cells. Some cells in the progenitor cell population continue to proliferate while others stop dividing and differentiate as neurons. The mechanism that maintains the balance between these two behaviours is not known, although previous work has implicated Delta-Notch signalling in the process. RESULTS: In normal development, the proliferative layer of the neuroepithelium includes both nascent neurons that transiently express Delta-1 (Dl1), and progenitor cells that do not. Using retrovirus-mediated gene misexpression in the embryonic chick retina, we show that where progenitor cells are exposed to Dl1 signalling, they are prevented from embarking on neuronal differentiation. A converse effect is seen in cells expressing a dominant-negative form of Dl1, Dl1(dn), which we show renders expressing cells deaf to inhibitory signals from their neighbours. In a multicellular patch of neuroepithelium expressing Dl1(dn), essentially all progenitors stop dividing and differentiate prematurely as neurons, which can be of diverse types. Thus, Delta-Notch signalling controls a cell's choice between remaining as a progenitor and differentiating as a neuron. CONCLUSIONS: Nascent retinal neurons, by expressing Dl1, deliver lateral inhibition to neighbouring progenitors; this signal is essential to prevent progenitors from entering the neuronal differentiation pathway. Lateral inhibition serves the key function of maintaining a balanced mixture of dividing progenitors and differentiating progeny. We propose that the same mechanism operates throughout the vertebrate CNS, enabling large numbers of neurons to be produced sequentially and adopt different characters in response to a variety of signals. A similar mechanism of lateral inhibition, mediated by Delta and Notch proteins, may regulate stem-cell function in other tissues.

Animals↗
PubMed1997

UKCCSG study of accelerated radiotherapy for pediatric brain stem gliomas. United Kingdom Childhood Cancer Study Group.

PURPOSE: Between 1991 and 1994, the United Kingdom Childhood Cancer Study Group (UKCCSG) conducted a multicenter study to assess the efficiency and tolerability of accelerated radiotherapy in children with a diagnosis of poor-prognosis brain stem glioma. METHODS AND MATERIALS: Patients eligible for study were those aged 3-16 years with tumors arising in the pons, medulla, or midbrain, not previously treated with radiotherapy or chemotherapy. Histologic confirmation was not mandatory, but computed tomography or magnetic resonance imaging and clinical findings had to be typical, and patients were selected with short prediagnosis symptom history (<3 months), cranial nerve palsies or long tract signs, and intrinsic diffuse lesions on scanning. The treatment dose was 48.6 Gy in 27 fractions, increased to 50.4 Gy in 28 fractions in January 1992, delivered twice daily (except weekends) with an interfraction interval of at least 8 h. Between January 1991 and July 1994, 28 available patients were recruited: 15 boys and 13 girls with ages ranging between 3 and 13 years (median 6). RESULTS: After treatment, neurologic improvement sustained for a period of at least 6 weeks without steroids was reported in 13 children (46%). On central review of postradiotherapy imaging, 50% of children showed evidence of partial response, but none exhibited a complete response. A further six patients (22%) had stable disease. The median survival time was 37 weeks (8.5 months); 1-year survival was 32%, and 2-year survival 11%. The pattern of relapse was local in all 26 patients who died of their disease; 1 patient had evidence of leptomeningeal seeding. Acute radiation morbidity was minimal, with only three patients (11%) exhibiting mild toxicity. No evidence of radiation-induced necrosis was found radiologically or histologically at postmortem. Ability to withdraw steroids following radiotherapy was the single most important prognostic variable in our study. CONCLUSION: The results of this study are comparable to previous outcomes of studies with conventional and hyperfractionated radiotherapy in poor-prognosis brain stem glioma. The fractionation regimen was shown to be tolerable with an acceptable morbidity profile. However, further research is required to improve the poor prognosis of these unfortunate children.

Adolescent↗
PubMed1997

Primary care--opportunities and threats. The changing meaning of the GP contract.

The meaning of the GP contract has changed since the last major upheaval in the mid-1960s. The government has always dealt with general practitioners as independent contractors, but the way in which it treated them in 1990 was entirely different from the way in which they were treated in 1966. In 1966, the profession's independent contractor status effectively served to protect professional autonomy. In 1990, with the change in the form of government towards a "contract state," general practitioners were treated as independent contractors more in the sense of business entrepreneurs. The article finishes by raising the issue of how general practitioners can gain control over the medicopolitical agenda in the future.

Attitude of Health Personnel↗
PubMed1997

Evaluation of color kinesis, a new echocardiographic method for analyzing regional wall motion in patients with dilated left ventricles.

The recently developed echocardiographic technology of color kinesis (CK) displays endocardial motion in color layers on a single end-systolic 2-dimensional echocardiographic frame. Previous work using this method is promising for quantitation of regional function, but there is limited experience in patients with severely reduced left ventricular function. Twenty patients (age 59 +/- 10 years) with dilated cardiomyopathy (left ventricular ejection fraction 22 +/- 8%) underwent CK imaging. Endocardial motion was quantitated by measuring the distance of endocardial motion during the systolic interval and also by calculating the endocardial velocity. CK measurements were compared among 4 wall motion grades (i.e., normal, hypokinetic, akinetic, and dyskinetic) assessed by qualitative wall motion scoring. There was a significant overall difference (p < 0.0001) in the mean systolic endocardial inward motion (i.e., contraction) and outward motion (i.e., expansion) among wall motion grades. The mean endocardial outward distance was significantly greater for the dyskinetic segments than for the other grades (p < 0.001). There were also differences in the mean velocity of endocardial motion among the wall motion grades. In the presence of left bundle branch block, there was no difference in the mean endocardial inward distance of the hypokinetic, akinetic, and dyskinetic septal segments. We conclude that in the absence of left bundle branch block, normal, hypokinetic, akinetic, and dyskinetic ventricular wall segments may be distinguished in patients with dilated cardiomyopathy on the basis of endocardial motion measured with CK.

Bundle-Branch Block↗
PubMed1997

Intercellular signals and cell-fate choices in the developing inner ear: origins of global and of fine-grained pattern.

The major regions of the inner ear begin to be distinguishable by their patterns of gene expression very early, before the otocyst has closed. Later, individual cells within a neurogenic or sensory patch become committed to specific pathways of differentiation. Insights gained from homologies with invertebrates and from studies of tissues other than the ear, combined with discoveries from screens for mutations affecting development in the zebrafish, are beginning to reveal the genes and signalling mechanisms that control these cell-fate choices in the developing inner ear.

Journal Article↗
PubMed1997

Device choice and experience level in endoscopic foreign object retrieval: an in vivo study.

BACKGROUND: Successful foreign object retrieval may depend on device choice and the experience level of the endoscopist, although these factors have not been systematically evaluated. METHODS: In anesthetized pigs, the ability to retrieve foreign objects (metal tack, button disc battery, wooden toothpick) placed endoscopically into the stomach was assessed. Seven university medical center gastroenterology attending physicians (5 clinical and 2 basic science research [BSR]), and 4 fellows-in-training participated. The devices used were the Roth retrieval net, rat tooth forceps, Dormia basket, polypectomy snare, and radial jaw forceps. The time to retrieve each object into an esophageal overtube within a 5 minute maximum was measured. RESULTS: Only the Roth net and Dormia basket were successful in retrieving the button disc battery, although the Roth net was superior (100% vs 27%, Fisher p < 0.025). All devices were equally successful at retrieving the tack (82% to 100%, p = NS). The snare was significantly faster than the Roth net (p < 0.05). For the tack, there was significantly fewer difficulties encountered with the snare than the Roth net (Fisher p < 0.03). The Roth net was incapable of retrieving the toothpick; the other devices were equally successful (91% to 100%). The clinical attendings had a significantly higher success rate (95%) than the fellows (82%, chi squared p < 0.05) or combined fellows/BSR attendings (80%, p < 0.02), and were significantly faster than the fellows (p < 0.0002) or the fellows/BSR attendings (p < 0.0003). CONCLUSIONS: The Roth net is the best device for retrieving smooth objects such as the button disc battery. For sharp objects, such as the tack and toothpick, best results were achieved with the snare, although the forceps were also effective. More experienced endoscopists had higher success rates and faster retrieval times. Both device choice and the experience level of the endoscopists have an impact on successful foreign object retrieval.

Animals↗
PubMed1997

Umbilical cord blood interleukin-6 levels and neonatal morbidity.

OBJECTIVE: To study umbilical cord interleukin-6 levels and the occurrence of neonatal sepsis, congenital pneumonia, necrotizing enterocolitis, and grade II-IV intraventricular hemorrhage. METHODS: Umbilical cord blood was collected from 133 preterm newborns. The study population was divided according to the presence or absence of neonatal complications. Interleukin-6 levels and clinical characteristics were compared by univariate and multivariate analyses. RESULTS: Sixteen neonates had adverse outcomes, and 117 were unaffected. The median interleukin-6 level was significantly higher in affected than in unaffected infants (145 pg/mL versus 0 pg/mL, P = .002). Elevated interleukin-6 levels were associated independently with neonatal morbidity in multiple logistic regression modeling that included gestational age, birth weight, and antenatal steroid exposure. CONCLUSION: Umbilical cord blood interleukin-6 levels are elevated in neonates who subsequently develop sepsis, congenital pneumonia, necrotizing enterocolitis, or grade II-IV intraventricular hemorrhage.

Adult↗
PubMed1997

Subclavian artery stenosis presenting as posterior cerebrovascular events after adjuvant radiotherapy for breast cancer.

Late radiotherapy-induced arteriopathy is recognized as an important cause of cerebrovascular disease in patients treated with radiotherapy, usually for head and neck cancers. This case report is an example of radiotherapy-induced left subclavian artery stenosis, which resulted in serious posterior cerebral circulation events after adjuvant radiotherapy for carcinoma of the left breast. In view of the relatively good long term outlook for this disease, it is important to recognize and consider early medical or surgical intervention of such arterial lesions. In this patient, earlier intensive investigations probably would have prevented disabling iatrogenic morbidity.

Adult↗
PubMed1997

Editorial

Explore the source record for details and available documents.

Journal Article↗
PubMed1997

The issue of never-married motherhood in Britain, 1920-70.

This article examines shifts in attitudes and changes in provision with regard to never-married mothers within three broad chronological periods. The first section considers attitudes towards these mothers in the period 1918-45, when the issue was conceptualized as one of public health and moral welfare. Second, the article examines the period between 1945 and 1970, when the dominant professional view of never-married mothers focused on identifying individual pathology, but when significant continuities in treatment can nevertheless be found. Third, the article looks briefly at the substantial change in policy and provision for what were then called 'one-parent families' during the 1970s. In conclusion it argues that while there were substantial changes in terms of the way in which unmarried motherhood was defined, from the point of view of the unmarried mothers themselves the continuities have been more striking. Unmarried mothers have been persistently singled out and labelled a social problem and, in all but a brief period during the late 1960s and 1970s, also as a moral problem.

History, 20th Century↗
PubMed1997

Organization and development of facial motor neurons in the kreisler mutant mouse.

The adult facial nerve contains the axons from two populations of efferent neurons. First, the branchiomotor efferent neurons that innervate the muscles of the second arch. These neurons project out of the hindbrain in the motor root and form the facial motor nuclei. Second, the preganglionic efferent neurons that innervate the submandibular and pterygopalatine ganglia. These neurons project from the hindbrain via the intermediate nerve and form the superior salivatory nucleus. The motor neurons of the facial nerve are known to originate within rhombomeres 4 and 5. In the kreisler mouse mutant there is a specific disruption of the hindbrain rhombomeres 5 and 6 appear to be absent. To investigate changes in the organization of the facial motor neurons in this mutant, we have used lipophilic dyes to trace the facial motor components both retrogradely and anterogradely. As expected, facial motor neurons are missing from rhombomere 5 in this mutant. In addition, the loss of these neurons correlates with the specific loss of the superior salivatory nucleus. In contrast, the branchiomeric neurons, that originate in rhombomere 4, appear to develop normally. This includes the caudal migration of their cell bodies forming the genu of the facial nerve. Our studies confirm that rhombomeres are critical to hindbrain development and that they are the fundamental unit at which motor neurons are specified.

Animals↗
PubMed1997

Alterations of the endogenous surfactant system in septic adult rats.

Sepsis is the most common factor leading to the acute respiratory distress syndrome (ARDS) and is associated with the highest mortality rate. It has been suggested that the pulmonary surfactant system is altered and contributes to the lung dysfunction associated with ARDS. The objective of this study was to characterize the lung injury, specifically the endogenous surfactant system in septic adult rats. Sepsis was induced in male Sprague-Dawley rats by cecal ligation and perforation and resulted in significant increases in heart rates, respiratory rates, and lactate levels along with positive blood cultures in septic animals compared with a sham control group. Two distinct septic groups were developed, a septic group and a sepsis with lung injury (septic+LI) group. The septic group had no significant differences in oxygenation compared with the sham group, whereas the septic+LI group had significantly lower PaO2 and higher A-a gradient values compared to both the sham and septic groups. The total surfactant pool size was significantly lower in the septic+LI group compared with the sham group. The small surfactant aggregate to large surfactant aggregate ratio was significantly lower in the septic group and was further reduced in the septic+LI group. There were also significantly higher levels of surfactant protein A (SP-A) in both septic and septic+LI groups compared to the sham group. These results demonstrated that the endogenous surfactant system was altered in systemic sepsis without lung dysfunction and is further altered when a lung injury is present.

Analysis of Variance↗
PubMed1996

Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ.

Modular PDZ domains, found in many cell junction-associated proteins, mediate the clustering of membrane ion channels by binding to their C-terminus. The X-ray crystallographic structures of the third PDZ domain from the synaptic protein PSD-95 in complex with and in the absence of its peptide ligand have been determined at 1.8 angstroms and 2.3 angstroms resolution, respectively. The structures reveal that a four-residue C-terminal stretch (X-Thr/Ser-X-Val-COO(-)) engages the PDZ domain through antiparallel main chain interactions with a beta sheet of the domain. Recognition of the terminal carboxylate group of the peptide is conferred by a cradle of main chain amides provided by a Gly-Leu-Gly-Phe loop as well as by an arginine side chain. Specific side chain interactions and a prominent hydrophobic pocket explain the selective recognition of the C-terminal consensus sequence.

Crystallography↗